ArticleNeuropharmacology
Delta9-tetrahydrocannabinol is a full agonist at CB1 receptors on GABA neuron axon terminals in the hippocampus.
Article in Neuropharmacology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 3 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- The Role of Hippocampal Interneuron Migration in Neurodevelopmental Disorders: A Systematic Review.Hippocampus · 2026Pooled it
- Neurometabolite Alterations Associated With Cannabis Use: A Proton Magnetic Resonance Spectroscopy Meta-Analysis.Human brain mapping · 2025Pooled it
- Pooled it
- Cannabis containing equivalent concentrations of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) induces less state anxiety than THC-dominant cannabis.Psychopharmacology · 2022Trial
- Cannabidiol and ΔToxicology · 2026Article
- ADHD Symptoms and Cannabis Use: The Role of Cannabinoid Receptor 1 and Neural Response Inhibition.medRxiv : the preprint server for health sciences · 2026Article
- From Synaptic Plasticity to Neurotoxicity: Endocannabinoid Influence on Addiction and Neurodegeneration.International journal of molecular sciences · 2025Review
- Kinin B1 receptor mediates acute cardiovascular and neural responses following cannabinoid receptor 1 activation in conscious male mice.Physiological reports · 2025Article
- Impaired mnemonic pattern separation associated with PTSD symptoms paradoxically improves with regular cannabis use.Npj mental health research · 2025Article
- Cannabigerol and Cannabinoid Receptors in Major Depressive Disorder: Network Pharmacology, Molecular Docking, andCurrent drug discovery technologies · 2025Article
- Decoding the Therapeutic Potential of Cannabis and Cannabinoids in Neurological Disorders.Current pharmaceutical design · 2025Review
- Neuroprotection and Beyond: The Central Role of CB1 and CB2 Receptors in Stroke Recovery.International journal of molecular sciences · 2023Review
- Hippocampal expression of the cannabinoid receptor type 1 in canine epilepsy.Scientific reports · 2023Article
- Adolescent Δ-9-tetrahydrocannabinol exposure induces differential acute and long-term neuronal and molecular disturbances in dorsal vs. ventral hippocampal subregions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Vaporized Delta-9-tetrahydrocannabinol Inhalation in Female Sprague Dawley Rats: A Pharmacokinetic and Behavioral Assessment.Current pharmaceutical design · 2023Article
- Enhancing axonal myelination in seniors: A review exploring the potential impact cannabis has on myelination in the aged brain.Frontiers in aging neuroscience · 2023Review
- Involvement of the GABAergic system in PTSD and its therapeutic significance.Frontiers in molecular neuroscience · 2023Review
- Prefrontal cortical distribution of muscarinic M2 and cannabinoid-1 (CB1) receptors in adult male mice with or without chronic adolescent exposure to Δ9-tetrahydrocannabinol.Cerebral cortex (New York, N.Y. : 1991) · 2022Article
- Synaptic changes induced by cannabinoid drugs and cannabis use disorder.Neurobiology of disease · 2022Review
- Molecular Targets of Cannabinoids Associated with Depression.Current medicinal chemistry · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Marijuana impairs learning and memory through actions of its psychoactive constituent, delta-9-tetrahydrocannabinol (Delta(9)-THC), in the hippocampus, through activation of cannabinoid CB1 receptors (CB1R). CB1Rs are found on glutamate and GABA neuron axon terminals in the hippocampus where they control neurotransmitter release. Previous studies suggest that Delta(9)-THC is a partial agonist of CB1Rs on glutamate axon terminals in the hippocampus, whereas its effects on GABA terminals have not been described. Using whole-cell electrophysiology in brain slices from C57BL6/J mice, we examined Delta(9)-THC effects on synaptic GABA IPSCs and postsynaptic GABA currents elicited by laser-induced photo-uncaging (photolysis) of alpha-carboxy-2-nitrobenzyl (CNB) caged GABA. Despite robust inhibition of synaptic IPSCs in wildtype mice by the full synthetic agonist WIN55,212-2, using a Tween-80 and DMSO vehicle, Delta(9)-THC had no effects on IPSCs in this, or in a low concentration of another vehicle, randomly-methylated beta-cyclodextrin (RAMEB, 0.023%). However, IPSCs were inhibited by Delta(9)-THC in 0.1% RAMEB, but not in neurons from CB1R knockout mice. Whereas Delta(9)-THC did not affect photolysis-evoked GABA currents, these responses were prolonged by a GABA uptake inhibitor. Concentration-response curves revealed that the maximal effects of Delta(9)-THC and WIN55,212-2 were similar, indicating that Delta(9)-THC is a full agonist at CB1Rs on GABA axon terminals. These results suggest that Delta(9)-THC inhibits GABA release, but does not directly alter GABA(A) receptors or GABA uptake in the hippocampus. Furthermore, full agonist effects of Delta(9)-THC on IPSCs likely result from a much higher expression of CB1Rs on GABA versus glutamate axon terminals in the hippocampus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.