New research in mice reveals how THC, the main psychoactive compound in cannabis, can reduce the effectiveness of risperidone, an antipsychotic drug used widely to treat people with schizophrenia. Earlier studies have suggested that cannabis use can reduce the effectiveness of antipsychotic treatments and increase rates of psychosis relapse, but the reason has not been clear.

Exposure to THC did not reduce the effectiveness of clozapine, another common antipsychotic drug, said researchers led by 2009 Young Investigator grantee Jonathon C. Arnold, Ph.D., at the University of Sydney, Australia.

The team’s study, published in the journal Neuropsychopharmacology, found that THC increases the activity of a protein transporter called P-gp, which shuttles drugs such as risperidone out of the brain. This reduces the level of the antipsychotic drug, to the point where it reduces its therapeutic impact.

Why is clozapine not similarly affected? It is not transported by the P-gp protein and is therefore unaffected by THC exposure. This suggests that clozapine might be a good first-line treatment for patients with schizophrenia who use cannabis, say Dr. Arnold and his colleagues.

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