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When Were Cannabinoids Discovered?

When Were Cannabinoids Discovered?

The discovery of cannabinoids has slowly revealed the cannabis plant to be a fountain of potential. Their identification even predates the discovery of the endocannabinoid system (ECS), and in fact was crucial to helping researchers uncover the physiological network.

Researchers have identified over 100 unique cannabinoids. Some of these molecules have changed the face of cannabis science, whereas others remain relatively enigmatic and untouched. Below, we’ll take a look at when the most familiar cannabinoids were discovered, and who deserves credit for these groundbreaking findings.

Early pioneers of cannabinoid research

Before individual cannabinoids were isolated and identified, an early group of forerunner scientists laid the critical foundations for these discoveries. Investigators started achieving crude cannabis extracts in the early 19th century, which would soon evolve into capturing specific molecules.

In 1840, a researcher by the name of Schlesinger reportedly obtained the first active extract from the flowers and leaves of hemp plants. Shortly after, another experimental mind named Decourtive conducted an ethanol extract of similar materials in 1848. He evaporated the alcohol and found a dark resin in its place. He named the substance “cannabin”.

Other researchers took it upon themselves to test the effects of this substance. Later in the 19th century, scientists prepared an alcohol extraction and added a lime solution to remove the chlorophyll. They went on to filter and treat the mixture with sulfuric acid, followed by evaporation. The researchers tested the leftover resin and found it to be of neutral pH. After trying “two-thirds of a grain” of the substance, they described its “powerful narcotic effects”.

Scientists were on the trail of a new compound, but they couldn’t quite figure out what was generating these effects. Many argued cannabis housed alkaloids, with Preobrajensky claiming the plant to possess nicotine.

In the hunt for alkaloids, Klein and colleagues isolated cannabimines A, B, C, and D. Shortly after, researchers isolated the alkaloids cannabisativine, from the roots of a Mexican landrace, and anhydrocannabisativine, from the roots and leaves of another wild Mexican strain.

Although these substances appeared to generate some effects in mice, it became clear that other compounds were responsible for the unique effects of the cannabis plant. Soon, scientists would stumble across a unique chemical family that underpinned these properties: cannabinoids.

When Were Cannabinoids Discovered?

• CBN (1899)

CBN, or cannabinol, was the first cannabinoid to be isolated from the cannabis plant. Thomas Wood, W.T. Spivey, and Thomas Easterfield made this groundbreaking discovery in 1899. They obtained the molecule from a sample of charas, a hand-rolled form of cannabis resin. After making an ethanol extract from the sample, they ran it through fractional distillation and produced a viscous oil.

They described the result of this process as “amber-coloured when seen in thin layers but ruby red when seen in mass”. They found the substance to possess psychoactive effects in doses as low as 0.05g. After conducting acetylation, they discovered CBN.

However, cannabis plants don’t create CBN through enzymatic processes. Instead, the cannabinoid results from the degradation of THC. Therefore, the research team may have been working with old samples of extracts in which the THC had broken down.

• CBD (1942)

United States chemist Roger Adams first isolated CBD (cannabidiol) from cannabis in 1942. He extracted the now world-famous cannabinoid from the flowers of Minnesota wild hemp. Adams conducted an ethanol extraction to create a “red oil”. He then ran the substance through distillation under diminished pressure and isolated cannabidiol from the mix of constituents.

Decades later, in 1963, researchers made another important discovery regarding CBD—the molecular structure of the cannabinoid. Raphael Mechoulam, organic chemist and professor at the Hebrew University of Jerusalem, made this important finding.

• CBG (1964)

CBG (cannabigerol) stems from cannabinoid acid CBGA, which plays an integral role in cannabinoid biosynthesis. Many cannabinoids that derive from enzymatic reactions start off life as CBGA, making it somewhat of a master precursor. Several enzymes act on this cannabinoid acid and convert it into other members of the cannabinoid family. For example, CBDA synthase converts CBGA into CBDA, which then decarboxylates into CBD when heated.

Raphael Mechoulam and Yechiel Gaoni joined forces in 1963 to work on cannabis research for the next four years. This pairing would result in a spree of pioneering discoveries in the world of cannabis science. In 1964, the pair set about investigating the pathways of cannabinoid biosynthesis in the plant. They soon solved the problem of a missing link: Where were all of these cannabinoids coming from? They identified CBGA as the bridge between other chemicals becoming cannabinoids.

• THC (1964)

THC produces most of the psychoactive effects associated with cannabis. This controversial molecule attaches to the CB1 receptor of the endocannabinoid system to produce these outcomes. Shortly after discovering CBG, Mechoulam and Gaoni cracked the code and identified and isolated THC (delta-9-tetrahydrocannabinol).

The duo went on to synthesise THC for the first time in 1965 and then again in 1967. Despite their immense success, Mechoulam attributes their discoveries to cannabis science conducted earlier in the century. Although they officially isolated THC during 1964, other scientists laid the groundwork for this discovery.

Both Roger Adams and Alex Todd managed to synthesise molecules extremely close in structure to THC in the 1940s. These researchers never managed to isolate the cannabinoid, but used cannabinoids such as CBD to create similar molecules. Mechoulam states they were likely limited by the literature and techniques available to them at the time.

• CBC (1966)

CBC (cannabichromene) makes up around 0.3% of cannabis plant extract. However, breeders have developed cultivars expressing significantly higher amounts. A non-psychoactive cannabinoid, researchers have explored the pharmacological actions of CBC, finding some intriguing potential.

Interestingly, two different teams identified CBC during the same year, using two different methods. Mechoulam and Gaoni isolated and identified the structure of CBC in 1966. Starting out with a hexane extract, the two researchers ran a chromatography test and identified CBD, THC, CBN, CBG, and CBC. Cannabichromene made up around 1.5% of the extract.

They took the fractions containing CBC and re-chromatographed them twice before distillation. Using this process, they isolated CBC and proceeded to identify the molecular structure of the cannabinoid. Reports also state that a team of German researchers—Claussen, Von Spulak, and Korte—managed to isolate CBC during the same year using benzene percolation of hemp.

Cannabinoids: The tip of the iceberg

The five molecules above make up the major cannabinoids found in cannabis plants. Scientists have probed these chemicals relatively in-depth. However, a host of over 100 cannabinoids and cannabinoid acids are waiting to be fully elucidated by researchers. The next few decades will surely see massive steps forward in the field of cannabis science.

Scientists have unveiled the chemical constituents of cannabis over many years—discoveries that led to their current popularity. Find out where it all began.

Who discovered CBD?

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  1. How was CBD discovered, and who discovered it?
  2. How was CBD oil first used?
  3. How long have people been using CBD oil?
  4. What is the endocannabinoid system?
  5. Bottom line

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.

CBD research

In 1940, Harvard-trained chemist Roger Adams successfully extracted CBD from cannabis. In 1963, Mechoulam described the chemical structure of CBD. Photo by: Gina Coleman/Weedmaps

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CBD research

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 research

Today, we have a better and more specific understanding of how CBD works to help people with various conditions. Photo by: Gina Coleman/Weedmaps

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cbd research

“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.

Endocannabinoid Receptor

The endocannabinoid system, or ECS, is a group of neurotransmitters made by the body and cell receptor sites.

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Endocannabinoid Receptor

“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.”

Bottom line

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.”

Tracing the trajectory of CBD, from its origin until the present day, offers a fascinating snapshot of this versatile cannabinoid and its history.