Can CBD be Used to Prevent or Treat Psychosis?

By Clare Knight, B.Sc.Reviewed by Dr. Liji Thomas, MD

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• What is CBD?
• What is Psychosis?
• Does CBD Affect the Symptoms of Psychosis?
• How Might CBD Improve Psychotic Symptoms?
• CBD: A New Class of Treatment for Psychosis?

What is CBD?

Despite being prohibited in the UK since 1928, cannabis has been used historically for medicinal purposes over more than 5,000 years.

A complex plant, cannabis contains over 100 cannabinoids, the best recognized being tetrahydrocannabinol (THC), which is the most prevalent psychoactive compound in cannabis.

More recently, however, there has been in growth in the awareness of a second, non-psychoactive cannabinoid and its potential medicinal benefits.

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Cannabidiol, more commonly known as CBD, is a phytocannabinoid and is one of the most prevalent cannabinoids in cannabis plants.

Derived from the hemp plant, it accounts for approximately 40% of the plant’s extract. While THC and CBD both interact with the body via the endocannabinoid system to alter the release of neurotransmitters in the brain, altering mood, appetite and pain response, their modes of action differ.

THC activates CB1 receptors within the brain, causing feelings of euphoria, but CBD is an antagonist at the CB1 receptors, meaning it will never elicit the ‘high’ commonly associated cannabis use, and can counteract CB1 activation following exposure to THC.

As interest in the potential medical benefits of cannabis has grown, people are also paying more interest in the possibility that CBD may be useful in psychiatric settings. While THC has been linked to an increased risk for psychosis, CBD is potentially beneficial for symptoms of psychosis.

What is Psychosis?

Psychosis refers to a group of symptoms rather than a discrete diagnosis. It is a medical umbrella term used to describe beliefs that are not rooted in reality or sensory experiences of things that do not exist. Psychosis may have multiple causes such as drug use, brain injury, extreme stress, sleep deprivation or mental illness (such as schizophrenia or bipolar disorder).

During an episode of psychosis, the individual may have hallucinations (seeing, hearing or smelling things that do not exist) or delusions (strongly held false beliefs, usually rooted in fear or suspicion). These symptoms often co-occur with cognitive disruptions such as disordered thoughts or difficulties in concentration.

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Does CBD Affect the Symptoms of Psychosis?

While CBD was formerly thought to lack pharmacological effects, subsequent studies in both animals and human volunteers have shown that it can reduce drug-induced psychotic symptoms and cognitive impairment following exposure to high levels of THC, potentially via the endocannabinoid system. Moreover, they suggest that CBD may lower the risk of psychosis in individuals using cannabis.

However, studies indicating the potential benefits of CBD in psychosis tended to be observational case and cohort studies, limiting firm conclusions as to the efficacy of CBD.

The first randomized placebo-controlled trial (RCT) in 2017 compared 88 patients with psychosis who received either CBD or placebo over a 6-week period as an adjunctive treatment to antipsychotics. Symptomatology, cognition and overall functioning was assessed pre- and post-treatment.

The conclusion is that patients treated with CBD show reductions in psychotic symptoms and improvement in functioning and cognitive abilities compared to those who received placebo. Moreover, patients receiving the active treatment were more likely to be rated as improved by their treating psychiatrist.

How Might CBD Improve Psychotic Symptoms?

Traditional antipsychotics are thought to work by targeting the release of certain neurotransmitters in the brain, namely noradrenaline, acetylcholine, serotonin, and most notably, dopamine. The dopamine hypothesis, which has dominated psychosis treatment to date, postulates that an excess of dopamine in the brain causes psychotic symptoms.

Antipsychotic medication binds to dopamine receptors, thus reducing dopamine production. However, in some psychotic patients dopamine production is thought to be relatively normal. Exploring the impact of other neurotransmitter systems may therefore lead to new classes of treatment.

A recent study explored the effect of CBD and placebo on treatment-naive individuals at high risk of developing psychosis and compared their brain activation via fMRI during a verbal learning task to un-medicated healthy controls.

Overall, at-risk individuals show lower levels of activation compared to health controls, but those who received CBD show significantly greater brain activation than those who received placebo.

The researchers conclude that CBD could partially normalize alterations to brain areas implicated in the development of psychosis.

CBD: A New Class of Treatment for Psychosis?

When the effects of CBD as an adjunct to conventional antipsychotic medication are examined, modest improvements are found on cognition and the impact of patients’ illness on their quality of life and global functioning.

However, the benefit is limited to positive symptoms of psychosis such as hallucinations and delusions. Negative symptoms such as affective flattening and mood disruption are not affected by CBD.

Furthermore, CBD was only administered as an adjunct treatment in the majority of studies; and all participants continued to receive their conventional antipsychotic treatment. To understand the potential benefit of CBD as a standalone treatment for psychosis, further research is required.