I've been thinking about starting this topic for a while, my primary research focus is drug mode-of-action and drug target identification, and I smoke cannabis so it's natural for me think about how the various physiological effects of cannabis are generated at the molecular level.
What I want to do here is mention some of the intricacies of drug action using cannabinoids present in cannabis as example compounds, where possible I will add peer reviewed primary research articles for reference but I also want to explain some of the possibilities, not necessarily the facts.
So to start with I will define some of terms I will use, and some I already have:
1. Molecular pharmacology: easiest to define this in contrast to "traditional" pharmacology.
Traditional pharmacology is concerned with how drugs affect a entire organism, and what the organism does to the drugs. Here we would mention bodily distribution of the drug (where it goes/accumulates in the body, where is doesn't go - typically known as pharmacodynamics), also drug metabolism (how the body modifies the drug, usually in order to excrete it - typically known as pharmacokinetics).
While I'm not a traditional pharmacologist we have to keep these things in the background when we talk about the effects of cannabis. In terms of bodily distribution we know cannabinoids cross the blood-brain-barrier, and hence get into the brain. But keep in mind the possibility of the brain having "compartments", cannabinoids could distribute unevenly in the brain. Also metabolism is one way the body tries to clear a drug. Generally most metabolism works to makes compounds more water soluble so they can be excreted through the kidneys, and while some of these modifications may inactivate the compound, they can also generate new compounds with different activities (a great example of this is glucuronidation of morphine, which generates a conjugate with even greater analgesic properties).
Generally molecular pharmacology looks at what targets a drug interacts with and how. Most drugs interact with proteins and perturb their function. In the case of cannabinoids, as you will be aware, the "major" receptors are the cannabinoid receptors (CB1 and CB2 subtypes). These are proteins the sit in the cell membrane with which cannabinoids physically interact with. But as you will see there are a number of other proteins for which we have evidence of an interaction with, some membrane bound (like the CB receptors), some inside the cell (such as PPARg). Cell surface receptors relay signals into the cells, to elicit a response. Other cell membrane proteins act as channels, allowing the influx of things (nutrients and ions for instance) which can’t cross the membrane directly. Any ion (a molecule/atom that carries a charge, tetrahydrocannabinolic acid for instance) has to enter the cell via a channel of some description, the force required to push a charged compound through the lipid (fatty) portion of the cell membrane is so great that only uncharged compounds (such as tetrahydrocannabinol) are able to enter the cell by crossing the membrane directly)
To understand the action of just a single drug, you must have an appreciation of the array of targets it interacts with, the relative affinities for those interactions (ie how strongly they bind to the protein), and the plasma/local concentration of that drug.
So what I will mention here is really a fusion of molecular and traditional pharmacology, which is what you need if you want to explain the array of physiological effects of any drug.
2. Exogenous cannabinoids
These are cannabinoids that originate outside the body. In contrast to endogenous, which are produced inside the body, such as anandamide. So in the simplest case, of a single exogenous cannabinoid that interacts with just one CB receptor we have to think about whether that compound activates (acts as a agonist) the receptor, or competes with the endogenous ligand for the receptor (acts as an antagonist). Bear in mind even in the case of an agonist, there may well be competition with the endogenous ligand, so the overall “receptor output” is a combination of the agonising effect of exogenous ligand, and the effects of competing off the endogenous ligand.
So, I think that will do for now. I will leave you with this:
There have been isolated at least 10 different cannabinoids from cannabis, and there is “evidence” for the possibility of 20-30 separate protein targets of these cannabinoids (including the CB receptors). Different cell types in the body express different proteins and we all know cannabis has a wide variety of different physiological effects, and that different types of cannabis elicit different (sometimes wildly different) response in different individuals... Just in case anyone though this shit is easy to understand, and I’m really only going to focus on psychoactive effects let alone the possibility that non-target mediated effects (such as the potent antioxidant activity of most cannabinoids) could also contribute to their physiological effects... Ugh what am I getting myself into...
(disclaimer: my typing sucks, if I haven't made sense, ask me a question)