The phytocannabinoid, Delta(9)-tetrahydrocannabivarin, can act through 5-HT(1)A receptors to produce antipsychotic effects.

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Cascio MG, Zamberletti E, Marini P, Parolaro D, Pertwee RG

The phytocannabinoid, Delta(9)-tetrahydrocannabivarin, can act through 5-HT(1)A receptors to produce antipsychotic effects.

Br J Pharmacol. 2015 Mar;172(5):1305-18. doi: 10.1111/bph.13000.

PubMed ID

25363799 [ View in PubMed

]

Abstract

BACKGROUND AND PURPOSE: This study aimed to address the questions of whether Delta(9)-tetrahydrocannabivarin (THCV) can (i) enhance activation of 5-HT1 A receptors in vitro and (ii) induce any apparent 5-HT(1)A receptor-mediated antipsychotic effects in vivo. EXPERIMENTAL APPROACH: In vitro studies investigated the effect of THCV on targeting by 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) of 5-HT(1)A receptors in membranes obtained from rat brainstem or human 5-HT(1)A CHO cells, using [(35)S]-GTPgammaS and 8-[(3)H]-OH-DPAT binding assays. In vivo studies investigated whether THCV induces signs of 5-HT(1)A receptor-mediated antipsychotic effects in rats. KEY RESULTS: THCV (i) potently, albeit partially, displaced 8-[(3) H]-OH-DPAT from specific binding sites in rat brainstem membranes; (ii) at 100 nM, significantly enhanced 8-OH-DPAT-induced activation of receptors in these membranes; (iii) produced concentration-related increases in 8-[(3)H]-OH-DPAT binding to specific sites in membranes of human 5-HT(1)A receptor-transfected CHO cells; and (iv) at 100 nM, significantly enhanced 8-OH-DPAT-induced activation of these human 5-HT(1)A receptors. In phencyclidine-treated rats, THCV, like clozapine (i) reduced stereotyped behaviour; (ii) decreased time spent immobile in the forced swim test; and (iii) normalized hyperlocomotor activity, social behaviour and cognitive performance. Some of these effects were counteracted by the 5-HT(1)A receptor antagonist, WAY100635, or could be reproduced by the CB(1) antagonist, AM251. CONCLUSIONS AND IMPLICATIONS: Our findings suggest that THCV can enhance 5-HT(1)A 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.

DrugBank Data that Cites this Article

Drugs

Tetrahydrocannabivarin

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tetrahydrocannabivarin	5-hydroxytryptamine receptor 1A	Protein	Humans	Yes	Agonist	Details