Interesting article [Cannabis Neuroprotective?]

[Blowmonkey]

New article from Erowid:

Cannabis Neuroprotective?

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 this and read the summary article “Cannabinoids and brain injury: therapeutic implications” by Mechoulam et al. 2002.5


References
1. van der Stelt M, Veldhuis WB, Bar PR, Veldink GA, et al. “Neuroprotection by Delta9-tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity.” J Neurosci. 2001; 21(17):6475-6479.
2. Marsicano G, Goodenough S, Monory K, Hermann H, et al. “CB1 cannabinoid receptors and on-demand defense against excitotoxicity.” Science. Oct 3, 2003; 302(5642):84-88.
3. Knoller N, Levi L, Shoshan I, Reichenthal E, et al. “Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial.” Crit Care Med. Mar 2002; 30(3):548-554.
4. Shen M, Piser TM, Seybold VS, Thayer SA. “Cannabinoid receptor agonists inhibit glutamatergic synaptic transmission in rat hippocampal cultures.” J Neurosci. Jul 15, 1996; 16(14):4322-4334.
5. Mechoulam R, Panikashvili D, Shohami E. “Cannabinoids and brain injury: therapeutic implications.” Trends Mol Med. Feb 2002; 8(2):58-61.

 

[BilZ0r]

It is interesting the talk about HU-211 or dexanabinol. On of my lecturers just wrote an article on it for IDrugs. As you can read, it's not really an cannabinoid... pharmacologically speaking.

I always get upset whenever I read cannabinoid neuroprotection articles, and its protective solely by being an antioxidant (like against MDMA 'toxicity').

Meanwhile, lets not forget, that there is evidence that at high doses, in the rat, cannabinoids are neurotoxic.

 

[Curious Yellow]

I personally feel brain damaged after smoking. A little slow in the head. It lasts for weeks and weeks. Maybe the electrical impulses are slowed down as they are forced to pass through the protective coating of tar enveloping my neurons.

 

[Dr. McBudstoke]

their neuroprotective nature could have something to do with leaving lipid deposits on the neurons.

i read that somewhere, wish i could remember where...

 

[BilZ0r]

I strongly doubt that. I heard some guys from NORML once saying that, but they obviously had no idea what they were talking about. Cannabinoids are neuroprotective because they are anti-oxidative, because the decrease glutamate release (which reduces excitotoxicity) and the may also induce some intracellular protective pathways.