The endocannabinoid system is composed of neurotransmitters known as endocannabinoids. Endocannabinoids are one of the most widely known, potent, and versatile signaling molecules known up to now. The receptors which serve to bind these neurotransmitters and pass on information are called the cannabinoid receptors. Two types of cannabinoid receptors are naturally found in the human body. This is probably possible due to the two receptors (i.e., CB1 and CB2 receptors) and enzymes regulating their endogenous ligands. Cannabidiol, CBD, binds to these receptors and then alters the function of these receptors and the resulting actions of the body on which these receptors and their ligands affect.
The difference of the targets to which CBD binds and exerts its effects on the body is also a point which increases doubt in the use of CBD as a pharmaceutical drug. In lab settings, controlled doses of the substance are administered to the non-human sources through carefully supervised techniques. The targets in the non-human sources are carefully studied first, before administering CBD to the subjects. That is why, the effects of CBD are not so properly studied in humans, which poses a possible threat as it may have some detrimental effects on the health of the user. CBD targets may differ between humans and animals. Therefore, the same blood concentration might still lead to different effects because of the difference in the basic body mechanisms in the human and non-human subjects. The targets to which CBD binds may even be the same in both studied animals and humans, for example, the affinity or duration of CBD binding to its targets might differ and consequently alter its effects.
CBD in Action
Along with a number of other side effects in the humans using CBD as a prolonged measure to combat brain disorder symptoms, one of the major concerns is the effect of this prolonged use on the reproductive system of the subject. Recent research has indicated that cannabinoids such as cannabidiol and THC have an impairing effect on the reproductive system. This was experimentally verified by studying the effects of CBD of fertilization in sea urchins. CBD is found to be detrimental for reproductive health in individuals who have a low sperm count in their semen. This is because, at very low sperm densities, CBD was found to inhibit active fertilization of the egg when used at a specific dosage. This meant that prolonged use of CBD is attributed to a decrease in the fertilization capacity of the sperm, thereby having a degenerative effect on the reproductive system of the individuals. Several cannabinoids such as THC and CBD were found to inhibit the much-needed acrosome reaction in the sperms, thereby showing another measure through which these substances can inhibit the fertilization of an egg by the sperm, and degrade the reproductive abilities of the individual.
The side effects of CBD are feared because this substance has not been researched enough like other drugs by clinical studies. The route of administering CBD to non-human subjects in experimental studies is largely different from the route which is used in the human subjects. The most common route of administration of CBD in humans is through using oral administration of cannabidiol oil drops, or through inhalation of the vapors of the substance which is almost similar to smoking. The administration in non-human subjects such as rodents is carried out either via the quick absorption routes such as intraperitoneal injection or via the oral route using drops. Due to the difference in the routes of administration of CBD in human and non-human subjects, the effective plasma levels reached via oral administration in non-human subjects and through inhalation in humans can differ by a considerable margin. Both these observations can lead to differing active blood concentrations of CBD. These distinct levels of CBD change the effective dosage, so the experimental studies of CBD to stimulate its effects on the brain disorders using non-human sources is not known to the researchers and remains to be a field of widespread research all over the world.
Just like most of the other chemicals, the cannabis extracts affect our brain by binding to a specific type of receptors present on the cells. When these cannabinoids bind to these receptors, they trigger some changes in the metabolic machinery of the cells. These receptors are present on the cells throughout the entirety of our central nervous system, and they are specifically called CB1 and CB2 receptors. Such receptors are found predominantly in the brain in the hippocampus and cerebellum. Because these receptors directly affect the function of the cell they are on, the psychic effects experienced after consuming marijuana have a rapid onset. The psychoactive cannabinoids such as THC result in euphoria, enhancement of sensory perception, increased heart rate, decreased pain stimuli, and difficulties in concentrating on specific tasks. These effects are due to the relative abundance of CB1 and CB2 receptors in the hippocampus. The effects may also include short term impairment of memory. These effects are largely due to the psychoactive agents found in cannabis such as tetrahydrocannabinol (THC).
The study was commissioned to evaluate the solubility, stability, acute toxicity, thermotolerance, and effects on lifespan of CBD in C. elegans as part of Canopy Growth’s ongoing commitment to provide the data required to support and influence public policy through research. To the best of the company’s knowledge, this study represents the first long-term toxicity and lifespan research regarding the effects of chronic exposure to cannabidiol—one of the cannabinoids found in cannabis.
“Despite widespread use of CBD, no life-long toxicity studies had been conducted to date to determine the impact—or potential impact—of long-term exposure to CBD,” shared Hunter Land, senior director of translational and discovery science at Canopy Growth. “These results serve as the only CBD life-long exposure data in an in vivo model to date, and the absence of long-term toxicity gives us the evidence we need as an industry to continue researching the potential health benefits for the broader application of CBD.”
Study represents the first research completed on the long-term toxicity and lifespan effects of cannabidiol in the preclinical model C. elegans
The study was conducted in partnership with NemaLife Inc., and is published in the Cannabis and Cannabinoid Research journal and available online.
Acute and long-term exposure studies of CBD at physiologically relevant concentrations were studied in the worm model Caenorhabditis elegans (C. elegans) on the basis that 60-80 percent of their genes are shared with humans, and their comparatively short lifespan of two to three weeks makes such studies feasible. In the C. elegans model, which is recognized as a valid model for this kind of research, CBD did not demonstrate any degree of acute or life-long toxicity or related liabilities at physiological concentrations. Instead, CBD extended mean lifespan up to 18 percent and increased late-stage life activity by up to 206 percent compared to the untreated controls within the study.
SMITHS FALLS, ON, CANADA — November 23, 2020 — Canopy Growth Corporation (“Canopy Growth” or the “company”) (TSX:WEED NASDAQ:CGC) and its medical division, Spectrum Therapeutics, have completed and published a new study on the long-term effects of cannabidiol (CBD), specifically focusing on toxicity and lifespan effects of CBD in the preclinical model C. elegans.