When and how did we learn about phytocannabinoids?


Cannabis has been consumed for medicine and fun for thousands of years. While societies long knew that cannabis had therapeutic benefits, it has not always been understood exactly how the plant produces those benefits. Phytocannabinoids – the compounds that make cannabis work -- are a discovery that has only been uncovered in the last few decades. 


What are phytocannabinoids?


Phytocannabinoids are the compounds within cannabis that are responsible for its therapeutic effects. These include household names like delta-9 Tetrahydrocannabinol (THC) and Cannabidiol (CBD), as well as minor ones like Delta-8 and CBN. In all, scientists believe that there are more than 100 phytocannabinoids found in cannabis plants.


Phytocannabinoids are powerful. The heady experience associated with cannabis is primarily caused by THC, but that's not all this cannabinoid can do. In addition to a wide range of use cases – sleep promotion, pain relief, stress relief – THC can also do different things when present alongside other cannabinoids. Before we explain further how phytocannabinoids work in the human body, let's take a closer look at the history of modern cannabis research and discoveries that have shaped our understanding about cannabis.\


Timeline of phytocannabinoid discoveries


This brief history includes some of the most important milestones in the discovery of and research into phytocannabinoids. 


•    1895: Researchers observe the existence of Cannabinol (CBN), a minor cannabinoid that develops as THC degrades. At this point, the structure and mechanism of action for phytocannabinoids remains unknown.

•    1930s: Researcher R.S. Kahn identifies and elucidated the structure of CBN, making it the first phytocannabinoid to be examined in this way. 

•    1940: Phytocannabinoids like THC, CBD, and CBN are studied for their pharmacological effects for the first time. These studies helped researchers determine that CBN was less potent than THC, and that CBD did not prompt any psychotropic activity at all. 

•    1944: Researchers determined that CBD could prolong sleep in mice that were already asleep, while CBN and THC could not. 

•    1964: Raphael Mechoulam and accompanying researchers elucidate the structure of THC for the first time. This discovery was especially important because THC is one of the most prominent phytocannabinoids found in cannabis, responsible for eliciting that famous euphoric feeling.

•    1984: Chemist John Huffman succeeds in synthesizing cannabinoids for the first time. Synthetic cannabinoids, such as dronabinol, are used today in pharmaceuticals for anti-nausea treatment in patients managing side effects from cancer treatment.

•    1988: Researchers identify the existence of cannabinoid receptors for the first time, establishing an understanding of how phytocannabinoids interact with the body. 

•    1990: Lisa Matsuda and her team of researchers identify a cannabinoid receptor in the brain of lab rats, submitting their findings to the National Academy of Science's Institute of Medicine. Further experiments demonstrated that THC activated this cannabinoid receptor, which is also found in the central nervous system of human beings. 

•    1992: Raphael Mechoulam and researchers William Devane and Dr. Lumir Hanus at the National Institute of Mental Health (NIMH) discover the endogenous cannabinoid anandamide, a cannabinoid made by the body (called an endocannabinoid). Researchers observed these endocannabinoids interact with the body in the same way as THC, shedding light on the mechanism of action by which cannabinoids influence how people feel.

•    1993: Mechoulam, Devane, and Hanus identify a second cannabinoid receptor clustered mainly in the immune system. They named this the CB2 receptor and dubbed Matsuda's previous discovery the CB1 receptor. 

•    1995: Mechoulam, Devane, and Hanus identify a second endocannabinoid like anandamide, called 2-arachidonoylglycerol (2-AG). Researchers also observed that this endocannabinoid interacted with both CB1 and CB2 receptors. 


A recent history of modern phytocannabinoid research


Many people justifiably consider 1964 to be the year when modern phytocannabinoid research began in earnest, when Mechoulam and his team of researchers first isolated THC and elucidated its chemical structure.

 
However, phytocannabinoids were first identified almost 70 years prior, when researchers discovered Cannabinol (CBN). At this time, though, the chemical structure of the compound eluded researchers. They simply knew that CBN existed.


It wasn't until the 1930s that CBN's chemical structure was elucidated by R. S. Kahn. Although CBN was the first phytocannabinoid to be identified in this way, researchers had yet to comprehend the scope of phytocannabinoids or their significance. However, that would soon change.


By the 1940s, phytocannabinoid research was coming into its own, ironically after the federal government had already made cannabis illegal for sale, possession, and consumption in 1937. Throughout the '40s and '50s, the first cannabis pharmacological experiments in the U.S. were conducted. These studies included known phytocannabinoids like THC, CBN, and Cannabidiol (CBD).


It was this research into the pharmacological influence of phytocannabinoids which paved the way for Mechoulam and others to identify the structure of these compounds in the 1960s and 1970s, as well as identify a key component of what makes cannabinoids work: the endogenous cannabinoid system (ECS). The ECS is an internal system of cannabinoid receptors and endogenous chemicals called endocannabinoids. The ECS regulates a wide range of bodily functions governed by the central nervous system and immune system. It is the ECS, and the phytocannabinoids' interactions with it and one another, that underpin the entirety of cannabis' therapeutic potential. 


The receptors of the ECS, which Mechoulam and other researchers called the CB1 and CB2 receptors, would later be discovered in the 1990s, and it was clear these were related to the pharmacological activity associated with phytocannabinoids. 


Today, it is this research that underpins our understanding of the therapeutic effects of cannabis. Phytocannabinoids, along with other compounds like the aromatic terpenes, interact with one another and the cannabinoid receptors of the ECS to produce a wide range of effects related to the mental and physical wellness of the consumer. That much is clear from this research, but how to harness these facts to further improve medical treatment outcomes and general well-being remains the focus of ongoing cannabis research.
 

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