Lex Pelger's Endocannabinoid System & Cannabinoids #1: An Introduction

Lex Pelger's Endocannabinoid System & Cannabinoids #1:  An Introduction

To understand the pathfinding role of cannabis, one of our oldest and most venerated of plant medicines, and its influence on the scientific discovery of an intricate, biochemical symphony, we must first recount the timeline of another ancient, treasured plant medicine: opium.

Besides being two of the earliest and most continually used plants in human history, cannabis and the opium poppy share a similar history: the science of understanding how these plants work has revealed ubiquitous yet hidden elements of human biochemistry. The story of the opioids simply occurred sooner for the opium poppy because the water soluble alkaloids in the latex that oozes from the cut flower pod were easier to find than the slippery fatty lipids of the old Indian hemp plant.

After millennia of utility as the primary painkiller used by doctors, it was only in 1803 that Dr. Friedrich Sertürner isolated morphine as the active ingredient in opium. Identifying that molecule enabled researchers to delve deeper into an understanding of why opium worked so well at lessening pain and powered a scientific search for the pathways used by morphine. Lo and behold, morphine acted like a hook that we could drop into the unexplored depths of the brain and pull up this huge class of molecules called endorphins. Or, endogenous morphine.

The active ingredient from opium poppy unveiled a hugely important and widespread human biochemical system that we’re still unraveling. 

The same story occurred with cannabis - but it started many decades later. That’s because, while alkaloids are soluble in water and easier to find, unveiling the mysterious architecture of the fatty lipids that make up the cannabinoids was a considerably more formidable task. 

After decades of chemical hunting, it was only in 1940 that Dr. Roger Adams first solved the riddle of cannabinoid structure when he laid out the full skeleton of CBN - cannabinol (the sleepy cannabinoid). Then it took another quarter century for Dr. Raphael Mechoulam and his team to isolate and find the full structure of THC, finally identifying the molecule that leads to the unique state of being high on grass in 1964. 

Within a year, government researchers had figured out a synthesis pathway that allowed them to produce kilogram batches of THC. This opened up the field to study because prior to this, researchers could only use the uneven batches of hemp from India that varied in their composition. With THC now readily available, it sparked a wave of research into the physiological and psychological effects of THC divorced from the other cannabinoids and components of the plants. Across the world, scientists tested the drug on college students, looking at effects all across the body and mind.

With the use of cannabis as medicine going all the way back to the first pharmacopeia of China - and the original founder of Chinese medicine giving cannabis a place of honor as one of the Superior Elixirs of Immortality - through the Ayurvedic system of India, the learned Arabic doctors and the Western physicians of the last centuries, the question remained: How did this weed affect so many organ systems and yield so many different states of mind?

In a surprising move, it was the US government that enabled the next step of cannabinoid science. Not only did the National Institute for Drug Abuse (NIDA) initially fund Dr. Mechoulam’s research that led to the final identification of the THC molecule, they also pulled together a gathering of scientists over Halloween of 1986 that brought together all the elements to spark the endocannabinoid revolution.

NIDA brought a swathe of cannabinoid researchers to Bethesda, Maryland and there a historic meeting took place that enabled the flowering of endocannabinoid science. Dr. Allyn Howlett, who had been looking for a ‘cannabinoid receptor’, met a research team from Pfizer that had a radioactive molecule that could be used to hunt for the place where cannabis binds. When they shared it with her, it allowed her to take the final step and find the CB1 receptor.

Not only did she find the receptor, she found so many of them in the brain that she assumed it must be a mistake. But it turns out that the CB1 receptor is the most widespread receptor in the important G-protein-coupled receptor class in the human brain. Later work revealed the CB2 receptor and they found it in every organ of the human body. Finally, in 1991, the big breakthrough: a team led by Dr. Mechoulam found anandamide (AEA) - a neurotransmitter made in the brains of every organism with a spinal cord that’s as widespread and important as serotonin and dopamine.

We finally understood the biochemical underpinnings explaining why cannabis was such a vital medicine throughout human history. And as the research blossomed, the importance of the endocannabinoid system continued to grow until it is now called by some the ‘homeostasis system’ of the body, responsible for maintaining balance in an organism and tying together the neuronal, hormonal and immune systems of the body.

In this series of articles, we’ll cover some of what we know about how cannabis works biochemically. And for all those politicians who waffle on the issue and skate around it by muttering that ‘we need more research’, that is true. Research can always go further.

But don’t spit on the fact that there’s so much work that’s been done that it takes someone maybe-five-years of reading the peer-reviewed literature just to get the basic outlines of what we do know about the endocannabinoid system.