Tuesday, April 2, 2013

Endocannabinoids - The Science

Today I'd like to do something Republicans do when confronted with a question. Look at the science. The science I'd like to look at is the science of endocannabinoids. Let's start with a definition. An endocannabinoid is a marijuana-like substance produced by the body that acts on specific receptors in the body. There are two known cannabinoid receptor systems in the body. They are the CB1 system and the CB2 system.

Since this is for a non-biochemistry trained audience (I'm an electrical engineer by trade) I'm going to make some simplifications. Those of you who are better trained please excuse my lapses unless they are egregious.

The CB1 system is mostly distributed in nerve tissue of the brain and the spine. The CB2 system is found in the immune system, the peripheral nervous system, the brain, and the digestive system. Various endocannabinoids in the body can either activate or inhibit the operation of the various systems by binding to the receptors in the system. Regulation is achieved by a balance of the chemicals involved. The systems can also evolve by increasing or decreasing the number of receptor sites in response to stimulation (bonding) or a lack of stimulation to those sites.

One of the neurotransmitters in the body that affects these systems is called anandamide which comes from a Sanskrit word which means bliss. The CB1 and CB2 receptors in the body were discovered by tracking where delta9-THC (one of the active ingredients in marijuana) traveled in the body and which receptors it was bound to. From the facts developed by that kind of study a team led by Dr. Raphael Mechoulam at the Hebrew University in Israel discovered the anandamide molecule. As discoverers they got to name it. Dr. Mechoulam is one of the pioneers in the field of cannabinoid science. Why he hasn't won a Nobel for his work is beyond me, unless it has something to do with the prejudices against cannabis. Let me quote (slightly edited for ease of text rendering) from his wiki:
Raphael Mechoulam (born 1930) is an Israeli professor of Medicinal Chemistry and Natural Products at the Hebrew University of Jerusalem in Israel. Mechoulam is best known for his work (together with Y. Gaoni) in the isolation, structure elucidation and total synthesis of delta9-tetrahydrocannabinol, the main active principle of cannabis and for the isolation and the identification of the endogenous cannabinoids anandamide from the brain and 2-arachidonoyl glycerol (2-AG) from peripheral organs together with his students, postdocs and collaborators.
All the above is probably enough general information to get you started if you want to delve deeper into the subject matter. Now I want to look at a more controversial aspect of all this. Marijuana. And specifically medical marijuana. As you can see from the above information, cannabinoids in the body affect a large number of systems in the body. I particularly like this quote from the CB2 wiki on the subject.
Changes in endocannabinoid levels and/or CB2 receptor expressions have been reported in almost all diseases affecting humans,[34] ranging from cardiovascular, gastrointestinal, liver, kidney, neurodegenerative, psychiatric, bone, skin, autoimmune, lung disorders to pain and cancer. The prevalence of this trend suggests that modulating CB2 receptor activity by either selective CB2 receptor agonists or inverse agonists/antagonists depending on the disease and its progression holds unique therapeutic potential for these pathologies [34]
That explains why some people claim wonder drug status for marijuana. Except things are not quite as simple as that. Marijuana is not marijuana. What do I mean by that? The anandamide analogs in cannabis are called generically CBDs. They include such chemicals as Cannabigerols (CBG), Cannabidiols (CBD), Tetrahydrocannabinols (THC), Cannabinol (CBN), and a number of other compounds. Their expression in a given cannabis plant varies. Some of the cannabinoids bind to various CB system receptors and some of them prevent binding to a receptor, mimicking the function of the various endocannabinoids in the body. So marijuana is not marijuana. Since there is no regulation in the marijuana industry due to its illegality at the Federal level this has led to various novel names for the different cannabis strains. Names such as "Northern Lights" and "Charlotte's Web". "Charlotte's Web" was named for a child with severe pediatric epilepsy. The strain called "Charlotte's Web" was developed especially to treat her condition. Thus the name. You can check out this eleven minute video introduced by a doctor and her mother to learn more about how this strain was developed and used.

Well obviously we need regulation of medical marijuana. Don't we? My answer is yes. Absolutely. But surprisingly what we are getting is self regulation. And it seems to be working fairly well. Various companies are springing up to fill the analysis void. They do High Pressure Liquid Chromatography and Mass Spectroscopy on submitted marijuana samples to determine the quantities of the various CBDs in the samples. One such company is SC Laboratories in California, but there are a number of others around the country in medical marijuana states.

Obviously the subject is involved and I could go on at much greater length. But I'm not going to do that. Instead I'll leave you with what I think are a few more helpful links.

FDA To Study Cannabis For PTSD - includes a video.
What If Cannabis Cured Cancer - with an appearance by Raphael Mechoulam in the video.
CB(2) cannabinoid receptor activation is cardioprotective in a mouse model of ischemia/reperfusion. Translation: if you are predisposed to heart disease regular cannabis use may improve your odds of living.
Marijuana Stops Lung Cancer
DEA Judge Rules On Medical Marijuana. The Judge says, "Marijuana, in its natural form, is one of the safest therapeutically active substances known to man."
Conditions treatable by cannabis with links to the medical literature.

And finally to wind this all up what is my political stance on the matter?

Medical Marijuana prohibition is a crime against humanity and a violation of the religious precept - heal the sick.

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