CB2 Receptor Mutations May Be A Key Cause of Mental Health Disorders - RxLeaf

CB2 Receptor Mutations May Be A Key Cause of Mental Health Disorders

Dragana Komnenov PhD

These three studies found genetic mutations in the coding for CB2 receptors in patients with major depression, bipolar disorder, and schizophrenia.

Mental health disorders are a leading cause of health impairment as these involve significant changes in thinking, perception, emotion, behavior and personal relationships. Disease that affects mental health is strongly restricting and causes great distress for the patient and his or her family.

The cause of mental health disorders are complex and varied. Some factors include genetic, neurobiological, psychological and environmental influences. People with anxiety, bipolar disorder, and depression have given anecdotal testimony that cannabis has helped alleviate their symptoms. And recently, the efficacy and safety of cannabis-based medicine for treatment and alleviation of mental illness has been tested more systematically.

Genetic Mutation in CB2 Receptor May Cause Depression

Depression stemming from stressful life events have high relapse and reoccurrence rates, even after successful treatment. Major depression is associated with mood changes and anhedonia (lack of interest in pleasurable things in life).

In this study published in PLoS One, researchers investigated the hypothesis that genetic alterations of CB2 receptor in the brain may be involved in depression and substance abuse disorders. The CB2 receptor is typically associated with the cells of immune functioning. This is the first study proving its direct involvement in psychiatric disorders.

depressed girl looking out rainy window

Here, researchers demonstrated that high incidence of a mutation called ‘Q63R, nut no H316Y’  in the CB2 gene was found in the depressed subjects. CB2 receptors and their gene transcripts are expressed in the brains of the mice without the mutation. In healthy mice, the CB2 receptors are activated following exposure to stressors and administration of the abused drugs.

The data demonstrated that the functional expression of CB2 receptors in the brain may provide novel targets for the effects of cannabinoids in depression, beyond immunocannabinoid activity.

Common CB2 Receptor Mutation Found in Bipolar Patients

In the case of the bipolar disorder (BD), the pathophysiology is poorly understood. Current pharmaceutical treatments are often not well tolerated and carry high rates of treatment resistance.

Mounting evidence suggests that immune system dysfunction may play a role in the pathophysiology of BD. Several studies provide evidence that the endocannabinoid system is involved in the psychiatric disorders like major depression, bipolar disorder and schizophrenia.

Therefore, one study focused on alterations in the gene called CNR2 which codes for the CB2 receptor. Eighty patients and one hundred and sixty subjects were recruited for the study. Each was genotyped to compare mutations in the genes coding for the CB2 receptor. Statistically, significant results were associated between BD and one of the genetic variants (SNP) encoding the CB2 receptor.  While further investigations are necessary, these results suggest that CB2 receptor may play a role in the Bipolar Disorder.

animation showing bipolar disorder

CB2 Receptor Mutation Common to Schizophrenic Patients

Schizophrenia is a chronic psychiatric condition, characterized by hallucinations, delusions, cognitive dysfunction, impaired neurodevelopment and neurodegeneration. Epidemiological and genetic studies strongly indicate a role of inflammation and immunity in pathogenesis of symptoms of schizophrenia.

As in the other 2 psychiatric conditions already discussed, the endocannabinoid system. As in bipolar disorder, there was an association study performed between single nucleotide polymorphisms (SNPs) in the CNR2 gene and schizophrenia in two-independent case control populations. The analysis of the first population revealed nominally significant associations between schizophrenia and two SNPs. And the associations were replicated in the second population. The R63 allele of rs2501432 (R63Q), the C allele of rs12744386 and the haplotype of the R63-C allele were significantly increased among 1920 patients with schizophrenia.

These findings indicate an increased risk of the genetic alterations of the gene encoding CB2 receptor, CNR2 and the psychiatric disorders. Therefore, the therapy targets should focus on this region of interest.

CB2 receptor mutation causing depression

Next steps will be to investigate if and how cannabinoid therapy corrects this genetic mutation. The theory is that endocannabinoid support, through the consumption of cannabinoids, can alleviate symptoms CB2 receptor mutation.




Dragana Komnenov
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