One of the most intriguing aspects of medical marijuana is the amount of science behind it. Sure the politicians of the world are often against Cannabis use or running around saying we need more research, but it’s clear that they are just not reading or paying attention to the literature that exists, which is remarkably good. There are more studies on Cannabis than on any other agent!
A Brief Overview of the Endocannabinoid System
While there are numerous studies about the health benefits of medical marijuana, we do need more science. Cannabis, it turns out, is a really complicated mixture of chemicals and it appears that many of these agents work together to produce the benefits we see from whole plant. In other words, it’s not as simple as purifying one or two medicines from the plant as the Pharmaceutical industry has done with many other medicines.
This idea that Cannabis’ many ingredients are working together is called The Entourage Effect.
The chemicals in Cannabis, called Cannabinoids, interact with already existing receptors on our cells. What, you say? There are Cannabinoid receptors on our cells just waiting for weed smoke to trigger them? Well, yes, sort of. Those receptors are part of a built-in signaling pathway that uses our own endogenous (built-in) Cannabinoids. Yes, we have built-in weed chemicals in our bodies that are part of our normal function.
These Cannabinoids and their receptors are called The Endocannabinoid System (ECS). There are 2 known receptor types CB1R and CB2R. As a general rule, the CB1R are located in the brain and other nervous tissue, and the CB2R are located on immune systems cells.
Undoubtedly, this is a gross simplification of the real system, as we know that different Cannabinoids have different effects on these cells, implying that there are likely more receptors yet to be identified and/or that the known receptors have different responses to various Cannabinoids, either by the strength of the binding/signaling, or by the specific reaction of the receptor to differing Cannabinoids.
The role of the ECS is not fully understood, but appears to be a subtle one, modulating the effect of other signaling pathways, rather than having a direct effect itself. More research is being done on this.
The Entourage Effect in Medical Marijuana
The idea is that marijuana contains many Cannabinoids, not just the THC and Cannabidiol (CBD) that are often discussed in the press. Marijuana contains about 80 Cannabinoids, and many other compounds called Terpenoids. It is felt that some of these other Cannabinoids work to offset the negative side effects that are produced by single Cannabinoids.
Essentially this theory states that as a group of compounds the Cannabinoids in marijuana work better than any one alone. Extract of marijuana (or just marijuana) is more effective than any single agent. Terpenoids may also contribute to modulating the effects of Cannabinoids.
Moreover, these minor Cannabinoids are likely to have more specific effects of their own, making having these Cannabinoids in the medicine, and coming to understand their roles, crucial. It’s important to understand how medical marijuana works, as well as the marijuana facts vs. the marijuana myths as well.
The Problem for Big Pharma
I don’t have a problem with large pharmaceutical companies (disclosure: my grandfather, Max Tishler, worked for Merck developing medications like sulfa and steroids). In fact, despite people’s misgivings about their profit motives, only pharmaceutical companies have the deep pockets and accountability to develop, test, and bring to market the medications we need.
However, The Entourage Effect presents a scientific and political challenge to Pharma’s approach. In the days before DNA sequencing and computer modeling of drug effects, almost all medications were found in the natural world by observation. Examples include Penicillin (derived from mold), Aspirin (derived from Willow tree bark), Cortisone (naturally occurring in the animal body). These were purified to a single compound for study and then manufactured by purification or synthesis.
This is a model that has worked well for over 150 years (Bayer patented aspirin in 1850) but presupposes that in each case there is one compound that causes a specific effect. A friend recently wondered to me whether extract of willow bark might have been more effective than purified aspirin, but that a single ingredient was being sought to make into pills to be sold. It is an interesting question, but I suspect the answer is no.
In many cases, like aspirin, we have come to understand the chemical and biological mechanism of action, and it is relatively straightforward. There could be helpful minor compounds in willow bark, not in aspirin, but aspirin does what we expect and is effective.
When we start looking at the implications of the Entourage Effect, however, they are staggering. If there are 80 Cannabinoids (let’s ignore the Terpenoids for a moment) and presupposing that they are all important, that’s 80! (factorial, not exclamation point) combinations. That’s about 7×10^118 (frankly that’s such a large number that I don’t know how to write it another way. It’s a 7 with 118 zeros after it. Billion is a large number too, but only has 9 zeros.)
How are we ever to sort out which of these agents is important and does what? Further, you have to test each of the likely combinations in animals and then in humans. It’s a daunting task. It’ll take dozens of supercomputers, thousands of researchers, and likely not happen in our lifetime.
As you can see, leaving aside the politics of Cannabis use and science, the task to “pillify” (my word) Cannabis is enormous. While I believe that ultimately it will be done and will benefit us all, in the meantime we have Cannabis, which has many health benefits.
Medical Cannabis can help to alleviate the symptoms of conditions including but not limited to chronic pain, arthritis, ALS, MS, chronic insomnia, cancer, glaucoma, depression, anxiety, and HIV/AIDS. To discuss whether you could be a suitable medical marijuana patient, call Inhale MD at (617) 477-8886 today.