26 May The Origins of Cannabis and the Discovery of the Endocannabinoid System
While prescribing CBD and medicinal cannabis to patients may seem like a new option, cannabis is a plant with a history spanning thousands of years. Over time, it has been utilised for various purposes, including medicinal, recreational, and industrial applications. Its journey from ancient use to contemporary scientific exploration is intertwined with the discovery of the endocannabinoid system (ECS)—a complex network in humans and animals that plays a crucial role in maintaining homeostasis, cellular communication, and internal regulation.
Ancient Origins and Early Uses of Cannabis
Cannabis is believed to have originated in Central Asia, with evidence of its use dating back over 12,000 years. Ancient civilizations, including the Chinese, Egyptians, and Indians, used cannabis for its psychoactive and medicinal properties. In 1841, an Irish physician returning from British India introduced cannabis to Western medicine. Initially, he tested dosing and safety on animals and used these findings to help treat symptoms of rabies, cholera, tetanus, and infantile convulsions in humans.
Through the 19th century, medicinal cannabis was considered mainstream medicine before its prohibition in the 20th century, leading to a cessation of medical use and further scientific research until recent times. Globally, different countries have varying legislation, but cannabis was legalised in Australia for medical purposes in 2016. Uptake was initially slow, but since 2019, there has been a significant increase in the number of Australians prescribed cannabis for medical reasons. In more recent years, this trend has also impacted the interest in prescribed cannabis for pets.
The Cannabis Plant, Phytocannabinoids, and Their Role
There are thousands of cannabis plant species, known as chemovars (commonly referred to as strains), each containing various combinations of cannabinoids, terpenes, and flavonoids. The two most studied and abundant phytocannabinoids are tetrahydrocannabinol (THC) and cannabidiol (CBD). While THC is known for its psychoactive effects, CBD is non-psychoactive, non-addictive, and has been studied for its potential therapeutic benefits, including anti-inflammatory, analgesic, and anxiolytic properties.
In addition to these major cannabinoids, there are over 140 other minor cannabinoids, as well as terpenes and flavonoids, found in the plant with additional analgesic, antidepressant, anti-inflammatory, and cytoprotective properties. The entourage effect is a theory suggesting that the various compounds in cannabis work synergistically to produce a more significant therapeutic effect at potentially lower doses than any single compound alone.
The Discovery of the Endocannabinoid System
The endocannabinoid system was named after the plant that led to its discovery. Despite its long history, the scientific understanding of cannabis and its effects on the human body remained limited until the mid-20th century. In 1964, Israeli chemist Raphael Mechoulam isolated and identified tetrahydrocannabinol (THC), the primary psychoactive component of cannabis. This groundbreaking discovery paved the way for further research into the plant’s active compounds and their interactions with the human body.
In the late 1980s to mid-1990s, scientists discovered the two cannabinoid receptors: CB1, primarily in the brain, and CB2, primarily in the immune system. These discoveries led to the realization that the body has a complex system, now known as the endocannabinoid system (ECS), which interacts with cannabinoids to regulate various physiological processes. It is important to understand the ECS as it is one of the targets of cannabinoid therapy.
Components of the Endocannabinoid System
The endocannabinoid system is composed of three main components:
- Endogenous Cannabinoids (Endocannabinoids): Naturally occurring compounds in the body that bind to cannabinoid receptors. The two primary endocannabinoids are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). They are synthesized and deployed as needed, rather than being stored in the body.
- Cannabinoid Receptors: CB1 receptors are predominantly found in the central nervous system, including the brain and spinal cord, while CB2 receptors are primarily located in the peripheral nervous system and immune cells.
- Enzymes: Responsible for the synthesis and degradation of endocannabinoids. Key enzymes include fatty acid amide hydrolase (FAAH), which breaks down anandamide, and monoacylglycerol lipase (MAGL), which degrades 2-AG.
Species-Specific Variations in the ECSResearch has shown that the ECS is present across nearly all animal species, with some variations in receptor distribution and function. Research has shown, in canines, CB1 receptors are found in the brain, salivary glands, hair follicles, skin, and hippocampus. Notably, younger dogs exhibit lower CB1 receptor expression compared to older dogs. Additionally, species differences have been observed, such as the higher density of CB1 receptors in the hindbrain structures of dogs, particularly the cerebellum, brainstem, and medulla oblongata. This anatomical variation helps explain the clinical presentation of dogs exposed to higher levels of THC.
CB2 receptors in dogs are primarily located in immune cells, including B cells, T cells, macrophages, mast cells. These receptors play a role in modulating the release of cytokines and have been shown to be upregulated during stress, inflammation, nerve damage, or illness. CB2 agonists have demonstrated strong anti-inflammatory properties and can reduce mast cell degranulation.
The journey of cannabis from ancient use to the discovery of the endocannabinoid system highlights the intricate relationship between humans and this remarkable plant over time. While the ECS was unknown to scientists until the mid-1990s, its identification has opened new avenues for understanding how cannabis and its compounds interact with the body. As research continues, the potential therapeutic applications of cannabinoids and the ECS hold promise for advancing medical and veterinary science, offering new hope for treating a variety of health conditions in both humans and animals.
See you next month!
Jen and the team at PetCann