Discriminative Properties of Hippocampal Hypoperfusion in Marijuana Users Compared to Healthy Controls: Implications for Marijuana Administration in Alzheimer’s Dementia.

ABSTRACT:

Background: Few studies have evaluated the impact of marijuana use on regional cerebral blood flow.

Objective: To determine whether perfusion in specific brain regions on functional neuroimaging, including those affected by Alzheimer’s disease pathology, are abnormal in marijuana users compared to controls.

Method: A group of 982 patients with a diagnosis of cannabis use disorder by DSM-IV and DSM-V criteria from a large multisite database were compared to a healthy control population (n=92) with perfusion neuroimaging with single photon emission computed tomography (SPECT) at rest and at a concentration task. Perfusion estimates of each scan were quantified using a standard atlas. Cerebral perfusion differences were calculated using a one-way ANOVA. Diagnostic separation was determined with discriminant analysis in the total sample. Feature selection was done with a minimum redundancy maximum relevancy (mRMR) algorithm to identify the most predictive regions in a subset of marijuana users (n = 436) with reduced psychiatric co-morbidities compared to the main group. 

Results: Marijuana users showed lower cerebral perfusion on average (p < .05). The discriminant analysis subsequently distinguished marijuana users from controls with correct classification of 96% and leave one out cross-validation of 92%. With concentration SPECT regions in the discriminant analysis, the results were similar with a correct classification of 95% with a leave-one-out cross validation of 90%. The AUC analysis for concentration SPECT regions from the discriminant analysis was also similar to the baseline regions with 95% accuracy, 90% sensitivity and 83% specificity. The mRMR analysis on the reduced co-morbidity subset showed right hippocampal hypoperfusion on concentration SPECT imaging was the most predictive region in separating marijuana subjects from controls. 

Conclusion: Multiple brain regions show low perfusion on SPECT in marijuana users. The most predictive region distinguishing marijuana users from healthy controls, the hippocampus, is a key target of Alzheimer’s disease pathology. This study raises the possibility of deleterious brain effects of marijuana use.