The Effect of Five Day Dosing With THCV on THC-induced Cognitive, Psychological and Physiological Effects in Healthy Male Human Volunteers: A Placebo-Controlled, Double-Blind, Crossover Pilot Trial

J Psychopharmacol. 2016 Feb;30(2):140-51. doi: 10.1177/0269881115615104. Epub 2015 Nov 17.

Abstract

Rationale: Cannabis is mostly grown under illegal and unregulated circumstances, which seems to favour a product increasingly high in its main cannabinoid ∆-9-tetrahydrocannabinol (THC). ∆-9-tetrahydrocannabivarin (THCV) is a relatively untested cannabinoid which is said to be a cannabinoid receptor neutral antagonist, and may inhibit the effects of THC.

Objectives: To explore the safety and tolerability of repeated THCV administration and its effects on symptoms normally induced by THC in a sample of healthy volunteers.

Methods: Ten male cannabis users (<25 use occasions) were recruited for this within-subjects, placebo-controlled, double-blind, cross-over pilot study. 10mg oral pure THCV or placebo were administered daily for five days, followed by 1mg intravenous THC on the fifth day.

Results: THCV was well tolerated and subjectively indistinguishable from placebo. THC did not significantly increase psychotic symptoms, paranoia or impair short-term memory, while still producing significant intoxicating effects. Delayed verbal recall was impaired by THC and only occurred under placebo condition (Z=-2.201, p=0.028), suggesting a protective effect of THCV. THCV also inhibited THC-induced increased heart rate (Z=-2.193, p=0.028). Nine out of ten participants reported THC under THCV condition (compared to placebo) to be subjectively weaker or less intense (χ(2)=6.4, p=0.011). THCV in combination with THC significantly increased memory intrusions (Z=-2.155, p=0.031).

Conclusion: In this first study of THC and THCV, THCV inhibited some of the well-known effects of THC, while potentiating others. These findings need to be interpreted with caution due to a small sample size and lack of THC-induced psychotomimetic and memory-impairing effect, probably owing to the choice of dose.

Keywords: THC; THCV; cannabinoid; cannabis; human; memory; psychosis; Δ9-tetrahydrocannabinol; Δ9-tetrahydrocannabivarin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cognition / drug effects*
  • Cross-Over Studies
  • Double-Blind Method
  • Dronabinol / administration & dosage
  • Dronabinol / analogs & derivatives*
  • Dronabinol / pharmacology
  • Hallucinogens / administration & dosage
  • Hallucinogens / pharmacology*
  • Heart Rate / drug effects
  • Humans
  • Male
  • Memory / drug effects*
  • Mental Recall / drug effects
  • Pilot Projects
  • Young Adult

Substances

  • Hallucinogens
  • tetrahydrocannabivarin 9
  • Dronabinol