The Endocannabinoid System
Homeostasis is a property of living organisms that regulates the internal environment to maintain a stable, constant condition. The same term applies to the cells that make up living things. Each healthy cell in your body is attempting to maintain a homeostatic state, balancing itself, internally, against the environment, without. It is becoming clear that the human body's own THC-like molecules, (ananamide, 2-AG), their binding receptors, plus the enzymes involved in their synthesis and breakdown, together called the endocannabinoid system, are key in maintaining cell homeostasis. The body's biochemical balancing act...
First discovered in the early 1990's the endocannabinoid system may well turn out to be one of the biggest medical discoveries since DNA. It will certainly be bigger than the discovery of the opiate system (in mid 1970's), since the receptors for the endocannabinoids are so incredibly abundant and prolific throughout humans affecting so many of its systems including nervous, digestive, immune, reproductive, respiratory, and more. As a result of playing a role in modulating the cellular events of these systems, plus illnesses arising out of them, discovery will lead to the development of many new pharmaceutical drugs. Far more than the opiate system, that acts only within the central nervous system, with only pain relief as its major efficacy. Enough new drugs, perhaps, to give pharma its second wind...
Most of what is know of the endocannabinoids was learned from experiments on nervous tissue, the result, no doubt, because of the psychoactive properties of the cannabis plant and the discovery of tetrahydrocannabinol in 1965. This, in turn, led to numerous animal experiments elucidating the biochemistry of the receptor system, that demonstrated efficacies for pain, inflammation, mood and appetite, to name a few. Primarily in this tissue was found what is termed the CB1 receptor, coupled to an already somewhat well characterized G-protein. But this receptor is unlike others previously found in that it was upstream of usual receptor sites. Previously receptors (opiate, glutamate and cholinergic) were found on what's called the post-synaptic part of a nerve junction. The CB1 receptor, however, exists at the opposite side of this junction, termed the pre-synapse. “Up the sleeve a bit.” Here it sends what are termed retrograde signals to the nerve cell membrane, the usual overall effect being down-regulation of neuro-transmitter release from the cell.
Reading the list of chemical messengers that are down regulated, including dopamine, epinephrine and serotonin, forces the question of how one could do anything; walk, talk, indeed, think at all, after, for example a deep “bong hit.” But down regulation of neuro-transmission is a huge over simplification of the issue. Firstly, turning down epinephrine, will slow things, to be sure, but down regulating an inhibitory neurotransmitter, could turn things up. Point being, we're dealing with nervous systems, the human's being the most complex, highly organized on the planet. So that over-all down regulation of neuro-transmission may not appear as bad as it sounds.
Interestingly, a precursor to ananamide, phosphatidylethanolamine (PE), a well-characterized phospholipid and important nutrient found in many foods with particularly high concentrations in Soy, eggs and animal brains. Also important to note that this key phospholipid is rarely found as a supplement although its two siblings, phosphatidylcholine (PC) and phosphatidylserine (PS), are. A fourth important phospholipid, phosphatidylinositol (PI) is also difficult to find as a supplement. Why PE is so scarce is of concern, since normal dietary sources, particularly with modern Western diets, do not always provide sufficient amounts of this nutrient.
Being a major precursor to the body's own THC, PE is borrowed from the cell membrane in a time of need, to manufacture, via an enzyme called transacylase, N-acyl- phosphatidylethanolamine (NAPE), subsequently, a multitude of phospholipases cleave NAPE to ananamide. Note that a common use for supplementing with PE is for the treatment of ADHD. Now, lets put this together. Given a shortage of PE we experience symptoms of ADHD, supplementing the symptoms decrease. We can draw from this that since PE is both a membrane lipid plus the precursor to a major neurotransmitter, ananamide, that supplementing reduces ADHD, that ananamide plays a role in ADHD. Furthermore, it is becoming apparent, through work at the Green Cross and with other researchers studying the effects of cannabis on this illness is that cannabis helps improve concentration, mental alertness and focus. Tying it up, supplementing the endocannabinoid system either with PE to make up the body's own THC or by administering THC itself to top up what's missing, will help people with ADHD.
One example of the knowledge that has been gained since the endocannabinoid system was discovered and how it is being applied. And this is only one type of receptor associated with this system.
There is a second set of known cannabinoid receptors called CB2. These receptors tend to be found outside the central nervous system, often on immune cells. One, critically important aspect of CB2 receptor binding is the release of cytokines from immune cells. These are small proteins that serve a variety of immune functions, including anti-inflammatory, anti-tumor and, importantly, they play a role in chronic pain.
Endocannabinoids are cell regulators. Balancing, protecting and keeping in order, with an over-all effect of down-regulation of neuro-transmission, quieting, slowing and moving away from inflammation. As a result of the enormous ubiquity of the receptors: (Cannabinoid receptors are the most abundant binding sites in the human brain.) The discovery of this system will open new doors to understanding our biochemistry and may well prove to be the most important medical discovery of the last century.
A. Paul Hornby, Ph.D.
September 7, 2008 |
