The Neurotoxic Effects of Cannabis on Brain: Review of Clinical and Experimental Data

Abstract

Cannabis is the most widely used illicit drug worldwide. Evidence indicated negative impact for cannabis on the brain. Animal research and in vitro studies using delta-9-THC (THC) or cannabis extracts with high THC content provided evidence for a detrimental effect on neuronal integrity with DNA damage, cell shrinkage, atrophy and apoptosis. The mechanisms by which herbal cannabis affects brain structure and function are not clear but impaired mitochondrial functioning, reduced glucose availability and inhibition of brain energetic metabolism by cannabis have been shown. Clinical studies investigating the effects of cannabis in humans found raised serum levels of proinflammatory cytokines in chronic cannabis users. Human studies also indicated increased oxidative stress biomarkers and reduced antioxidants in blood of chronic cannabis users. Preclinical data on the effect of cannabis or THC on oxidative stress, however, were less conclusive in that cannabis might increase or attenuate oxidative stress and neurotoxicity. The aim of this review is to summarize the evidence from animal and clinical studies pertaining to the toxic effects of cannabis and its main psychoactive ingredient THC on the brain and possible mechanisms involved.