For such a tiny molecule, CBD has captured a ton of interest in recent years. CBD is now ubiquitous as a medicine and a nutraceutical, with users relying on it to ease ills as diverse as anxiety, insomnia, and inflammation.
While it may seem difficult to imagine a world without CBD, its discovery and entry onto the global stage was, in fact, relatively recent. Tracing the trajectory of CBD, from its origin until the present day, offers a fascinating snapshot of this versatile cannabinoid and its history.
How was CBD discovered, and who discovered it?
Like many cannabinoids, the origin story of CBD begins in a lab. In 1940, Harvard-trained chemist Roger Adams successfully extracted CBD from cannabis. Dr. Raphael Mechoulam, known as the “godfather of cannabis research,” then took the baton from Adams, honing his focus on the cannabinoid. In 1963, Mechoulam described the chemical structure of CBD.
This advancement helped create a foundation for understanding the cannabinoid and how it might be used in a therapeutic context. The discovery of the chemical structure of CBD contributed to demystifying the chemical structure of THC a year later. This finding was a big deal; it linked psychoactive and euphoric effects to THC and dissociated CBD as an intoxicating compound.
In a recent interview, Mechoulam explained some of his early motivations for diving into cannabis research. “[In the early 1960s] I was surprised to find out that while morphine had been isolated from opium 150 years previously, and cocaine had been isolated 100 years previously, the chemistry of cannabis was not well known,” he says. “The active compound or compounds had never been isolated in pure form, and the structures were not known. In order to understand the pharmacology and do clinical trials, you need a strong chemical basis.” This search led Mechoulam and his associates to delve deep into the chemistry of cannabinoids, with a special focus on CBD.
How was CBD oil first used?
The 1940s and 1950s saw the rise of pharmacological experiments using CBD oil extracted from cannabis. “Raphael Mecholulam carried out the first CBD oil experiments when testing various extracts of cannabis, including THC,” explains Dr. Tom Ingegno, integrative health specialist and medical cannabis practitioner. “THC was proven to be the distinctive psychoactive compound in primate testing, but Mechoulam discovered some milder effects in CBD.”
Research into CBD oil's therapeutic uses gathered momentum in the 1980s when Mechoulam and other scientists began conducting game-changing research on CBD for epilepsy. “The compound (CBD) turned out to be of extreme interest,” said Mechoulam in the interview. “We found, after a lot of preclinical work in rats and mice, that CBD had anti-epileptic qualities.”
In a small clinical trial conducted in 1977 by Brazilian researchers, four epileptic patients were given a daily dose of 200mg of CBD, while five were given a placebo. Two of the patients taking CBD showed a remarkable improvement with no convulsions over the three months they received treatment. One showed a partial improvement, and one showed no improvement. None of the placebo patients demonstrated any improvement.
How long have people been using CBD oil?
CBD oil as we know it has been on shelves since the early 21st century. “CBD's mass marketing and widespread use seemed to coincide closely with the legalization movement and the rise of reliable studies in 2005,” explains Ingegno. “Across the board, most of the research shows that it had a positive effect on mood and sleep due to its ability to mimic naturally occurring endocannabinoids.”
Ingegno, who has expertise in Chinese medicine, also stresses that CBD's use stretches back into the annals of history. “Humans have been cultivating Cannabis sativa for well over 5,000 years,” points out Ingegno. “Some of the oldest known Chinese herbal texts are written by Shen Nong, or the 'Divine Farmer.' Half of his writings were about farming and the other half were about the medicinal use of plants. Guess which plant was featured in both parts? Cannabis sativa.” Ingegno emphasizes that regardless of how the ancient Chinese consumed cannabis, they were receiving some of the benefits of CBD.
“CBD oil's popularity has skyrocketed in the last 20 years,” says Ingegno. “We now have a better and more specific understanding of how it works to help people with various conditions.”
What is the endocannabinoid system?
Ultimately, CBD's popularity boils down to the molecule's purported therapeutic effects on the body. The endocannabinoid system is critical to understanding how and why cannabis may be well-suited as a medicine for the human body.
“The endocannabinoid system, or ECS, is a group of neurotransmitters made by the body and cell receptor sites,” explains Ingegno. “The neurotransmitters look similar to exogenous cannabinoids (the ones we get from cannabis). The cell receptor sites activate when we ingest cannabis, or our body produces endocannabinoids.”
The ECS is one of the most influential systems in the human body, contributing to homeostasis or balance. The ECS influences functions as diverse as stress, appetite, energy, reproduction, pain, and sleep.
The discovery of the endocannabinoid system was surprisingly recent, dating back to the early 1990s. Again, the discovery of the ECS components was a joint effort, in which Mechoulam was instrumental. “There was no conception [of endocannabinoids],” explains Mechoulam. “We did some work and found that most probably, the plant cannabinoids act through a specific mechanism.” In the mid-1980s, Allyn Howlett discovered the CB1 receptor, and in 1993, the CB2 receptor was discovered.
Gradually, a picture of the endocannabinoid system as a network containing cannabinoid receptors, endocannabinoids, and enzymes began to form.
“Receptors don't exist because there's a plant out there; receptors exist because we, through compounds made in our body, activate them,” stresses Mechoulam. In 1992, after Mechoulam and his team had been looking for endogenous compounds that activate cannabinoid receptors, they identified anandamide. The endocannabinoid is responsible for engendering feelings of pleasure and bliss, leading to it being dubbed “the bliss molecule.”
The trajectory of CBD looks set to continue into the future, with diverse research on the horizon. Mechoulam is currently focusing his attention on cannabidiolic acid (CBDA), the precursor that converts to CBD over time or when exposed to heat.
“It turns out that cannabidiol acid in the studies we have undertaken so far is more potent than cannabidiol itself,” Mechoulam stated in a speech in 2019. “The chances are that slowly and to a certain extent, cannabidiol acid will prove to be parallel to cannabidiol oil in its activity because in many aspects, it's much more active.”
Mechoulam sees cannabidiol acid slowly replacing CBD as the natural cannabidiol of importance. “We have a publication which shows that it is more potent for treating pain and depression and we have seen a few other examples,” he states. “These findings will be published over the next few years or maybe even over the next few months.”