Randomized Laboratory Study of Single-Dose Cannabis, Dronabinol, and Placebo in Patients With Schizophrenia and Cannabis Use Disorder
Mary F. Brunette, Robert M. Roth, Christi L. Trask, Jibran Y. Khokhar, James Ford, Soo Hwan Park, Sara M. Hickey, Thomas A. Zeffiro, Haiyi Xie
Schizophrenia Bulletin June 20, 2024 DOI: 10.1093/schbul/sbae097 via OpenAlex
Summary
A single modest dose of oral THC (15 mg dronabinol) worsened verbal learning and attention in people with schizophrenia and co-occurring cannabis use disorder, without exacerbating psychotic symptoms several hours after administration. Smoked low-dose THC cigarettes did not produce these cognitive effects. Higher blood THC levels were linked to increased negative symptoms. Drug liking was greater with THC than placebo. The findings suggest that oral THC may impair cognition in this population even at modest doses, while not acutely worsening psychosis.
Study at a glance
| Characteristics | Randomized controlled trial Placebo-controlled Peer reviewed |
|---|---|
| Sample size | 130 |
| Population | People with schizophrenia and co-occurring cannabis use disorder (SCZ-CUD) and people with cannabis use disorder only (CUD-only) |
| Intervention | smoked 3.5% THC cigarettes |
| Dose | 15 mg dronabinol, 3.5% THC cigarettes |
| Duration | Several hours after drug administration |
| Topics | Cannabis |
| Keywords | Dronabinol Placebo Psychosis Schizophrenia object-oriented programming Randomized controlled trial |
| Citations | 5 |
| Key finding | Oral dronabinol (15 mg) worsened verbal learning and attention in SCZ-CUD participants without exacerbating positive or negative symptoms several hours after administration. |
Abstract
BACKGROUND AND HYPOTHESIS: Up to 43% of people with schizophrenia have a lifetime cannabis use disorder (CUD). Tetrahydrocannabinol (THC) has been shown to exacerbate psychosis in a dose-dependent manner, but little research has assessed its effects on schizophrenia and co-occurring CUD (SCZ-CUD). In this double-dummy, placebo-controlled trial (total n = 130), we hypothesized that a modest dose of THC would worsen cognitive function but not psychosis. STUDY DESIGN: Effects of single-dose oral THC (15 mg dronabinol) or smoked 3.5% THC cigarettes vs placebo in SCZ-CUD or CUD-only on positive and negative symptoms of schizophrenia (only for SCZ-CUD), cognition, and drug experiences assessed several hours after drug administration. SCZ-only and healthy control participants were also assessed. STUDY RESULTS: Drug liking was higher in THC groups vs placebo. Neither smoked THC nor oral dronabinol predicted positive or negative symptom subscale scores 2 and 5 h, respectively, after drug exposure in SCZ-CUD participants. The oral dronabinol SCZ-CUD group, but not smoked THC SCZ-CUD group, performed worse than placebo on verbal learning (B = -9.89; 95% CI: -16.06, -3.18; P = .004) and attention (B = -0.61; 95% CI: -1.00, -0.23; P = .002). Every 10-point increment in serum THC + THCC ng/ml was associated with increased negative symptoms (0.40 points; 95% CI: 0.15, 0.65; P = .001; subscale ranges 7-49) and trends were observed for worse positive symptoms and performance in verbal learning, delayed recall, and working memory. CONCLUSIONS: In people with SCZ-CUD, a modest single dose of oral THC was associated with worse cognitive functioning without symptom exacerbation several hours after administration, and a THC dose-response effect was seen for negative symptoms.