Nutrient chapter

Delta-9-tetrahydrocannabinol / THC

Delta-9-tetrahydrocannabinol / THC. Species, exposure and limitations are retained in each linked claim.

51 recorded mechanisms · 5 availability situations · 1 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

A cloned complementary DNA encoded a G protein-coupled receptor that inhibits adenylate cyclase in a dose-dependent, stereoselective and pertussis-toxin-sensitive manner, is more responsive to psychoactive than to non-psychoactive cannabinoids, and whose messenger RNA is found in the brain regions that have cannabinoid receptors.
Human cannabinoid receptor 1 / CB1 / CNR1 → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/2165569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db", "start_char": 0, "end_char": 1256, "text_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db"}
experimental_model
Cloning and heterologous expression of a complementary DNA from rat brain
exposure
Cannabinoid binding and adenylate cyclase inhibition in the transfected cells
limitations
The founding cloning paper. It establishes a receptor, which is what displaced the membrane-disruption explanation of cannabinoid action.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat receptor expressed in cells
plain_language
Cannabis acts on a specific receptor, not by melting cell membranes as was assumed.
primary_references
[thc-p2165569] Structure of a cannabinoid receptor and functional expression of the cloned cDNA. (1990). https://pubmed.ncbi.nlm.nih.gov/2165569/ DOI: 10.1038/346561a0
tissue_or_cell_type
Brain and neural cell lines
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 62–73
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning and heterologous expression of a complementary DNA from rat brain · source_derived_draft · unverified_draft
### thc-cb1-cloned A cloned complementary DNA encoded a G protein-coupled receptor that inhibits adenylate cyclase in a dose-dependent, stereoselective and pertussis-toxin-sensitive manner, is more responsive to psychoactive than to non-psychoactive cannabinoids, and whose messenger RNA is found in the brain regions that have cannabinoid receptors. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Cannabis acts on a specific receptor, not by melting cell membranes as was assumed. organism: Rat receptor expressed in cells tissue_or_cell_type: Brain and neural cell lines experimental_model: Cloning and heterologous expression of a complementary DNA from rat brain limitations: The founding cloning paper. It establishes a receptor, which is what displaced the membrane-disruption explanation of cannabinoid action. exposure: Cannabinoid binding and adenylate cyclase inhibition in the transfected cells evidence_span: {"source_cache": "artifacts/thc-research/2165569.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db", "start_char": 0, "end_char": 1256, "text_sha256": "8d92b7104006ccc194ab498aa8f559606353e6ccc4b5aa7af0a9502c9bfc37db"} [thc-p2165569] Structure of a cannabinoid receptor and functional expression of the cloned cDNA. (1990). https://pubmed.ncbi.nlm.nih.gov/2165569/ DOI: 10.1038/346561a0
Complete structured claim and evidence
A human cannabinoid receptor was cloned and found to be expressed in testis as well as brain.
Human cannabinoid receptor 1 / CB1 / CNR1 → The CB1 ligand-binding pocket source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/1718258.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6cd532c253d8e3d3d40738876bf1ba5a38d5c678355f5e871fb5a853aa3362e0", "start_char": 0, "end_char": 1497, "text_sha256": "6cd532c253d8e3d3d40738876bf1ba5a38d5c678355f5e871fb5a853aa3362e0"}
experimental_model
Molecular cloning of the human receptor with tissue expression analysis
exposure
Expression analysis across tissues
limitations
Extends the receptor to humans and finds it outside the brain, which is the first hint that the system is not purely neural.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human receptor
plain_language
The same receptor turns up in tissue far from the brain.
primary_references
[thc-p1718258] Molecular cloning of a human cannabinoid receptor which is also expressed in testis. (1991). https://pubmed.ncbi.nlm.nih.gov/1718258/ DOI: 10.1042/bj2790129
tissue_or_cell_type
Brain and testis
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 75–86
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Molecular cloning of the human receptor with tissue expression analysis · source_derived_draft · unverified_draft
### thc-cb1-human-testis A human cannabinoid receptor was cloned and found to be expressed in testis as well as brain. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The same receptor turns up in tissue far from the brain. organism: Human receptor tissue_or_cell_type: Brain and testis experimental_model: Molecular cloning of the human receptor with tissue expression analysis limitations: Extends the receptor to humans and finds it outside the brain, which is the first hint that the system is not purely neural. exposure: Expression analysis across tissues evidence_span: {"source_cache": "artifacts/thc-research/1718258.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6cd532c253d8e3d3d40738876bf1ba5a38d5c678355f5e871fb5a853aa3362e0", "start_char": 0, "end_char": 1497, "text_sha256": "6cd532c253d8e3d3d40738876bf1ba5a38d5c678355f5e871fb5a853aa3362e0"} [thc-p1718258] Molecular cloning of a human cannabinoid receptor which is also expressed in testis. (1991). https://pubmed.ncbi.nlm.nih.gov/1718258/ DOI: 10.1042/bj2790129
Complete structured claim and evidence
The murine CB2 peripheral cannabinoid receptor was cloned, expressed and shown to function as a cannabinoid receptor distinct from the brain receptor.
Mouse peripheral cannabinoid receptor CB2 / Cnr2 → Delta-9-tetrahydrocannabinol / THC source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/8679694.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4", "start_char": 0, "end_char": 967, "text_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4"}
experimental_model
Cloning, expression and functional characterisation of the murine CB2 receptor
exposure
Heterologous expression with ligand binding
limitations
Establishes a second, peripheral receptor. It is the mouse orthologue.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse receptor
plain_language
A second receptor exists, and it sits mostly outside the brain.
primary_references
[thc-p8679694] Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. (1996). https://pubmed.ncbi.nlm.nih.gov/8679694/ DOI: 10.1016/0167-4781(96)00047-4
tissue_or_cell_type
Peripheral and immune tissue
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 88–99
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cloning, expression and functional characterisation of the murine CB2 receptor · source_derived_draft · unverified_draft
### thc-cb2-cloned The murine CB2 peripheral cannabinoid receptor was cloned, expressed and shown to function as a cannabinoid receptor distinct from the brain receptor. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: A second receptor exists, and it sits mostly outside the brain. organism: Mouse receptor tissue_or_cell_type: Peripheral and immune tissue experimental_model: Cloning, expression and functional characterisation of the murine CB2 receptor limitations: Establishes a second, peripheral receptor. It is the mouse orthologue. exposure: Heterologous expression with ligand binding evidence_span: {"source_cache": "artifacts/thc-research/8679694.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4", "start_char": 0, "end_char": 967, "text_sha256": "6140a784856b6848c64e4be175012e45a0c7343fa524308753bee15fc57162d4"} [thc-p8679694] Molecular cloning, expression and function of the murine CB2 peripheral cannabinoid receptor. (1996). https://pubmed.ncbi.nlm.nih.gov/8679694/ DOI: 10.1016/0167-4781(96)00047-4
Complete structured claim and evidence
CB1 and CB2 receptors were characterised for expression and adenylate cyclase modulation within the immune system.
Human cannabinoid receptor 2 / CB2 / CNR2 → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/9070350.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c", "start_char": 0, "end_char": 2231, "text_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c"}
experimental_model
Expression and adenylate cyclase modulation across immune cell populations
exposure
Cannabinoid agonists with cAMP measurement
limitations
Maps which immune cells carry which receptor. Expression and cAMP modulation are measured; immune function outcomes are not.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse and human immune cells
plain_language
Immune cells carry the second receptor and respond through the same messenger.
primary_references
[thc-p9070350] Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. (1997). https://pubmed.ncbi.nlm.nih.gov/9070350/ DOI: 10.1006/taap.1996.8034
tissue_or_cell_type
Immune system
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 101–112
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Expression and adenylate cyclase modulation across immune cell populations · source_derived_draft · unverified_draft
### thc-cb2-immune CB1 and CB2 receptors were characterised for expression and adenylate cyclase modulation within the immune system. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Immune cells carry the second receptor and respond through the same messenger. organism: Mouse and human immune cells tissue_or_cell_type: Immune system experimental_model: Expression and adenylate cyclase modulation across immune cell populations limitations: Maps which immune cells carry which receptor. Expression and cAMP modulation are measured; immune function outcomes are not. exposure: Cannabinoid agonists with cAMP measurement evidence_span: {"source_cache": "artifacts/thc-research/9070350.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c", "start_char": 0, "end_char": 2231, "text_sha256": "ee1863096eec8d8a18cd47cbc858ebaba4cf13d8bb3b78cd5179e1c1200c130c"} [thc-p9070350] Cannabinoid receptors CB1 and CB2: a characterization of expression and adenylate cyclase modulation within the immune system. (1997). https://pubmed.ncbi.nlm.nih.gov/9070350/ DOI: 10.1006/taap.1996.8034
Complete structured claim and evidence
The crystal structure of the human CB1 receptor was determined, resolving the architecture of its ligand-binding pocket.
The crystallographic model of the human CB1 receptor → The CB1 ligand-binding pocket source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/27768894.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eca46f11c563fdc4265930c57c7d856782d2130b77721d8470e779a3efaf6cc1", "start_char": 0, "end_char": 1042, "text_sha256": "eca46f11c563fdc4265930c57c7d856782d2130b77721d8470e779a3efaf6cc1"}
experimental_model
X-ray crystallography of the human CB1 receptor
exposure
Antagonist-bound receptor crystallography
limitations
A structure of one conformational state with one ligand class bound. It does not by itself explain agonist efficacy differences.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human receptor
plain_language
The receptor has a defined shape, and the drug fits into a specific slot in it.
primary_references
[thc-p27768894] Crystal Structure of the Human Cannabinoid Receptor CB1. (2016). https://pubmed.ncbi.nlm.nih.gov/27768894/ DOI: 10.1016/j.cell.2016.10.004
tissue_or_cell_type
Purified receptor
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 114–125
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of the human CB1 receptor · source_derived_draft · unverified_draft
### thc-cb1-structure The crystal structure of the human CB1 receptor was determined, resolving the architecture of its ligand-binding pocket. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The receptor has a defined shape, and the drug fits into a specific slot in it. organism: Human receptor tissue_or_cell_type: Purified receptor experimental_model: X-ray crystallography of the human CB1 receptor limitations: A structure of one conformational state with one ligand class bound. It does not by itself explain agonist efficacy differences. exposure: Antagonist-bound receptor crystallography evidence_span: {"source_cache": "artifacts/thc-research/27768894.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eca46f11c563fdc4265930c57c7d856782d2130b77721d8470e779a3efaf6cc1", "start_char": 0, "end_char": 1042, "text_sha256": "eca46f11c563fdc4265930c57c7d856782d2130b77721d8470e779a3efaf6cc1"} [thc-p27768894] Crystal Structure of the Human Cannabinoid Receptor CB1. (2016). https://pubmed.ncbi.nlm.nih.gov/27768894/ DOI: 10.1016/j.cell.2016.10.004
Complete structured claim and evidence
The crystal structure of the human CB2 receptor was determined, showing how its binding pocket differs from that of CB1.
Human cannabinoid receptor 2 / CB2 / CNR2 → Delta-9-tetrahydrocannabinol / THC source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/30639103.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f", "start_char": 0, "end_char": 1108, "text_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f"}
experimental_model
X-ray crystallography of the human CB2 receptor
exposure
Ligand-bound receptor crystallography
limitations
A companion structure for the second receptor, from the same structural programme.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human receptor
plain_language
The two receptors are shaped differently, which is why drugs can prefer one.
primary_references
[thc-p30639103] Crystal Structure of the Human Cannabinoid Receptor CB2. (2019). https://pubmed.ncbi.nlm.nih.gov/30639103/ DOI: 10.1016/j.cell.2018.12.011
tissue_or_cell_type
Purified receptor
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 127–138
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography of the human CB2 receptor · source_derived_draft · unverified_draft
### thc-cb2-structure The crystal structure of the human CB2 receptor was determined, showing how its binding pocket differs from that of CB1. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The two receptors are shaped differently, which is why drugs can prefer one. organism: Human receptor tissue_or_cell_type: Purified receptor experimental_model: X-ray crystallography of the human CB2 receptor limitations: A companion structure for the second receptor, from the same structural programme. exposure: Ligand-bound receptor crystallography evidence_span: {"source_cache": "artifacts/thc-research/30639103.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f", "start_char": 0, "end_char": 1108, "text_sha256": "e8e9d44274299ee2844e8fdb56ae1a20709f3fde09ed0ef99ee406a4e46a3c7f"} [thc-p30639103] Crystal Structure of the Human Cannabinoid Receptor CB2. (2019). https://pubmed.ncbi.nlm.nih.gov/30639103/ DOI: 10.1016/j.cell.2018.12.011
Complete structured claim and evidence
The cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex.
Human cannabinoid receptor 2 / CB2 / CNR2 → Heterotrimeric Gi/o proteins source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/32004460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92", "start_char": 0, "end_char": 885, "text_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92"}
experimental_model
Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi
exposure
Agonist-bound receptor coupled to Gi
limitations
Captures the active, G-protein-coupled state rather than an antagonist-bound one, which is what makes the coupling claim structural rather than inferred.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human receptor complex
plain_language
The receptor was caught in the act of holding its signalling partner.
primary_references
[thc-p32004460] Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. (2020). https://pubmed.ncbi.nlm.nih.gov/32004460/ DOI: 10.1016/j.cell.2020.01.007
tissue_or_cell_type
Purified signalling complex
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 140–151
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi · source_derived_draft · unverified_draft
### thc-cb2-gi-structure The cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The receptor was caught in the act of holding its signalling partner. organism: Human receptor complex tissue_or_cell_type: Purified signalling complex experimental_model: Cryo-electron microscopy of the CB2 receptor bound to heterotrimeric Gi limitations: Captures the active, G-protein-coupled state rather than an antagonist-bound one, which is what makes the coupling claim structural rather than inferred. exposure: Agonist-bound receptor coupled to Gi evidence_span: {"source_cache": "artifacts/thc-research/32004460.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92", "start_char": 0, "end_char": 885, "text_sha256": "928d847ab187a3e3fe459d16f2b1e4068e3378ba613d8122ae49173f03a42c92"} [thc-p32004460] Cryo-EM Structure of the Human Cannabinoid Receptor CB2-Gi Signaling Complex. (2020). https://pubmed.ncbi.nlm.nih.gov/32004460/ DOI: 10.1016/j.cell.2020.01.007
Complete structured claim and evidence
Cannabinoids inhibited adenylate cyclase in neuroblastoma cell membranes with a pharmacology matching their psychoactivity.
Delta-9-tetrahydrocannabinol / THC → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/6092901.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5", "start_char": 0, "end_char": 1329, "text_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5"}
experimental_model
Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes
exposure
Cannabinoid concentration-response on adenylate cyclase
limitations
One of the two founding pharmacology papers for Gi coupling. A transformed cell line, and cAMP is a proximal readout.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Cultured neuroblastoma cells
plain_language
The drug turns down the enzyme that makes the cell’s main second messenger.
primary_references
[thc-p6092901] Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. (1984). https://pubmed.ncbi.nlm.nih.gov/6092901/ DOI: 10.1016/s0026-895x(25)15066-9
tissue_or_cell_type
Cell membranes
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 153–164
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes · source_derived_draft · unverified_draft
