Funded by: •GW Pharmaceuticals Acknowledgements: The authors wish to thank Mrs Lesley Stevenson for technical support and Dr John Raymond, Dr Keith Parker and Dr Ethan Russo for providing human 5-HT1A CHO cells. This research was supported by a grant from GW Pharmaceuticals to M. G. C. and R. G. P.Peer reviewedPostprin

Cascio, Maria Grazia

Marini, Pietro

Parolaro, Daniela

Pertwee, Roger G.

Zamberletti, Erica

British Journal of Pharmacology

English

PubMed

Maria Grazia Cascio

Erica Zamberletti

Pietro Marini

Daniela Parolaro

Roger G Pertwee

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The phytocannabinoid, Δ9-tetrahydrocannabivarin, can act through 5-HT1Areceptors to produce antipsychotic effects

Funded by: •GW Pharmaceuticals Acknowledgements: The authors wish to thank Mrs Lesley Stevenson for technical support and Dr John Raymond, Dr Keith Parker and Dr Ethan Russo for providing human 5-HT1A CHO cells. This research was supported by a grant from GW Pharmaceuticals to M. G. C. and R. G. P.Peer reviewe

Aberdeen University Research

The phytocannabinoid, Δ(9) -tetrahydrocannabivarin, can act through 5-HT1 A receptors to produce antipsychotic effects

Background and Purpose This study aimed to address the questions of whether Î9-tetrahydrocannabivarin (THCV) can (i) enhance activation of 5-HT1A receptors in vitro and (ii) induce any apparent 5-HT1A 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-HT1A receptors in membranes obtained from rat brainstem or human 5-HT1A CHO cells, using [35S]-GTPÎ3S and 8-[3H]-OH-DPAT binding assays. In vivo studies investigated whether THCV induces signs of 5-HT1A receptor-mediated antipsychotic effects in rats. Key Results THCV (i) potently, albeit partially, displaced 8-[3H]-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-[3H]-OH-DPAT binding to specific sites in membranes of human 5-HT1A receptor-transfected CHO cells; and (iv) at 100 nM, significantly enhanced 8-OH-DPAT-induced activation of these human 5-HT1A 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-HT1A receptor antagonist, WAY100635, or could be reproduced by the CB1 antagonist, AM251. Conclusions and Implications 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

Archivio istituzionale della ricerca - Università dell'Insubria

The phytocannabinoid, delta-9-tetrahydrocannabivarin, can act through 5-HT1A receptors to produce antipsychotic effects

https://aura.abdn.ac.uk/bitstream/2164/5584/1/bph13000.pdf

The phytocannabinoid, Δ(9) -tetrahydrocannabivarin, can act through 5-HT1 A receptors to produce antipsychotic effects

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Aberdeen University Research

Archivio istituzionale della ricerca - Università dell'Insubria