2-Arachidonoylglycerol / 2-AG

evidence_span

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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

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

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

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

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

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

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

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

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