Updated: Oct 9, 2022
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Welcome to Higher Learning LV's Study Summary series. This series reviews and summarizes peer-reviewed research studies and was developed specifically for cannabis industry professionals. These study summaries provide easily digested quick reads for a variety of important issues regarding the commerce and chemistry of legal cannabis.
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A 2019 study entitled "The Endocannabinoid System of Animals" that was published in the journal Animals explored how the endocannabinoid system (ECS) manifests in the animal kingdom. The study compared the efficacy of major hemp/cannabis-derived cannabinoids, including cannabidiol (CBD) and tetrahydrocannabinol (THC), in animals with how they affect humans.
Many cannabis consumers and enthusiasts are unaware that all mammals feature an ECS. In common pets like cats, dogs, and horses, the ECS shares many characteristics with that found in humans, binding with the same molecules (including CBD and THC). Consumers may be surprised to learn that more simple pets, including gold fish and turtles, also feature an ECS.
The commonality of the ECS among creatures on Earth allows researchers to study animals with the goal of better understanding how best to maintain not only their health, but also to develop treatments and therapies for humans. "This review article introduces the reader to the ECS in animals and documents its potential as a source of emerging therapeutics," noted the study.
"Many cannabis consumers and enthusiasts are unaware that all mammals feature an ECS. In common pets like cats, dogs, and horses, the ECS shares many characteristics with that found in humans."
In All Animals—Except Protozoa & Insects
"Common to nearly all animals except the Phyla Protozoa and Insecta, the endocannabinoid system arose...concurrently with the development of the nervous system as multicellular animals developed increasing complexity," reported the study. It noted that the ECS was unknown to the world of science until as recently as the the mid-1990s, but that research into "this fascinating and clinically useful system" is rapidly advancing.
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The study reported that, compared to the "studies and information available about both the medical and health benefits derived from cannabinoids in the human animal, there is still a paucity of information regarding the same benefits in animals, except for the laboratory animal species in which experimental studies have been performed."
To get an idea of just how pervasive the ECS is among animals, the study's authors showcased the very few species "that did not show evidence of cannabinoid binding." These included the "sea anemone (A. albocincta) and sponge (T. aurantium)" for which the study noted "CB1 receptors were [found], but CB2 receptors were not detected." Even these primitive creatures feature CB1 receptors—just like humans, dogs, cats, ferrets, and monkeys.
"Even worms and nematodes have been found to feature a crude ECS."
Even worms and nematodes have been found to feature a crude ECS. "The earthworm (L. terrestris), velvet worm (P. novae-zealandiae), and mat nematode (P. redivivus) were compared to a standard CB1 [receptor] in rat cerebellar tissue and were found to have high affinity binding interactions at concentrations typically found with CB1 receptors."
Interestingly, insects feature no ECS. "Insects (Apis mellifera [western honey bee]), Drosophila melanogaster [common fruit fly], Gerris marginatus [water strider], Spodoptera frugiperda [fall armyworm moth larva], and Zophobas atratus [darkling beetle]) do not [feature] cannabinoid receptors," reported the study.
The study reported that the terpenes produced by cannabis—the molecules responsible for the sometimes pungent aroma and flavor of the herb—alongside cannabinoids, provide "potent anti-inflammatory activity." The scientists identified a number of terpenes that have demonstrated pronounced anti-inflammatory benefits, including "α-pinene [the most common terpene in the world], β-myrcene [the most common terpene in cannabis], β-caryophyllene [BCP; one of the most common terpenes in cannabis], and limonene [the second most common terpene in the world]."
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"Of the terpenes, both β-caryophyllene and limonene have been found to bind to cannabinoid receptors, which reduce inflammation." More precisely, these terpenes bind with the CB2 receptor in the ECS. The study noted that BCP and limonene "can compete with THC for CB binding sites" and, thus "both [terpenes are] known to antidote THC excesses by replacing the THC bound to the CB receptor with one of these two terpenes."
"Historically, lemon products and spicy products with black pepper and cloves have been used due to their limonene and beta caryophyllene content, respectively, for excesses of THC, panic attacks, and tachycardia [increased heart rate]," reported the study.
