Acute Effects of a Single, Oral dose of d9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) Administration in Healthy Volunteers

R.      Martin-Santos; J.      A. Crippa; A.      Batalla; S.      Bhattacharyya; Z.      Atakan; S.      Borgwardt; P.      Allen; M.      Seal; K.      Langohr; M.      Farre; AW.      Zuardi; P.      K. McGuire

Abstract

Rationale: Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately.

Objective: To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers.

Methods: A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor.

Results: Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p<0.01), an increase in heart rate (p<0.05). There were no differences between CBD and placebo on any symptomatic, physiological variable.

Conclusions: In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.

Keywords: Cannabis, Δ-9-THC-tetrahydrocannabinol, cannabidiol, unique dose, pharmacological acute effects, humans, induced anxiety, induced psychosis, review, placebo controlled trial.