Bart D. Peters

Objective: The aim of the present study was to gain more insight into the positive and negative effects of cannabis in the prodromal phase of schizophrenia and in the ultra-high-risk (UHR) state for psychosis. Method: A theory-driven questionnaire was used to examine subjective effects in the prodromal phase in male subjects with a recent onset of schizophrenia or related disorder (n = 52) and in the UHR state in help-seeking male subjects screened for being at UHR for psychosis (n = 17); both groups were compared to cannabis-using controls from the general population (n=52). Results: Recent-onset patients and UHR subjects reported feeling more anxious, depressed and suspicious immediately after cannabis use. Some patients also reported feeling less depressed after cannabis use. Recent-onset patients reported increased visual and acoustic hallucinations, and confusion after cannabis use. Of the recent-onset patients 37% reported that their very first psychotic symptoms occurred during cannabis intoxication. Long-term effects of cannabis reported more often by both patient groups were depression, less control over thoughts and social problems. Conclusions: These results suggest that schizophrenia patients in the prodromal phase and subjects at UHR for psychosis are more sensitive to some negative effects of cannabis, in particular psychotic effects, compared to cannabis users from the general population. Although limited by the retrospective design in the recent-onset patients, the present study adds qualitative evidence to longitudinal studies that suggest that cannabis is a component cause in the onset of the first psychotic episode. Further studies are needed on the objective and subjective effects of cannabis in UHR subjects.

An important question that arises in policy discussions concerning the use of cannabis is whether the possible harmful effects of cannabis are reversible. To review studies on residual neuropsychological, structural and functional brain abnormalities that may have resulted from the long-term use of cannabis. When we searched Medline (January 1966 - December 2003) and EMBASE (January 1988 - December 2003) using the key words 'cannabis', 'marijuana', 'neuropsychological test', 'cognition', 'CT-scan', 'MRI', 'PET', 'SPECT' and 'brain', we found 29 studies in our area of interest. We selected only those neuropsychological and functional brain imaging studies in which the patients had a controlled abstinence period longer than 98 hours. On the basis of six studies we concluded that there was insufficient evidence to prove conclusively that long-term cannabis use causes or does not cause residual abnormalities. The results of our review were also inconclusive whether cannabis use during adolescence may have a lasting effect on cognitive functioning and brain structure. However, we could not rule out the possibility that (1) certain cognitive and cerebral abnormalities existed in patients before cannabis use began and (2) that patients were suffering from subacute effects of cannabis. So far, research into the residual effects of cannabis use has been inadequate. Future studies should concentrate on the effect of cannabis use during early adolescence. More insight should come from longitudinal studies involving neuropsychological measurements and brain imaging before cannabis use begins. The abstinence period should be at least seven weeks.