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Cannabinoids Neuroprotective?
by Earth Erowid
Nov 2003
Citation:   Erowid E. "Cannabinoids Neuroprotective?" Erowid Extracts. Nov 2003;5:7.
Research has begun to accumulate over the past few years showing that cannabinoids are neuroprotective against brain injury resulting from toxins, hypoxia, and head trauma. Cannabinoids are, loosely, chemicals that are similar in structure to the psychoactive components in cannabis and/or chemicals that activate the cannabinoid receptor system in the body. Researchers have found protective effects not only from the plant-derived cannabinoids such as THC, but also from endogenous cannabinoids (those occurring naturally in the body, such as anandamide) and some synthetic pharmaceutical cannabinoids.

The research with the cannabis-source cannabinoids, conducted in mice, rats, and in vitro, has shown remarkable effectiveness in reducing brain damage from injected toxins, hypoxia, and head trauma.1 Other research has found that anandamide levels in the brains of rats naturally rise after brain injury or death and the cannabinoid system may play a primary role in limiting brain damage.2

Because psychoactivity is considered an unwanted side effect, much of the current research is being done with synthetic cannabinoid system agonists. One synthetic cannabinoid, Dexanabinol (HU-211), is already in phase 3 trials (medium scale, involving humans) headed towards governmental approval as a neuroprotective pharmaceutical. Research conducted in Israel that gave 67 patients with serious head trauma either Dexanabinol or placebo confirms similar research in rats showing reduced damage and faster recovery among those receiving the cannabinoids.3 Although other promising head trauma treatments have failed in the demanding and complex phase 3 research trials, many interested in the field of neuroinjury are excited about the findings to date.

The mechanisms by which the cannabinoids reduce damage from both toxic and traumatic injury to the brain are not yet fully understood. Although some researchers have suggested that the cannabinoids may offer protection through a strong antioxidant effect, this is now considered unlikely to account for much of the protection, since cannabinoid-receptor antagonists block the beneficial effects and the doses of the cannabinoids given are very low.

Perhaps the current best guess for how these chemicals provide their protective effects is that their general dampening of neural activity reduces excitotoxicity (damage caused by overly excited neurons). One of the specific ways this happens is through the inhibition of the glutamate system in the brain. The glutamatergic neurons are part of the excitatory system in the brain; inhibiting glutamate reduces the activity of other neurons. At least in some parts of the brain, activation of the CB1 cannabinoid receptor (a specific type of cannabinoid receptor) has been shown to block pre-synaptic release of glutamate. CB1 receptor activation is also known to inhibit certain calcium channels, directly reducing the production of nitric oxide and other potentially damaging reactive oxygen species.1,4

For more information and a more complete list of references, see erowid.org/extracts/n5/cannabinoids.shtml and read the summary article "Cannabinoids and brain injury: therapeutic implications" by Mechoulam et al. 2002.5