### thc-cannabinoid-inhibits-ac Cannabinoids inhibited adenylate cyclase in neuroblastoma cell membranes with a pharmacology matching their psychoactivity. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The drug turns down the enzyme that makes the cell’s main second messenger. organism: Cultured neuroblastoma cells tissue_or_cell_type: Cell membranes experimental_model: Cannabinoid pharmacology of adenylate cyclase in neuroblastoma cell membranes limitations: One of the two founding pharmacology papers for Gi coupling. A transformed cell line, and cAMP is a proximal readout. exposure: Cannabinoid concentration-response on adenylate cyclase evidence_span: {"source_cache": "artifacts/thc-research/6092901.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5", "start_char": 0, "end_char": 1329, "text_sha256": "996df269d90c0b0e02d12157d4ebc3dd16e6be5013bc741cf4ed9b798f0e7eb5"} [thc-p6092901] Cannabinoid inhibition of adenylate cyclase. Pharmacology of the response in neuroblastoma cell membranes. (1984). https://pubmed.ncbi.nlm.nih.gov/6092901/ DOI: 10.1016/s0026-895x(25)15066-9
Complete structured claim and evidence
The biochemistry of the cannabinoid inhibition of adenylate cyclase in neuroblastoma membranes showed the response to be guanine-nucleotide dependent.
Heterotrimeric Gi/o proteins → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/2984538.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1ac047a734fcf178fc62cc2e117533f5ebc2b0779132c0315d3d954c4c728e5", "start_char": 0, "end_char": 1743, "text_sha256": "e1ac047a734fcf178fc62cc2e117533f5ebc2b0779132c0315d3d954c4c728e5"}
experimental_model
Biochemistry of the cannabinoid adenylate cyclase response in neuroblastoma membranes
exposure
Guanine nucleotide dependence of the response
limitations
The biochemical companion paper establishing G-protein dependence.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Cultured neuroblastoma cells
plain_language
The inhibition runs through a G protein, as a receptor response should.
primary_references
[thc-p2984538] Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes. (1985). https://pubmed.ncbi.nlm.nih.gov/2984538/ DOI: 10.1016/s0026-895x(25)12377-8
tissue_or_cell_type
Cell membranes
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 166–177
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Biochemistry of the cannabinoid adenylate cyclase response in neuroblastoma membranes · source_derived_draft · unverified_draft
### thc-ac-inhibition-biochemistry The biochemistry of the cannabinoid inhibition of adenylate cyclase in neuroblastoma membranes showed the response to be guanine-nucleotide dependent. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The inhibition runs through a G protein, as a receptor response should. organism: Cultured neuroblastoma cells tissue_or_cell_type: Cell membranes experimental_model: Biochemistry of the cannabinoid adenylate cyclase response in neuroblastoma membranes limitations: The biochemical companion paper establishing G-protein dependence. exposure: Guanine nucleotide dependence of the response evidence_span: {"source_cache": "artifacts/thc-research/2984538.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e1ac047a734fcf178fc62cc2e117533f5ebc2b0779132c0315d3d954c4c728e5", "start_char": 0, "end_char": 1743, "text_sha256": "e1ac047a734fcf178fc62cc2e117533f5ebc2b0779132c0315d3d954c4c728e5"} [thc-p2984538] Cannabinoid inhibition of adenylate cyclase. Biochemistry of the response in neuroblastoma cell membranes. (1985). https://pubmed.ncbi.nlm.nih.gov/2984538/ DOI: 10.1016/s0026-895x(25)12377-8
Complete structured claim and evidence
Cannabinoid receptors coupled to both Gs and Gi and could consequently stimulate or inhibit cAMP formation, with an identical rank order of agonist potency in both assays but markedly different intrinsic activities, anandamide and CP-55,940 being much less efficacious at stimulating cAMP than at inhibiting it, and forskolin enhancing the potency of some agonists a hundred-fold while not affecting others.
Human cannabinoid receptor 1 / CB1 / CNR1 → Cellular cyclic AMP accumulation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/9864268.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a39487ffec2ec3efa585fd49076c7498e8db3bf0ab943fe267e431b93dc7483d", "start_char": 0, "end_char": 1502, "text_sha256": "a39487ffec2ec3efa585fd49076c7498e8db3bf0ab943fe267e431b93dc7483d"}
experimental_model
Quantified potency and intrinsic activity of cannabinoid ligands on cAMP in CHO cells expressing human CB1
exposure
A ligand series measured for both stimulation and inhibition of cAMP, with and without forskolin
limitations
Reports that the receptor couples to Gs as well as Gi and that ligands differ between the two pathways. It is a transfected overexpression system, where Gs coupling is more readily observed.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human receptor in CHO cells
plain_language
The same receptor can push cAMP up as well as down, and which way depends on which drug is bound.
primary_references
[thc-p9864268] Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses. (1998). https://pubmed.ncbi.nlm.nih.gov/9864268/ DOI: 10.1016/s0022-3565(24)37876-0
tissue_or_cell_type
Transfected cells
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 179–190
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantified potency and intrinsic activity of cannabinoid ligands on cAMP in CHO cells expressing human CB1 · source_derived_draft · unverified_draft
### thc-agonist-specific-trafficking Cannabinoid receptors coupled to both Gs and Gi and could consequently stimulate or inhibit cAMP formation, with an identical rank order of agonist potency in both assays but markedly different intrinsic activities, anandamide and CP-55,940 being much less efficacious at stimulating cAMP than at inhibiting it, and forskolin enhancing the potency of some agonists a hundred-fold while not affecting others. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The same receptor can push cAMP up as well as down, and which way depends on which drug is bound. organism: Human receptor in CHO cells tissue_or_cell_type: Transfected cells experimental_model: Quantified potency and intrinsic activity of cannabinoid ligands on cAMP in CHO cells expressing human CB1 limitations: Reports that the receptor couples to Gs as well as Gi and that ligands differ between the two pathways. It is a transfected overexpression system, where Gs coupling is more readily observed. exposure: A ligand series measured for both stimulation and inhibition of cAMP, with and without forskolin evidence_span: {"source_cache": "artifacts/thc-research/9864268.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a39487ffec2ec3efa585fd49076c7498e8db3bf0ab943fe267e431b93dc7483d", "start_char": 0, "end_char": 1502, "text_sha256": "a39487ffec2ec3efa585fd49076c7498e8db3bf0ab943fe267e431b93dc7483d"} [thc-p9864268] Dual activation and inhibition of adenylyl cyclase by cannabinoid receptor agonists: evidence for agonist-specific trafficking of intracellular responses. (1998). https://pubmed.ncbi.nlm.nih.gov/9864268/ DOI: 10.1016/s0022-3565(24)37876-0
Complete structured claim and evidence
CB1 controls GABA release by inhibiting calcium entry into presynaptic axon terminals via N-type Cav2.2 channels, with a power relationship of exponent 2.2 between unitary inhibitory current amplitude and intrabouton calcium.
Human cannabinoid receptor 1 / CB1 / CNR1 → Presynaptic calcium influx at the axon terminal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/24899717.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "037d9888adff577901a9dc0d0cd27fdb4fd755da283857a848a15484dd53d2ed", "start_char": 0, "end_char": 1204, "text_sha256": "037d9888adff577901a9dc0d0cd27fdb4fd755da283857a848a15484dd53d2ed"}
experimental_model
Paired recordings and presynaptic calcium imaging in mouse hippocampal slices
exposure
CB1 activation and removal of tonic activity at interneuron-pyramidal cell connections
limitations
Identifies the specific channel and gives the power relationship between calcium and release. It concerns inhibitory terminals of one interneuron class.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
The receptor works by closing the calcium gate that triggers transmitter release.
primary_references
[thc-p24899717] Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release. (2014). https://pubmed.ncbi.nlm.nih.gov/24899717/ DOI: 10.1523/jneurosci.0247-14.2014
tissue_or_cell_type
Hippocampus
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 192–203
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired recordings and presynaptic calcium imaging in mouse hippocampal slices · source_derived_draft · unverified_draft
### thc-cb1-calcium-channel CB1 controls GABA release by inhibiting calcium entry into presynaptic axon terminals via N-type Cav2.2 channels, with a power relationship of exponent 2.2 between unitary inhibitory current amplitude and intrabouton calcium. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The receptor works by closing the calcium gate that triggers transmitter release. organism: Mouse tissue_or_cell_type: Hippocampus experimental_model: Paired recordings and presynaptic calcium imaging in mouse hippocampal slices limitations: Identifies the specific channel and gives the power relationship between calcium and release. It concerns inhibitory terminals of one interneuron class. exposure: CB1 activation and removal of tonic activity at interneuron-pyramidal cell connections evidence_span: {"source_cache": "artifacts/thc-research/24899717.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "037d9888adff577901a9dc0d0cd27fdb4fd755da283857a848a15484dd53d2ed", "start_char": 0, "end_char": 1204, "text_sha256": "037d9888adff577901a9dc0d0cd27fdb4fd755da283857a848a15484dd53d2ed"} [thc-p24899717] Presynaptic calcium channel inhibition underlies CB₁ cannabinoid receptor-mediated suppression of GABA release. (2014). https://pubmed.ncbi.nlm.nih.gov/24899717/ DOI: 10.1523/jneurosci.0247-14.2014
Complete structured claim and evidence
Distinct domains of the CB1 receptor mediate desensitisation and internalisation, so the two adaptive responses are separable.
Human cannabinoid receptor 1 / CB1 / CNR1 → CB1 receptor desensitisation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/10234009.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73965589817407e173255ab6db300e7969b0e91a4ca4cd3d39cee1f5873d1e05", "start_char": 0, "end_char": 1911, "text_sha256": "73965589817407e173255ab6db300e7969b0e91a4ca4cd3d39cee1f5873d1e05"}
experimental_model
Mutational mapping of CB1 receptor domains against desensitisation and internalisation
exposure
Sustained agonist exposure with receptor trafficking measurement
limitations
Separates two adaptive processes that are often conflated. It is a recombinant system.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Recombinant receptor
plain_language
Going deaf to the drug and removing the receptor from the surface are two different things.
primary_references
[thc-p10234009] Distinct domains of the CB1 cannabinoid receptor mediate desensitization and internalization. (1999). https://pubmed.ncbi.nlm.nih.gov/10234009/ DOI: 10.1523/jneurosci.19-10-03773.1999
tissue_or_cell_type
Transfected cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 205–216
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mutational mapping of CB1 receptor domains against desensitisation and internalisation · source_derived_draft · unverified_draft
### thc-desensitisation-domains Distinct domains of the CB1 receptor mediate desensitisation and internalisation, so the two adaptive responses are separable. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Going deaf to the drug and removing the receptor from the surface are two different things. organism: Recombinant receptor tissue_or_cell_type: Transfected cells experimental_model: Mutational mapping of CB1 receptor domains against desensitisation and internalisation limitations: Separates two adaptive processes that are often conflated. It is a recombinant system. exposure: Sustained agonist exposure with receptor trafficking measurement evidence_span: {"source_cache": "artifacts/thc-research/10234009.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "73965589817407e173255ab6db300e7969b0e91a4ca4cd3d39cee1f5873d1e05", "start_char": 0, "end_char": 1911, "text_sha256": "73965589817407e173255ab6db300e7969b0e91a4ca4cd3d39cee1f5873d1e05"} [thc-p10234009] Distinct domains of the CB1 cannabinoid receptor mediate desensitization and internalization. (1999). https://pubmed.ncbi.nlm.nih.gov/10234009/ DOI: 10.1523/jneurosci.19-10-03773.1999
Complete structured claim and evidence
Rapid CB1 receptor desensitisation defines the time course of ERK1/2 MAP kinase signalling.
CB1 receptor desensitisation → ERK1/2 MAP kinase signalling source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/17681354.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dda88f2600ad5892232cf931091df54c5fc62b303062f725df663d65778c4821", "start_char": 0, "end_char": 1915, "text_sha256": "dda88f2600ad5892232cf931091df54c5fc62b303062f725df663d65778c4821"}
experimental_model
Time-course measurement of CB1 desensitisation against ERK signalling
exposure
Agonist exposure with kinase and receptor measurement
limitations
Ties the adaptation timescale to a downstream kinase, which is what makes desensitisation measurable as a signalling change rather than only as binding.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Cultured cells
plain_language
How fast the receptor goes deaf sets how long the downstream signal lasts.
primary_references
[thc-p17681354] Rapid CB1 cannabinoid receptor desensitization defines the time course of ERK1/2 MAP kinase signaling. (2008). https://pubmed.ncbi.nlm.nih.gov/17681354/ DOI: 10.1016/j.neuropharm.2007.06.005
tissue_or_cell_type
Transfected cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 218–229
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Time-course measurement of CB1 desensitisation against ERK signalling · source_derived_draft · unverified_draft
### thc-desensitisation-erk Rapid CB1 receptor desensitisation defines the time course of ERK1/2 MAP kinase signalling. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: How fast the receptor goes deaf sets how long the downstream signal lasts. organism: Cultured cells tissue_or_cell_type: Transfected cells experimental_model: Time-course measurement of CB1 desensitisation against ERK signalling limitations: Ties the adaptation timescale to a downstream kinase, which is what makes desensitisation measurable as a signalling change rather than only as binding. exposure: Agonist exposure with kinase and receptor measurement evidence_span: {"source_cache": "artifacts/thc-research/17681354.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dda88f2600ad5892232cf931091df54c5fc62b303062f725df663d65778c4821", "start_char": 0, "end_char": 1915, "text_sha256": "dda88f2600ad5892232cf931091df54c5fc62b303062f725df663d65778c4821"} [thc-p17681354] Rapid CB1 cannabinoid receptor desensitization defines the time course of ERK1/2 MAP kinase signaling. (2008). https://pubmed.ncbi.nlm.nih.gov/17681354/ DOI: 10.1016/j.neuropharm.2007.06.005
Complete structured claim and evidence
CB1 receptors and related molecular elements of the endocannabinoid system were downregulated in epileptic human hippocampus.
Epileptic human hippocampus → Human cannabinoid receptor 1 / CB1 / CNR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/18354002.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "20b254a1e7d4462dcad993b76e889a26d729d604c71e2456c2d13a2a1420c728", "start_char": 0, "end_char": 2055, "text_sha256": "20b254a1e7d4462dcad993b76e889a26d729d604c71e2456c2d13a2a1420c728"}
experimental_model
Post-mortem and surgical human hippocampal tissue from epilepsy
exposure
Measurement of CB1 and endocannabinoid system elements in epileptic tissue
limitations
A human tissue measurement, but in diseased tissue where the disease itself may drive the change. It is not a measurement of cannabis users.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human
plain_language
In diseased human hippocampus the whole system is turned down, receptor included.
primary_references
[thc-p18354002] Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. (2008). https://pubmed.ncbi.nlm.nih.gov/18354002/ DOI: 10.1523/jneurosci.4465-07.2008
tissue_or_cell_type
Hippocampus
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 231–242
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Post-mortem and surgical human hippocampal tissue from epilepsy · source_derived_draft · unverified_draft
### thc-cb1-downregulation-human CB1 receptors and related molecular elements of the endocannabinoid system were downregulated in epileptic human hippocampus. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: In diseased human hippocampus the whole system is turned down, receptor included. organism: Human tissue_or_cell_type: Hippocampus experimental_model: Post-mortem and surgical human hippocampal tissue from epilepsy limitations: A human tissue measurement, but in diseased tissue where the disease itself may drive the change. It is not a measurement of cannabis users. exposure: Measurement of CB1 and endocannabinoid system elements in epileptic tissue evidence_span: {"source_cache": "artifacts/thc-research/18354002.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "20b254a1e7d4462dcad993b76e889a26d729d604c71e2456c2d13a2a1420c728", "start_char": 0, "end_char": 2055, "text_sha256": "20b254a1e7d4462dcad993b76e889a26d729d604c71e2456c2d13a2a1420c728"} [thc-p18354002] Downregulation of the CB1 cannabinoid receptor and related molecular elements of the endocannabinoid system in epileptic human hippocampus. (2008). https://pubmed.ncbi.nlm.nih.gov/18354002/ DOI: 10.1523/jneurosci.4465-07.2008
Complete structured claim and evidence
Arachidonylethanolamide, an arachidonic acid derivative isolated from porcine brain, competitively inhibited binding of a radiolabelled cannabinoid probe to synaptosomal membranes and produced concentration-dependent inhibition of the electrically evoked twitch of the mouse vas deferens, a characteristic effect of psychotropic cannabinoids.
Anandamide / arachidonylethanolamide → Human cannabinoid receptor 1 / CB1 / CNR1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/1470919.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "45d534b5ac88c3edf040431942aea2f8421399c88e3931e8bc28b4b5e438f2f2", "start_char": 0, "end_char": 757, "text_sha256": "45d534b5ac88c3edf040431942aea2f8421399c88e3931e8bc28b4b5e438f2f2"}
experimental_model
Isolation from porcine brain with mass spectrometry, NMR and synthetic confirmation
exposure
Screen for endogenous ligands of the cannabinoid receptor
limitations
