A Single Dose of THC Impaired Cognition But Did Not Worsen Psychosis in People With Schizophrenia

Oral dronabinol (15 mg) worsened verbal learning (B = -9.89) and attention (B = -0.61) in the schizophrenia-CUD group compared to placebo. Neither smoked nor oral THC worsened positive or negative psychotic symptoms at 2 and 5 hours post-dose. However, higher serum THC levels were associated with worse negative symptoms (0.40 points per 10 ng/ml increase) regardless of administration route.

Double-dummy, placebo-controlled trial with 130 total participants comparing single-dose oral dronabinol (15 mg), smoked 3.5% THC cannabis, or placebo. Groups included people with schizophrenia plus CUD, CUD only, schizophrenia only, and healthy controls. Symptoms and cognition assessed hours after administration.

Up to 43% of people with schizophrenia have cannabis use disorder. This controlled trial provides critical safety data showing a moderate THC dose did not trigger psychotic episodes in this population, while confirming the cognitive costs, information needed to guide clinical decision-making.

The finding that moderate THC does not acutely worsen psychosis in people with existing schizophrenia and CUD challenges some assumptions, while the dose-dependent negative symptom relationship and cognitive impairment provide evidence for encouraging moderation or cessation.

Single dose limits generalizability to chronic use effects, relatively low THC dose (3.5% flower is below market average), acute effects may differ from chronic effects, controlled setting may differ from real-world use, participants may have developed tolerance