The History of CBD is filled with exciting discoveries and largely contributed to our understanding of the Endocannabinoid System. The decades-long quest to understand cannabis has enlightened us about the incredible power the ECS holds, and the vital function it plays in our evolution and overall well-being.

Today we’ll outline the history of CBD and other breakthrough discoveries about the EC System.

1940: Discovering Cannabinoids

CBD has come a long way over the last few decades. Importantly, Roger Adams, a Harvard-trained scientist, first isolated CBD in 1940 (and likely CBDa) following his initial discovery of CBN, a degraded form of THC.

By 1963, Dr. Raphael Mechoulam, or the “godfather of cannabis research,” described CBD’s chemical structure, giving light to its therapeutic potential. Mechoulam outlined THC’s chemical structure a year later, thereby distinguishing its psychoactive qualities from CBD’s non-psychoactive effects.

From here, researchers strove to understand just what it was about THC that made consumers feel “high.” Specifically, they sought to understand why cannabinoids made people feel hungry, calm, and relatively pain-free. Though preliminary animal studies confirmed these experiences, the mechanisms by which cannabinoid exerted their effects was unclear – until they discovered the Endocannabinoid System.

1988: Cannabinoid Receptor Discovery

Researchers discovered the first cannabinoid receptor in 1988 by studying the impact of cannabinoids on rat brains. Specifically, they noted that rats’ brains – and indeed the brains of all mammalian species – have an abundance of these receptors, which they soon dubbed “CB1 receptors”.

They observed a particular affinity to THC, noting a relatively high concentration of CB1 receptors in parts of the brain that manages things like memory, emotion, cognition, and general motor skills. Scientists identified a second type of cannabinoid receptors (called CB2 receptors) in 1993, which are primarily located in other organs and peripheral tissue. Notably, these receptors seemed to play a vital role in stress and pain regulation.

The fact that cannabinoid receptors are so prevalent in the body was intriguing. Why would mammals have these receptors if not for an evolutionary need? What’s more, why should our bodies require plant-based cannabinoids when we could theoretically produce them ourselves?

1992: Anandamide Discovery

Scientists discovered the first endocannabinoid (internally produced cannabinoid) in 1992 when they isolated the neurotransmitter in CB1 receptors of big brain tissue. Though technically called N-arachidonoylethanolamine, most use the term anandamide, which is Sanskrit for bliss.

Like THC, anandamide activates cannabinoid receptors to initiate a series of reactions within the body. In doing, it may affect many physiological functions, including mood, pain perception, appetite, and fertility.

Importantly, researchers noted that our bodies produce anandamide on-demand to help us cope with stress-related issues. Experts also suggest that we produce anandamide during exercise to promote endurance, which may help explain the “runner’s high” phenomenon.

1995: Discovering 2-AG

Dr. Mechoulam discovered another endocannabinoid, 2-Arachidonoylglycerol (2-AG) in canine gut tissue in 1995. The cannabinoid is more prevalent than its predecessor, with concentrations up to 170 times higher in the mammalian brain than anandamide. Researchers suggest that this endocannabinoid plays a vital role in maintaining homeostasis amidst a multitude of external stressors, noting a surge of 2-AG production following traumatic brain injury.

1997: Endocannabinoid Metabolism

Ben Cravatt characterized the FHHA molecule in 1996 as the primary degenerative enzyme for anandamide. A year later, Italian scientists identified MAGL as the key degenerative enzyme for the endocannabinoid 2-AG. This knowledge led researchers to suggest that inhibiting these enzymes should increase endocannabinoid levels to extend cannabinoid receptor signaling.

These three major discoveries (endocannabinoids, cannabinoid receptors, and metabolic enzymes) made up the base of what we now call the Endocannabinoid System.

1998: Proposing the Entourage Effect

The Entourage Effect was first outlined in a 1998 article by S. Ben-Shabat published in the European Journal of Pharmacology. Specifically, the author suggests that 2-AG binds with cannabinoid receptors better with the help of other non-cannabinoid compounds. The theory suggests that, like the endogenous system, plant-based cannabinoids likely work better when consumed in conjunction with other phytocannabinoids, terpenes, and plant-based elements. If accurate, the Entourage Effect likely explains why different cannabis cultivars exert seemingly different effects.

2001: Unique Cannabinoid Signaling

Scientists learned in 2001 that cannabinoids communicate backward across synaptic gaps. The process called “retrograde signaling” helps control how fast or slow other neurotransmitters fire. Essentially, cannabinoids help regulate hyperactivity to reduce trauma-related pain and inflammation. The process also helps promote neurogenesis and stem cell migration.

2004: Proposing Clinical Endocannabinoid Deficiency

Dr. Ethan Russo made headlines when he proposed the concept of Clinical Endocannabinoid Deficiency in 2004. According to Russo, a poor endocannabinoid tone could be the blame for a number of seemingly unrelated health problems, including migraines, IBS, fibromyalgia, and clinical depression. Notably, patients often experience a comorbid cluster of symptoms, which could be caused by an endocannabinoid deficiency. This may explain why many phytocannabinoids seem to alleviate many of these issues, including both psychoactive THC and non-psychoactive CBD.

2005 and Beyond: Fine-Tuning Our Understanding of CBD History

Research regarding the Endocannabinoid System has flourished since discovering CBD in 1940. For example, researchers have learned how cannabinoids travel within cell walls via fatty acid-binding proteins. They’ve also discovered some of the vital ways cannabinoids contribute to basic cell functionality to slow the aging process and minimize the development of certain neurodegenerative diseases.

We’ve also learned that other plant compounds (not just cannabis) can interact with CB receptors and that regular human activities like fasting, exercise, and acupuncture can alter our endocannabinoid tone.

Though there is still much to learn, CBD’s discovery has led to amazing breakthroughs in cannabinoid research. We can’t wait to see what we learn next.

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The History of CBD and the EC System