The isolation of the first endogenous ligand. The bioassay is a peripheral tissue twitch, not a central behavioural effect.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Pig brain, with mouse bioassay
plain_language
The brain makes its own version of the drug, and it is built from a fatty acid.
primary_references
[thc-p1470919] Isolation and structure of a brain constituent that binds to the cannabinoid receptor. (1992). https://pubmed.ncbi.nlm.nih.gov/1470919/ DOI: 10.1126/science.1470919
tissue_or_cell_type
Brain and vas deferens
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 244–255
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolation from porcine brain with mass spectrometry, NMR and synthetic confirmation · source_derived_draft · unverified_draft
### thc-anandamide-isolated Arachidonylethanolamide, an arachidonic acid derivative isolated from porcine brain, competitively inhibited binding of a radiolabelled cannabinoid probe to synaptosomal membranes and produced concentration-dependent inhibition of the electrically evoked twitch of the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The brain makes its own version of the drug, and it is built from a fatty acid. organism: Pig brain, with mouse bioassay tissue_or_cell_type: Brain and vas deferens experimental_model: Isolation from porcine brain with mass spectrometry, NMR and synthetic confirmation limitations: The isolation of the first endogenous ligand. The bioassay is a peripheral tissue twitch, not a central behavioural effect. exposure: Screen for endogenous ligands of the cannabinoid receptor evidence_span: {"source_cache": "artifacts/thc-research/1470919.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "45d534b5ac88c3edf040431942aea2f8421399c88e3931e8bc28b4b5e438f2f2", "start_char": 0, "end_char": 757, "text_sha256": "45d534b5ac88c3edf040431942aea2f8421399c88e3931e8bc28b4b5e438f2f2"} [thc-p1470919] Isolation and structure of a brain constituent that binds to the cannabinoid receptor. (1992). https://pubmed.ncbi.nlm.nih.gov/1470919/ DOI: 10.1126/science.1470919
Complete structured claim and evidence
Anandamide interacted specifically with cannabinoid receptors and inhibited adenylate cyclase, reproducing the signature response of the plant cannabinoids.
Anandamide / arachidonylethanolamide → Adenylyl cyclase catalytic activity, model specified source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/8515284.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d", "start_char": 0, "end_char": 1015, "text_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d"}
experimental_model
Receptor binding and adenylate cyclase assays with anandamide
exposure
Anandamide against cannabinoid receptors and cyclase
limitations
Confirms the endogenous ligand reproduces the receptor signature of the drug.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat brain preparations
plain_language
The natural ligand does the same thing to the same enzyme as the drug.
primary_references
[thc-p8515284] Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. (1993). https://pubmed.ncbi.nlm.nih.gov/8515284/ DOI: 10.1111/j.1471-4159.1993.tb03576.x
tissue_or_cell_type
Brain membranes
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 257–268
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor binding and adenylate cyclase assays with anandamide · source_derived_draft · unverified_draft
### thc-anandamide-inhibits-cyclase Anandamide interacted specifically with cannabinoid receptors and inhibited adenylate cyclase, reproducing the signature response of the plant cannabinoids. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The natural ligand does the same thing to the same enzyme as the drug. organism: Rat brain preparations tissue_or_cell_type: Brain membranes experimental_model: Receptor binding and adenylate cyclase assays with anandamide limitations: Confirms the endogenous ligand reproduces the receptor signature of the drug. exposure: Anandamide against cannabinoid receptors and cyclase evidence_span: {"source_cache": "artifacts/thc-research/8515284.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d", "start_char": 0, "end_char": 1015, "text_sha256": "36a5b1eec5097dbdfd0224629f4d8449f8688d0476820823ffcbe3b92d68c66d"} [thc-p8515284] Anandamide, a brain endogenous compound, interacts specifically with cannabinoid receptors and inhibits adenylate cyclase. (1993). https://pubmed.ncbi.nlm.nih.gov/8515284/ DOI: 10.1111/j.1471-4159.1993.tb03576.x
Complete structured claim and evidence
Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses, travelling from the depolarised postsynaptic neuron back to the presynaptic terminal.
2-Arachidonoylglycerol / 2-AG → Retrograde endocannabinoid signalling from postsynaptic neuron to presynaptic terminal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/11279497.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f93de867c0ce253b42d9c248504f4471431310bdc0629fec2a8c49d2eba55e8e", "start_char": 0, "end_char": 1117, "text_sha256": "f93de867c0ce253b42d9c248504f4471431310bdc0629fec2a8c49d2eba55e8e"}
experimental_model
Paired recordings in rat hippocampal slices with CB1 antagonists
exposure
Postsynaptic depolarisation with presynaptic release measurement
limitations
Establishes the direction of the signal, which is what makes the system a feedback loop rather than a transmitter pathway.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
The signal runs backwards across the synapse, which almost nothing else does.
primary_references
[thc-p11279497] Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. (2001). https://pubmed.ncbi.nlm.nih.gov/11279497/ DOI: 10.1038/35069076
tissue_or_cell_type
Hippocampus
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 270–281
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired recordings in rat hippocampal slices with CB1 antagonists · source_derived_draft · unverified_draft
### thc-retrograde-hippocampus Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses, travelling from the depolarised postsynaptic neuron back to the presynaptic terminal. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The signal runs backwards across the synapse, which almost nothing else does. organism: Rat tissue_or_cell_type: Hippocampus experimental_model: Paired recordings in rat hippocampal slices with CB1 antagonists limitations: Establishes the direction of the signal, which is what makes the system a feedback loop rather than a transmitter pathway. exposure: Postsynaptic depolarisation with presynaptic release measurement evidence_span: {"source_cache": "artifacts/thc-research/11279497.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f93de867c0ce253b42d9c248504f4471431310bdc0629fec2a8c49d2eba55e8e", "start_char": 0, "end_char": 1117, "text_sha256": "f93de867c0ce253b42d9c248504f4471431310bdc0629fec2a8c49d2eba55e8e"} [thc-p11279497] Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. (2001). https://pubmed.ncbi.nlm.nih.gov/11279497/ DOI: 10.1038/35069076
Complete structured claim and evidence
Endogenous cannabinoids mediate retrograde signals from depolarised postsynaptic neurons to presynaptic terminals, suppressing transmitter release.
2-Arachidonoylglycerol / 2-AG → GABA release from inhibitory terminals source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/11301031.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3604f96d0bb63e313cf39b0905f250a3d05ec58f88529cceda5fda4bbda8006", "start_char": 0, "end_char": 1026, "text_sha256": "e3604f96d0bb63e313cf39b0905f250a3d05ec58f88529cceda5fda4bbda8006"}
experimental_model
Recordings from depolarised postsynaptic neurons with presynaptic terminal measurement
exposure
Depolarisation-induced suppression with cannabinoid antagonists
limitations
An independent report of the same retrograde mechanism from a different group in the same year.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rodent
plain_language
A second laboratory saw the same backwards signal in the same year.
primary_references
[thc-p11301031] Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. (2001). https://pubmed.ncbi.nlm.nih.gov/11301031/ DOI: 10.1016/s0896-6273(01)00247-1
tissue_or_cell_type
Hippocampus
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 283–294
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recordings from depolarised postsynaptic neurons with presynaptic terminal measurement · source_derived_draft · unverified_draft
### thc-retrograde-independent Endogenous cannabinoids mediate retrograde signals from depolarised postsynaptic neurons to presynaptic terminals, suppressing transmitter release. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: A second laboratory saw the same backwards signal in the same year. organism: Rodent tissue_or_cell_type: Hippocampus experimental_model: Recordings from depolarised postsynaptic neurons with presynaptic terminal measurement limitations: An independent report of the same retrograde mechanism from a different group in the same year. exposure: Depolarisation-induced suppression with cannabinoid antagonists evidence_span: {"source_cache": "artifacts/thc-research/11301031.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e3604f96d0bb63e313cf39b0905f250a3d05ec58f88529cceda5fda4bbda8006", "start_char": 0, "end_char": 1026, "text_sha256": "e3604f96d0bb63e313cf39b0905f250a3d05ec58f88529cceda5fda4bbda8006"} [thc-p11301031] Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals. (2001). https://pubmed.ncbi.nlm.nih.gov/11301031/ DOI: 10.1016/s0896-6273(01)00247-1
Complete structured claim and evidence
Endogenous cannabinoids retrogradely inhibited presynaptic calcium influx at excitatory synapses onto Purkinje cells.
2-Arachidonoylglycerol / 2-AG → Presynaptic calcium influx at the axon terminal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/11301030.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c696bee2c487e7deca703c5c903b38935f6d635f29bbf4ebf498869eaa4491c0", "start_char": 0, "end_char": 1025, "text_sha256": "c696bee2c487e7deca703c5c903b38935f6d635f29bbf4ebf498869eaa4491c0"}
experimental_model
Presynaptic calcium imaging at excitatory synapses onto cerebellar Purkinje cells
exposure
Depolarisation-induced suppression of excitation with calcium measurement
limitations
Extends the mechanism to excitatory synapses in a different brain region and measures the calcium step directly.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rodent
plain_language
The same backwards signal works on excitatory terminals too, by closing the same calcium gate.
primary_references
[thc-p11301030] Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11301030/ DOI: 10.1016/s0896-6273(01)00246-x
tissue_or_cell_type
Cerebellum
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 296–307
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Presynaptic calcium imaging at excitatory synapses onto cerebellar Purkinje cells · source_derived_draft · unverified_draft
### thc-retrograde-purkinje Endogenous cannabinoids retrogradely inhibited presynaptic calcium influx at excitatory synapses onto Purkinje cells. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The same backwards signal works on excitatory terminals too, by closing the same calcium gate. organism: Rodent tissue_or_cell_type: Cerebellum experimental_model: Presynaptic calcium imaging at excitatory synapses onto cerebellar Purkinje cells limitations: Extends the mechanism to excitatory synapses in a different brain region and measures the calcium step directly. exposure: Depolarisation-induced suppression of excitation with calcium measurement evidence_span: {"source_cache": "artifacts/thc-research/11301030.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c696bee2c487e7deca703c5c903b38935f6d635f29bbf4ebf498869eaa4491c0", "start_char": 0, "end_char": 1025, "text_sha256": "c696bee2c487e7deca703c5c903b38935f6d635f29bbf4ebf498869eaa4491c0"} [thc-p11301030] Retrograde inhibition of presynaptic calcium influx by endogenous cannabinoids at excitatory synapses onto Purkinje cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11301030/ DOI: 10.1016/s0896-6273(01)00246-x
Complete structured claim and evidence
Diacylglycerol lipase-alpha was localised around the postsynaptic spine, placing the production site of 2-arachidonoylglycerol in close proximity to the presynaptic CB1 receptor.
Diacylglycerol lipase alpha / DAGLA → The postsynaptic dendritic spine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/16672646.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd4ddba9cf6987282758f17ce79c5624f9a3cc6c02044a4a45c0664ef6fd21c3", "start_char": 0, "end_char": 1832, "text_sha256": "dd4ddba9cf6987282758f17ce79c5624f9a3cc6c02044a4a45c0664ef6fd21c3"}
experimental_model
Immunoelectron microscopy localising diacylglycerol lipase-alpha
exposure
Subcellular localisation against presynaptic CB1
limitations
An anatomical result that makes the signalling geometry concrete: the enzyme that makes the messenger sits directly opposite the receptor.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rodent
plain_language
The factory for the messenger sits directly across the synapse from its receptor.
primary_references
[thc-p16672646] Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. (2006). https://pubmed.ncbi.nlm.nih.gov/16672646/ DOI: 10.1523/jneurosci.0054-06.2006
tissue_or_cell_type
Postsynaptic spine
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 309–320
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Immunoelectron microscopy localising diacylglycerol lipase-alpha · source_derived_draft · unverified_draft
### thc-dagla-localisation Diacylglycerol lipase-alpha was localised around the postsynaptic spine, placing the production site of 2-arachidonoylglycerol in close proximity to the presynaptic CB1 receptor. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The factory for the messenger sits directly across the synapse from its receptor. organism: Rodent tissue_or_cell_type: Postsynaptic spine experimental_model: Immunoelectron microscopy localising diacylglycerol lipase-alpha limitations: An anatomical result that makes the signalling geometry concrete: the enzyme that makes the messenger sits directly opposite the receptor. exposure: Subcellular localisation against presynaptic CB1 evidence_span: {"source_cache": "artifacts/thc-research/16672646.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd4ddba9cf6987282758f17ce79c5624f9a3cc6c02044a4a45c0664ef6fd21c3", "start_char": 0, "end_char": 1832, "text_sha256": "dd4ddba9cf6987282758f17ce79c5624f9a3cc6c02044a4a45c0664ef6fd21c3"} [thc-p16672646] Localization of diacylglycerol lipase-alpha around postsynaptic spine suggests close proximity between production site of an endocannabinoid, 2-arachidonoyl-glycerol, and presynaptic cannabinoid CB1 receptor. (2006). https://pubmed.ncbi.nlm.nih.gov/16672646/ DOI: 10.1523/jneurosci.0054-06.2006
Complete structured claim and evidence
The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission.
Diacylglycerol lipase alpha / DAGLA → 2-Arachidonoylglycerol / 2-AG source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/20159446.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed", "start_char": 0, "end_char": 1097, "text_sha256": "a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed"}
experimental_model
Conditional and constitutive DAGLα manipulation with synaptic recordings
exposure
DAGLα deletion with retrograde suppression measurement
limitations
Assigns the retrograde messenger to a specific enzyme product by removing the enzyme.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
One enzyme makes the messenger that carries the backwards signal.
primary_references
[thc-p20159446] The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. (2010). https://pubmed.ncbi.nlm.nih.gov/20159446/ DOI: 10.1016/j.neuron.2010.01.021
tissue_or_cell_type
Brain slices
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 322–333
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Conditional and constitutive DAGLα manipulation with synaptic recordings · source_derived_draft · unverified_draft
### thc-dagla-makes-2ag The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: One enzyme makes the messenger that carries the backwards signal. organism: Mouse tissue_or_cell_type: Brain slices experimental_model: Conditional and constitutive DAGLα manipulation with synaptic recordings limitations: Assigns the retrograde messenger to a specific enzyme product by removing the enzyme. exposure: DAGLα deletion with retrograde suppression measurement evidence_span: {"source_cache": "artifacts/thc-research/20159446.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed", "start_char": 0, "end_char": 1097, "text_sha256": "a83e761bbc9dd85f5c5ec84424a876a33b0914b1e6723ed809db0b1854cf00ed"} [thc-p20159446] The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission. (2010). https://pubmed.ncbi.nlm.nih.gov/20159446/ DOI: 10.1016/j.neuron.2010.01.021
Complete structured claim and evidence
Diacylglycerol lipase knock-out mice lost retrograde endocannabinoid signalling and showed reduced adult neurogenesis.
Experimental diacylglycerol lipase knockout mouse genotype → Adult neurogenesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/20147530.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "87c25db27ffa9aaeb9ee619ad5adc8fbc8223da9dea61fddc86ad0d455431f2b", "start_char": 0, "end_char": 1709, "text_sha256": "87c25db27ffa9aaeb9ee619ad5adc8fbc8223da9dea61fddc86ad0d455431f2b"}
experimental_model
Diacylglycerol lipase knock-out mice with synaptic and neurogenesis measurement
exposure
Constitutive DAGL deletion
limitations
A whole-animal consequence of removing the enzyme, beyond the synaptic recording.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
Without the messenger the brain also makes fewer new neurons.
primary_references
[thc-p20147530] Loss of retrograde endocannabinoid signaling and reduced adult neurogenesis in diacylglycerol lipase knock-out mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20147530/ DOI: 10.1523/jneurosci.5693-09.2010
tissue_or_cell_type
Hippocampus
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 335–346
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diacylglycerol lipase knock-out mice with synaptic and neurogenesis measurement · source_derived_draft · unverified_draft
