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