Comorbid cannabis abuse has a significant negative impact on the course and treatment of schizophrenia. Comorbid cannabis abuse is highly prevalent in schizophrenia and schizophrenics prefer cannabis to other illicit drugs. There are no pharmacological studies characterizing the effects of cannabis in schizophrenics. The existing literature is limited by its exclusive reliance on naturalistic, retrospective self-report studies. These studies suggest that cannabis may reduce certain symptoms associated with schizophrenia at the expense of worsening others. Studying the effects of cannabis on the symptoms of schizophrenia is the first step in understanding the problem of cannabis abuse and schizophrenia. Cannabis continues to be a public health problem in the general population. While an association between cannabis use and psychosis in """"""""healthy"""""""" individuals has been reported, the magnitude of cannabis' psychogenic effects has not been adequately studied using standardized assessments. This investigation proposes to answer the following questions: 1. Does THC have anxiolytic and euphoric effects in schizophrenia? 2. Is there altered cannabinoid sensitivity in schizophrenia: does THC increase psychosis and cognitive deficits in schizophrenics, is THC psychogenic in controls and finally, are schizophrenics more vulnerable to the effects of THC? Study subjects will be stable schizophrenics with previous cannabis exposure and matched controls. They will be tested under three conditions: placebo, 2.5 and 5mg THC delivered IV. Primary outcome measures are: PANSS, Visual Analogue Scale for Mood Disorders, CADSS (perceptual alteration scale) and tests sensitive to frontal and temporal cortical function. Secondary measures include measures of drug liking, movement rating scales and long term follow-up assessment of cannabis use.
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