### thc-dagl-null-neurogenesis Diacylglycerol lipase knock-out mice lost retrograde endocannabinoid signalling and showed reduced adult neurogenesis. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Without the messenger the brain also makes fewer new neurons. organism: Mouse tissue_or_cell_type: Hippocampus experimental_model: Diacylglycerol lipase knock-out mice with synaptic and neurogenesis measurement limitations: A whole-animal consequence of removing the enzyme, beyond the synaptic recording. exposure: Constitutive DAGL deletion evidence_span: {"source_cache": "artifacts/thc-research/20147530.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "87c25db27ffa9aaeb9ee619ad5adc8fbc8223da9dea61fddc86ad0d455431f2b", "start_char": 0, "end_char": 1709, "text_sha256": "87c25db27ffa9aaeb9ee619ad5adc8fbc8223da9dea61fddc86ad0d455431f2b"} [thc-p20147530] Loss of retrograde endocannabinoid signaling and reduced adult neurogenesis in diacylglycerol lipase knock-out mice. (2010). https://pubmed.ncbi.nlm.nih.gov/20147530/ DOI: 10.1523/jneurosci.5693-09.2010
Complete structured claim and evidence
Diacylglycerol lipase-alpha has a key role in metabotropic glutamate receptor-dependent endocannabinoid mobilisation.
Metabotropic glutamate receptor signalling → 2-Arachidonoylglycerol / 2-AG source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/17584991.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5d27e66f2883f2d105cb492c1a5acd7a1aa7a27b81577ddd3759ee252622d0ac", "start_char": 0, "end_char": 1860, "text_sha256": "5d27e66f2883f2d105cb492c1a5acd7a1aa7a27b81577ddd3759ee252622d0ac"}
experimental_model
Pharmacological and genetic dissection of mGluR-dependent endocannabinoid mobilisation
exposure
Metabotropic glutamate receptor stimulation with DAGLα inhibition
limitations
Links the messenger production to a specific upstream receptor, which is what makes the system demand-driven.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rodent
plain_language
Glutamate signalling is one of the triggers that tells the cell to make the messenger.
primary_references
[thc-p17584991] A key role for diacylglycerol lipase-alpha in metabotropic glutamate receptor-dependent endocannabinoid mobilization. (2007). https://pubmed.ncbi.nlm.nih.gov/17584991/ DOI: 10.1124/mol.107.037796
tissue_or_cell_type
Brain slices
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 348–359
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological and genetic dissection of mGluR-dependent endocannabinoid mobilisation · source_derived_draft · unverified_draft
### thc-mglur-mobilisation Diacylglycerol lipase-alpha has a key role in metabotropic glutamate receptor-dependent endocannabinoid mobilisation. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Glutamate signalling is one of the triggers that tells the cell to make the messenger. organism: Rodent tissue_or_cell_type: Brain slices experimental_model: Pharmacological and genetic dissection of mGluR-dependent endocannabinoid mobilisation limitations: Links the messenger production to a specific upstream receptor, which is what makes the system demand-driven. exposure: Metabotropic glutamate receptor stimulation with DAGLα inhibition evidence_span: {"source_cache": "artifacts/thc-research/17584991.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5d27e66f2883f2d105cb492c1a5acd7a1aa7a27b81577ddd3759ee252622d0ac", "start_char": 0, "end_char": 1860, "text_sha256": "5d27e66f2883f2d105cb492c1a5acd7a1aa7a27b81577ddd3759ee252622d0ac"} [thc-p17584991] A key role for diacylglycerol lipase-alpha in metabotropic glutamate receptor-dependent endocannabinoid mobilization. (2007). https://pubmed.ncbi.nlm.nih.gov/17584991/ DOI: 10.1124/mol.107.037796
Complete structured claim and evidence
Fatty acid amide hydrolase is the principal enzyme hydrolysing fatty acid amides including anandamide, terminating their signalling.
Fatty acid amide hydrolase / FAAH → Anandamide / arachidonylethanolamide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/15952893.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3213ef73e4fe6ef00bd2a0f1c09319ebc1e000f9cfd200ce3c1852f1e045c62c", "start_char": 0, "end_char": 724, "text_sha256": "3213ef73e4fe6ef00bd2a0f1c09319ebc1e000f9cfd200ce3c1852f1e045c62c"}
experimental_model
Review of fatty acid amide hydrolase structure and function
exposure
Hydrolysis of fatty acid amides including anandamide
limitations
A review, labelled as such, used for the enzymology. The structural claim is recorded from the crystal structure paper separately.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mammalian enzyme
plain_language
One enzyme destroys the natural ligand within seconds of it being made.
primary_references
[thc-p15952893] Structure and function of fatty acid amide hydrolase. (2005). https://pubmed.ncbi.nlm.nih.gov/15952893/ DOI: 10.1146/annurev.biochem.74.082803.133450
tissue_or_cell_type
Membrane-bound enzyme
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 361–372
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of fatty acid amide hydrolase structure and function · source_derived_draft · unverified_draft
### thc-faah-degrades-anandamide Fatty acid amide hydrolase is the principal enzyme hydrolysing fatty acid amides including anandamide, terminating their signalling. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: One enzyme destroys the natural ligand within seconds of it being made. organism: Mammalian enzyme tissue_or_cell_type: Membrane-bound enzyme experimental_model: Review of fatty acid amide hydrolase structure and function limitations: A review, labelled as such, used for the enzymology. The structural claim is recorded from the crystal structure paper separately. exposure: Hydrolysis of fatty acid amides including anandamide evidence_span: {"source_cache": "artifacts/thc-research/15952893.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3213ef73e4fe6ef00bd2a0f1c09319ebc1e000f9cfd200ce3c1852f1e045c62c", "start_char": 0, "end_char": 724, "text_sha256": "3213ef73e4fe6ef00bd2a0f1c09319ebc1e000f9cfd200ce3c1852f1e045c62c"} [thc-p15952893] Structure and function of fatty acid amide hydrolase. (2005). https://pubmed.ncbi.nlm.nih.gov/15952893/ DOI: 10.1146/annurev.biochem.74.082803.133450
Complete structured claim and evidence
The crystal structure of fatty acid amide hydrolase bound to URB597 revealed a deacylating water molecule and gave insight into how the enzyme is inactivated by carbamate inhibitors.
URB597, a carbamate fatty acid amide hydrolase inhibitor → Fatty acid amide hydrolase / FAAH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/20493882.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5acef9899dc5e90f996fb08c58b547c167bdbb2c879e1bd669a531fd10c3368", "start_char": 0, "end_char": 1382, "text_sha256": "c5acef9899dc5e90f996fb08c58b547c167bdbb2c879e1bd669a531fd10c3368"}
experimental_model
Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597
exposure
Inhibitor-bound structure
limitations
Identifies the water molecule that explains why the inhibitor is slowly reversible. Rat enzyme structure.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat enzyme
plain_language
The structure shows exactly how the enzyme is jammed, down to a single water molecule.
primary_references
[thc-p20493882] Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation. (2010). https://pubmed.ncbi.nlm.nih.gov/20493882/ DOI: 10.1016/j.jmb.2010.05.034
tissue_or_cell_type
Purified enzyme
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 374–385
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597 · source_derived_draft · unverified_draft
### thc-faah-mechanism The crystal structure of fatty acid amide hydrolase bound to URB597 revealed a deacylating water molecule and gave insight into how the enzyme is inactivated by carbamate inhibitors. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The structure shows exactly how the enzyme is jammed, down to a single water molecule. organism: Rat enzyme tissue_or_cell_type: Purified enzyme experimental_model: Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597 limitations: Identifies the water molecule that explains why the inhibitor is slowly reversible. Rat enzyme structure. exposure: Inhibitor-bound structure evidence_span: {"source_cache": "artifacts/thc-research/20493882.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c5acef9899dc5e90f996fb08c58b547c167bdbb2c879e1bd669a531fd10c3368", "start_char": 0, "end_char": 1382, "text_sha256": "c5acef9899dc5e90f996fb08c58b547c167bdbb2c879e1bd669a531fd10c3368"} [thc-p20493882] Crystal structure of fatty acid amide hydrolase bound to the carbamate inhibitor URB597: discovery of a deacylating water molecule and insight into enzyme inactivation. (2010). https://pubmed.ncbi.nlm.nih.gov/20493882/ DOI: 10.1016/j.jmb.2010.05.034
Complete structured claim and evidence
Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system.
Monoacylglycerol lipase / MGLL → 2-Arachidonoylglycerol / 2-AG source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/20855465.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab326436e1ae7e9672e4170f62162a4ec30278a2a2380fd9c1cc64f1a88d0bf8", "start_char": 0, "end_char": 1490, "text_sha256": "ab326436e1ae7e9672e4170f62162a4ec30278a2a2380fd9c1cc64f1a88d0bf8"}
experimental_model
Monoacylglycerol lipase manipulation with endocannabinoid measurement
exposure
MAGL inhibition and genetic disruption
limitations
Establishes the enzyme as the tone-setting step for the other endocannabinoid.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
A second enzyme controls how much of the other messenger is around at rest.
primary_references
[thc-p20855465] Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system. (2010). https://pubmed.ncbi.nlm.nih.gov/20855465/ DOI: 10.1124/mol.110.068304
tissue_or_cell_type
Nervous system
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 387–398
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Monoacylglycerol lipase manipulation with endocannabinoid measurement · source_derived_draft · unverified_draft
### thc-magl-sets-tone Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: A second enzyme controls how much of the other messenger is around at rest. organism: Mouse tissue_or_cell_type: Nervous system experimental_model: Monoacylglycerol lipase manipulation with endocannabinoid measurement limitations: Establishes the enzyme as the tone-setting step for the other endocannabinoid. exposure: MAGL inhibition and genetic disruption evidence_span: {"source_cache": "artifacts/thc-research/20855465.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ab326436e1ae7e9672e4170f62162a4ec30278a2a2380fd9c1cc64f1a88d0bf8", "start_char": 0, "end_char": 1490, "text_sha256": "ab326436e1ae7e9672e4170f62162a4ec30278a2a2380fd9c1cc64f1a88d0bf8"} [thc-p20855465] Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system. (2010). https://pubmed.ncbi.nlm.nih.gov/20855465/ DOI: 10.1124/mol.110.068304
Complete structured claim and evidence
After repeated administration the MAGL inhibitor JZL184 lost its analgesic activity and produced cross-tolerance to CB1 agonists in mice, effects phenocopied by genetic disruption of Mgll, and chronic blockade also caused physical dependence and impaired endocannabinoid-dependent synaptic plasticity.
JZL184, a monoacylglycerol lipase inhibitor → Human cannabinoid receptor 1 / CB1 / CNR1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/20729846.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9c812c031525007d63883a15d43c6f342366dba7fa85ad0a9fef7152aa47ee7d", "start_char": 0, "end_char": 1167, "text_sha256": "9c812c031525007d63883a15d43c6f342366dba7fa85ad0a9fef7152aa47ee7d"}
experimental_model
Repeated MAGL inhibitor administration in mice with genetic confirmation
exposure
Repeated JZL184 administration, with Mgll genetic disruption as confirmation
limitations
A tolerance result produced by raising the natural ligand rather than by giving a drug. The genetic phenocopy is what rules out an off-target effect of the inhibitor.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
Flooding the system with its own messenger produces the same tolerance and dependence as the drug does.
primary_references
[thc-p20729846] Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. (2010). https://pubmed.ncbi.nlm.nih.gov/20729846/ DOI: 10.1038/nn.2616
tissue_or_cell_type
Nervous system
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 400–411
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Repeated MAGL inhibitor administration in mice with genetic confirmation · source_derived_draft · unverified_draft
### thc-magl-blockade-antagonism After repeated administration the MAGL inhibitor JZL184 lost its analgesic activity and produced cross-tolerance to CB1 agonists in mice, effects phenocopied by genetic disruption of Mgll, and chronic blockade also caused physical dependence and impaired endocannabinoid-dependent synaptic plasticity. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Flooding the system with its own messenger produces the same tolerance and dependence as the drug does. organism: Mouse tissue_or_cell_type: Nervous system experimental_model: Repeated MAGL inhibitor administration in mice with genetic confirmation limitations: A tolerance result produced by raising the natural ligand rather than by giving a drug. The genetic phenocopy is what rules out an off-target effect of the inhibitor. exposure: Repeated JZL184 administration, with Mgll genetic disruption as confirmation evidence_span: {"source_cache": "artifacts/thc-research/20729846.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9c812c031525007d63883a15d43c6f342366dba7fa85ad0a9fef7152aa47ee7d", "start_char": 0, "end_char": 1167, "text_sha256": "9c812c031525007d63883a15d43c6f342366dba7fa85ad0a9fef7152aa47ee7d"} [thc-p20729846] Chronic monoacylglycerol lipase blockade causes functional antagonism of the endocannabinoid system. (2010). https://pubmed.ncbi.nlm.nih.gov/20729846/ DOI: 10.1038/nn.2616
Complete structured claim and evidence
Cannabinoid CB1 receptor knockout mice showed increased mortality, hypoactivity and hypoalgesia.
Experimental CB1 receptor knockout mouse genotype → Mortality in the mouse colony source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/10318961.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee2674f143f23f9030564139676e845091ab75adaa02b8ab0220bc77860e38ef", "start_char": 0, "end_char": 1144, "text_sha256": "ee2674f143f23f9030564139676e845091ab75adaa02b8ab0220bc77860e38ef"}
experimental_model
CB1 receptor knockout mice characterised for survival, activity and nociception
exposure
Constitutive CB1 deletion
limitations
Shows what removing the receptor costs the animal at baseline, independently of any drug. The increased mortality is a colony observation.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
Animals without the receptor are worse off before any drug is given.
primary_references
[thc-p10318961] Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. (1999). https://pubmed.ncbi.nlm.nih.gov/10318961/ DOI: 10.1073/pnas.96.10.5780
tissue_or_cell_type
Whole body
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 413–424
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CB1 receptor knockout mice characterised for survival, activity and nociception · source_derived_draft · unverified_draft
### thc-cb1-null-phenotype Cannabinoid CB1 receptor knockout mice showed increased mortality, hypoactivity and hypoalgesia. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Animals without the receptor are worse off before any drug is given. organism: Mouse tissue_or_cell_type: Whole body experimental_model: CB1 receptor knockout mice characterised for survival, activity and nociception limitations: Shows what removing the receptor costs the animal at baseline, independently of any drug. The increased mortality is a colony observation. exposure: Constitutive CB1 deletion evidence_span: {"source_cache": "artifacts/thc-research/10318961.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ee2674f143f23f9030564139676e845091ab75adaa02b8ab0220bc77860e38ef", "start_char": 0, "end_char": 1144, "text_sha256": "ee2674f143f23f9030564139676e845091ab75adaa02b8ab0220bc77860e38ef"} [thc-p10318961] Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice. (1999). https://pubmed.ncbi.nlm.nih.gov/10318961/ DOI: 10.1073/pnas.96.10.5780
Complete structured claim and evidence
THC and methanandamide had differential effects in CB1 knockout and wild-type mice, with the effects of THC dependent on the receptor while some effects of the anandamide analogue were not.
Experimental CB1 receptor knockout mouse genotype → Delta-9-tetrahydrocannabinol / THC source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/14718593.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "422efbafe3e999138f4591acf2a7e5126919ba85d84637aeb320927062c5b2a8", "start_char": 0, "end_char": 1836, "text_sha256": "422efbafe3e999138f4591acf2a7e5126919ba85d84637aeb320927062c5b2a8"}
experimental_model
THC and methanandamide compared in CB1 knockout and wild-type mice
exposure
THC and a stable anandamide analogue across genotypes
limitations
The comparison of two agonists across the same genotypes is what shows the receptor accounts for the drug but not for everything cannabinoid-like.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
Take the receptor away and the drug stops working, though not every cannabinoid-like effect disappears with it.
primary_references
[thc-p14718593] Differential effects of delta9-tetrahydrocannabinol and methanandamide in CB1 knockout and wild-type mice. (2004). https://pubmed.ncbi.nlm.nih.gov/14718593/ DOI: 10.1124/jpet.103.055376
tissue_or_cell_type
Whole body
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 426–437
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · THC and methanandamide compared in CB1 knockout and wild-type mice · source_derived_draft · unverified_draft
### thc-thc-requires-cb1 THC and methanandamide had differential effects in CB1 knockout and wild-type mice, with the effects of THC dependent on the receptor while some effects of the anandamide analogue were not. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Take the receptor away and the drug stops working, though not every cannabinoid-like effect disappears with it. organism: Mouse tissue_or_cell_type: Whole body experimental_model: THC and methanandamide compared in CB1 knockout and wild-type mice limitations: The comparison of two agonists across the same genotypes is what shows the receptor accounts for the drug but not for everything cannabinoid-like. exposure: THC and a stable anandamide analogue across genotypes evidence_span: {"source_cache": "artifacts/thc-research/14718593.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "422efbafe3e999138f4591acf2a7e5126919ba85d84637aeb320927062c5b2a8", "start_char": 0, "end_char": 1836, "text_sha256": "422efbafe3e999138f4591acf2a7e5126919ba85d84637aeb320927062c5b2a8"} [thc-p14718593] Differential effects of delta9-tetrahydrocannabinol and methanandamide in CB1 knockout and wild-type mice. (2004). https://pubmed.ncbi.nlm.nih.gov/14718593/ DOI: 10.1124/jpet.103.055376
Complete structured claim and evidence
