The cannabinoid receptor blocker rimonabant unexpectedly reduced anxiety and hostility in schizophrenia patients | Research

The takeaway

In a small terminated trial, rimonabant (20 mg/day for 16 weeks) reduced psychiatric symptoms, particularly anxiety/depression and hostility, in overweight schizophrenia patients, though it did not produce weight loss.

Read this if you are interested in novel drug targets for schizophrenia treatment beyond traditional antipsychotics.

Rimonabant reduced anxiety/depression scores (p=0.0004) in schizophrenia patients

What the researchers found

Fifteen overweight patients with schizophrenia on second-generation antipsychotics were randomized to rimonabant (20 mg/day) or placebo for 16 weeks. The trial was terminated early when rimonabant was withdrawn from the European market.

Surprisingly, rimonabant was associated with significantly greater reduction in overall psychiatric symptom scores compared to placebo (BPRS difference -1.9, p=0.02). This was driven by improvements in anxiety/depression (p=0.0004) and hostility (p=0.02) subscales.

No significant differences were found for weight, blood pressure, fasting lipids, glucose, depression scale scores, or negative symptoms. Rimonabant was well tolerated with no significant adverse events in this small sample.

The authors concluded that the endocannabinoid system remained a promising target for schizophrenia pharmacotherapy despite the trial's premature termination.

Why it matters

The unexpected psychiatric benefits of a CB1 antagonist in schizophrenia patients suggested the endocannabinoid system played a role in psychiatric symptoms beyond psychosis itself, though the very small sample size limited conclusions.

The numbers in context

15 randomized (7 rimonabant, 8 placebo), 5 completed per group. BPRS total difference: -1.9 (p=0.02). Anxiety/depression: -1.4 (p=0.0004). Hostility: -0.7 (p=0.02). No weight or metabolic effects.

How the study worked

Randomized, double-blind, placebo-controlled, 16-week trial. Target enrollment was 60 but terminated at 15 participants (7 rimonabant, 5 completed per group). Overweight criteria: BMI 27+ with dyslipidemia or BMI 30+. Weekly exercise and dietary counseling offered.

What this study cannot tell us

Extremely small sample (15 randomized, 10 completers). Premature termination limits conclusions. No weight loss observed despite this being the primary outcome target. Multiple comparisons in a small trial increase false positive risk.

How to read the evidence

Extremely small prematurely terminated RCT (n=15). Results are hypothesis-generating only.

When this study was published

Published in 2011. Rimonabant was withdrawn from development, but endocannabinoid system research in schizophrenia continues.

The bigger picture

Despite rimonabant's withdrawal from clinical development, the psychiatric improvements observed supported continued investigation of the endocannabinoid system as a treatment target in schizophrenia.

Questions still open

Would other CB1 antagonists without rimonabant's psychiatric risk profile show similar benefits in schizophrenia? Is the endocannabinoid system a viable antipsychotic target?

Common questions

Could blocking the endocannabinoid system help schizophrenia?

In this very small trial, the CB1 blocker rimonabant unexpectedly improved anxiety and hostility scores. However, with only 15 participants and premature termination, these results require much larger studies to confirm.

Why was this trial stopped?

Rimonabant was withdrawn from the European market because it caused depression and suicidal thoughts in some obesity patients. This schizophrenia trial was terminated as a result, not because of problems in these patients.

Read the original research

Effects of the cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study.

Journal of clinical psychopharmacology, 31(1), 86-91

View on PubMed ↗Publisher’s paper ↗

Citation

Kelly, Deanna L; Gorelick, David A; Conley, Robert R; Boggs, Douglas L; Linthicum, Jared; Liu, Fang; Feldman, Stephanie; Ball, M Patricia; Wehring, Heidi J; McMahon, Robert P; Huestis, Marilyn A; Heishman, Stephen J; Warren, Kimberly R; Buchanan, Robert W. (2011). Effects of the cannabinoid-1 receptor antagonist rimonabant on psychiatric symptoms in overweight people with schizophrenia: a randomized, double-blind, pilot study.. Journal of clinical psychopharmacology, 31(1), 86-91. https://doi.org/10.1097/JCP.0b013e318204825b