ArticleMolecular pharmacology2009
Modulation of excitatory synaptic transmission by Delta 9-tetrahydrocannabinol switches from agonist to antagonist depending on firing rate.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Pooled it
- Differential Effects of Cannabinoid Receptor 2 Agonists on HIV Replication and Inflammatory Activation in Monocyte-Derived Macrophages and Induced Pluripotent Stem Cell-Derived Microglia.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Young Adult Cannabis Use and Circulating Endocannabinoid Concentrations on Cognitive Performance.Frontiers in adolescent medicine · 2025Article
- Analgesic Properties of Next-Generation Modulators of Endocannabinoid Signaling: Leveraging Modern Tools for the Development of Novel Therapeutics.The Journal of pharmacology and experimental therapeutics · 2024Review
- Pharmacological Characterization of the Endocannabinoid Sensor GRABCannabis and cannabinoid research · 2024Article
- Non-canonical type 1 cannabinoid receptor signaling regulates night visual processing in the inner rat retina.iScience · 2024Article
- A Complete Endocannabinoid Signaling System Modulates Synaptic Transmission between Human Induced Pluripotent Stem Cell-Derived Neurons.Molecular pharmacology · 2023Article
- Confound, Cause, or Cure: The Effect of Cannabinoids on HIV-Associated Neurological Sequelae.Viruses · 2021Review
- Monoacylglycerol lipase inhibitor JZL184 prevents HIV-1 gp120-induced synapse loss by altering endocannabinoid signaling.Neuropharmacology · 2018Article
- Electrophysiological Measurement of Cannabinoid-Mediated Synaptic Modulation in Acute Mouse Brain Slices.Current protocols in neuroscience · 2016Article
- Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure.Experimental neurology · 2012Article
- Contributions of endocannabinoid signaling to psychiatric disorders in humans: genetic and biochemical evidence.Neuroscience · 2012Review
- The dual neuroprotective-neurotoxic profile of cannabinoid drugs.British journal of pharmacology · 2011Review
- Dual neuroprotective and neurotoxic effects of cannabinoid drugs in vitro.Cellular and molecular neurobiology · 2011Article
- Cannabidiol inhibits synaptic transmission in rat hippocampal cultures and slices via multiple receptor pathways.British journal of pharmacology · 2011Article
- Cannabinoid-Induced Hyperemesis: A Conundrum-From Clinical Recognition to Basic Science Mechanisms.Pharmaceuticals (Basel, Switzerland) · 2010Review
- JWH018, a common constituent of 'Spice' herbal blends, is a potent and efficacious cannabinoid CB receptor agonist.British journal of pharmacology · 2010Article
- Homer 1a gates the induction mechanism for endocannabinoid-mediated synaptic plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2010Article
- Cannabinoid CB1 receptor-dependent long-term depression in autaptic excitatory neurons.Journal of neurophysiology · 2009Article
- Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Delta(9)-tetrahydrocannabinol (THC), the principal psychoactive ingredient in marijuana, acts as a partial agonist on presynaptic cannabinoid type 1 (CB1) receptors to inhibit neurotransmitter release. Here, we report that THC inhibits excitatory neurotransmission between cultured rat hippocampal neurons in a manner highly sensitive to stimulus rate. THC (1 microM) inhibited excitatory postsynaptic currents (EPSCs) and whole-cell I(Ca) evoked at 0.1 Hz but at 0.5 Hz THC had little effect. The cannabinoid receptor full agonists [(R)-(+)-[2,3-dihydro-5-methyl-3[(4-morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl)methanone mesylate salt] (Win55212-2) (100 nM) and 2-arachidonylglycerol (1 microM) inhibited EPSCs independent of stimulation at 0.1 or 0.5 Hz. THC occupied CB1 receptors at 0.5 Hz, but the receptors failed to couple to presynaptic Ca(2+) channels. Consequently, 1 microM THC blocked the inhibition of EPSC amplitude by Win55212-2 when EPSCs were evoked at 0.5 Hz. A depolarizing prepulse to 0 mV reversed THC inhibition of I(Ca), but reversal of the inhibition produced by Win55212-2 required a pulse to +80 mV, suggesting that the voltage-dependent reversal of Gbetagamma inhibition of voltage-gated Ca(2+) channels accounts for the frequency-dependence of cannabinoid action. THC blocked depolarization-induced suppression of EPSCs evoked at 0.5 Hz, indicating that it inhibited retrograde endocannabinoid signaling in a frequency-dependent manner. Thus, THC displayed a state-dependent switching from agonist to antagonist that may account for its complex actions in vivo.
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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.