Purpose: The increasing use of synthetic cannabinoids ("designer drugs" like "Mr. NiceGuy" and "Mabsuton") is a cause for major public health concerns. THC, the active substance in cannabis, is a partial agonist to cannabinoid subtype 1 receptor (CB1R), whereas synthetic cannabinoids are full agonists. Synthetic cannabinoids are considered highly addictive and cause severe adverse effects. The purpose of our study was to assess whether chronic use of synthetic cannabinoids alters brain volume and whether chronic use of synthetic cannabinoids alters neuronal activity of working memory and executive functions.
Material & Methods: Thirty volunteers participated in the study: 15 synthetic cannabinoids chronic users were recruited from rehabilitation centers, and 15 healthy controls with no history of drug abuse were recruited from the community. All participants undertook a high resolution T1 MRI scan to assess brain volume and performed a functional MRI task of working-memory, the N-back task.
Results: Synthetic cannabinoids users showed significant diminished total gray matter volume compared to controls, as well as reduced gray matter volume in several cortical regions: right orbitofrontal cortex, right superior frontal gyrus, left fusiform gyrus, bilateral insula, right superior temporal gyrus, and right precuneus. Moreover, synthetic cannabinoids users showed diminished brain activations in the precuneus and bilateral parahippocampal gyri compared to controls while performing the working-memory N-back task. Synthetic cannabinoids users had also significantly longer reaction times and lower accuracy rates compared to controls.
Conclusion: To the best of our knowledge this is the first study showing overall reduced gray matter volume in addition to specific gray matter volume decrease in several brain regions associated with addiction and drug induced psychosis. Furthermore, impairment in the neural brain mechanisms responsible for executive functions was found in synthetic cannabinoids users. Our results of diminished activation during the N-back task in users compared to controls, implicates vulnerability of the working-memory network to the deleterious effects of synthetic cannabinoids. This may have major implications for our understanding of the long-term consequences of synthetic cannabinoids.
