The (Faux) Controversy Surrounding THC:
Tetrahydrocannabinol, aka THC, is the most abundant cannabinoid in modern cannabis and is often defined as the ‘main psychotropic component’ of the cannabis plant. This is the cannabinoid most responsible for the intoxicating effects of cannabis, the reason for its widespread and centuries long use as a recreational drug, and consequently, the reason for its continued federally illegal status as a potential drug of abuse. While these points are widely accepted, they do not discount the fact that THC is also considered an important medicinal cannabinoid as well.
For decades, THC use has been supported by physicians for a variety of conditions in people, but there is much less known about its effects in veterinary species. This is due, in part, to the aforementioned legal hurdles and the resultant paucity of veterinary research results, but also due to the persistent stigma surrounding this molecule. As a result, many have dismissed its potential use in veterinary medicine
Further complicating the issue are the numerous misconceptions that exist about THC and its use in pets. It’s easy to find statements such as “THC is toxic to dogs” or “avoid products containing any THC” when researching various media sources. These notions are misleading and, at the very least, need to be clarified. The multitudes of publications stating that this molecule is toxic, without any qualification or description, only leads to more confusion. In fact, in a recently published veterinary research paper, the author stated that “THC is toxic to dogs” in the introduction, and yet, the product utilized in the study contained THC.3 Veterinary medical providers are understandably hesitant to consider the possibilities because they are receiving mixed messages. This decades old attitude of fear surrounding THC needs to change.
Therefore, as a professional community, we must strive to understand THC and its effects, so that we can make responsible decisions about utilizing cannabis containing this remarkably diverse and physiologically active component.
The Endocannabinoid System (ECS) and the Role of THC:
Basic knowledge of the endocannabinoid system (ECS) is essential to understand how the different phytocannabinoids (plant-based cannabinoids) interact with it.
The ECS is an intricate regulatory system found within all complex animals, from fish to humans. It supports such diverse functions as memory, digestion, motor function, immune response, appetite, pain, blood pressure, bone growth, and the protection of neural tissues.4 Overall, it is responsible for the homeostasis of the body, and accomplishes this through interaction with other major physiologic systems. While a thorough description of the ECS is beyond the scope of this article, to briefly summarize, it is comprised of7:
- Cannabinoid receptors. G-protein coupled receptors CB1 and CB2, however, receptors from other physiologic systems also play a part.
CB1 receptors are mainly located in the nervous system
CB2 receptors are mainly located in the tissues of the immune system
- Endogenous ligands (Endocannabinoids). Synthesized on demand, the most well-known and studied are Anandamide and 2-AG.
- Enzymes needed for ligand biosynthesis and inactivation. MAGL and FAAH are examples.
Phytocannabinoids, such as THC and CBD, are similar in structure to endocannabinoids, and also interact with the ECS. THC is a partial agonist for both CB1 and CB2 receptors,5 and can have profound, wide ranging physiological effects on any species with an endocannabinoid system (ECS), both human and animal. It is highly lipid soluble and rapidly distributed into the tissues and crosses the blood-brain barrier. Regardless of the species, THC’s intoxicating effects are due to its interaction with the CB1 receptor. 15
Species variations in the effects of THC:
There is a difference between humans and various companion animal species when it comes to metabolizing phytocannabinoids, and there is much we need to learn. We know that the effects observed in different species are related to the endocannabinoid system and concentration and locations of the cannabinoid (CB) receptors, especially the CB1 receptor in the brain.
Cannabis is extremely safe for people, as there has never been a reported death due to ‘overdose’ of cannabis for human beings.8 This is due to the location of the CB1 receptors in the human body and the fact that they are not prevalent in the brain stem or medulla oblongata, the organs responsible for controlling vital autonomic functions such as respiration and heartbeat.6 That is why, as opposed to opioids, cannabinoids do not cause fatal consequences by depressing respiration in people.
