Oral THC Affected Cognition Without a Parallel Symptom-Scale Increase in a Schizophrenia Study
An oral THC condition worsened selected cognitive outcomes without a significant parallel increase in measured psychotic symptoms several hours later. That combination of findings does not show that THC is harmless in schizophrenia or that all routes have identical effects.
Several populations and treatment conditions
The double-dummy laboratory study involved 130 participants across schizophrenia/cannabis-use-disorder and comparison groups. The full sample size was not the number of patients receiving each active treatment.
Active conditions included 15 mg oral dronabinol or a 3.5% THC cannabis cigarette, with corresponding placebo procedures. Participants with schizophrenia and cannabis use disorder were stable in treatment, restricting generalization to acute illness or people without established cannabis exposure.
Tasks and symptom scales gave different answers
In the schizophrenia/cannabis-use-disorder group, oral dronabinol was associated with worse verbal learning and attention than placebo. The smoked condition did not produce the same significant cognitive contrasts.
Assigned active treatment did not significantly predict positive- or negative-symptom subscale scores at the later assessments. This was a time-specific null finding, not proof that symptoms never changed earlier or that repeated use has no psychiatric consequences.
Do not turn route comparisons into a safety hierarchy
The oral and smoked exposures differed in formulation, delivery and assessment timing. A nonsignificant smoked-treatment contrast cannot establish that inhaled cannabis is universally safer than oral THC.
The investigators also explored concentration-related associations, which answer a different question from randomized treatment assignment. Functional and symptom findings must retain their endpoint, population and timing. The study provides controlled evidence of selected cognitive effects while leaving broader psychiatric risk and individual clinical decisions unresolved.
Related: Interpreting clinical cannabinoid outcomes.
Primary research
Randomized Laboratory Study of Single-Dose Cannabis, Dronabinol, and Placebo in Patients With Schizophrenia and Cannabis Use Disorder. Schizophrenia Bulletin (2024).
