Does intravenous Δ9-tetrahydrocannabinol increase dopamine release? A SPET study

Area of Science:

• Neuroscience
• Psychopharmacology

Background:

• Intravenous delta-9-tetrahydrocannabinol (THC) can induce transient psychotic symptoms.
• The precise mechanism behind THC's psychotomimetic effects, particularly its relationship with striatal dopamine (DA) release, remains unclear.
• One hypothesis suggests THC stimulates DA release in the striatum, contributing to psychosis.

Purpose of the Study:

• To investigate whether intravenous THC administration increases striatal DA release compared to a placebo.
• To determine if there is a correlation between THC-induced DA release and the severity of positive psychotic symptoms.

Main Methods:

• A double-blind, randomized, placebo-controlled study involving eleven healthy male volunteers.
• Participants received intravenous THC (2.5 mg) or placebo.
• 123I-iodobenzamide ([123I]IBZM) single photon emission tomography (SPET) was used to assess striatal DA release.
• The Positive and Negative Syndrome Scale (PANSS) was employed to evaluate psychotomimetic effects.

Main Results:

• Intravenous THC significantly increased positive and general psychotic symptoms, as measured by the PANSS, 30 minutes post-administration.
• No significant differences in striatal binding index (caudate or putamen) were observed between THC and placebo conditions.
• There was no significant relationship found between the degree of positive psychotic symptoms and striatal DA release.

Conclusions:

• The study did not find evidence supporting a significant increase in striatal DA release following intravenous THC administration.
• The results suggest that striatal dopamine may not play a central role in the psychotomimetic effects of THC.
• These findings challenge the hypothesis that THC-elicited psychosis is mediated by increased striatal dopamine release.