Abstract
Background: Cannabis use can increase the risk of psychosis, and the acute administration of its key psychoactive ingredient, delta-9-tetrahydrocannabinol (∆9-THC), can induce transient psychotomimetic symptoms. Methods: A double-blind, randomized, placebo-controlled crossover design was used to investigate the symptomatic effects of acute intravenous administration of ∆9-THC (1.19 mg/2 mL) in 16 healthy participants (seven males) with modest previous cannabis exposure. Results: In the 20 min following acute ∆9-THC administration, symptomatic effects of at least mild severity were present in 94% of the cohort, with moderate to severe symptoms having a much lower prevalence (19%). Nearly one-third (31%) of the volunteers were still experiencing protracted mild symptomatic effects 2.5 h after exposure to ∆9-THC. Compared to the Δ9-THC challenge, most of the study participants did not experience any symptomatic effects following placebo administration (62%). Acute physical reactions were 2.5 times more frequent after Δ9-THC (31%) than placebo (12%). Male and female participants differed in terms of acute Δ9-THC effects, with some negative symptoms occurring more frequently in female (56% to 89%) than male participants (0% to 29%), and acute physical reactions occurring exclusively in the female gender (56%). Conclusions: These results have implications for future research, also in light of cannabis being the most widely used illicit drug.
Highlights
Psychosis is a severe mental disorder resulting from a complex interplay between genetic and environmental determinants leading to a disruption of central nervous system function [1]
More severe symptomatic effects were experienced by a smaller proportion of participants, with 10 volunteers reporting at least moderate symptoms (62%; ≥4 on at least one Positive and Negative Syndrome Scale [45] (PANSS) item) and three of them reporting moderate to severe symptoms (19%; ≥5 on at least one PANSS item)
Administration; (d) After delta-9-tetrahydrocannabinol administration. The purpose of this clinical investigation was to systematically assess the transient psychotic. The purpose of this clinical investigation was to systematically assess the transient psychotic reaction to the intravenous administration of pure ∆9-THC in healthy subjects in a controlled setting, reaction to the intravenous administration of pure Δ9-THC in healthy subjects in a controlled setting, which was in line with the evidence that this cannabinoid represents a valid pharmacologic model for which was in line with the evidence that this cannabinoid represents a valid pharmacologic model psychosis [10,11,12]
Summary
Psychosis is a severe mental disorder resulting from a complex interplay between genetic and environmental determinants leading to a disruption of central nervous system function [1]. Over the last two decades, there has been growing interest in the drug-induced model of psychosis, due to the potential of several pharmacological agents to elicit psychotomimetic symptoms that resemble those observed in psychosis patients [3]. Compared to animal models, which have been implicated as not adequately modeling the complexity of the disorder [9], the transient symptoms induced by acute challenge with psychotomimetic drugs in healthy individuals are of interest, as they may share pathophysiological mechanisms with the full-blown disorder. Cannabis use can increase the risk of psychosis, and the acute administration of its key psychoactive ingredient, delta-9-tetrahydrocannabinol (∆9-THC), can induce transient psychotomimetic symptoms. Methods: A double-blind, randomized, placebo-controlled crossover design was used to investigate the symptomatic effects of acute intravenous administration of ∆9-THC (1.19 mg/2 mL) in 16 healthy participants (seven males) with modest previous cannabis exposure
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