THC impaired spatial memory through a cannabinoid receptor mechanism, since the impairment was prevented by receptor blockade.
Delta-9-tetrahydrocannabinol / THC → Spatial memory performance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/8856831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0", "start_char": 0, "end_char": 1652, "text_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0"}
experimental_model
Spatial memory testing in rats with a CB1 antagonist
exposure
THC with antagonist pretreatment
limitations
The antagonist arm is what makes this a receptor mechanism rather than a general sedative effect.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
The memory effect runs through the receptor, not through general sedation.
primary_references
[thc-p8856831] Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism. (1996). https://pubmed.ncbi.nlm.nih.gov/8856831/ DOI: 10.1007/bf02246347
tissue_or_cell_type
Hippocampus and behaviour
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 439–450
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Spatial memory testing in rats with a CB1 antagonist · source_derived_draft · unverified_draft
### thc-thc-spatial-memory THC impaired spatial memory through a cannabinoid receptor mechanism, since the impairment was prevented by receptor blockade. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The memory effect runs through the receptor, not through general sedation. organism: Rat tissue_or_cell_type: Hippocampus and behaviour experimental_model: Spatial memory testing in rats with a CB1 antagonist limitations: The antagonist arm is what makes this a receptor mechanism rather than a general sedative effect. exposure: THC with antagonist pretreatment evidence_span: {"source_cache": "artifacts/thc-research/8856831.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0", "start_char": 0, "end_char": 1652, "text_sha256": "cd2ffb6c04147c50bc6a9e311032669fe18406690188a1d058b7e80aa09810e0"} [thc-p8856831] Delta 9-tetrahydrocannabinol impairs spatial memory through a cannabinoid receptor mechanism. (1996). https://pubmed.ncbi.nlm.nih.gov/8856831/ DOI: 10.1007/bf02246347
Complete structured claim and evidence
The CB1 antagonist SR141716A attenuated the memory impairment produced by THC or by anandamide.
SR141716A / rimonabant, a CB1 receptor antagonist → Spatial memory performance source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/9862397.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f", "start_char": 0, "end_char": 1576, "text_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f"}
experimental_model
Memory impairment by THC or anandamide with SR141716A pretreatment
exposure
THC or anandamide with a CB1 antagonist
limitations
Shows the antagonist rescues the impairment for both the drug and the natural ligand.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
Blocking the receptor protects the memory, whichever agonist caused the problem.
primary_references
[thc-p9862397] The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta9-tetrahydrocannabinol or anandamide. (1998). https://pubmed.ncbi.nlm.nih.gov/9862397/ DOI: 10.1007/s002130050733
tissue_or_cell_type
Behaviour
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 452–463
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Memory impairment by THC or anandamide with SR141716A pretreatment · source_derived_draft · unverified_draft
### thc-antagonist-rescues-memory The CB1 antagonist SR141716A attenuated the memory impairment produced by THC or by anandamide. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Blocking the receptor protects the memory, whichever agonist caused the problem. organism: Rat tissue_or_cell_type: Behaviour experimental_model: Memory impairment by THC or anandamide with SR141716A pretreatment limitations: Shows the antagonist rescues the impairment for both the drug and the natural ligand. exposure: THC or anandamide with a CB1 antagonist evidence_span: {"source_cache": "artifacts/thc-research/9862397.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f", "start_char": 0, "end_char": 1576, "text_sha256": "59e00778f9e8b2a2aba64063224de431ef098aaffcf26dca95fd9ddb36981a1f"} [thc-p9862397] The cannabinoid CB1 receptor antagonist SR141716A attenuates the memory impairment produced by delta9-tetrahydrocannabinol or anandamide. (1998). https://pubmed.ncbi.nlm.nih.gov/9862397/ DOI: 10.1007/s002130050733
Complete structured claim and evidence
Hippocampal CB1 receptors mediate the memory-impairing effects of THC.
CB1 receptors in the hippocampus → Spatial memory performance source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/19322169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443", "start_char": 0, "end_char": 1794, "text_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443"}
experimental_model
Region-specific CB1 manipulation with memory testing
exposure
THC with hippocampal CB1 manipulation
limitations
Localises the effect to one structure, which the whole-animal antagonist studies cannot do.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rodent
plain_language
It is the receptors in one brain structure that account for the memory effect.
primary_references
[thc-p19322169] Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol. (2009). https://pubmed.ncbi.nlm.nih.gov/19322169/ DOI: 10.1038/npp.2009.31
tissue_or_cell_type
Hippocampus
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 465–476
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Region-specific CB1 manipulation with memory testing · source_derived_draft · unverified_draft
### thc-hippocampal-cb1-memory Hippocampal CB1 receptors mediate the memory-impairing effects of THC. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: It is the receptors in one brain structure that account for the memory effect. organism: Rodent tissue_or_cell_type: Hippocampus experimental_model: Region-specific CB1 manipulation with memory testing limitations: Localises the effect to one structure, which the whole-animal antagonist studies cannot do. exposure: THC with hippocampal CB1 manipulation evidence_span: {"source_cache": "artifacts/thc-research/19322169.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443", "start_char": 0, "end_char": 1794, "text_sha256": "30928c5217e21de0bdcdac0c5485e1608c9e1ee354404319a78ee8ac369b9443"} [thc-p19322169] Hippocampal CB(1) receptors mediate the memory impairing effects of Delta(9)-tetrahydrocannabinol. (2009). https://pubmed.ncbi.nlm.nih.gov/19322169/ DOI: 10.1038/npp.2009.31
Complete structured claim and evidence
Prolonged THC administration produced hippocampal neurotoxicity in rats.
Delta-9-tetrahydrocannabinol / THC → Hippocampal neuronal damage after prolonged THC exposure source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/9651215.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60", "start_char": 0, "end_char": 974, "text_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60"}
experimental_model
Prolonged THC administration with hippocampal histology
exposure
Chronic high-dose THC exposure
limitations
A structural damage endpoint at high chronic doses in rats. The doses are far above ordinary human exposure, which is the main limit on reading it across.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
At high chronic doses in rats the same structure shows physical damage.
primary_references
[thc-p9651215] Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. (1998). https://pubmed.ncbi.nlm.nih.gov/9651215/ DOI: 10.1523/jneurosci.18-14-05322.1998
tissue_or_cell_type
Hippocampus
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 478–489
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prolonged THC administration with hippocampal histology · source_derived_draft · unverified_draft
### thc-thc-hippocampal-damage Prolonged THC administration produced hippocampal neurotoxicity in rats. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: At high chronic doses in rats the same structure shows physical damage. organism: Rat tissue_or_cell_type: Hippocampus experimental_model: Prolonged THC administration with hippocampal histology limitations: A structural damage endpoint at high chronic doses in rats. The doses are far above ordinary human exposure, which is the main limit on reading it across. exposure: Chronic high-dose THC exposure evidence_span: {"source_cache": "artifacts/thc-research/9651215.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60", "start_char": 0, "end_char": 974, "text_sha256": "8e38fbb1327a18b89adb1a015aa7f59e7e60472a5f19bcf4032dbd2ba827be60"} [thc-p9651215] Hippocampal neurotoxicity of Delta9-tetrahydrocannabinol. (1998). https://pubmed.ncbi.nlm.nih.gov/9651215/ DOI: 10.1523/jneurosci.18-14-05322.1998
Complete structured claim and evidence
Appetite suppression and weight loss followed administration of the cannabinoid antagonist SR141716.
SR141716A / rimonabant, a CB1 receptor antagonist → Food intake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/9718088.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4714909d64a1c671c1c3dcec0496b80cc6a09e0a8d0368ed6b8be8aa284456e2", "start_char": 0, "end_char": 590, "text_sha256": "4714909d64a1c671c1c3dcec0496b80cc6a09e0a8d0368ed6b8be8aa284456e2"}
experimental_model
The CB1 antagonist SR141716 given for appetite and body weight measurement
exposure
SR141716 administration with food intake and weight measurement
limitations
Establishes that blocking the receptor suppresses appetite, which is the mirror of the drug effect. Rimonabant was later withdrawn for psychiatric adverse effects, which is not in this record.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rodent
plain_language
Blocking the receptor takes hunger away, which is why the drug increases it.
primary_references
[thc-p9718088] Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. (1998). https://pubmed.ncbi.nlm.nih.gov/9718088/ DOI: 10.1016/s0024-3205(98)00322-1
tissue_or_cell_type
Whole body
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 491–502
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · The CB1 antagonist SR141716 given for appetite and body weight measurement · source_derived_draft · unverified_draft
### thc-antagonist-suppresses-appetite Appetite suppression and weight loss followed administration of the cannabinoid antagonist SR141716. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Blocking the receptor takes hunger away, which is why the drug increases it. organism: Rodent tissue_or_cell_type: Whole body experimental_model: The CB1 antagonist SR141716 given for appetite and body weight measurement limitations: Establishes that blocking the receptor suppresses appetite, which is the mirror of the drug effect. Rimonabant was later withdrawn for psychiatric adverse effects, which is not in this record. exposure: SR141716 administration with food intake and weight measurement evidence_span: {"source_cache": "artifacts/thc-research/9718088.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4714909d64a1c671c1c3dcec0496b80cc6a09e0a8d0368ed6b8be8aa284456e2", "start_char": 0, "end_char": 590, "text_sha256": "4714909d64a1c671c1c3dcec0496b80cc6a09e0a8d0368ed6b8be8aa284456e2"} [thc-p9718088] Appetite suppression and weight loss after the cannabinoid antagonist SR 141716. (1998). https://pubmed.ncbi.nlm.nih.gov/9718088/ DOI: 10.1016/s0024-3205(98)00322-1
Complete structured claim and evidence
CB1 cannabinoid receptor activation modulated food intake in mice, with agonists and antagonists moving intake in opposite directions.
Human cannabinoid receptor 1 / CB1 / CNR1 → Food intake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/15778743.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "813967ae44806749032cc8f98384086ca5ae7f0c4a6367a56cbb375680e205ac", "start_char": 0, "end_char": 1724, "text_sha256": "813967ae44806749032cc8f98384086ca5ae7f0c4a6367a56cbb375680e205ac"}
experimental_model
CB1-mediated modulation of food intake measured in mice
exposure
Cannabinoid agonists and antagonists on feeding
limitations
A bidirectional pharmacological test of the same axis in a second species.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
The receptor sets appetite in both directions.
primary_references
[thc-p15778743] CB1 cannabinoid receptor-mediated modulation of food intake in mice. (2005). https://pubmed.ncbi.nlm.nih.gov/15778743/ DOI: 10.1038/sj.bjp.0706157
tissue_or_cell_type
Whole body
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 504–515
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CB1-mediated modulation of food intake measured in mice · source_derived_draft · unverified_draft
### thc-cb1-food-intake CB1 cannabinoid receptor activation modulated food intake in mice, with agonists and antagonists moving intake in opposite directions. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The receptor sets appetite in both directions. organism: Mouse tissue_or_cell_type: Whole body experimental_model: CB1-mediated modulation of food intake measured in mice limitations: A bidirectional pharmacological test of the same axis in a second species. exposure: Cannabinoid agonists and antagonists on feeding evidence_span: {"source_cache": "artifacts/thc-research/15778743.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "813967ae44806749032cc8f98384086ca5ae7f0c4a6367a56cbb375680e205ac", "start_char": 0, "end_char": 1724, "text_sha256": "813967ae44806749032cc8f98384086ca5ae7f0c4a6367a56cbb375680e205ac"} [thc-p15778743] CB1 cannabinoid receptor-mediated modulation of food intake in mice. (2005). https://pubmed.ncbi.nlm.nih.gov/15778743/ DOI: 10.1038/sj.bjp.0706157
Complete structured claim and evidence
Plasma cannabinoid pharmacokinetics following controlled oral THC and oromucosal cannabis extract administration resolved the time courses of THC and its metabolites.
Delta-9-tetrahydrocannabinol / THC → 11-hydroxy-delta-9-tetrahydrocannabinol source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/21078841.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9", "start_char": 0, "end_char": 1727, "text_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9"}
experimental_model
Controlled oral THC and oromucosal cannabis extract with serial plasma sampling
exposure
Controlled oral THC and oromucosal extract dosing
limitations
A controlled human pharmacokinetic study with the metabolites measured. Oral and oromucosal routes only; it does not describe smoked exposure.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human
plain_language
The drug is measured alongside the two metabolites it becomes.
primary_references
[thc-p21078841] Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. (2011). https://pubmed.ncbi.nlm.nih.gov/21078841/ DOI: 10.1373/clinchem.2010.152439
tissue_or_cell_type
Plasma
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 517–528
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Controlled oral THC and oromucosal cannabis extract with serial plasma sampling · source_derived_draft · unverified_draft
### thc-thc-metabolites Plasma cannabinoid pharmacokinetics following controlled oral THC and oromucosal cannabis extract administration resolved the time courses of THC and its metabolites. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The drug is measured alongside the two metabolites it becomes. organism: Human tissue_or_cell_type: Plasma experimental_model: Controlled oral THC and oromucosal cannabis extract with serial plasma sampling limitations: A controlled human pharmacokinetic study with the metabolites measured. Oral and oromucosal routes only; it does not describe smoked exposure. exposure: Controlled oral THC and oromucosal extract dosing evidence_span: {"source_cache": "artifacts/thc-research/21078841.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9", "start_char": 0, "end_char": 1727, "text_sha256": "0ae96dadadcd8c1ee096e38d9a531fc9182b5670b97837d6d1ddad9cd611e2f9"} [thc-p21078841] Plasma cannabinoid pharmacokinetics following controlled oral delta9-tetrahydrocannabinol and oromucosal cannabis extract administration. (2011). https://pubmed.ncbi.nlm.nih.gov/21078841/ DOI: 10.1373/clinchem.2010.152439
Complete structured claim and evidence
The median area under the curve of THC was threefold higher and that of THC-COOH 70% lower in CYP2C9*3/*3 homozygotes than in CYP2C9*1/*1 homozygotes, with a trend toward increased sedation, while CYP2C9*2 status made no difference.
The CYP2C9*3 variant allele → Plasma THC concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/19005461.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67758630ab5ff7fc0505e51bda1d2fa1b24ec91f1569d14717bf2ec83c03e34e", "start_char": 0, "end_char": 601, "text_sha256": "67758630ab5ff7fc0505e51bda1d2fa1b24ec91f1569d14717bf2ec83c03e34e"}
experimental_model
Oral THC in 43 healthy volunteers genotyped for CYP2C9
exposure
Oral THC across CYP2C9 genotypes
limitations
A pharmacogenetic study with a clear exposure difference. The sedation finding is described as a trend.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human
plain_language
People with two copies of one variant get three times the drug exposure from the same dose.
primary_references
[thc-p19005461] Interindividual variation in the pharmacokinetics of Delta9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9. (2009). https://pubmed.ncbi.nlm.nih.gov/19005461/ DOI: 10.1038/clpt.2008.213
tissue_or_cell_type
Whole body
trigger_kind
machinery_impairment Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 530–541
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Oral THC in 43 healthy volunteers genotyped for CYP2C9 · source_derived_draft · unverified_draft
