Cannabidiol has been shown to help people with a wide range of psychiatric disorders, including anxiety, psychosis, and depression. The mechanisms responsible for these effects, however, are still poorly understood.

In a recent study, published in Frontiers in Pharmacology, a group of scientists from the University of São Paulo in Brazil reviewed all the available research in order to learn more about the mechanisms at play when psychiatric disorders are treated with CBD. The study suggests that CBD’s therapeutic effects are caused by a number of acute mechanisms as well as changes in the structure of the brain over time, known as neuroplasticity.

Neuroplasticity and psychotropic drugs

In neuroscience, the term neuroplasticity applies to the capacity of the brain to adapt and change in response to experience. The authors of the Brazilian study note that psychiatric disorders may result from significant neuroplastic changes, which in turn leads to altered brain functions and behaviors. They point to several neuropsychiatric conditions that have been associated with stress-induced changes and decreased adult hippocampal neurogenesis (the birth of neurons). 

They also highlight the fact that the therapeutic effects of several psychotropic drugs usually need 2–6 weeks to be clinically recognized, suggesting that structural reorganization of the brain must take place for an improvement in such disorders. Antidepressants are probably the most studied class of medication associated with plastic brain changes.

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CBD’s effects in psychiatric disorders

CBD has been proven to offer a broad spectrum of therapeutic actions, which include anxiolytic, antipsychotic, antidepressant, anticonvulsant, and neuroprotective effects. These have been studied over a large range of psychiatric and neurodegenerative disorders. Although most of these putative therapeutic properties were initially described in animal models, clinical studies have supported the beneficial effects of CBD in anxiety, schizophrenia, epilepsy, and multiple sclerosis.

Some neuroimaging studies clearly demonstrated that CBD affects brain areas involved in the neurobiology of psychiatric disorders. In the recently published paper, the authors describe one study that showed how a single dose of CBD, administered orally in healthy volunteers, reduced the activity of the left amygdala-hippocampal complex, hypothalamus, and posterior cingulate cortex while increasing the activity of the left parahippocampal gyrus compared with placebo.

Mechanisms of CBD effects in neuropsychiatric disorders

While the mechanism of action of CBD remains contested and unclear, many of the possible pathways associated with CBD’s effects have been studied extensively in recent years. Some of the effects are thought to be related to CBD’s influence on the endocannabinoid system via the CB1 and CB2 receptors. While there are contradictory results, the authors state that CBD seems to exert an antagonist or negative modulatory action, but with a low affinity, at CB1 and CB2 receptors.

After reviewing all the research on the matter, the authors conclude that CBD can also regulate, directly or indirectly, the activity of peroxisome proliferator-activated receptor gamma (PPARγ), serotonin 5HT1A receptor, adenosine transporter, members of the TRPV family, as well at the CB1 and CB2 receptors.

CBD and neuroplastic effects in chronic stress

In mice that are suffering from anxiety and depression-like behaviors and cognitive impairment, the chronic administration of CBD has been shown to counteract the behavioral and neuroplastic consequences such as reduced levels of neurotrophins and impaired hippocampal neurogenesis and neuroinflammatory response.

Although several reports have investigated the potential use of cannabis derivatives in mood and anxiolytic disorders, the effects of cannabinoids on hippocampal neurogenesis was an unexplored issue until the mid-2000’s. Since then, the authors note, CBD has proven to enhance neurogenesis in mice. While a number of other studies that also suggest CBD induces neurogenesis, the authors point out that “the role of neurogenesis in CBD effects is complex and may depend on the stress level (of the patient)”.

There is also evidence to suggest CBD can help the synapses in the brain remodel themselves, effectively ‘rewiring’ the brain.  

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Conclusions

The authors of the study confirm that, while there is, of course, a lot of unanswered questions, CBD’s ability to reduce inflammation-associated neurodegeneration, its antioxidant properties, lack of psychoactivity, and many potentially beneficial effects make it a drug that could provide a “useful new approach to treat several neuropsychiatric disorders.”

It appears that a number of different mechanisms are involved in CBD’s therapeutic effects. These include well-studied acute mechanisms – such as interaction with 5HT1A-mediated neurotransmission, TRPV1 receptors, and inhibition of anandamide metabolism – as well as plastic changes that take place over time. The authors conclude that it’s these neuroplastic changes which contribute to the behavioral effects seen in response to chronic CBD treatment.