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