If cannabis was a band, it would be fair to call THC the lead vocalist. Between countless pop culture references and its mind-altering psychoactive properties, it's no wonder that THC is familiar to many. But who discovered THC and how did we come to know so much about its role in cannabis' anti-inflammatory, analgesic, neuroprotective, antioxidant, and muscle relaxant properties? A dive into THC's history offers fascinating insights into our current understanding of the cannabinoid.
Who discovered THC?
The official discovery of THC is commonly attributed to Dr. Raphael Mechoulam, affectionately referred to as the godfather of cannabis science. “THC was discovered in 1964 by Dr. Raphael Mechoulam and his colleagues at Israel's Weizmann Institute of Science,” explains Chris Kilham, Medicine Hunter and author of the forthcoming book The Lotus and the Bud. Mechoulam had already singled out cannabis as a plant of interest and had isolated cannabidiol, or CBD, the previous year.
Although Mechoulam and his team were responsible for isolating and describing THC's structure, Harvard-trained chemist Roger Adams also played a key role in the discovery of the compound. Adams was the first to identify THC and explore its relationship to CBD but never isolated THC directly from the plant. Rather, he synthesized it in the laboratory. It wasn't until the 1960s that the technology became available, enabling Mechoulam and his team to isolate THC directly from the plant itself.
This breakthrough was pivotal to setting cannabis research in motion, encouraging other scientists to explore other cannabinoids and their effects on the body. “Since the discovery of THC, many other brilliant scientists have also made key advances in this field,” says Kilham.
How was THC discovered?
In the 19th century, the use of cannabis resin in India and hashish in Parisian literary circles led many scientists to attempt to unlock cannabis and its compounds. By the 1930s and 1940s, the chemical structure of the cannabis plant and its pharmacological effects still evaded experts. While the active therapeutic compounds derived from cocaine and opium had already been isolated, scientists had not yet zeroed in on the active constituent of cannabis or defined its molecular structure.
Eager to unpack the mysteries of cannabis, Mechoulam undertook research in Israel, where the government's stance on cannabis was more permissive than in the US. The 1960s saw technological advances that enabled Mechoulam and his team to embark on a chemical evaluation of cannabis. They hoped to uncover its active constituent, the substance that was largely responsible for producing the psychoactive, intoxicating effects seen in users. Their research led to them discovering THC in hashish extract.
When their team first isolated THC, the National Institutes of Health came knocking and launched US research into THC's pharmacological effects. Much of the early research on THC was carried out using the THC isolated by Mechoulam and his team.
Although Mechoulam was the first to officially isolate THC, it's vital to point out that humans have been aware of cannabis' effects for millennia — even if they didn't know what was causing them. Archaeologists have found evidence of cannabis with high levels of THC in western China dating back 2,500 years. These artifacts suggest that humans may have been intentionally cultivating and selecting THC-rich cannabis specimens for a very long time.
How was THC first used?
As historical records indicate, THC was used among ancient peoples, including the Chinese, Indians, and Persians. In the modern era, research into THC ramped up in the mid-1960s and early 1970s. This rise occurred in response to the widespread use of cannabis as a recreational drug in the US and other Western nations. At the time, scientists focused their research on testing whether the psychotropic properties of cannabis could be attributed to THC. Any interest in THC's therapeutic potential was sidelined by an overwhelming preoccupation with the psychoactive effects of the cannabinoid and its influence on the human body and wider society.
During that era, experiments compared the effects of cannabis to other recreational drugs, explored THC dependency, and investigated the effects of THC on biological systems. Researchers delved into studies in animal and human populations that gauged how cannabis elevated mood, precipitated anxiety or paranoia, produced auditory or sensory changes in perception, and altered one's sense of time.
While this early research undeniably helped shape our understanding of THC's effects on the body, these studies did little to explain how the cannabinoid produced these effects. Greater awareness of the medicinal applications of THC developed later alongside the discovery of the body's endocannabinoid system.
What is the endocannabinoid system?
The endocannabinoid system (ECS) represents a critical part of understanding THC and its potent effects on the human body. Humans and other mammals contain an endocannabinoid system within their bodies, which plays a significant role in maintaining homeostasis, or balance, in the body. This unique system also influences regulatory processes as diverse as appetite, sleep, mood, stress, energy levels, and reproduction. The ECS produces endogenous cannabinoids (produced internally) and responds to exogenous cannabinoids (produced externally), like the ones found in cannabis, which are called phytocannabinoids.
“In 1998, while conducting a study at St. Louis University School of Medicine, professor of physiology Dr. Allyn Howlett and pharmacologist Dr. William Devane determined that the brains of mammals possessed receptor sites that reacted to cannabinoids,” explains Chris Kilham. “These sites, dubbed cannabinoid receptors, turn out to be the most abundant neurotransmitter receptor sites in the brain.”
There are two main types of cannabinoid receptors in the body: CB1 and CB2.
CB1 and CB2 receptors are distributed throughout the central and peripheral nervous systems. “In the brain, these receptors are located in the brain stem, cerebral cortex, hippocampus, cerebellum, basal ganglia, hypothalamus, and amygdala. They are also found in the liver, kidneys, spleen, gonads, and heart,” explains Kilham.
THC is what's known as a partial agonist at both CB1 and CB2 receptors, meaning that it can partially bind to both receptor sites. The psychoactive effects for which THC is famed arise from its affinity for the CB1 receptor, however.
“After the discovery of the CB2 receptor, two graduate students of Raphael Mechoulam, Dr. Lumir Hanus and Dr. William Devane, and their team at The Hebrew University in Jerusalem discovered anandamide (AEA), an endogenous cannabinoid,” says Kilham.
Anandamide is an analog of THC that is produced by the body. “Ananda is the Sanskrit word for “bliss,” and is used to describe yogic ecstasy. It's a perfect name for the compound, as anandamide is equal to THC in psychoactivity,” points out Kilham. “In other words, we make a compound in our own bodies that by its very nature, and by our basic biology, promotes mind expansion.” The discovery led to anandamide being dubbed “the bliss molecule.”
To this day, Dr. Mechoulam and his many collaborators continue to plumb the remarkable depths of the ECS and the various cannabinoids that affect its function.
The final word on THC
These days, THC is valued both for its mind-altering psychoactive properties and its array of potential therapeutic benefits. Current research into THC is mostly focused on uncovering its effects on various illnesses and conditions.
This research is helping to shift the stigmatization associated with the cannabinoid and cannabis itself while promoting an understanding of it as a medicinal compound. There's no doubt that ongoing research into THC, and its effects on the ECS, will continue to inform our understanding of this remarkable cannabinoid.