In veterinary patients, there are species differences in the locations of these CB receptors and as a result, differences in the effects of THC. One of the most important facts to consider is that the canine is the species that has the highest concentration of CB1 receptors in the hind brain structures; the cerebellum, brainstem, and medulla oblongata, and consequently, is the most sensitive to the effects of THC.9,10,21
For the above reasons, excessive stimulation of these CB1 receptors leads to adverse effects in the motor, balance, and coordination functions that are controlled by the cerebellum. That is why, when they receive too much THC, dogs suffer from a unique set of symptoms known as static ataxia.11 We know less about the ECS in cats, but statistically, they are less likely to suffer from accidental intoxications due to dietary indiscretion, as dogs often do. Symptoms of static ataxia12 typically manifest as one or more of the following:
- Severe ataxia and stupor
- Rocking side to side with a wide based stance
- Glazed over eyes, mydriasis
- Urinary incontinence
- Falling over
- Changes in heart rate, typically bradycardia
- Seizures, other neurologic effects
When this occurs, it is typically from doses of THC that are vastly inappropriate, usually via accidental ingestion of human products. The clinical presentation can vary depending on the dose of THC the dog was exposed to, the time frame since exposure, as well as size, age, and any other underlying medical conditions present.
When required, inpatient treatment consists of decontamination, if appropriate, and general supportive care (maintaining hydration, body temperature, anti-emetics, etc.), but may require hospitalization and closer monitoring, lasting from 1-3 days on average. Intravenous Lipid Emulsion (ILE) has been suggested and used with varied success.15 Even in severe cases, the majority of dogs that suffer from this type of adverse event recover completely with basic supportive care and no long-term side effects.12
THC has a Wide Safety Margin Compared to most Pharmaceuticals:
Remember that the adverse effects of THC are dose dependent. And while the severity of signs in some cases can be extreme, THC is still considered to have a wide safety margin in dogs. An LD50 has not yet been established.15 The minimum lethal oral dose is greater than 3000 mg/kg, a dose that is 1000 times the dosage where behavioral effects are observed.12 In fact, in the study where dogs were given oral doses of up to 3 grams (3000 mg) per kilogram, no deaths ensued.13 In another report of over 200 case studies with which the ASPCA’s poison control center consulted, dogs suffered from adverse reactions after consuming various high doses of marijuana, the highest dose being 26.8 grams (2680 mg) per kilogram. This retrospective analysis of case reports dealt with these pets accidentally ingesting marijuana in various forms, the majority being the dried flower, therefore making exact amounts of THC difficult to assess. All the dogs developed clinical signs and were treated by a veterinarian.
Most importantly, in the above review, despite the severity of clinical signs that developed, every one of the dogs who were followed up with made a full recovery.14 If we were to compare the excessive doses listed above with similar excessive doses of other pharmaceutical classes, it is doubtful that the patients would fare so well. And yet, veterinarians rightly focus on the beneficial effects of pharmaceuticals, not the potential for adverse signs when an accidental overdose is given. We need to approach THC in the same way. If given in a safe, cautious manner, signs of toxicity can be avoided!
Potential clinical indications for THC:
Since its discovery in 1964, a long list of medicinal qualities of THC has been elucidated, and we are still continually discovering new beneficial uses. There is currently research being done on the therapeutic use of cannabis for multiple species all around the world. Some of the more common and well-known physiologic effects of THC5 are:
- Anxiolytic (at low doses)
- Appetite stimulant/Anti-emetic (works peripherally and centrally)
- Gastrointestinal support
- Promotes sleep
- Reduces intraocular pressure
Despite some species variations, many of the same biological interactions occur across species,6 possibly because the CB1 structure remains similar among mammals.21 Therefore, clinicians may begin to consider the above potential indications for their patients.
In addition, numerous anecdotal reports exist for the successful use of THC in veterinary patients for multiple reasons. For example, the senior pet with severe pain that is uncontrolled by traditional medications or CBD-only products, the cancer patient suffering from the effects of the disease, as well as the side effects of traditional chemotherapy drugs, or the cat with severe inappetence that will not take any food willingly. These are all situations where THC, when used judiciously, may be helpful, and the benefits may far outweigh any potential risks.
Arguments in support of the addition of THC in veterinary medical cannabis formulations:
There is sound, scientifically based evidence to support the argument for the added benefit of THC in the medicinal use of cannabis.16
–The “entourage effect.” This concept refers to the synergistic activity and increased medicinal benefit and safety when using whole plant products, those that contain all the active medicinal components from the plant. Numerous studies have shown that using cannabis in this manner results in effects that are far superior to using a product with a single isolated cannabinoid, such as a CBD-only product. In fact, only very small amounts of THC are needed to achieve this end, and CBD acts to modulate the undesirable effects of THC.16,18
-Enhanced potency. Increasing the THC component of the cannabinoid profile in a balanced product increases the strength of the effects. This cannabinoid is more powerful for numerous conditions and its addition can improve the efficacy and duration of the desired clinical benefit.
