People who get psychotic symptoms from THC already have different hippocampal brain activity at baseline

This was a pseudo-randomized, double-blind, repeated-measures, within-subject crossover study. Thirty-six healthy males received 10 mg oral THC and placebo on separate occasions. Psychopathological assessments and fMRI during a verbal learning task were performed under both conditions. Participants were classified into THC-psychosis-sensitive (n=14) and non-sensitive (n=22) groups.

Identifying who is at risk for psychotic reactions to cannabis before they happen is one of the most important unsolved problems in cannabis research. This study suggests that hippocampal activation during learning could serve as a biomarker, potentially allowing identification of vulnerable individuals before they experience adverse effects.

This study suggests that susceptibility to THC-induced psychosis is not random but reflects pre-existing differences in brain function. The hippocampus is one of the brain regions richest in cannabinoid receptors, and its role in memory and pattern recognition may make altered hippocampal function a vulnerability factor for psychotic experiences when cannabinoid signaling is disrupted.

The sample included only healthy men, and findings may differ in women or in clinical populations. The classification into sensitive and non-sensitive groups was based on a single THC exposure. The study cannot determine whether the hippocampal difference is genetic, developmental, or environmental in origin. Sample sizes within subgroups were relatively small (14 and 22).