Early-onset of chronic cannabis useeffects on cognitive function and brain activity

Resumo

Introduction Cannabis is the most widely available illicit drug. However, investigations examining the presence, nature, and duration of long-term non-acute effects of cannabis on neuropsychological performance and brain activity present equivocal findings. One explanation for these discrepant findings may be the existence of methodological differences between studies. Another may be that cannabis is more toxic for some populations than others, and also might be mediated by individual genetic differences. Objectives To study the effects of early onset chronic cannabis use on cognition and brain activity, and to explore the interaction between these variables and genetic variance on a functional polymorphism within the dopamine system (COMT val158met). Methods Two studies were designed: (1) A systematic review of the neuroimaging studies on cannabis use in the literature until January 2009. The search was conducted using Medline, EMBASE, LILACS, and PsyLit indexing services. (2) An experimental case control, before and after 28 days of abstinence, fMRI study, in a sample of 31 early onset chronic cannabis users (before age 16) and 31 healthy controls during an inhibitory cognitive task (MSIT). A comprehensive neuropsychological assessment was also conducted. All subjects provided a blood sample for genotyping. The Ethical Research Committee of the Institution approved the study. Results (1) Sixty-six studies were identified, of which 41 met the inclusion criteria; 33 functional (SPECT/PET/fMRI) and 8 structural (volumetric/DTI) imaging studies. The high degree of heterogeneity across studies precluded a meta-analysis. Functional studies suggested that resting global and prefrontal blood flow were lower in cannabis users than in controls. Results from activation studies employing cognitive task have been inconsistent, due to the heterogeneity of the methods used. Studies of acute administration of THC or marijuana report increased resting activity and activation of frontal and anterior cingulate cortex during cognitive tasks. Only three of the structural imaging studies found differences between users and controls. (2) In the fMRI study both groups performed all conditions of the MSIT task within normal limits, indicating that the level of cognitive complexity was not different between them. However, the results supported significant differences in neural activation during performance of a MSIT task as a function of COMT genotype. At 7 days of abstinence cannabis users showed deficits on verbal memory and a pattern of performance improvement on measures of visual memory, semantic verbal fluency, psychomotor speed and inhibition response. After 28 days of abstinence cannabis users showed virtually no significant differences from control subjects on the neuropsychological battery. Conclusions Functional neuroimaging studies suggested a modulation of global and prefrontal metabolisms both during resting state and after the administration of THC/marijuana cigarettes. Minimal evidence of major cannabis effects on brain structure has been reported. Early onset chronic cannabis use has not been associated with impairments on the brain inhibitory network, although a modulation of COMT val158met genotype on the neural activation and behavioural performance during inhibition response was found. In our sample, the episodic memory deficits of early onset chronic cannabis use group were reversible after 28 days of cannabis abstinence.