### thc-cyp2c9-exposure The median area under the curve of THC was threefold higher and that of THC-COOH 70% lower in CYP2C9*3/*3 homozygotes than in CYP2C9*1/*1 homozygotes, with a trend toward increased sedation, while CYP2C9*2 status made no difference. Condition category: machinery_impairment nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: People with two copies of one variant get three times the drug exposure from the same dose. organism: Human tissue_or_cell_type: Whole body experimental_model: Oral THC in 43 healthy volunteers genotyped for CYP2C9 limitations: A pharmacogenetic study with a clear exposure difference. The sedation finding is described as a trend. exposure: Oral THC across CYP2C9 genotypes evidence_span: {"source_cache": "artifacts/thc-research/19005461.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67758630ab5ff7fc0505e51bda1d2fa1b24ec91f1569d14717bf2ec83c03e34e", "start_char": 0, "end_char": 601, "text_sha256": "67758630ab5ff7fc0505e51bda1d2fa1b24ec91f1569d14717bf2ec83c03e34e"} [thc-p19005461] Interindividual variation in the pharmacokinetics of Delta9-tetrahydrocannabinol as related to genetic polymorphisms in CYP2C9. (2009). https://pubmed.ncbi.nlm.nih.gov/19005461/ DOI: 10.1038/clpt.2008.213
Complete structured claim and evidence
CYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein.
Human cytochrome P450 2C9 → Delta-9-tetrahydrocannabinol / THC source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/38583809.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1", "start_char": 0, "end_char": 1645, "text_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1"}
experimental_model
Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein
exposure
THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1
limitations
Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human enzymes
plain_language
Three enzymes share the job, and a fat-carrying protein changes how fast they do it.
primary_references
[thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191
tissue_or_cell_type
Recombinant system
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 543–554
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein · source_derived_draft · unverified_draft
### thc-multiple-cyps CYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Three enzymes share the job, and a fat-carrying protein changes how fast they do it. organism: Human enzymes tissue_or_cell_type: Recombinant system experimental_model: Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein limitations: Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system. exposure: THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1 evidence_span: {"source_cache": "artifacts/thc-research/38583809.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1", "start_char": 0, "end_char": 1645, "text_sha256": "29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1"} [thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191
Complete structured claim and evidence
Evidence emerged that cannabidiol partially inhibits the CYP2C-catalysed hydroxylation of THC to 11-OH-THC, with the probability particularly high for oral intake, but the effect was small compared with the variability caused by other factors, and significantly higher exposure and shorter time to peak were found in women than men.
Cannabidiol → Hydroxylation of THC to 11-OH-THC source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/16306858.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "686c5587340a5590db33367328f93f4be704262c3d92b53f627ff01b154943da", "start_char": 0, "end_char": 2129, "text_sha256": "686c5587340a5590db33367328f93f4be704262c3d92b53f627ff01b154943da"}
experimental_model
Randomised double-blind placebo-controlled crossover in 24 volunteers
exposure
Oral THC 10 mg versus cannabis extract containing 10 mg THC plus 5.4 mg cannabidiol
limitations
A human randomised crossover. The authors conclude the cannabidiol effect is small relative to other variability, so a pharmacokinetic explanation for extract-versus-THC differences is improbable at these doses.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human
plain_language
Cannabidiol does slow one step of THC breakdown, but not enough to explain much.
primary_references
[thc-p16306858] Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. (2005). https://pubmed.ncbi.nlm.nih.gov/16306858/ DOI: 10.1097/01.ftd.0000177223.19294.5c
tissue_or_cell_type
Plasma
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 556–567
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomised double-blind placebo-controlled crossover in 24 volunteers · source_derived_draft · unverified_draft
### thc-cbd-inhibits-hydroxylation Evidence emerged that cannabidiol partially inhibits the CYP2C-catalysed hydroxylation of THC to 11-OH-THC, with the probability particularly high for oral intake, but the effect was small compared with the variability caused by other factors, and significantly higher exposure and shorter time to peak were found in women than men. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Cannabidiol does slow one step of THC breakdown, but not enough to explain much. organism: Human tissue_or_cell_type: Plasma experimental_model: Randomised double-blind placebo-controlled crossover in 24 volunteers limitations: A human randomised crossover. The authors conclude the cannabidiol effect is small relative to other variability, so a pharmacokinetic explanation for extract-versus-THC differences is improbable at these doses. exposure: Oral THC 10 mg versus cannabis extract containing 10 mg THC plus 5.4 mg cannabidiol evidence_span: {"source_cache": "artifacts/thc-research/16306858.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "686c5587340a5590db33367328f93f4be704262c3d92b53f627ff01b154943da", "start_char": 0, "end_char": 2129, "text_sha256": "686c5587340a5590db33367328f93f4be704262c3d92b53f627ff01b154943da"} [thc-p16306858] Randomized, double-blind, placebo-controlled study about the effects of cannabidiol (CBD) on the pharmacokinetics of Delta9-tetrahydrocannabinol (THC) after oral application of THC verses standardized cannabis extract. (2005). https://pubmed.ncbi.nlm.nih.gov/16306858/ DOI: 10.1097/01.ftd.0000177223.19294.5c
Complete structured claim and evidence
Cannabidiol pretreatment potentiated blood and brain THC levels with both acute and chronic administration in adolescent rats, potentiated the inhibition of body weight gain caused by chronic THC, and mildly augmented its anxiogenic, locomotor-suppressant and social-interaction effects.
Cannabidiol → Brain THC concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/21667074.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "da582d1624586305da4993ae0e27e4d07352e46eda2ac97c88cc924f2a8ed598", "start_char": 0, "end_char": 1688, "text_sha256": "da582d1624586305da4993ae0e27e4d07352e46eda2ac97c88cc924f2a8ed598"}
experimental_model
Adolescent rats given ascending THC doses over 21 days with and without equivalent cannabidiol
exposure
Ascending THC 1 to 10 mg/kg over 21 days with cannabidiol pretreatment
limitations
A chronic animal study at equivalent doses, reaching the opposite conclusion to the human single-dose work on whether cannabidiol opposes THC.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
In young rats cannabidiol made THC stronger, not weaker.
primary_references
[thc-p21667074] Cannabidiol potentiates Δ⁹-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. (2011). https://pubmed.ncbi.nlm.nih.gov/21667074/ DOI: 10.1007/s00213-011-2342-0
tissue_or_cell_type
Blood, brain and behaviour
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 569–580
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Adolescent rats given ascending THC doses over 21 days with and without equivalent cannabidiol · source_derived_draft · unverified_draft
### thc-cbd-potentiates-thc Cannabidiol pretreatment potentiated blood and brain THC levels with both acute and chronic administration in adolescent rats, potentiated the inhibition of body weight gain caused by chronic THC, and mildly augmented its anxiogenic, locomotor-suppressant and social-interaction effects. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: In young rats cannabidiol made THC stronger, not weaker. organism: Rat tissue_or_cell_type: Blood, brain and behaviour experimental_model: Adolescent rats given ascending THC doses over 21 days with and without equivalent cannabidiol limitations: A chronic animal study at equivalent doses, reaching the opposite conclusion to the human single-dose work on whether cannabidiol opposes THC. exposure: Ascending THC 1 to 10 mg/kg over 21 days with cannabidiol pretreatment evidence_span: {"source_cache": "artifacts/thc-research/21667074.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "da582d1624586305da4993ae0e27e4d07352e46eda2ac97c88cc924f2a8ed598", "start_char": 0, "end_char": 1688, "text_sha256": "da582d1624586305da4993ae0e27e4d07352e46eda2ac97c88cc924f2a8ed598"} [thc-p21667074] Cannabidiol potentiates Δ⁹-tetrahydrocannabinol (THC) behavioural effects and alters THC pharmacokinetics during acute and chronic treatment in adolescent rats. (2011). https://pubmed.ncbi.nlm.nih.gov/21667074/ DOI: 10.1007/s00213-011-2342-0
Complete structured claim and evidence
Higher levels of cannabis use were associated with increased risk for psychosis in all included studies, with an odds ratio of 3.90 for schizophrenia and other psychosis-related outcomes among the heaviest users compared with non-users, across 66,816 individuals.
Cannabis use → Psychotic symptoms source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/26884547.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f62f6a3846a5e753f3268581ec2d6cedb08c6844df6ba9dd32f74bc09947231", "start_char": 0, "end_char": 1584, "text_sha256": "4f62f6a3846a5e753f3268581ec2d6cedb08c6844df6ba9dd32f74bc09947231"}
experimental_model
Systematic review and meta-analysis of 10 studies and 66,816 individuals
exposure
Level of cannabis consumption before psychosis onset
limitations
A dose-response meta-analysis of observational studies. Observational designs cannot separate use that causes psychosis from use that precedes it for other reasons.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human
plain_language
The heaviest users had about four times the risk, and the risk rose with the amount used.
primary_references
[thc-p26884547] Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. (2016). https://pubmed.ncbi.nlm.nih.gov/26884547/ DOI: 10.1093/schbul/sbw003
tissue_or_cell_type
Whole body
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 582–593
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Systematic review and meta-analysis of 10 studies and 66,816 individuals · source_derived_draft · unverified_draft
### thc-psychosis-dose-response Higher levels of cannabis use were associated with increased risk for psychosis in all included studies, with an odds ratio of 3.90 for schizophrenia and other psychosis-related outcomes among the heaviest users compared with non-users, across 66,816 individuals. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The heaviest users had about four times the risk, and the risk rose with the amount used. organism: Human tissue_or_cell_type: Whole body experimental_model: Systematic review and meta-analysis of 10 studies and 66,816 individuals limitations: A dose-response meta-analysis of observational studies. Observational designs cannot separate use that causes psychosis from use that precedes it for other reasons. exposure: Level of cannabis consumption before psychosis onset evidence_span: {"source_cache": "artifacts/thc-research/26884547.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4f62f6a3846a5e753f3268581ec2d6cedb08c6844df6ba9dd32f74bc09947231", "start_char": 0, "end_char": 1584, "text_sha256": "4f62f6a3846a5e753f3268581ec2d6cedb08c6844df6ba9dd32f74bc09947231"} [thc-p26884547] Meta-analysis of the Association Between the Level of Cannabis Use and Risk of Psychosis. (2016). https://pubmed.ncbi.nlm.nih.gov/26884547/ DOI: 10.1093/schbul/sbw003
Complete structured claim and evidence
After adjustment for age, sex, socioeconomic status, urbanicity, childhood trauma, baseline predisposition and other drug, tobacco and alcohol use, cannabis use raised the cumulative incidence of psychotic symptoms four years later with an adjusted odds ratio of 1.67, and the effect was much stronger in those with any predisposition at baseline, a 23.8 percentage point risk difference against 5.6 in those without.
Pre-existing predisposition for psychosis → Psychotic symptoms source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/15574485.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "56846f52ea834853e8aa27f64700905e072d53611066a7c58df74269b65ec290", "start_char": 0, "end_char": 1860, "text_sha256": "56846f52ea834853e8aa27f64700905e072d53611066a7c58df74269b65ec290"}
experimental_model
Prospective cohort of 2437 young people with baseline predisposition assessment
exposure
Cannabis use at baseline with psychotic symptoms at four-year follow-up
limitations
A prospective design with adjustment for predisposition, trauma and other drugs, which is what makes the interaction finding interpretable.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human
plain_language
The risk lands overwhelmingly on people already predisposed.
primary_references
[thc-p15574485] Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. (2005). https://pubmed.ncbi.nlm.nih.gov/15574485/ DOI: 10.1136/bmj.38267.664086.63
tissue_or_cell_type
Whole body
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 595–606
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Prospective cohort of 2437 young people with baseline predisposition assessment · source_derived_draft · unverified_draft
### thc-psychosis-predisposition-interaction After adjustment for age, sex, socioeconomic status, urbanicity, childhood trauma, baseline predisposition and other drug, tobacco and alcohol use, cannabis use raised the cumulative incidence of psychotic symptoms four years later with an adjusted odds ratio of 1.67, and the effect was much stronger in those with any predisposition at baseline, a 23.8 percentage point risk difference against 5.6 in those without. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The risk lands overwhelmingly on people already predisposed. organism: Human tissue_or_cell_type: Whole body experimental_model: Prospective cohort of 2437 young people with baseline predisposition assessment limitations: A prospective design with adjustment for predisposition, trauma and other drugs, which is what makes the interaction finding interpretable. exposure: Cannabis use at baseline with psychotic symptoms at four-year follow-up evidence_span: {"source_cache": "artifacts/thc-research/15574485.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "56846f52ea834853e8aa27f64700905e072d53611066a7c58df74269b65ec290", "start_char": 0, "end_char": 1860, "text_sha256": "56846f52ea834853e8aa27f64700905e072d53611066a7c58df74269b65ec290"} [thc-p15574485] Prospective cohort study of cannabis use, predisposition for psychosis, and psychotic symptoms in young people. (2005). https://pubmed.ncbi.nlm.nih.gov/15574485/ DOI: 10.1136/bmj.38267.664086.63
Complete structured claim and evidence
Cannabis use was associated with an earlier onset of psychosis in a systematic meta-analysis.
Cannabis use → Age at onset of psychosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/21300939.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "89d48d713734797db84d74790a6a0eb51c99f4a40f9d7e6b64fd57edf4c0c0f5", "start_char": 0, "end_char": 1963, "text_sha256": "89d48d713734797db84d74790a6a0eb51c99f4a40f9d7e6b64fd57edf4c0c0f5"}
experimental_model
Systematic meta-analysis of age at onset of psychosis in cannabis users
exposure
Cannabis use against age at psychosis onset
limitations
Measures timing rather than incidence. Earlier onset in users is consistent with precipitation, with confounding, or with both.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Human
plain_language
Among people who develop psychosis, users develop it younger.
primary_references
[thc-p21300939] Cannabis use and earlier onset of psychosis: a systematic meta-analysis. (2011). https://pubmed.ncbi.nlm.nih.gov/21300939/ DOI: 10.1001/archgenpsychiatry.2011.5
tissue_or_cell_type
Whole body
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 608–619
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Systematic meta-analysis of age at onset of psychosis in cannabis users · source_derived_draft · unverified_draft
### thc-psychosis-earlier-onset Cannabis use was associated with an earlier onset of psychosis in a systematic meta-analysis. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Among people who develop psychosis, users develop it younger. organism: Human tissue_or_cell_type: Whole body experimental_model: Systematic meta-analysis of age at onset of psychosis in cannabis users limitations: Measures timing rather than incidence. Earlier onset in users is consistent with precipitation, with confounding, or with both. exposure: Cannabis use against age at psychosis onset evidence_span: {"source_cache": "artifacts/thc-research/21300939.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "89d48d713734797db84d74790a6a0eb51c99f4a40f9d7e6b64fd57edf4c0c0f5", "start_char": 0, "end_char": 1963, "text_sha256": "89d48d713734797db84d74790a6a0eb51c99f4a40f9d7e6b64fd57edf4c0c0f5"} [thc-p21300939] Cannabis use and earlier onset of psychosis: a systematic meta-analysis. (2011). https://pubmed.ncbi.nlm.nih.gov/21300939/ DOI: 10.1001/archgenpsychiatry.2011.5
Complete structured claim and evidence
Lifelong n-3 polyunsaturated fatty acid dietary insufficiency specifically ablated long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens.
Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids → Endocannabinoid-mediated long-term synaptic depression source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"}
experimental_model
Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays
exposure
Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids
limitations
A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
Starve the diet of these fats and one specific form of synaptic learning disappears.
primary_references
[thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
tissue_or_cell_type
Prelimbic prefrontal cortex and accumbens
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 621–632
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays · source_derived_draft · unverified_draft
### thc-n3-ablates-ltd Lifelong n-3 polyunsaturated fatty acid dietary insufficiency specifically ablated long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens. Condition category: nutrient_deficiency nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Starve the diet of these fats and one specific form of synaptic learning disappears. organism: Mouse tissue_or_cell_type: Prelimbic prefrontal cortex and accumbens experimental_model: Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays limitations: A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change. exposure: Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids evidence_span: {"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"} [thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
Complete structured claim and evidence
