The psychoactive plant cannabinoid, Delta9-tetrahydrocannabinol, is antagonized by Delta8- and Delta9-tetrahydrocannabivarin in mice in vivo.
R G Pertwee, A Thomas, L A Stevenson, R A Ross, Stephen A Varvel, Aron H Lichtman, B R Martin, R K Razdan
British Journal of Pharmacology March 2007 DOI: 10.1038/sj.bjp.0707124 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical in vitro and in vivo pharmacology study Peer reviewed |
|---|---|
| Population | Mouse brain membranes, mouse isolated vasa deferentia, and live mice |
| Interventions | eDelta(9)-THCV CP55940 R-(+)-WIN55212 Delta(9)-tetrahydrocannabinol |
| Dose | O-4394 and O-4395 at i.v. doses of 0.1, 0.3, 1.0 and/or 3 mg kg(-1); Delta(9)-tetrahydrocannabinol at 3 or 10 mg kg(-1) (i.v.); O-4395 and O-4394 induced effects at 3 or 10 mg kg(-1) (i.v.) and antinociception above 10 mg kg(-1) (i.v.); O-4395 induced hypothermia at 3 mg kg(-1) (i.v.) and above |
| Measures | tail-flick test, rectal temperature, ring immobility, [(3)H]-CP55940 binding, [(35)S]GTPgammaS binding assay |
| Topics | Cannabis |
| Key points | O-4394 and O-4395 bind CB(1) receptors with potencies similar to cannabis-derived Delta(9)-THCV and can antagonize Delta(9)-tetrahydrocannabinol in vivo, attenuating THC-induced antinociception and hypothermia; O-4395 also antagonized THC-induced ring immobility. At higher doses the compounds produced cannabinoid-like effects themselves. |
Abstract
To follow up in vitro evidence that Delta(9)-tetrahydrocannabivarin extracted from cannabis (eDelta(9)-THCV) is a CB(1) receptor antagonist by establishing whether synthetic Delta(9)-tetrahydrocannabivarin (O-4394) and Delta(8)-tetrahydrocannabivarin (O-4395) behave as CB(1) antagonists in vivo. O-4394 and O-4395 were compared with eDelta(9)-THCV as displacers of [(3)H]-CP55940 from specific CB(1) binding sites on mouse brain membranes and as antagonists of CP55940 in [(35)S]GTPgammaS binding assays performed with mouse brain membranes and of R-(+)-WIN55212 in mouse isolated vasa deferentia. Their ability to antagonize in vivo effects of 3 or 10 mg kg(-1) (i.v.) Delta(9)-tetrahydrocannabinol in mice was then investigated. O-4394 and O-4395 exhibited similar potencies to eDelta(9)-THCV as displacers of [(3)H]-CP55940 (K (i)=46.6 and 64.4 nM, respectively) and as antagonists of CP55940 in the [(35)S]GTPgammaS binding assay (apparent K (B)=82.1 and 125.9 nM, respectively) and R-(+)-WIN55212 in the vas deferens (apparent K (B)=4.8 and 3.9 nM respectively). At i.v. doses of 0.1, 0.3, 1.0 and/or 3 mg kg(-1) O-4394 and O-4395 attenuated Delta(9)-tetrahydrocannabinol-induced anti-nociception (tail-flick test) and hypothermia (rectal temperature). O-4395 but not O-4394 also antagonized Delta(9)-tetrahydrocannabinol-induced ring immobility. By themselves, O-4395 and O-4394 induced ring immobility at 3 or 10 mg kg(-1) (i.v.) and antinociception at doses above 10 mg kg(-1) (i.v.). O-4395 also induced hypothermia at 3 mg kg(-1) (i.v.) and above. O-4394 and O-4395 exhibit similar in vitro potencies to eDelta(9)-THCV as CB(1) receptor ligands and as antagonists of cannabinoid receptor agonists and can antagonize Delta(9)-tetrahydrocannabinol in vivo.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
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