The Chemistry of Care

Written by Jon Gettman

May 1, 2022

Raphael Mechoulam

I met Raphael Mechoulam in May 2004 at the 3rd National Clinical Conference on Cannabis Therapeutics in Charlottesville, Virginia.  Dr. Mechoulam, along with his colleagues at Hebrew University, first isolated THC as the active ingredient in cannabis and identified its chemical structure in groundbreaking research during the early 1960s.  He is considered the father of modern cannabinoid research and was speaking at the conference on “The Cannabinoid System in Neuroprotection”.  Dr. Mechoulam is a pioneer in the study and understanding of the therapeutic properties of CBD.

I, on the other hand, was speaking at the conference about a minor public policy matter.  Before my remarks was a moving presentation by Valerie Corral on “Cannabis Use in Hospice” and following me were presentations by Arnold Trebach on “A Humane Drug Control System” and Richard Bonnie on “Medical Ethics and Cannabis Prohibition.”

This was 18 years ago, and all the issues that were addressed at this conference remain relevant and important today.  It was an exciting time, but as was common with this issue it remained a time filled with both optimism and uncertainty about the future.  Now, with the benefit of hindsight, one looks back and sees a work in progress, work that provided the foundation for the Cannabis care system that is emerging today.  And it is clear today, with such hindsight, that this foundation is a scientific one; it is important that we understand this.  But these, however, are issues for another time.  They just set the context for this seemingly trivial anecdote of my chance to meet Dr. Mechoulam.

I had the good fortune to introduce myself to Dr. Mechoulam in the hallway outside the conference hall and thank him for his work.  The whole encounter took a matter of minutes, he was very gracious, and I’m sure this was far more memorable for me than for him.  But there was a short paper Mechoulam had published in 1991 along with William Devane (who played a key and important role in the discovery of the endocannabinoid system) and two additional colleagues that had interested me, and I spent my minute with Mechoulam telling him of my interest in and appreciation of some points expressed in that paper.

The paper was “A Random Walk Through a Cannabis Field” and was published in Pharmacology, Biochemistry & Behavior (Volume 40, pages 461-464).  This is a peculiar but fascinating article, explained best (of course) in the author’s own words: “This overview covers various aspects of our research in the field of Cannabis and presents some thoughts and ideas, which may help to advance this field.”

Indeed.

The first part of the paper presents some historical and linguistic notes about the absence of the term Cannabis from the Old Testament.  Next, noting “a historical jump of circa 2500 years” is a discussion of some of the “chemical, biochemical and pharmacological aspects of Cannabis research”.  Here the authors discuss the extremely high stereospecificity of cannabis action and “synthesis of a new labelled ligand for the Cannabis receptor.”  From the first part the authors conclude that “the interplay of politics and drugs is not uniquely a modern issue:” From the second part, they observe that “cannabinoid action is associated with finding or interaction with biological substances [such as receptor sites]’’.  As such, the labeled ligand will be of some use in future research.  

That’s all very cool.  It’s what follows, though, that deserves our attention as it gets to the root of it all.  Dr. Mechoulam and his co-authors ask this: “Why do we have cannabinoid receptors (and presumably endogenous cannabinoid ligands)?”

To begin with, Mechoulam et al explain that:

Presumably, the Cannabis agonists act on coordination of movement via the cannabinoid receptors in the cerebellum and in the basal ganglia and on memory via the receptors in the hippocampus.  In humans, these cannabinoid actions are rather marginal, and it seems that other activities should also be investigated.

This is 1991, at the advent of the discovery of the endogenous cannabinoid receptor system.  For research in this area, this was a monumental leap forward.  The mechanism of action for the observed effects of cannabis had eluded scientists until the receptor system was discovered by Allyn Howlett, William Devane and their colleagues in 1988.  The locations of cannabinoid receptors in the human brain were determined by Miles Herkenham and Allison Lynn in 1990.  The paradigm of contemporary research was shifting from how cannabis affected the brain to how to utilize those effects for therapeutic and medical purposes.

Raphael Mechoulam

Paradigm shifts pose new questions that guide not only research, but our general understanding of what research discovers.  The significance of the receptor system discovery is still sinking in today.  One of the immediate questions it posed at the time, though, is now that we have discovered that humans have the natural neurobiological system – what does it do?

The authors note that receptors are also located in the limbic system, the part of the brain responsible for behavior and emotion.  These are the other activities referenced above.  “Cannabis is used by man not for its actions on memory or movement coordination but for its actions on mood and emotions.”

These topics are addressed in the discussion section of the paper, and when it comes to this central question the authors state clearly that they “can only speculate.”  And so, they ask:

Is it possible that the main task of the cannabinoid receptor (presumably via the putative natural cannabis ligand) is to modify our emotions, to serve as one of the links which transmit, or transform or translate objective or subjective events into perceptions and emotions?

This goes far beyond the scope of therapeutic and medical practice in the sense that it addresses all human use of cannabinoids.   We learn from understanding how the humans benefit from both endogenous cannabinoids they are born with and from the exogenous cannabinoids found in natural cannabis.  And while applied research and practice have been prioritizing specific therapeutic properties that address individual patient needs, basic research continues to address our need to understand the underlying mechanisms of action and our understanding of research in both areas allows us to visit and re-visit the fundamental question of why we have a cannabinoid receptor system.  Perhaps, more importantly, the fundamental question is not why do we have one but what do we do with it?

Raphael Mechoulam
Raphael Mechoulam

Mechoulam and colleagues conclude with these thoughts:

We know next to nothing on the chemistry of emotions. For thousands of years love and hate, happiness and sorrow have been left to the poets.  What is happiness? It is hard to describe. . . 

After quoting a wonderful poem, “Happiness”, by Patricia Goedicke, the final thoughts the authors present are these:

Can we translate this wonderful poem into biochemical cycles? Of course not. Let us hope, however, that through better understanding of Cannabis chemistry in the brain we may also approach the chemistry of emotions.

The nature of the paper and the context of the discussion invite further speculation.  We can learn about the natural effects of cannabinoids from observing the social behavior of people who use them.  In terms of science, let’s leave the realm of the natural sciences for the moment and settle in the realm of the social sciences, in observing behavior.

Over the last several decades a community has emerged from interest in, concern about, and reliance on cannabinoid therapeutics.  This community is linked by a common emotion. It’s not an emotion caused by cannabis use, not everyone in this community uses cannabis, or has used cannabis.  Yet this community is defined by their interest in cannabis and the source of their interest is care.  

When we study cannabis we learn about the chemistry of movement, and memory, and about the chemistry of emotions.  But in studying cannabis we learn about the chemistry of care.  This is a community of care; it is the nature of our professional practice and our personal values.  We learn about cannabis so that we may take better care of others.  This makes us happy.

Jon Gettman, Ph. D. is an Associate Professor in Criminology and Criminal Justice at Shenandoah University and Chair of the Board of Directors of the Academy of Cannabis Education. 

In Memoriam

Raphael Mechoulam

(1930 – 2023)

 

Maccarrone M. Tribute to Professor Raphael Mechoulam, The Founder of Cannabinoid and Endocannabinoid Research. Molecules. 2022 Jan 5;27(1):323. doi: 10.3390/molecules27010323. PMID: 35011553; PMCID: PMC8746417.

Pertwee, R.  (2020) The 90TH Birthday of Professor Raphael Mechoulam, a Top Cannabinoid Scientist and Pioneer.  The International Alliance for Cannabinoid Medicines.

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