In n-3-deficient mice, presynaptic CB1 receptors that normally respond to endocannabinoids were uncoupled from their effector Gi/o proteins.
Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids → Coupling of presynaptic CB1 receptors to their Gi/o effector proteins source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"}
experimental_model
Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays
exposure
Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids
limitations
A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
The receptor was still there but no longer connected to what it talks to.
primary_references
[thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
tissue_or_cell_type
Prelimbic prefrontal cortex and accumbens
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 634–645
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays · source_derived_draft · unverified_draft
### thc-n3-uncouples-cb1 In n-3-deficient mice, presynaptic CB1 receptors that normally respond to endocannabinoids were uncoupled from their effector Gi/o proteins. Condition category: nutrient_deficiency nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The receptor was still there but no longer connected to what it talks to. organism: Mouse tissue_or_cell_type: Prelimbic prefrontal cortex and accumbens experimental_model: Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays limitations: A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change. exposure: Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids evidence_span: {"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"} [thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
Complete structured claim and evidence
The dietary-induced reduction of CB1 receptor function in mood-controlling structures was associated with impaired emotional behaviour, identifying a plausible synaptic substrate for the behavioural alterations reported with n-3 deficiency in western diets.
Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids → Emotional behaviour in the tested mouse assays source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"}
experimental_model
Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays
exposure
Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids
limitations
A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Mouse
plain_language
The animals behaved differently, and the synapse gives a reason why.
primary_references
[thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
tissue_or_cell_type
Prelimbic prefrontal cortex and accumbens
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 647–658
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays · source_derived_draft · unverified_draft
### thc-n3-emotional-behaviour The dietary-induced reduction of CB1 receptor function in mood-controlling structures was associated with impaired emotional behaviour, identifying a plausible synaptic substrate for the behavioural alterations reported with n-3 deficiency in western diets. Condition category: nutrient_deficiency nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The animals behaved differently, and the synapse gives a reason why. organism: Mouse tissue_or_cell_type: Prelimbic prefrontal cortex and accumbens experimental_model: Lifelong n-3 deficient diet in mice with synaptic recordings and receptor coupling assays limitations: A dietary manipulation with a molecular readout, receptor-effector uncoupling, rather than only a behavioural one. It is a lifelong deficiency, not a short-term change. exposure: Lifelong dietary insufficiency of n-3 polyunsaturated fatty acids evidence_span: {"source_cache": "artifacts/thc-research/21278728.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281", "start_char": 0, "end_char": 953, "text_sha256": "d19499dcf42cdfc31c0fc46420a1bc84babcbfcd366cf1cb37f3fed8f5d38281"} [thc-p21278728] Nutritional omega-3 deficiency abolishes endocannabinoid-mediated neuronal functions. (2011). https://pubmed.ncbi.nlm.nih.gov/21278728/ DOI: 10.1038/nn.2736
Complete structured claim and evidence
The olive oil diet increased brain anandamide and oleoylethanolamide without changing tissue fatty acid composition and without changing 2-arachidonoylglycerol, while the safflower oil diet increased linoleoylethanolamide and linoleic acid in brain, jejunum and liver.
Dietary olive oil → Anandamide / arachidonylethanolamide source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/18316044.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3", "start_char": 0, "end_char": 1668, "text_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3"}
experimental_model
Rats fed five different dietary fats with tissue endocannabinoid and fatty acid measurement
exposure
Short-term feeding of palm, olive, safflower, fish or arachidonic acid enriched diets
limitations
A five-arm dietary comparison measuring the mediators directly. Short-term feeding, and some changes occurred without any change in tissue fatty acid composition.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
Which fat is eaten changes which of these messengers the brain has, sometimes without changing the tissue fat itself.
primary_references
[thc-p18316044] Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine. (2008). https://pubmed.ncbi.nlm.nih.gov/18316044/ DOI: 10.1016/j.bbalip.2008.01.006
tissue_or_cell_type
Brain, liver and small intestine
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 660–671
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats fed five different dietary fats with tissue endocannabinoid and fatty acid measurement · source_derived_draft · unverified_draft
### thc-diet-shapes-endocannabinoids The olive oil diet increased brain anandamide and oleoylethanolamide without changing tissue fatty acid composition and without changing 2-arachidonoylglycerol, while the safflower oil diet increased linoleoylethanolamide and linoleic acid in brain, jejunum and liver. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Which fat is eaten changes which of these messengers the brain has, sometimes without changing the tissue fat itself. organism: Rat tissue_or_cell_type: Brain, liver and small intestine experimental_model: Rats fed five different dietary fats with tissue endocannabinoid and fatty acid measurement limitations: A five-arm dietary comparison measuring the mediators directly. Short-term feeding, and some changes occurred without any change in tissue fatty acid composition. exposure: Short-term feeding of palm, olive, safflower, fish or arachidonic acid enriched diets evidence_span: {"source_cache": "artifacts/thc-research/18316044.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3", "start_char": 0, "end_char": 1668, "text_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3"} [thc-p18316044] Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine. (2008). https://pubmed.ncbi.nlm.nih.gov/18316044/ DOI: 10.1016/j.bbalip.2008.01.006
Complete structured claim and evidence
The arachidonic acid diet increased anandamide and 2-arachidonoylglycerol in jejunum without effect on liver, and the fish oil diet decreased liver levels of most N-acylethanolamines with similar changes in their precursors.
Dietary arachidonic acid → 2-Arachidonoylglycerol / 2-AG source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/18316044.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3", "start_char": 0, "end_char": 1668, "text_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3"}
experimental_model
Rats fed five different dietary fats with tissue endocannabinoid and fatty acid measurement
exposure
Short-term feeding of palm, olive, safflower, fish or arachidonic acid enriched diets
limitations
A five-arm dietary comparison measuring the mediators directly. Short-term feeding, and some changes occurred without any change in tissue fatty acid composition.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
Feeding the precursor raises the messengers, and feeding fish oil lowers them.
primary_references
[thc-p18316044] Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine. (2008). https://pubmed.ncbi.nlm.nih.gov/18316044/ DOI: 10.1016/j.bbalip.2008.01.006
tissue_or_cell_type
Brain, liver and small intestine
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 673–684
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rats fed five different dietary fats with tissue endocannabinoid and fatty acid measurement · source_derived_draft · unverified_draft
### thc-arachidonic-diet-raises-both The arachidonic acid diet increased anandamide and 2-arachidonoylglycerol in jejunum without effect on liver, and the fish oil diet decreased liver levels of most N-acylethanolamines with similar changes in their precursors. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Feeding the precursor raises the messengers, and feeding fish oil lowers them. organism: Rat tissue_or_cell_type: Brain, liver and small intestine experimental_model: Rats fed five different dietary fats with tissue endocannabinoid and fatty acid measurement limitations: A five-arm dietary comparison measuring the mediators directly. Short-term feeding, and some changes occurred without any change in tissue fatty acid composition. exposure: Short-term feeding of palm, olive, safflower, fish or arachidonic acid enriched diets evidence_span: {"source_cache": "artifacts/thc-research/18316044.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3", "start_char": 0, "end_char": 1668, "text_sha256": "fa2ad40ef984af77cc4c50a6126ce53354a2fd56fe6fada84871e2382cef07b3"} [thc-p18316044] Influence of dietary fatty acids on endocannabinoid and N-acylethanolamine levels in rat brain, liver and small intestine. (2008). https://pubmed.ncbi.nlm.nih.gov/18316044/ DOI: 10.1016/j.bbalip.2008.01.006
Complete structured claim and evidence
Dietary docosahexaenoic acid supplementation altered select physiological endocannabinoid-system metabolites in brain and plasma.
Omega-3 / n-3 fatty acids, study-specified mixture → Brain endocannabinoid and N-acylethanolamine levels source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/thc-research/20071693.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd1db87651b7b35784fcd3a50377a11cf8d9a513df35d28860b4fc4e7221a0c1", "start_char": 0, "end_char": 1580, "text_sha256": "cd1db87651b7b35784fcd3a50377a11cf8d9a513df35d28860b4fc4e7221a0c1"}
experimental_model
Dietary docosahexaenoic acid supplementation with brain and plasma endocannabinoid metabolite measurement
exposure
Dietary DHA supplementation
limitations
Tests the opposite manipulation to deficiency and finds selective rather than global change.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rodent
plain_language
Adding these fats back moves some of the messengers, not all of them.
primary_references
[thc-p20071693] Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma. (2010). https://pubmed.ncbi.nlm.nih.gov/20071693/ DOI: 10.1194/jlr.m002436
tissue_or_cell_type
Brain and plasma
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 686–697
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary docosahexaenoic acid supplementation with brain and plasma endocannabinoid metabolite measurement · source_derived_draft · unverified_draft
### thc-dha-alters-metabolites Dietary docosahexaenoic acid supplementation altered select physiological endocannabinoid-system metabolites in brain and plasma. Condition category: nutrient_deficiency nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Adding these fats back moves some of the messengers, not all of them. organism: Rodent tissue_or_cell_type: Brain and plasma experimental_model: Dietary docosahexaenoic acid supplementation with brain and plasma endocannabinoid metabolite measurement limitations: Tests the opposite manipulation to deficiency and finds selective rather than global change. exposure: Dietary DHA supplementation evidence_span: {"source_cache": "artifacts/thc-research/20071693.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cd1db87651b7b35784fcd3a50377a11cf8d9a513df35d28860b4fc4e7221a0c1", "start_char": 0, "end_char": 1580, "text_sha256": "cd1db87651b7b35784fcd3a50377a11cf8d9a513df35d28860b4fc4e7221a0c1"} [thc-p20071693] Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma. (2010). https://pubmed.ncbi.nlm.nih.gov/20071693/ DOI: 10.1194/jlr.m002436
Complete structured claim and evidence
Sham feeding emulsions containing oleic acid or linoleic acid caused a nearly twofold accumulation of jejunal endocannabinoids, whereas emulsions containing stearic acid or alpha-linolenic acid had no such effect, and corn oil raised them relative to mineral oil which contains no fatty acids.
Linoleic acid → Jejunal endocannabinoid concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/23463697.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079", "start_char": 0, "end_char": 1315, "text_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079"}
experimental_model
Sham-feeding protocol in rats with jejunal endocannabinoid measurement and peripheral CB1 antagonists
exposure
Sham feeding of defined fatty acid emulsions with peripherally restricted CB1 antagonists
limitations
Sham feeding separates oral exposure from absorption, and the peripherally restricted antagonists separate a gut mechanism from a brain one.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
Tasting certain fats, without swallowing them, makes the gut produce these messengers within minutes.
primary_references
[thc-p23463697] Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats. (2013). https://pubmed.ncbi.nlm.nih.gov/23463697/ DOI: 10.1096/fj.13-227587
tissue_or_cell_type
Jejunum and behaviour
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 699–710
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sham-feeding protocol in rats with jejunal endocannabinoid measurement and peripheral CB1 antagonists · source_derived_draft · unverified_draft
### thc-fat-triggers-gut-endocannabinoids Sham feeding emulsions containing oleic acid or linoleic acid caused a nearly twofold accumulation of jejunal endocannabinoids, whereas emulsions containing stearic acid or alpha-linolenic acid had no such effect, and corn oil raised them relative to mineral oil which contains no fatty acids. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: Tasting certain fats, without swallowing them, makes the gut produce these messengers within minutes. organism: Rat tissue_or_cell_type: Jejunum and behaviour experimental_model: Sham-feeding protocol in rats with jejunal endocannabinoid measurement and peripheral CB1 antagonists limitations: Sham feeding separates oral exposure from absorption, and the peripherally restricted antagonists separate a gut mechanism from a brain one. exposure: Sham feeding of defined fatty acid emulsions with peripherally restricted CB1 antagonists evidence_span: {"source_cache": "artifacts/thc-research/23463697.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079", "start_char": 0, "end_char": 1315, "text_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079"} [thc-p23463697] Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats. (2013). https://pubmed.ncbi.nlm.nih.gov/23463697/ DOI: 10.1096/fj.13-227587
Complete structured claim and evidence
Rats displayed strong preference for emulsions containing linoleic acid in a two-bottle-choice sham-feeding test, and the preference was blocked by the peripherally restricted CB1 antagonists AM6546 and URB447.
Jejunal endocannabinoid concentration → Preference for dietary unsaturated fat source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/thc-research/23463697.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079", "start_char": 0, "end_char": 1315, "text_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079"}
experimental_model
Sham-feeding protocol in rats with jejunal endocannabinoid measurement and peripheral CB1 antagonists
exposure
Sham feeding of defined fatty acid emulsions with peripherally restricted CB1 antagonists
limitations
Sham feeding separates oral exposure from absorption, and the peripherally restricted antagonists separate a gut mechanism from a brain one.
nutrient_topic
THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. · Delta-9-tetrahydrocannabinol / THC
organism
Rat
plain_language
The gut messenger is what makes the animal want more of that fat, and blocking it outside the brain removes the wanting.
primary_references
[thc-p23463697] Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats. (2013). https://pubmed.ncbi.nlm.nih.gov/23463697/ DOI: 10.1096/fj.13-227587
tissue_or_cell_type
Jejunum and behaviour
THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21) · lines 712–723
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Sham-feeding protocol in rats with jejunal endocannabinoid measurement and peripheral CB1 antagonists · source_derived_draft · unverified_draft
### thc-gut-endocannabinoids-drive-preference Rats displayed strong preference for emulsions containing linoleic acid in a two-bottle-choice sham-feeding test, and the preference was blocked by the peripherally restricted CB1 antagonists AM6546 and URB447. Condition category: normal nutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates. plain_language: The gut messenger is what makes the animal want more of that fat, and blocking it outside the brain removes the wanting. organism: Rat tissue_or_cell_type: Jejunum and behaviour experimental_model: Sham-feeding protocol in rats with jejunal endocannabinoid measurement and peripheral CB1 antagonists limitations: Sham feeding separates oral exposure from absorption, and the peripherally restricted antagonists separate a gut mechanism from a brain one. exposure: Sham feeding of defined fatty acid emulsions with peripherally restricted CB1 antagonists evidence_span: {"source_cache": "artifacts/thc-research/23463697.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079", "start_char": 0, "end_char": 1315, "text_sha256": "cf035f4613f2090d3eaa60f90857a2dd265f69435b63d470e3dbe82f2350a079"} [thc-p23463697] Endocannabinoid signaling in the gut mediates preference for dietary unsaturated fats. (2013). https://pubmed.ncbi.nlm.nih.gov/23463697/ DOI: 10.1096/fj.13-227587
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

