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Update November, 2005

One might think that the active ingredients in marijuana would be more extensively studied in a variety of diseases. Cannabinoids (active ingredient) seems to have therapeutic effects in amyotrophic lateral sclerosis (an adult-onset motor neuron disorder), but the researchers always seem obliged to say things like "However, Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the predominant cannabinoid in marijuana, induces mind-altering effects and is partially addictive, compromising its clinical usefulness." (P. Weydt et at Cannabinol delays symptom onset in SOD1 (G93A) transgenic mice without affecting survival. Amyotroph Lateral Scler Other Motor Neuron Disord 2005, 6 (3):182-4.)

A recent article in the Journal of Clinical Investigation (November, 2005) is an extremely important contribution to the study of long-term cannabinoid effects. It is entitled "Cannabinoids promote embryonic and adult hippocampus neurogenesis and produce anxiolytic- and antidepression-like effects" by Chinese and Canadian researchers (Wen Jiang et al). Starting with the important fact that (JE Malberg, 2004) that the hippocampus can create new neurons even in adults, the literature is exploding with information about what promotes neurogenesis and what happens because of it. This is a complicated field because some forms of cannabinoids inhibit the neurogenesis in the hippocampus. What these researchers found was that not only can a synthetic cannabinoid (HU210) promote neurogenesis but it can do so in a manner consistent with brain changes related to (we're talking rats) the reduction of anxiety and depression (the importance of neurogenesis in the hippocampus was studied earlier in relation to depression). This is counter to the known supression effects upon such neurogenesis of "all other drugs of abuse" (alcohol, opiates, nicotine and cocaine). This research is preliminary and there are indications that even in animal studies researchers might want to retain a sense of humor (maybe they should consult with stoners before designing their studies, since the measure of anxiety has to do with speed of going to a food pellet and eating it in an unfamiliar cage when food-deprived for 48 hours, after mass cannabinoid use in the treatment group).

Update: February, 2005

There is some preliminary animal research at the Complutense University and the Cajal Institute in Madrid reporting that ingredients in marijuana might stall decline from Alzheimer's disease. These people are strong researchers: Maria de Ceballos, Journal of Neuroscience.

Earlier Cannabinoid Research: Neuroprotective Effect

Esther Shohami and colleagues at Hebrew University's Medical Faculty in Jerusalem report that an endogenous cannabinoid plays a role in the complex protective response prompted by a brain injury. The compound, 2-Arachidonoyl glycerol (2-AG) reportedly occurs in the brain and the intestine. It can "protect cerebral rat neurons from ischemia in vitro" (Sinor AD et al.), and "synthetic cannabinoids have been shown to reduce neuronal death in the hippocampus of rats after experimentally induced ischemia" (Nagayama T et al.). In this study, the researchers subjected mice to head trauma and analyzed the 2-AG response following this injury. 2-AG levels rose, peaking at tenfold after 4 hours. When the researchers injected additional 2-AG, the mice "developed 50 percent less edema and recovered faster". More directly relevant to Alzheimer's research, "the treated mice also suffered less neuronal cell death".

The researchers counted neurons in the CA3 area of the hippocampus, and report that "control mice (head trauma without exogenous 2-AG) had lost about 40 percent of neurons in that brain area seven days after the trauma, whereas treated mice lost about 10 percent". (The hippocampus is among the brain areas most affected by neuronal death in AD.) The authors write that these results are the first to record the neuroprotective effects of this cannabinoid. In previous work, the authors had shown that 2-AG suppresses the formation of reactive oxygen species and the inflammatory cytokine tumor necrosis factor-alpha, both of which contribute to the pathophysiology of brain injury. Oxidative damage and inflammation seem to cause the loss of cells in AD.

October 4, 2001. Nature.

   
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