Cannabis And The Receptor Conundrum

" Jojo left his home in Tucson, Arizona
For some California Grass.
Get back, get back.
Get back to where you once belonged"

The above lines taken from the Beatles song 'get back' simply illustrates that Jojo had gone to procure some grass. Though it is not clear what exactly the songwriter had meant by grass, probably he meant marijuana and not the proverbially greener grass on the other side. Also known as pot, weed, Mary Jane, cannabis, shit, hemp and a variety of other fanciful names, marijuana is obtained from the plant Cannabis sativa (also Cannabis indica). The active chemical ingredient, delta-9 tetra hydro cannabinol (THC), is lipid soluble; hence crosses the blood brain barrier well. When ingested or smoked, it enters the brain via blood and combines with CB1 (cannabinoid) receptors 'already' present in the brain.

Think about morphine, a CNS depressant drug obtained from Papaver somniferum, the poppy plant. When morphine is smoked or injected, it enters the circulation and stimulate opioid receptors, 'already present' in the brain; mu, kappa and delta. Stimulation of mu receptor in particular, is associated with euphoria and drug dependence. Morphine and its synthetic or semisynthetic analogs like heroin are opioids: chemical compounds that act on the opioid receptors. They are opiates too, since they are obtained from opium. All these opioid narcotics act by combining with the preformed (already present) receptors.

There are other examples like those too. The question is why should our bodies have these receptors in the first place? It is to be borne in mind that these receptors respond not only to exogenous ligands (ligands= molecules that the receptor binds with); they combine with endogenous ligands too. In the former example of cannabis, the endogenous ligand is anandamide; a chemical that the brain produces. It gives us pleasure ('ananda' means 'bliss' in Sanskrit) and make us forget our perceived sufferings. We forget our pain as well as our painful experiences. In fact, dronabinol (MARINOL), a synthetic cannabinoid, has been used to suppress the intense vomiting of cancer patients undergoing chemotherapy, the cachexia and anorexia of AIDS, and in reduction of intra-ocular pressure in glaucoma.

Levonantradol, another analog may be used in pain relief. Endocannabinoids has also been implicated in obesity, diabetes, drug dependence (soon one may be cured of his nicotine/tobacco habits by manipulating/blocking these receptors). Rimonabant, a novel anti-obesity (anorectic) drug which works by blocking CB1 receptors, is used in the treatment of metabolic syndrome.

If you take the second example of morphine, you will see that there are endogenous ligands for morphine too. Enkephalin, endorphin, and dynorphins are endogenous (=produced by the body) opioid peptides, most of which are derived from POMC (prepro opio melanocortin). They have potent analgesic properties, and are secreted in response to stress, pain, exercise and other stimuli.

Thus, it can be seen that our body has its own intrinsic balancing mechanisms, in a sense that when we feel pain--> the body automatically secretes endorphins to make-up for it. Hence, the 'evolutionary logic' of these narcotic receptors may be accounted for: arising out of necessity. It is a mere coincidence that these exogenous substances show affinity and efficacy at the receptor site. Or, is it due to the 'selection pressure' on the human genome which responds (or reacts) against the presence of these environmental substances in nature, as what happens in an immune exposure?

More research is needed to come to a conclusion.

Last modified: July 11, 2009

Doping: To Dope or Not to Dope?

The answer to this vexing question will vary on whom you ask the question. From the point of view of athletics and sport, the answer is a clear and resounding no. This is because, the WADA (world anti doping agency) will bar anyone from participating in a sports event, who dopes. Doping here means taking of drugs which enhance performance or drugs which are narcotics.

Drugs belonging to this category include androgens and anabolic steroids (DHEA, nandrolone, stanozolol etc.); hormones (EPO or erythropoietin: which produces blood in the body thus increasing better oxygen delivery to the tissues, somatotropin or growth hormone etc.); beta 2 adrenoceptor stimulant like salbutamol-which broaden the airway; diuretics (drugs that increase urine formation, thereby reducing weight-->may matter a lot, where weight of the person is an important criterion for a particular category); narcotics (heroin, oxycodone, morphine etc.); stimulants (amphetamine, ephedrine etc.). This list also includes blood doping, where athletes take out some of their own blood from their bodies, stores them and adds to their bodies later. This means that since our bodies have the ability to replenish the lost blood, it will produce that amount of blood within our own body, thus our athlete in question will have his own stored blood as a bonus. Recently, the WADA added cannabinoids (marijuana, cannabis, hashish) to the list, while taking pseudoephedrine (a drug used as decongestant and in cough), and caffeine (a common beverage found in tea, coffee etc.) off the list.

Alternatively, if your question was directed to an electronics professional, he would instantly have answered 'yes' to your question. For, doping here means a process, by which p type or n type semiconductors are produced from tetravalent molecules like silicon or germanium. Silicon, for example, is a tetravalent molecule, that is, it has 4 electrons in its outer shell. Like us humans, molecules too prefer a stable position. For this, they tend to form an 'octet' with neighboring molecules, since inert elements, which are very stable, have 8 electrons in their outer shell. What we get as a result is a silicon lattice, due to this octet formation. This being stable, is an insulator and it thus can not conduct electricity. Now if we dope (=add some impurity) them with a pentavalent molecule (e.g. arsenic, has 5 valence electrons), then even after forming an octet, an electron will be surplus. Now it has nowhere to go, no free electron to bind with, it will roam free in the lattice, allowing a current to flow through the doped material. The lattice is not unduly disturbed as the sizes of the molecules nearly match well. We have succeeded in creating an n type semiconductor, n type because there is a surplus electron and electrons are negatively charged. Similarly, we could produce a p type material by adding a trivalent impurity like boron. These semiconductors are of immense importance in electronics and telecommunications, medical physics, biophysics, computers and countless others.

Thus both a yes and no can be the answer of a single question like this.