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Schizophrenia is a chronic, severe, and debilitating mental health disorder that affects about 1 percent of adults globally. The disorder is clinically heterogeneous; symptoms can include auditory and visual hallucinations, delusions, suspiciousness, blunted affect, limited speaking, anhedonia, avolition, and disorganized thought. These symptoms often appear between late adolescence and early adulthood. Men are more likely to be diagnosed with schizophrenia at an earlier age than women, suggesting that estrogen is protective. For this reason, women become vulnerable to the onset of symptoms again during menopause.
Schizophrenics frequently have psychiatric comorbidities, including depression (about 5 percent commit suicide), panic disorder, PTSD, obsessive-compulsive disorder, and anxiety disorders. Given these significant symptoms, schizophrenia is too often underdiagnosed; consequently, it is difficult to precisely quantify disease duration. They also have a heightened risk of premature mortality due to these symptoms.
Most patients abuse alcohol, tobacco, or cannabis. This is likely for self-medication to relieve adverse psychiatric symptoms or reduce the side effects caused by antipsychotic medications. The neural mechanisms underlying the actions and benefits of nicotine are well known.
Cannabis use has been implicated in the development of psychosis; however, the linkage is complicated. Adults carrying susceptibility genes for both tobacco addiction and schizophrenia are substantially more susceptible. The potency of cannabis is determined by the concentration of THC. As the THC concentration has increased and the CBD concentration decreased, the psychotomimetic proclivities of cannabis have increased. Multiple risk genes play a role in the development of psychosis associated with THC.
The two primary constituents of cannabis, THC and CBD, differentially affect schizophrenia-related psychosis. THC exacerbates schizophrenia symptoms, whereas CBD alleviates them. CBD has the added benefit of decreasing the Parkinson’s-esque side effects induced by antipsychotic drugs.
Schizophrenics are more susceptible to the psychosis-inducing effects of THC than healthy individuals. THC exacerbates both positive and negative symptoms. In contrast, CBD lacks psychoactive activity and reward properties because it cannot bind to endogenous cannabinoid receptors, and it also interferes with the ability of THC to bind to its native receptors. CBD attenuates the psychoactive effects of THC and produces an anti-anxiety-like effect by stimulating certain serotonin receptors.
The benefits of CBD
In patients with schizophrenia, CBD (800 mg/day) was as effective as an equivalent dose of an atypical, second-generation antipsychotic drug in reducing both positive and negative symptoms with fewer side effects. In another study, when CBD (1,000 mg/day) was co-administered with an antipsychotic to schizophrenics, it reduced the positive symptoms to a greater extent than an antipsychotic medication alone. However, CBD did not improve the cognitive impairments in patients diagnosed with chronic schizophrenia who were also receiving antipsychotic treatment.
The potential mechanisms
Adjunctive CBD therapy (600 mg/day) for 28 days improved functional connectivity in the Default Mode Network of the brain. Why is this important? This brain network becomes activated when you focus on internal mental processes, such as interoception (How do I feel right now?), recalling old memories, and imagining events in your future.
The decrease in positive symptom severity mentioned above may be due to changes in the concentrations of glutamate and N-acetyl-aspartate in CBD-treated participants. N-acetyl-aspartate is an indicator of neuronal viability; its levels are typically reduced in schizophrenia.
Another potential mechanism was suggested by a study that found that elevated levels of endogenous cannabinoids might trigger some aspects of psychosis. The benefits of CBD may be due to its ability to antagonize these endocannabinoids.
Conclusions
Converging evidence from recent studies indicates the potential benefits of administering CBD in conjunction with conventional antipsychotic medications to curtail schizophrenia-related psychosis. The evidence also clearly suggests that THC should not be used by patients with schizophrenia or by those who carry susceptibility genes.
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