Recent research is Journal of Psychopharmacology This suggests that cannabidiol, a non-intoxicating compound found in cannabis, may not be an effective treatment for psychotic disorders. After analyzing data from multiple clinical trials, scientists found no significant evidence that the substance improved symptoms of psychosis compared to a placebo or standard drug. The findings indicate that although the compound is generally safe to use, patients and health care providers should view this compound as experimental rather than a proven treatment for these mental health conditions.
Cannabis is a complex plant containing dozens of active compounds. The best known is delta-9-tetrahydrocannabinol (THC), which is responsible for the psychotic high associated with marijuana use. High levels of THC exposure are associated with an increased risk of developing psychotic disorders.
Mental disorders such as schizophrenia are mental health conditions that alter a person’s sense of reality. Symptoms often include hallucinations, delusions, and severe cognitive problems. Current antipsychotic medications can help manage these symptoms, but they often come with severe side effects, and the medical community is seeking milder alternatives.
Cannabidiol, commonly known as CBD, is another major compound found in cannabis, but it does not cause intoxicating effects. Laboratory and animal studies suggest that CBD may actually reduce psychotic symptoms. Early experimental studies show evidence that it interacts with the body’s endocannabinoid system, a complex cell signaling network that helps regulate functions such as mood, sleep, and memory.
Specifically, CBD is thought to increase levels of anandamide, a brain chemical associated with feelings of well-being. It also interacts with serotonin receptors to calm nervous system activity. These promising signs in a laboratory setting have led to significant interest in clinical trials testing CBD in human patients with psychosis.
Some medical experts highlight these trials as some of the most influential psychiatric research in recent years. But individual studies are often too few to give a definitive answer about whether the chemical actually helps patients in the real world. The team of researchers sought to combine and evaluate all the evidence from previous human studies.
The research team was led by Mattia Marchi from the University of Modena-Reggio Emilia in Italy and a group of medical scientists specializing in mental health. They aimed to determine whether CBD is truly effective and tolerable for people diagnosed with schizophrenia spectrum disorders.
To achieve this goal, scientists performed a systematic review and meta-analysis. Meta-analysis is a statistical method that combines the results of multiple independent studies to find common trends and provide more reliable estimates of treatment effects. The team searched major scientific and medical databases for randomized controlled trials published up to July 2025.
Randomized controlled trials are considered the gold standard in medical research. They randomly assign participants to receive either the treatment being tested or a comparison substance, such as a fake pill known as a placebo. The authors narrowed their focus to eight specific trials.
Six of these studies were published in peer-reviewed scientific journals, and two were unpublished trials obtained from public registries. The analysis included 288 adult participants diagnosed with a mental disorder. Within this group, 116 participants received CBD treatment, and 117 were placed in a control group receiving either a placebo or an existing antipsychotic medication.
An additional 55 participants took part in a crossover study, receiving both treatments at different times. In a crossover design, patients might take CBD for a period of time, take a break, and then take a placebo. This structure allows researchers to compare how the same individuals respond to both options.
CBD was administered orally. The median daily dose was 800 milligrams, but the exact amount varied between studies. The length of the trials varied widely, with researchers following patients from 20 minutes to 12 weeks after treatment.
When looking at the combined data, researchers found that CBD did not produce statistically significant improvements in psychosis severity. They assessed multiple categories of symptoms, including positive symptoms such as hallucinations and delusions. They also investigated negative symptoms that involve loss of normal functioning, such as emotional flattening and social withdrawal.
In all of these areas and tests of cognitive impairment, the substance failed to perform significantly better than the control treatment. One study directly compared CBD to an antipsychotic drug called amisulpride. This particular trial found no difference in effectiveness between the two, but it was not designed to prove that they were completely equivalent.
Safety and tolerability were also major focuses of the review. The authors noted that CBD tended to be well tolerated by participants. Rates of side effects and study discontinuation were very similar between groups receiving CBD and those receiving placebo or standard medication.
One trial reported deaths in participants in the CBD group. However, the coroner ruled out CBD intoxication as the cause of death. The team also broke down the data into smaller subgroups to see if certain factors were influencing the results.
They looked at trial length and compared acute, short-term, and long-term effects. None of these periods showed significant benefit from CBD intake. Interestingly, this data suggested that an exception may exist for patients who were actively using cannabis.
A study of participants who regularly used recreational cannabis found slightly greater improvements when treated with CBD. Researchers suggest that this may reflect that CBD helps reduce the negative effects of recreational cannabis use, rather than directly treating the underlying psychotic disorder itself. This particular finding is based on a very small amount of data, making it a preliminary observation rather than a proven fact.
The authors also discussed the economic realities of CBD treatment. They noted that the pharmaceutical-grade CBD preparations tested in these trials were significantly more expensive than commonly used antipsychotics. Inexpensive CBD formulations are widely available in retail stores, but these commercially available products typically vary widely in dosage, purity, and regulation, so you cannot assume they will have the same effects as medical-grade formulations.
The reader should be aware that the current body of research has several limitations. The most important problems are the small number of available trials and the small total number of participants. This small sample size reduces the statistical power of the analysis. This means that the subtle but potentially real benefits of CBD may be being missed.
There were also significant differences in design among the included studies. Some trials followed patients for only a few minutes after a single dose, which does not reflect how drugs are typically used to treat chronic mental health conditions over long periods of time. Additionally, the quality of evidence across studies was rated as low to very low, primarily due to issues such as incomplete reporting and potential bias in how the original experiments were performed.
Researchers stress that larger clinical trials are needed to reach more definitive conclusions. In particular, they suggest that future research should focus on patients with psychosis directly related to cannabis use. By targeting this specific group, scientists may be able to uncover whether CBD acts as a specific antidote to marijuana-induced psychosis.
Until such data emerge, the authors advise that CBD remains an experimental approach. Current evidence does not support clinical use as a standard treatment for schizophrenia or related conditions. Large-scale clinical trials are currently underway at multiple research centers and are expected to provide better quality data to establish exactly what role CBD may play in future psychiatric care.
The study, “Cannabidiol for Psychotic Disorders: A Meta-Analysis of Randomized Controlled Trials,” was authored by Mattia Marchi, Karim Rachedi, Alessia Bof, Giulio Mele, Luca Pingani, Silvia Ferrari, and Gian Maria Galeazzi.
