The phytocannabinoid, Δ9‐tetrahydrocannabivarin, can act through 5‐HT1A receptors to produce antipsychotic effects

Summary & key facts

This study tested the cannabis compound THCV in lab tissues and in rats. In lab tests, THCV (at 100 nM) increased activation of serotonin 5-HT1A receptors. In rats given PCP to produce schizophrenia-like symptoms, a 2 mg/kg dose of THCV reduced abnormal behaviors and improved social and cognitive measures. The authors say some THCV effects depend on 5-HT1A receptors and that THCV may have therapeutic potential, but these results are preclinical (lab and animal) findings.

Key facts:

• In rat brainstem membranes, THCV partially displaced the 5-HT1A receptor ligand 8-[3H]-OH-DPAT and, at 100 nM, significantly enhanced 8-OH-DPAT-induced receptor activation in [35S]GTPγS assays.
• In human 5-HT1A receptor-expressing CHO cell membranes, THCV produced concentration-related increases in 8-[3H]-OH-DPAT binding and, at 100 nM, enhanced 8-OH-DPAT-induced receptor activation.
• In PCP-treated rats (a commonly used model of schizophrenia-like symptoms), THCV given at 2 mg/kg intraperitoneally reduced stereotyped behavior, decreased time spent immobile in the forced swim test, and helped normalize hyperlocomotion, s
• Some of the behavioural effects of THCV in rats were reduced by the 5-HT1A receptor antagonist WAY100635, which suggests those effects involve 5-HT1A receptors.
• Some similar behavioural effects could also be produced by the CB1 antagonist AM251, indicating that CB1 receptors contribute to some outcomes.
• The experiments reported are laboratory (in vitro) assays and tests in rats (the paper used 204 rats in total for the in vivo work); the study did not include human clinical trials.
• The authors conclude that THCV can enhance 5-HT1A receptor activation and state that THCV has potential to improve some negative, cognitive and positive symptoms of schizophrenia, while noting these conclusions are based on preclinical data

Abstract

Our findings suggest that THCV can enhance 5-HT₁A receptor activation, and that some of its apparent antipsychotic effects may depend on this enhancement. We conclude that THCV has therapeutic potential for ameliorating some of the negative, cognitive and positive symptoms of schizophrenia.

Topics

Cannabis and Cannabinoid Research Neuroscience and Neuropharmacology Research Neurotransmitter Receptor Influence on Behavior

Categories

Health Sciences Medicine Pharmacology

Tags

5-HT receptor 8-OH-DPAT Agonist Biochemistry Biology Biotechnology Chemistry Chinese hamster ovary cell Endocrinology In vivo Internal medicine Medicine NMDA receptor Pharmacology Phencyclidine Receptor Serotonin

Substances

Cannabis

Conditions & symptoms

Difficulty focusing Feeling disconnected from others