Cannabinoids: Next Generation Antidepressants?

Two reviews (one & two) published this month (July 2009) highlight the emerging role of the endocannabinoid system (ECS) as one of the most important mediators of our stress response, and further research into ECS could bring us new antidepressants and anxiolytic drugs—a few drugs are already a success in animal models! There are two approaches to exploiting the ECS against depression and anxiety. One is developing a cannabis based medicine (pill, spray, etc) that targets the Cannabinoid Type 1 Receptor (CB1R). The other approach utilizes our bodies own enzymes (I.e., FAAH) that degrade the THC-like compounds, synthesized from arachadonic acid, namely Anandamide (AEA) and 2-Arachidonyl glycerol (2-AG). This treatment requires compounds that inhibit the breakdown of AEA and 2-AG, thus raising the levels of AEA and 2-AG for the duration of the drug treatment. Normally, AEA and 2-AG are rapidly made, used, and degraded by our body.

Furthermore, AEA may be the only known neurotransmitter that is synthesized on demand and it signals retroactivley or “backwards”—again it’s the first and only. Yet, if you check any recent biochemical pathway charts in medical textbooks, AEA is usually missing from the chart– nearly 20 years after it’s discovery! And AEA has NEVER been used in a clinical trial even though acetominophen, once metabolized inhibits AEA degradation! Since, one of the most widely used OTC drugs in the world works partially through the ECS, why are there no clinical trials with non-toxic AEA?

Most likely the biggest break through in depression and cannabinoid research occurred at the University of Saskatchewan in Canada, when researchers gave a drug, code named “HU-210″ to rats. HU-210 is 100 to 1000x more potent than THC, depending on the experimental assay. After a few weeks of treatment, analysis of the rat brains revealed that HU-210 caused neurogenesis. Meaning the rats grew new brain cells from stem cells, and those brain cells matured into neurons. This occurred specifically in the hippocampus. The Authors speculated that this compound could be a cure for depression and this could also be considered a stem cell based therapy.

As the patents on billion-drugs (like questionably effective drugs such as SSRI’s) are near expiration, cannabinoids stand as a clear beacon of therapeutic promise. Other governments (UK, Israel, the Netherlands, Spain, Germany…) have realized this, eased cannabis research restrictions, and allowed legitimate companies to emerge, which focus solely on developing and distributing cannabinoid medicines. If our governemnt waits too much longer and restrictions on cannabis research are not eased, U.S. researchers will miss out on this centuries medical breakthroughs. And that would truly be depressing…

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THC Inhibits Atherosclerosis in Mice