There’s a reason ingesting phytocannabinoids such as THC and CBD impacts us, and it’s not (just) plant medicine magic. If taking something into the body produces a certain effect, it follows that there must be some mechanism for processing that substance. That mechanism is the Endocannabinoid System or ECS, and it’s a relatively recent discovery. But what is the ECS, exactly, and why might it matter beyond the medicinal use of cannabis and its derivatives?


You probably already know that people have been using cannabis for thousands of years, but did you know that cannabis wasn’t always illegal in the U.S.? Early colonial iterations of government considered cannabis no big whoop, but today it shares classification with heroin, a yes big whoop drug due to its toxicity and highly addictive potential. That’s a pretty notable shift in a relatively short period of time.

Early 19th century versions of the pharmacopeia, a cache of over 200 medicines, side effects, and directions for use, lists cannabis as a medicinal herb. The Marihuana Tax Act of 1937 [sic] imposed sale, cultivation, and possession restrictions leading to federal illegality for the once legal cross-border import. (In recent years, the once-prolific, racist-inflected term “marijuana” has fallen largely into disuse.)


Cannabis’s illegality made numerous long-term impacts ranging from the scientific to the social (read: fuel for the prison industrial complex intensified by the war on drugs, begun by Nixon in 1971 and expanded by Reagan via the Comprehensive Crime Control Act of 1984, which especially targeted cannabis). Where the former is concerned, federal and largely global illegality has slowed scientific research. Cannabis scientists must jump through unnecessary hoops work within and specific, arbitrary parameters.

In 1964, Dr. Raphael Mechoulam and his team built upon existing research on CBD to isolate and characterize THC. In 1988, Allyn Howlett and William Devane located the first cannabinoid receptors, or CB1 receptors, in the brain, and in 1990, Lisa Matsuda successfully led a team to map and clone these receptors. Characterization of CB2 receptors shortly followed, and combined these form the basis for the ECS.

What is the Endocannabinoid System?

Nearly all animals have an ECS, with receptors taking up real estate all over the body. This system regulates a variety of functions, due in large part to its ubiquitous presence. CB1 and CB2 receptors combine with cannabinoids produced either within or outside the body, to produce different effects.

CB1 receptors are concentrated in the brain but are also present in peripheral neurons, fat cells (adipocytes), liver cells (hepatocytes), the endocrine system, and parts of the gastrointestinal tract. The highest concentrations in the brain are in the cerebellum and basal ganglia, followed by the amygdala, hippocampus, and cerebral cortex. CB1 receptors occur in low densities in the brain stem and the part of the brain that regulates respiratory function. This may partially explain why high doses of cannabis are nontoxic. They don’t slow or stop breathing the way high concentrations of opioids do.

CB2 receptors are less common and structurally different from CB1 receptors. They occur mostly in the immune system and the cells that produce antibodies (known as B lymphocytes).

What does the ECS do?

The ECS plays a major role in regulating pain, mood, memory, appetite, and pleasure. That’s because CB1 receptors are found on neurons in so many different parts of the brain and body. Nausea, for example, occurs in the gut but is registered by the brain. CB1 receptors occur in both locations, which may be why CBD has been shown to diminish nausea in chemotherapy patients.

In a recent (November 2020) lecture for the International Association for Cannabis Medicines, Dr. Daniele Piomelli of the University of California Irvine speculated that we (human and nonhuman mammals) may have had an ECS for hundreds of thousands of years. In his estimation, the ECS, and further investigation into it, is very likely a source for better medicine.

Here, “better” can mean both more specific and more efficacious. There are a host of beneficial impacts to inhibiting the degradation of endocannabinoids (cannabinoids produced inside the body which are on-demand and short-lived) like anandamide and 2-AG, for example. Dr. Piomelli outlined a list of potential advantages, which vary depending on the endocannabinoid but collectively include things like reduced anxiety-like and depression-like behavior, increased social behavior in autism spectrum disorders, reduced seizure activity, and reduced withdrawal symptoms from morphine and nicotine. Side effects are minimal and relatively benign, and mostly revolve around sedation. Dr. Piomelli also concluded that we can feel confident about the predictive nature of animal studies on the human ECS.

Interaction with THC & CBD

THC and CBD are phytocannabinoids or cannabinoids produced by plants. When administered, these compounds combine with ECS like two puzzle pieces fitting together. Remember that scientists isolated THC and CBD before the ECS. Those discoveries prompted more investigation to determine why and how these chemicals work the ways they do. Since research is still young, there’s a lot more to learn. However, the summary of our synergistic relationship to phytocannabinoids boils down to: we have a naturally occurring app for that.

THC & CBD are exogenous, i.e. introduced from agents outside the body, which may be why there is no direct mechanism for breaking them down the way there is for the cannabinoids we produce ourselves (endocannabinoids, endo meaning within.) The lack of a mechanism to degrade these compounds partially explains why the effects are felt much longer (minutes or hours) than those of endocannabinoids.

Endocannabinoid Deficiency

Former Director of Research and Development at the International Cannabis and Cannabinoids Institute Dr. Ethan Russo postulates that the reason why some people suffer from chronic, hard to treat pain syndromes, like migraines, may be clinical endocannabinoid deficiency syndrome, or EDS. Research is, you guessed it, ongoing, and easier to conduct outside the US, which is why Dr. Russo has worked for foreign companies for nearly the last two decades. While EDS hasn’t been classified as such, Dr. Piomelli affirms there’s good reason to believe it will be.

Celia Gold

Celia Gold is a New York-based writer and herbalist-in-training with special interest in aromatherapy and flavor matrices. She has written about herbalism broadly and niches in the cannabis industry for The Alchemist's Kitchen, Green Entrepreneur, PRØHBTD, Autostraddle, and others.

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