Δ 8 -Tetrahydrocannabivarin has potent anti-nicotine effects in several rodent models of nicotine dependence

Br J Pharmacol. 2019 Dec;176(24):4773-4784. doi: 10.1111/bph.14844. Epub 2019 Oct 28.

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 behaviour following forced abstinence, nicotine-triggered reinstatement of nicotine-seeking behaviour, acquisition of nicotine-induced conditioned place preference, anxiety-like behaviour 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 behaviour 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug-Seeking Behavior / drug effects*
  • Hyperalgesia / prevention & control*
  • Mice
  • Nicotine / administration & dosage
  • Rats
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
  • Receptor, Cannabinoid, CB2 / agonists*
  • Self Administration
  • Smoking Cessation Agents / pharmacology*
  • Substance Withdrawal Syndrome / prevention & control*
  • Tobacco Use Disorder / metabolism
  • Tobacco Use Disorder / prevention & control*

Substances

  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Smoking Cessation Agents
  • Nicotine