title: Neuroprotective antioxidants from marijuana.
abstract: Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.
authors.affiliation: Laboratory of Cellular and Molecular Regulation, NIMH, Bethesda, Maryland 20892, USA. aidan@codon.nih.gov
authors.forename: A J
authors.initials: AJ
authors.lastname: Hampson
authors.forename: M
authors.initials: M
authors.lastname: Grimaldi
authors.forename: M
authors.initials: M
authors.lastname: Lolic
authors.forename: D
authors.initials: D
authors.lastname: Wink
authors.forename: R
authors.initials: R
authors.lastname: Rosenthal
authors.forename: J
authors.initials: J
authors.lastname: Axelrod
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002186:Cannabinoids / Q000494:pharmacology*; D002188:Cannabis / Q000737:chemistry*; D002540:Cerebral Cortex / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats
chemical_list: D000975:Antioxidants; D002186:Cannabinoids; D018696:Neuroprotective Agents