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 and P. K. McGuire
Affiliation: Department of Psychiatry, Institut Clinic de Neurociencies, Hospital Clinic, IDIBAPS, CIBERSAM, and Department of Psychiatry and Clinical Psychobiology, University of Barcelona, Villarroel, 170. 08036-Barcelona, Spain.
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.
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