Cannabidiol against psychotic disorders

© iStock / Feodora Chiosea

New study highlights positive effects of CBD in treating psychoses such as schizophrenia

Psychotic disorders such as schizophrenia are heterogeneous and often debilitating conditions.

The introduction of D2 dopaminergic receptor antagonists in the 1950 years has revolutionized the treatment of psychotic disorders and they remain the mainstay of the therapeutic arsenal against psychosis.

However, traditional antipsychotics are associated with a number of side effects and a significant proportion of patients do not get adequate remission of symptoms. It is therefore necessary to develop new treatments, especially those whose mechanism of action is not a D2 receptor antagonist. Cannabidiol (CBD), a non-toxic constituent of the cannabis plant, has emerged as a potential new class of antipsychotics with a unique mechanism of action.

A recent analysis concluded that patients with psychosis had significantly higher levels of endocannabinoid anandamide in cerebrospinal fluid and blood, and higher expression of the main cannabinoid central receptor 1 (CB1) on peripheral immune cells. This high endocannabinoid tone has been observed at all stages of the disease, from prodrome to chronic psychosis. Alterations of CB1 receptor expression have also been observed in post-mortem tissues and in vivo in patients with psychosis. If the endocannabinoid system plays a role in psychotic physiopathology, it is interesting to note that the pharmaceutical compounds that modulate this system could have therapeutic value.

Cannabidiol (CBD), a phytocannabinoid of cannabis sativa, has been reported as one of these potential treatments. Although the main psychoactive ingredient of cannabis, delta-9-tetrohydrocannabinol (THC), has anxiogenic, psychotomimetic and amnesic effects, CBD is nontoxic and has anxiolytic, antipsychotic and anticonvulsant properties, with no adverse effects on memory. Epidemiological findings support these opposing profiles; there is considerable evidence that cannabis is a risk factor in the development of psychosis and adverse outcomes in cannabis users. However, the adverse effects of cannabis use on the risk of subsequent onset and progression of psychosis are particularly evident in people who consume high THC and low CBD cannabis, rather than those who consume cannabis. who use hashish cannabis (with a lower THC level and a higher CBD level). This trend is consistent with the evidence that CBD not only has opposite effects to THC, but may also block some of its undesirable (and particularly psychotomimetic) effects.

It is important to note that CBD has a different mechanism of action than dopamine receptor antagonists and could therefore represent a completely new class of antipsychotic treatment. This would be associated with many benefits. First, by avoiding dopamine receptor antagonism, undesirable effects such as extrapyramidal symptoms and an increase in prolactin can be avoided. Second, if CBD acts by different molecular pathways to current antipsychotics, it could be used not only as a single agent, but potentially as an adjunct to existing antipsychotics, with potential additional efficiencies. While the CBD is currently being tested for a number of psychiatric disorders and physical health problems, the study synthesizes and summarizes current evidence regarding the therapeutic potential of CBD in the treatment of psychosis.

Evidence for the antipsychotic potential of cannabidiol

The accumulated evidence regarding the antipsychotic potential of CBD comes from several different sources. These include preclinical work, experimental studies on healthy human volunteers comparing the neurocognitive effects of THC and CBD, and studies to determine whether CBD can block or mitigate the symptomatic effects of THC. .

Preclinical data

Indirect evidence for the antipsychotic and anxiolytic effects of CBD comes from preclinical studies, where the specific features of psychotic disorders are modeled in animals and allow the potential therapeutic effects of molecular and behavioral levels to be examined.


Hyperlocomotion is considered a model of positive psychotic symptoms and can be treated with antipsychotics. CBD has been shown to reduce amphetamine (dopamine agonist) and ketamine (N-methyl-d-aspartate receptor antagonist (NMDA) induced hyperlocomotion without inducing catalepsy, suggesting that it has beneficial effects similar to antipsychotics without harmful motor side effects, with a profile similar to that of atypical antipsychotic clozapine.

Experimental and neuroimaging studies in humans

Neuroimaging studies that noninvasively examine neural substrate systems, upon which CBD can act to produce its antipsychotic and anxiolytic effects in vivo, complement the knowledge about the antipsychotic potential of MDC.

THC and CBD have been shown to have opposite effects on regional brain activation in a variety of cognitive tasks in healthy individuals. It is interesting to note that this phenomenon has been observed in areas of the brain where patients with psychosis are dysfunctional and during tasks that are known to be impaired by cannabis use.

Further evidence of the protective effects of CBD against the psychotomimetic, anxiogenic and cognitive effects of THC comes from experimental studies in which both cannabinoids were co-administered. THC can be used as an experimental model of psychosis in humans because its acute administration in healthy people can induce transient psychotic symptoms (including positive and negative symptoms), as well as cognitive deficits similar to those observed in schizophrenics.

In summary, more and more studies suggest that CBD alleviates the propromotic, anxiety and cognitive effects of THC in healthy individuals, both neurophysiologically and behaviorally (psychopathologically). In addition, CBD has anti-THC effects on regional brain activation and functional connectivity in a range of cognitive tasks (including saliency treatment, learning and memory, response inhibition, and cognitive processing). treatment of fear) in areas known to be disrupted in patients with psychosis. Together, this accumulated evidence confirms the potential therapeutic role of CBD in the treatment of psychosis and is consistent with the independent evidence that CBD has antipsychotic effects in patients with this condition (see below).

Clinical tests

Early clinical trials suggest that CBD is safe, well tolerated and may have antipsychotic effects in patients with psychosis. There is some evidence that CBD may be particularly effective in the early stages of the disorder, such as in patients at high clinical risk and those with a first psychotic episode.

Neuroimaging research suggests that CBD may exert its therapeutic effects by modulation of brain function in regions known to be altered in patients with psychosis according to various cognitive paradigms. Questions remain about the complete side effect profile of CBD, with reports of increased liver enzymes and potential liver toxicity, but the most commonly reported side effects (such as diarrhea and sedation) are probably both mild and benign. Since CBD has antipsychotic effects without acting directly on dopamine receptors, it may represent a new type of treatment for psychosis.


Tags : cbdDopamineÉtudeNeurosciencepsychiatryschizophrenia