Brain dysfunction in chronic users of legal marijuana with known cannabinoid concentration

Objectives: To study brain effects of legal marijuana sold in authorized pharmacies of the Uruguayan regulated market, with a previously known concentration of cannabinoids.

Methods: We prospectively evaluated 17 young regular users (19-35 years, 26.6 ± 4.3 [mean ± SD], 11 men) of legal marijuana dispensed in authorized pharmacies (THC 5%, CBD 10-11%) using 99mTc-ECD SPECT. Subjects had no previous psychiatric or neurological pathology, with a history of consumption of 6-24 months (16 ± 5.7), weekly dose of 2-25 g (9.8 ± 6.3) and 24-96 hours since the last consumption (37.4 ± 19.9). The variety of pharmacies represented 60-100% of the total cannabis consumed (80 ± 14.6%), although all subjects had previous consumption of other varieties with an average of 8 years (1-17 years), with no history of other drug use (except tobacco, and alcohol without abuse criteria). The control group comprised 25 subjects with similar age (19-36 years, 26.7 ± 5.4) and sex (19 men). Images were analyzed in SPM8. Uncorrected p values <0.001 at the voxel level and clusters >100 voxels were reported.

Results: Users showed 6 clusters of significant hypoperfusion (4 of which survived correction for multiple comparisons) located in the left frontal polar cortex, bilateral orbitofrontal cortex with right predominance, bilateral ventromedial frontal cortex, right temporal, left anterior temporal and brain stem. No areas of significant hyperactivity were found.

Conclusions: The complete regulation of the cannabis market in the Uruguayan model provides a unique opportunity to relate the effects of the drug with a defined variety with known concentration of the main cannabinoids. Regular use of legal cannabis dispensed in authorized pharmacies produces bilateral prefrontal and temporal hypoperfusion involving paralimbic areas of the reward system, implicated in drug dependence. These regions are involved in cognition, social behavior and emotional regulation. Findings may contribute to develop more efficient policies to reduce risks and mitigate damage of marijuana use. Research support: Comisión Sectorial de Investigación Científica (CSIC).