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Br J Pharmacol. 2019 Aug 27. doi: 10.1111/bph.14844. [Epub ahead of print]

Δ8 -Tetrahydrocannabivarin has potent anti-nicotine effects in multiple rodent models of nicotine dependence.

Author information

1
Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland, USA.
2
Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA.
3
Beijing Institute of Pharmacology and Toxicology, Beijing, China.
4
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia, USA.
5
Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.

Abstract

BACKGROUND AND PURPOSE:

Both types of cannabinoid receptors - CB1 and CB2 - regulate brain functions relating to addictive drug-induced reward and relapse. CB1 receptor antagonists and CB2 receptor agonists have anti-addiction efficacy, in animal models, against a broad range of addictive drugs. Δ9 -Tetrahydrocannabivarin (Δ9 -THCV) - a cannabis constituent - acts as a CB1 antagonist and a CB2 agonist. Δ8 -Tetrahydrocannabivarin (Δ8 -THCV) is a Δ9 -THCV analogue with similar combined CB1 antagonist/CB2 agonist properties.

EXPERIMENTAL APPROACH:

We tested Δ8 -THCV in seven different rodent models relevant to nicotine dependence - nicotine self-administration, cue-triggered nicotine-seeking behavior following forced abstinence, nicotine-triggered reinstatement of nicotine-seeking behavior, acquisition of nicotine-induced conditioned place preference, anxiety-like behavior induced by nicotine withdrawal, somatic withdrawal signs induced by nicotine withdrawal, and hyperalgesia induced by nicotine withdrawal.

KEY RESULTS:

Δ8 -THCV significantly attenuated intravenous nicotine self-administration, and both cue-induced and nicotine-induced relapse to nicotine-seeking behavior in rats. Δ8 -THCV also significantly attenuated nicotine-induced conditioned place preference and nicotine withdrawal in mice.

CONCLUSIONS AND IMPLICATIONS:

We conclude that Δ8 -THCV may have therapeutic potential for the treatment of nicotine dependence. We also suggest that tetrahydrocannabivarins should be tested for possible anti-addiction efficacy in a broader range of preclinical animal models, against other addictive drugs, and eventually in humans.

KEYWORDS:

CB1 cannabinoid receptor; CB2 cannabinoid receptor; Cannabis; addiction; cannabinoid; drug dependence; nicotine; pre-clinical animal models; Δ8-tetrahydrocannabivarin

PMID:
31454413
DOI:
10.1111/bph.14844

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