CB2 Receptor Mutations May Cause Mental Health Disorders - RxLeaf
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CB2 Receptor Mutations May Cause 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. Indeed, disease that affects mental health is strongly restricting and causes great distress for the patient and his or her family. Recent scientific studies are finding that genetic mutations in the CB2 receptor may cause depression and other mental health disorders.

Basically, the causes 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. Recently, doctors are emplotying more and more systematic testing for the efficacy and safety of cannabis-based medicine. This includes cannabis’ ability to treat and alleviate mental illness.

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. Indeed, CB2 receptors and their gene transcripts express in the brains of the mice without the mutation. In healthy mice, the CB2 receptors activate 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), we don’t yet fully understand the pathophysiology. Patients often do not tolerate current pharmaceutical treatments. They 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 psychiatric disorders involve the endocannabinoid system. These are disorders like depression, bipolar disorder, and schizophrenia.

Basically one study focused on alterations in the gene called CNR2 which codes for the CB2 receptor. Doctors recruited eighty patients and one hundred and sixty subjects the study. Afterwards, the doctors genotyped each one to compare mutations in the genes coding for the CB2 receptor. Statistically, significant results associate 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. Basically, hallucinations, delusions, cognitive dysfunction, impaired neurodevelopment and neurodegeneration characterize it. Epidemiological and genetic studies strongly indicate a role of inflammation and immunity in pathogenesis of symptoms of schizophrenia.

Here are some of the results:

  • Significantly, like bipolar disorder, single nucleotide polymorphisms (SNPs) in the CNR2 gene and schizophrenia in two-independent case control populations associate together.
  • The analysis of the first population reveals nominally significant associations between schizophrenia and two SNPs.
  • The second population replicates the association.
  • The R63 allele of rs2501432 (R63Q), the C allele of rs12744386 and the haplotype of the R63-C allele significantly increase among 1920 patients with schizophrenia.

Basically, these findings indicate an increased risk of the genetic alterations of the gene encoding CB2 receptor, CNR2 and  psychiatric disorders. Accordingly therapies should focus on this region of interest.

CB2 receptor mutation causing depression

Finally, next steps will investigate if and how cannabinoid therapy corrects this mutation. Accordingly the theory is that endocannabinoid support, through the consumption of cannabinoids, will alleviate symptoms CB2 receptor mutations.

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Dragana Komnenov
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