Neuroprotective Antioxidants from Marijuana^a

Abstract

A BSTRACT : 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 ⌬ 9tetrahydrocannabinol (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 ␣ -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.

Cannabinoids and Epilepsy

“…CBD reduces oxidative toxicity in an in vitro glutamate excitotoxicity assay [123], and raises adenosine to oppose lipopolysaccharideinduced inflammation and tumor necrosis factor-α release [118,124]. In mice with middle cerebral artery occlusion, CBD triggered a CB 1 R-independent decrease in reperfusion injury, inflammation, and death.…”

Incidental use of ecstasy: no evidence for harmful effects on cognitive brain function in a prospective fMRI study

“…More specifically, it has been suggested that cannabis attenuates the neurotoxic effects of ecstasy, as cannabis and ecstasy may have opposite effects on oxidative stress . Ecstasy is thought to cause increased oxidative stress, thereby enhancing the risk for serotonergic neurotoxicity (Green et al 2003), whereas cannabis may act as an antioxidant (Hampson et al 2000), and therefore, possibly has neuroprotective effects (Sinor et al 2000).…”

Cannabinoid as a neuroprotective strategy in perinatal hypoxic-ischemic injury

“…Although the exact mechanisms of the neuroprotective effect of cannabinoids are not completely understood, cannabinoids have been suggested to be involved in numerous processes, such as the modulation of calcium homeostasis and excitability [111,112] , regulation of immune and inflammatory responses [113,114] , activation of cytoprotective signalling pathways [112] , as well as modulations of synaptic plasticity, excitatory glutamatergic transmissions [111] and their hypothermic and antioxidant properties [115] . In this regard, the endocannabinoid system may also represent a pivotal neuroprotective mechanism both in chronic neurodegenerative disorders and in acute forms of neuronal injury.…”