O3.4. DOES CANNABIS INDUCE PSYCHOSIS BY ALTERING GLUTAMATE SIGNALING IN THE STRIATUM?

Background The neurobiological mechanisms underlying the association between cannabis use and acute or long-lasting psychosis are not completely understood. While some evidence suggests altered striatal dopamine may underlie the association, direct evidence that cannabis use affects either acute or chronic striatal dopamine is inconclusive. In contrast, pre-clinical research suggests that cannabis may affect dopamine via modulation of glutamate signaling. Methods A double-blind, randomized, placebo-controlled, crossover design was used to investigate whether altered striatal glutamate, as measured using proton magnetic resonance spectroscopy, underlies the acute psychotomimetic effects of intravenously administered delta-9-tetrahydrocannabinol (Δ9-THC; 1.19 mg/2 ml), the key psychoactive ingredient in cannabis, in a set of 16 healthy participants (7 males) with modest previous cannabis exposure. Results Compared to placebo, acute administration of Δ9-THC significantly increased Glutamate (Glu) + Glutamine (Gln) metabolites (Glx) in the left caudate head (P=0.027). Furthermore, compared to individuals who weren’t sensitive to the psychotomimetic effects of Δ9-THC, individuals who developed transient psychotic-like symptoms (~70% of the sample) had significantly lower baseline Glx (placebo; P=0.023) and a 2.27-times higher increase following Δ9-THC administration. Lower baseline Glx values (r=-0.55; P=0.026) and higher previous cannabis exposure (r=0.52; P=0.040) were associated with a higher Δ9-THC-induced Glx increase.