Model Failure

I was reading about a recent endocannabinoid conference and came across this interesting bit:

What is clear from these presentations is that FDA model of approving drugs is simply unfit to manage the science that is coming. The conventional concept of one drug targeting one receptor is all that model can approve. The Pharma industry is thus hyper focused on the path the central planners laid out. I believe this simple failed framework (more so than any DEA/NIDA conspiracy) is more responsible for the failure of cannabinoid based medicines to make it past regulatory hurdles and back into widespread use seen in the 1860s.

There is certainly merit to the concern that we have government funded ‘Scientific’ Institutions with titles that are in and of themselves a confirmation bias like ‘National Institute on drug abuse‘ as opposed to ‘drug outcomes or drug benefits‘ and scientists who accept this funding seemed to have well funded but poorly laid out study design that received a lot of consternation amongst the community uninfluenced by this institution of confirmation bias. I will provide a few examples in a later post but felt it was more important to focus on the exciting work that is making their model obsolete.

First, the complexity of 88 Phytocannabinoids is awe inspiring. Take just one of the diverse compounds and measure where it ‘hits’ in the human body and you don’t have a finger playing one note on an instrument, but instead you have a 10 handed hydra playing a soft and subtle symphony on over 50 receptors and peptides. This entails 2 of the most prevalent GPCRs in the human body (CNR1 and CNR2) and 6 TRPV receptors (temperature gated and often Capsaicin triggered), 6 different lipid rafts (Fatty Acid Binding Proteins interestingly enough being study at Stony Brook NY) that shuttle cannabinoids between aqueous and lipid compartments in the body, 3 receptors of unknown function (GPR55, GPR119, GPR18) that communicate with LPI (lysophosphatidylinositol) and at least 6 different endocannabinoids (AEA, 2-AG, NADA, NAGly,OEA, LPI) all influenced by dozens of enzymes which metabolize them (DAGLa, DAGLb, MAGL, ABHD6, ABHD12, FAAH). This is one cannabinoid and the plants often have half a dozen to dozen dominant cannabinoids based on their genetics.

He goes on to discuss other chemicals found in cannabis. What this all comes down to is that our understanding of how plant medicines work is very limited and that the current regulatory structure is unable to deal with medicines that affect (not as side effects) numerous systems in the body.

And on top of that there are all the different cannabinoid actions, some are promoters (agonists) of action and some retard action (antagonists) and it is the balance of those that have the effect. And it may be that without the balance the desired effect can’t be achieved or is not achieved as well.

All this will upset medicine as we know it. It will certainly upset Conservatives, compassionate and otherwise.

Update: 8 July 2014 0534z

You can see an interview of the author of the above piece, learn more about his company Medicinal Genomics, and learn more about Medicinal Cannabis at Kevin McKernan.