PMC:3951193 / 28516-31074 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3951193","sourcedb":"PMC","sourceid":"3951193","source_url":"http://www.ncbi.nlm.nih.gov/pmc/3951193","text":"Antipsychotic drugs\nFirst-generation antipsychotic drugs, such as haloperidol and chlorpromazine (thorazine), are dopamine D2 receptor inverse agonist. Second-generation “atypical” antipsychotics (e.g., risperidone, olanzapine, clozapine, and aripiprazole) antagonize D2 and 5-HT2A, and also target other neuroreceptors. Acute administration of chlorpromazine enhanced the hypothermic response to THC [102]. Subchronic administration of haloperidol increased CB1 density in rat brains, indicated by increased binding of [3H]CP55,940 in the substantia nigra\u003eglobus pallidus\u003estriatum. Subchronic haloperidol also potentiated CP55,940-stimulated [35S]GTPγS binding in the substantia nigra [103]. Sundram et al. [104] confirmed haloperidol's effects on [3H]CP55,940 binding, and obtained similar results with chlorpromazine and olanzapine. In monkeys trained to discriminate THC, haloperidol sensitized the THC discriminative stimulus [105]. Risperidone increased [3H]CP55,940 binding in rat brain without altering CB1 mRNA levels [106]. Four weeks of aripiprazole upregulated CB1 in rat frontal cortex [107]. Clozapine decreased [3H]CP55,940 binding in rat brain [104], and attenuated THC-induced disruption of spatial working memory in the rat radial maze task [108].\nSeveral researchers have proposed that CB1 upregulation during antipsychotic drug treatment may explain appetite enhancement, weight gain, and CB1 supersensitivity. D'Souza et al. [109] conducted a double-blind study on the effects of adding haloperidol to THC. Compared to THC alone, the combination of drugs significantly worsened verbal recall, distractibility, and vigilance scores. The drug combination did not affect other testing parameters, such as euphoric effects and motor outcomes. Another double-blind study showed that haloperidol reversed THC-induced increases in the Positive and Negative Syndrome Scale (used for measuring symptom severity in schizophrenia), but did not affect the THC-induced “high” in healthy male volunteers [110]. A double-blind study in healthy male volunteers showed that olanzapine reduced the effects of THC as measured on the positive and negative syndrome scale, and the visual analogue scale for psychedelic effects, but the reduction fell short of statistical significance, p = 0.67 [111].\nIn summary, antipsychotic drugs likely upregulate CB1 expression in parts of the rodent brain. In human clinical studies, antipsychotic drugs do not affect THC-induced “high” or “euphoria,” but dampen dysphoria and worsen verbal recall and 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