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

The takeaway

In a controlled trial of 130 participants, a single moderate dose of THC impaired verbal learning and attention in people with co-occurring schizophrenia and cannabis use disorder but did not worsen psychotic symptoms, though higher blood THC levels were associated with worse negative symptoms.

Psychiatrists treating dual-diagnosis patients, schizophrenia researchers, cannabis and psychosis researchers

THC impaired verbal learning and attention but did not worsen psychotic symptoms in schizophrenia

What the researchers found

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.

Why it matters

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 numbers in context

130 participants; 15 mg oral dronabinol or 3.5% THC smoked; dronabinol impaired verbal learning (B = -9.89, p = .004) and attention (B = -0.61, p = .002) in SCZ-CUD group; no symptom worsening at 2 and 5 hours; every 10 ng/ml serum THC increase associated with 0.40-point increase in negative symptoms (p = .001)

How the study worked

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.

What this study cannot tell us

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

How to read the evidence

Well-designed placebo-controlled trial with multiple comparison groups; single-dose design limits generalizability to chronic use

When this study was published

Published 2025

The bigger picture

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.

Questions still open

Would higher THC doses or repeated dosing worsen psychotic symptoms? Is the dose-response relationship for negative symptoms clinically meaningful? Could these findings inform safer-use guidelines for people with schizophrenia who will not stop using cannabis?

Common questions

Does THC make schizophrenia worse?

In this controlled trial, a single moderate dose of THC did not worsen psychotic symptoms in people with both schizophrenia and cannabis use disorder. However, it did impair verbal learning and attention, and higher blood THC levels were linked to worse negative symptoms.

Is smoked cannabis or oral THC more impairing for people with schizophrenia?

Oral dronabinol was associated with cognitive impairment (worse verbal learning and attention) in the schizophrenia-CUD group, while smoked cannabis was not, possibly due to differences in how THC is absorbed and metabolized.

Read the original research

Randomized Laboratory Study of Single-Dose Cannabis, Dronabinol, and Placebo in Patients With Schizophrenia and Cannabis Use Disorder.

Schizophrenia bulletin, 51(2), 479-492

View on PubMed ↗Publisher’s paper ↗

Citation

Brunette, Mary F; Roth, Robert M; Trask, Christi; Khokhar, Jibran Y; Ford, James C; Park, Soo Hwan; Hickey, Sara M; Zeffiro, Thomas; Xie, Haiyi. (2025). Randomized Laboratory Study of Single-Dose Cannabis, Dronabinol, and Placebo in Patients With Schizophrenia and Cannabis Use Disorder.. Schizophrenia bulletin, 51(2), 479-492. https://doi.org/10.1093/schbul/sbae097