Pain & Endocannabinoids
The review reported that the endocannabinoids 2-AG and anandamide (which are mimicked by the phytocannabinoids CBD and THC, respectively) "modulate the neural conduction of pain signals by reducing the...neural signal of pain and by reducing inflammation by activating cannabinoid receptors."
It noted that the CB2 receptors of the ECS "up-regulate with peripheral nerve damage" and that ECS receptors "regulate neuroimmune interactions and interfere with inflammatory hyperalgesia [increased sensitivity to pain]."
"The endocannabinoids anandamide and 2-AG are produced in tissue that has been injured and activate cannabinoid receptors to suppress the sensitization of the nerve...and/or to suppress inflammation," reported the study. It also noted that the endocannabinoid anandamide (also known as the "bliss molecule" due to its important role in managing mood) modulates pain by inhibiting pain signals via the activation of CB1 receptors in the ECS and that it reduces inflammation "by activating CB2 and other receptors."
The review noted that the endocannabinoid 2-AG "plays a role in the descending modulation [decrease] of pain during acute stress" and that both anandamide and 2-AG are produced "as the body's first response to tissue injury."
The study noted that the two major cannabinoids, CBD and THC, "can benefit cancer patients by increasing appetite and reducing nausea" and stated that these characteristics of the ECS "make it an essential component of most cancer therapies."
The study also noted that "CBD reduces the production of [pro-cancer] factors in gliomas in a dose-dependent fashion" and reported that THC, "when co-administered with CBD, synergistically inhibited [cancer] proliferation and caused [cancer] cell cycle arrest" in laboratory studies involving human glioblastoma cancer cells.
Cannabinoid Safety for Dogs
"The psychoactive effects of THC are undesirable in all veterinary species," reported the study, stating that "dogs in particular will suffer from 'static ataxia' upon exposure to THC at doses [above] 0.5 mg/kg." The study labeled the THC sensitivity of dogs as "exquisite" and wrote that states with medical or adult-use cannabis laws "have seen an increase in animal ER admissions for THC toxicosis."
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The Mayo Clinic describes static ataxia as "poor muscle control that causes clumsy voluntary movements" and that it may result in "difficulty with walking and balance, coordination, swallowing, and eye movements."
Despite their sensitivity to THC, the study reported that dogs experience "a relatively good safety profile for CBD" and also for THC, but only when the latter cannabinoid is given "in moderate amounts." Your takeaway: Excessive doses of THC are bad for dogs (humans should not attempt to get their pets high, thinking they are doing them a favor).
The study labeled the sensitivity of dogs to THC as "exquisite" and wrote that states with medical or adult-use cannabis laws "have seen an increase in animal ER admissions for THC toxicosis."
"Oral tolerance to THC can be achieved in the dog following 7–10 days of a low, sub-psychotropic dose of 0.05–0.1 mg/kg twice daily by mouth," reported the study, saying that such an approach removes "the adverse neurological effects of THC." It reported that, in addition to undesired psychotropic effects, large doses of THC can also act as a sedative to dogs. "Concurrent use of CBD, in equal or greater amounts than THC, will assist in this tolerizing process," noted the scientists.
The study also noted that "excessive" and prolonged stimulation of the ECS "can create memory deficits" in humans.
The study summarized the data it collected by stating that "it is clear that the endocannabinoid system is not just present in nearly all animals, but plays an integral role in maintaining homeostasis for a number of organ systems."
The ECS "modulates the nervous and immune systems and other organ systems to relieve pain and inflammation, modulate metabolism and neurologic function, promote healthy digestive processes, and support reproductive function and embryologic development."
It noted that the ECS "modulates the nervous and immune systems and other organ systems through a complex system of receptors and chemical signaling molecules to relieve pain and inflammation, modulate metabolism and neurologic function, promote healthy digestive processes, and support reproductive function and embryologic development."
"The future looks bright as cannabinoid research, in the post-cannabis prohibition era, is finally able to provide additional discoveries regarding the role [that] the endocannabinoid system plays in the pathogenesis of disease and the maintenance of health," concluded the study's authors.
View the original study.
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