August 29, 2010 (Amsterdam, The Netherlands) — Although the use of cannabis is believed to heighten the risk for schizophrenia and psychotic episodes, a meta-analysis of existing data and a new study suggest these associations may be even more complex than previously thought.
At the 23rd European College of Neuropsychopharmacology Congress, Murat Yücel, PhD, and colleagues from the University of Melbourne in Australia reported that patients with schizophrenia having a history of cannabis use had superior neuropsychological functioning compared with nonusers. The conclusion was drawn from their meta-analysis of 10 studies involving 572 patients with schizophrenia, but the investigators emphasized this does not imply neuroprotection.
Furthermore, from their own study of 85 individuals with first-episode psychosis (FEP), they found that regular users of cannabis performed better on tests of visual memory, working memory, and executive functioning. In addition, patients who began using cannabis by the age of 16 years (ie, early users) had less neuropsychological impairment than patients who began using cannabis later.
"Patients with schizophrenia generally use more cannabis than the general population, and there must be a reason. As researchers, we are interested in what that association is about," Dr. Yücel told Medscape Medical News. "Our key finding is that the relationship between cannabis and psychosis is complex. In healthy persons, heavy or long-term use of cannabis has negative effects on cognition and memory, but in psychosis the relationship is apparently not as clear."
The findings of both the meta-analysis and experimental data together indicate that the use of cannabis in established schizophrenia and also in FEP is associated with better cognitive performance than the lack of using cannabis, although this does not indicate that it is neuroprotective, he said. The investigators believe that the subgroup of cannabis users may be characterized by better underlying cognition function and perhaps only developed schizophrenia after exposure to cannabis.
Global Cognition Index Better With Cannabis Use
In the meta-analysis, neuropsychological variables were grouped according to the 6 cognitive domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia battery. A global cognition index was calculated by averaging effect sizes from each domain for each study.
Patients with a history of cannabis use were found to have superior neuropsychological functioning. The finding was largely driven by studies that included patients with a lifetime history of cannabis use rather than current or recent use. In 1 study, greater frequency of cannabis use was associated with better cognitive performance. Overall, earlier starting age of cannabis use (16 years or younger) was associated with superior cognitive performance compared with later use, Dr. Yucel reported.
"We found that patients with a history of cannabis use had superior neuropsychological functioning, with an average effect size of 0.50 across all the cognitive domains investigated," he said.
The mean weighted effect size associated with lifetime cannabis use was 0.55 (P = .001) for global cognition, 0.65 (P = .001) for processing speed, and 0.64 (P = .003) for working memory.
New Data in FEP
In the second study, 85 FEP patients were compared with 43 healthy non–cannabis-using controls with FEP. Regular use was defined as at least 2 years of use and use of at least 2 g per week. None of the FEP cannabis users had ever used cannabis regularly (ie, weekly for at least 12 months). Healthy controls had no current or past history of illicit substance abuse or dependence.
Relative to controls, FEP cannabis users displayed only selective neuropsychological impairments, whereas FEP nonusers displayed generalized deficits. When the 2 clinical groups were directly compared, the cannabis users performed better on tests of visual memory, working memory, and executive functioning. Patients with early-onset cannabis use had less neuropsychological impairment than patients with later onset of use. The early cannabis users were younger than the later-onset users but did not differ in duration or monthly quantity of cannabis use, diagnosis, treatment, or antipsychotic levels, he added.
The investigators speculated that age of onset of cannabis use as a moderator of the association between cannabis and psychotic illness may be related to the effects of cannabis on the developing brain. "We contend that the association between better cognitive performance and cannabis use is driven by a subgroup of ‘neurocognitively less impaired' patients who only develop psychosis after early initiation into cannabis use. As such, early cannabis use may be an independent risk factor for the development of psychosis," he said.
"In other words, cannabis is potentially tipping some persons over the edge, maybe in combination with a genetic predisposition. We wonder if, in the absence of cannabis, they may not have developed the illness," he added.
The investigators are following up the patients and will soon have 10-year data on approximately 80% of the cohort.
"It will be important to see the long-term data," commented Richard Tranter, MBChB, consultant psychiatrist at the North West Wales NHS Trust, Bangor, United Kingdom, who said he was intrigued by these findings. "A large body of data is suggesting that cannabis can be an important predisposing factor for schizophrenia. The current study suggests, however, there may be a group that is different—who, if they are exposed to cannabis, may sustain damage perhaps because of some elementary factors in the brain, but if you get them off cannabis they may be fine. The other possibility is that cannabis is actually having a positive effect. We will have to wait for the 10-year data to determine this."
The study author and Dr. Tranter have disclosed no relevant financial relationships.
23rd European College of Neuropsychopharmacology (ECNP) Congress: Abstract P.3.a.005. Presented August 29, 2010.
http://www.medscape.com/viewarticle/727681?src=mp&spon=25&uac=97984HK
regards, taniafdi ^_^
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