CBD Showed Antipsychotic Effects Comparable to Standard Medication With Fewer Side Effects | Research

The takeaway

A critical review found that cannabidiol demonstrated antipsychotic properties in both animal and human studies, with one clinical trial showing efficacy comparable to amisulpride but with a side effect profile similar to placebo.

Read this if you or someone you know has schizophrenia and you want to understand the research on CBD as an alternative treatment.

CBD matched amisulpride for antipsychotic efficacy with placebo-like side effects in first RCT.

What the researchers found

This review examined the evidence for cannabidiol (CBD) as a potential antipsychotic medication. While THC is associated with increased psychosis risk, CBD appears to have the opposite effect.

In animal studies, CBD showed antipsychotic properties in rodents and rhesus monkeys, though results varied depending on the behavioral test used, treatment duration, and experimental conditions.

The most striking finding came from a randomized, double-blind controlled clinical trial in which CBD produced antipsychotic effects comparable to amisulpride (a standard antipsychotic medication) in patients with acute schizophrenia. The crucial difference was side effects: while amisulpride caused the typical antipsychotic side effects (weight gain, metabolic changes, movement disorders), CBD's side effect profile was similar to placebo.

The clinical improvement from CBD was significantly associated with elevated levels of anandamide, an endocannabinoid, suggesting CBD may work by boosting the body's own cannabinoid system rather than through direct receptor binding.

Why it matters

Current antipsychotic medications all share a similar mechanism (dopamine receptor blockade) and come with significant side effects that lead many patients to stop taking them. CBD appears to work through an entirely different mechanism (endocannabinoid modulation) and demonstrated a dramatically better side effect profile, potentially offering the first mechanistically distinct antipsychotic in decades.

The numbers in context

One RCT showed CBD was comparable to amisulpride for antipsychotic efficacy. CBD's side effect profile was similar to placebo. Clinical improvement correlated with elevated anandamide levels.

How the study worked

Critical review of published literature including animal behavioral studies, individual case reports, and the first randomized double-blind controlled clinical trial of CBD for schizophrenia. The review examined both efficacy data and proposed mechanisms of action.

What this study cannot tell us

Only one RCT existed at the time of this review. Animal study results were inconsistent across different experimental conditions. The mechanisms of CBD's antipsychotic action were not fully understood. The review was published before subsequent larger clinical trials could confirm or challenge the initial findings.

How to read the evidence

Moderate evidence based on a critical review including one RCT and multiple preclinical studies. The clinical evidence is promising but from a single trial.

When this study was published

Published in 2016. Additional clinical trials of CBD for psychosis have since been conducted, with some supporting and others questioning these findings.

The bigger picture

The finding that a cannabis-derived compound could treat the same condition (psychosis) that another cannabis compound (THC) can trigger captures the complexity of the endocannabinoid system. If confirmed in larger trials, CBD could represent a paradigm shift in antipsychotic treatment by offering effective symptom control without the metabolic and neurological side effects that plague current medications.

Questions still open

Will CBD's antipsychotic efficacy hold up in larger, multi-center trials? What is the optimal dose and formulation of CBD for antipsychotic use? Could CBD be used as an adjunct to lower doses of standard antipsychotics, reducing side effects while maintaining efficacy?

Common questions

Can CBD treat schizophrenia?

One clinical trial found CBD was as effective as a standard antipsychotic (amisulpride) with far fewer side effects. However, this was a single trial, and CBD has not been approved for this use. Additional research has produced mixed results.

How can CBD be antipsychotic when THC causes psychosis?

THC and CBD work through very different mechanisms. THC directly activates CB1 receptors, which can trigger psychotic symptoms in vulnerable people. CBD appears to boost the body's own endocannabinoid (anandamide), which may have a protective, antipsychotic function.

Read the original research

Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence.

Frontiers in pharmacology, 7, 422

View on PubMed ↗

Citation

Rohleder, Cathrin; Müller, Juliane K; Lange, Bettina; Leweke, F M. (2016). Cannabidiol as a Potential New Type of an Antipsychotic. A Critical Review of the Evidence.. Frontiers in pharmacology, 7, 422.