When the receptor adapts to continuous exposure

Condition: machinery_impairment · Sustained occupancy by an exogenous agonist such as THC.

Normal role: CB1 receptors signal through Gi/o in response to endocannabinoids released on demand and cleared within seconds.

Recorded consequence: The receptor desensitises through one domain and internalises through another, and with chronic exposure receptor number falls. Signalling through ERK is cut short as the receptor desensitises.

Scope: Recombinant receptor and human tissue Cultured cells

When the cell cannot make its own messenger

Condition: machinery_impairment · Genetic deletion of diacylglycerol lipase.

Normal role: Diacylglycerol lipase alpha makes 2-arachidonoylglycerol at the postsynaptic spine on demand.

Recorded consequence: Retrograde suppression of transmission is lost and adult neurogenesis falls, while the receptor itself remains present for an exogenous drug to occupy.

Scope: Mouse brain slices and in vivo

When the natural messenger is never cleared

Condition: machinery_impairment · Sustained pharmacological or genetic loss of monoacylglycerol lipase.

Normal role: Monoacylglycerol lipase degrades 2-arachidonoylglycerol and keeps endocannabinoid signalling transient.

Recorded consequence: Analgesia is lost, cross-tolerance to CB1 agonists appears, physical dependence develops and endocannabinoid-dependent plasticity is impaired.

Scope: Mouse pharmacology with a genetic phenocopy

When the receptor THC acts on is absent

Condition: machinery_impairment · Constitutive CB1 receptor knockout in mice.

Normal role: CB1 receptors mediate the central effects of THC and carry endocannabinoid retrograde signalling.

Recorded consequence: Baseline mortality rises and activity and pain thresholds change, and the behavioural effects of THC are lost while those of some other ligands are not.

Scope: Mouse genetics

When the clearing enzyme is slow

Condition: machinery_impairment · Homozygosity for the CYP2C9*3 variant allele.

Normal role: CYP2C9 hydroxylates THC to 11-OH-THC, which is then oxidised to THC-COOH.

Recorded consequence: THC exposure is roughly tripled, the carboxy metabolite falls by 70%, and sedation tends to increase.

Scope: Human pharmacogenetic study of oral THC

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Does the cannabinoid receptor only inhibit adenylyl cyclase, or can it also stimulate it?The founding pharmacology established a pertussis-toxin-sensitive, Gi-mediated inhibition of adenylate cyclase, and that inhibition is the basis on which the receptor was identified and cloned. A later study in CHO cells expressing human CB1 reported coupling to Gs as well, with agonists differing in their relative efficacy at stimulating versus inhibiting cAMP, and called this agonist-specific trafficking. The systems differ: a neuroblastoma line with native receptor against a transfected line overexpressing human CB1, where Gs coupling is more readily observed. Whether the stimulatory arm operates at native receptor densities is not established here.Read the recorded disagreement

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Whether the on-demand, seconds-long kinetics of endocannabinoid signalling can be reproduced by any dosing schedule of an exogenous agonist.Every record here shows the natural ligands made on demand and destroyed by dedicated enzymes; no record in this collection compares that time course with a drug exposure.
Whether n-3 status changes the response to THC in people, given that dietary deficiency uncouples the same receptor THC acts on.The uncoupling record is a lifelong dietary model in mice measured with endocannabinoids, not with THC, and no record here administers the drug against a varied dietary fat background.
Whether the dietary fat effects on endocannabinoid levels are large enough to matter at ordinary human intakes.The feeding studies use defined single-fat diets or sham-fed emulsions in rats, which are not ordinary mixed human diets.
Whether the psychosis association reflects causation, shared predisposition, or self-medication, and in what proportion.Every psychosis record here is observational. The prospective cohort adjusts for baseline predisposition and finds the effect concentrated in the predisposed, which is consistent with more than one explanation.
Whether cannabidiol opposes or potentiates THC in people, given that a human crossover found only weak inhibition of one metabolic step while chronic dosing in adolescent rats raised brain THC and augmented its behavioural effects.The two records differ in species, age, dose ratio and duration, and no record here tests chronic equivalent-dose co-administration in adults.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

Delta-9-tetrahydrocannabinol / THC

The mechanisms

A human cannabinoid receptor was cloned and found to be expressed in testis as well as brain.

The murine CB2 peripheral cannabinoid receptor was cloned, expressed and shown to function as a cannabinoid receptor distinct from the brain receptor.

CB1 and CB2 receptors were characterised for expression and adenylate cyclase modulation within the immune system.

The crystal structure of the human CB1 receptor was determined, resolving the architecture of its ligand-binding pocket.

The crystal structure of the human CB2 receptor was determined, showing how its binding pocket differs from that of CB1.

The cryo-EM structure of the human CB2 receptor in complex with Gi resolved the active-state signalling complex.

Cannabinoids inhibited adenylate cyclase in neuroblastoma cell membranes with a pharmacology matching their psychoactivity.

The biochemistry of the cannabinoid inhibition of adenylate cyclase in neuroblastoma membranes showed the response to be guanine-nucleotide dependent.

CB1 controls GABA release by inhibiting calcium entry into presynaptic axon terminals via N-type Cav2.2 channels, with a power relationship of exponent 2.2 between unitary inhibitory current amplitude and intrabouton calcium.

Distinct domains of the CB1 receptor mediate desensitisation and internalisation, so the two adaptive responses are separable.

Rapid CB1 receptor desensitisation defines the time course of ERK1/2 MAP kinase signalling.

CB1 receptors and related molecular elements of the endocannabinoid system were downregulated in epileptic human hippocampus.

Anandamide interacted specifically with cannabinoid receptors and inhibited adenylate cyclase, reproducing the signature response of the plant cannabinoids.

Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses, travelling from the depolarised postsynaptic neuron back to the presynaptic terminal.

Endogenous cannabinoids mediate retrograde signals from depolarised postsynaptic neurons to presynaptic terminals, suppressing transmitter release.

Endogenous cannabinoids retrogradely inhibited presynaptic calcium influx at excitatory synapses onto Purkinje cells.

Diacylglycerol lipase-alpha was localised around the postsynaptic spine, placing the production site of 2-arachidonoylglycerol in close proximity to the presynaptic CB1 receptor.

The endocannabinoid 2-arachidonoylglycerol produced by diacylglycerol lipase alpha mediates retrograde suppression of synaptic transmission.

Diacylglycerol lipase knock-out mice lost retrograde endocannabinoid signalling and showed reduced adult neurogenesis.

Diacylglycerol lipase-alpha has a key role in metabotropic glutamate receptor-dependent endocannabinoid mobilisation.

Fatty acid amide hydrolase is the principal enzyme hydrolysing fatty acid amides including anandamide, terminating their signalling.

The crystal structure of fatty acid amide hydrolase bound to URB597 revealed a deacylating water molecule and gave insight into how the enzyme is inactivated by carbamate inhibitors.

Monoacylglycerol lipase activity is a critical modulator of the tone and integrity of the endocannabinoid system.

Cannabinoid CB1 receptor knockout mice showed increased mortality, hypoactivity and hypoalgesia.

THC and methanandamide had differential effects in CB1 knockout and wild-type mice, with the effects of THC dependent on the receptor while some effects of the anandamide analogue were not.

THC impaired spatial memory through a cannabinoid receptor mechanism, since the impairment was prevented by receptor blockade.

The CB1 antagonist SR141716A attenuated the memory impairment produced by THC or by anandamide.

Hippocampal CB1 receptors mediate the memory-impairing effects of THC.

Prolonged THC administration produced hippocampal neurotoxicity in rats.

Appetite suppression and weight loss followed administration of the cannabinoid antagonist SR141716.

CB1 cannabinoid receptor activation modulated food intake in mice, with agonists and antagonists moving intake in opposite directions.

Plasma cannabinoid pharmacokinetics following controlled oral THC and oromucosal cannabis extract administration resolved the time courses of THC and its metabolites.

The median area under the curve of THC was threefold higher and that of THC-COOH 70% lower in CYP2C9*3/*3 homozygotes than in CYP2C9*1/*1 homozygotes, with a trend toward increased sedation, while CYP2C9*2 status made no difference.

CYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein.

Cannabidiol pretreatment potentiated blood and brain THC levels with both acute and chronic administration in adolescent rats, potentiated the inhibition of body weight gain caused by chronic THC, and mildly augmented its anxiogenic, locomotor-suppressant and social-interaction effects.

Higher levels of cannabis use were associated with increased risk for psychosis in all included studies, with an odds ratio of 3.90 for schizophrenia and other psychosis-related outcomes among the heaviest users compared with non-users, across 66,816 individuals.

Cannabis use was associated with an earlier onset of psychosis in a systematic meta-analysis.

Lifelong n-3 polyunsaturated fatty acid dietary insufficiency specifically ablated long-term synaptic depression mediated by endocannabinoids in the prelimbic prefrontal cortex and accumbens.

In n-3-deficient mice, presynaptic CB1 receptors that normally respond to endocannabinoids were uncoupled from their effector Gi/o proteins.

The dietary-induced reduction of CB1 receptor function in mood-controlling structures was associated with impaired emotional behaviour, identifying a plausible synaptic substrate for the behavioural alterations reported with n-3 deficiency in western diets.

The olive oil diet increased brain anandamide and oleoylethanolamide without changing tissue fatty acid composition and without changing 2-arachidonoylglycerol, while the safflower oil diet increased linoleoylethanolamide and linoleic acid in brain, jejunum and liver.

The arachidonic acid diet increased anandamide and 2-arachidonoylglycerol in jejunum without effect on liver, and the fish oil diet decreased liver levels of most N-acylethanolamines with similar changes in their precursors.

Dietary docosahexaenoic acid supplementation altered select physiological endocannabinoid-system metabolites in brain and plasma.

Sham feeding emulsions containing oleic acid or linoleic acid caused a nearly twofold accumulation of jejunal endocannabinoids, whereas emulsions containing stearic acid or alpha-linolenic acid had no such effect, and corn oil raised them relative to mineral oil which contains no fatty acids.

Rats displayed strong preference for emulsions containing linoleic acid in a two-bottle-choice sham-feeding test, and the preference was blocked by the peripherally restricted CB1 antagonists AM6546 and URB447.

Availability and dependencies

The sources

Recorded disagreements

Open questions in this collection

The median area under the curve of THC was threefold higher and that of THC-COOH 70% lower in CYP2C93/3 homozygotes than in CYP2C91/1 homozygotes, with a trend toward increased sedation, while CYP2C9*2 status made no difference.