–Specific clinical indications. THC provides unique effects that cannot be achieved by using cannabis preparations without it. For example, the anti-emetic effects, appetite stimulation, broncho-dilatory effects and reduction of intraocular pressure are all largely due to THC and using a product without it is less likely to be successful.
Many practitioners with clinical experience will attest to the benefits of utilizing this powerful cannabinoid. Recently, while discussing this topic with noted veterinary cancer specialist and alternative practitioner, Dr. Trina Hazzah, DVM, DACVIM(O), CVCH, she stated “From an oncology perspective, it is rare that CBD works well without THC, for a sustained, durable response.”
Evidence to support the safety of THC in veterinary patients:
Fortunately, we have colleagues in other areas of the world that are not subject to the same legal restraints placed on scientific research using THC in veterinary patients. There are some recent veterinary studies using THC in companion animals, and more on the way. Researchers are shifting their focus to safety and efficacy of cannabis for companion animals, as opposed to the numerous papers highlighting the toxicity or deleterious effects.
In fact, a small study20 not yet published, used 2 different formulas of THC and CBD, (in ratios of 2:1 and 1:2), as well as MCT oil placebo on healthy dogs. This randomized, 3 group, parallel dose evaluation study sought to determine the safety and bioavailability of these 2 cannabinoids, as well as their influence on pain and inflammatory pathways associated with the ECS. The doses used were conservative and closely approximated those typically used in a clinical setting (0.24 mg/kg THC and 0.12 mg/kg CBD or vice-versa.) The results reported in the company press release showed that both THC and CBD have the ability to modify pain and inflammatory responses in dogs. Importantly, the dogs treated in this study had no psychotropic or adverse effects.
Another recently published paper19 looked at the safety and tolerability of escalating doses of 3 different cannabis formulations: CBD, THC, and a ratio product containing both CBD and THC in a 1.5:1 ratio. This randomized, placebo controlled, blinded, parallel study tested the above formulas against 2 placebos in healthy dogs, and evaluated the occurrence and severity of adverse events (AEs) during a series of up to 10 increasing doses. In the THC group, the researchers were able to increase the dose of THC in the majority of subjects to approximately 49 mg/kg, an extremely high dose. Despite this, most overall side effects in this group were mild. In the CBD:THC ratio group, the severity of side effects was increased over the other study groups, prompting the need for further research. It is important to note that this study used a rapid dose escalation rate, short escalation interval, and remarkably high doses. However, it is reasonable to infer, using this information combined with other research and anecdotal evidence, that if the THC was given using a protocol of lower starting doses combined with a longer dose escalation interval, as is typically recommended, the safety margin would likely increase exponentially.
This information, and other significant research will continue to improve our knowledge base and confidence in using these powerful substances.
For more information on dosing of medical cannabis for veterinary patients, click here: (Internal link to dosing article.)
What does the future hold?
While some of the current studies available have yielded valuable results, others may have asked more questions than answered, as well as uncovered more deficits in our knowledge than was previously realized. Nevertheless, it is encouraging to see the worldwide effort currently underway to obtain this vital information. We have much to learn, and this process of information gathering will take decades or more.
We need research data for all manner of veterinary cannabinoid therapeutics, such as: determining species-specific safety and efficacy profiles, indications for different disease conditions, cannabinoid ratios and their effects, long term studies, etc. This information will continue to slowly emerge and our knowledge about both the indications, and contraindications, of THC in various species will continue to grow. Until then, it is imperative that we proceed slowly and cautiously, but with open minds….and to use the credible information that we DO have, from all sources.
It is important to note that, at this time, THC containing products derived from marijuana are still considered Schedule 1 controlled substances and cannot be prescribed by veterinarians. The laws that currently exist for medical cannabis use, by their express language, seem only to apply to human patients. However, it is worthwhile to add that in California, as of 2019, veterinarians are legally allowed to discuss the use of medical cannabis in their patients, within the bounds of the veterinary-client-patient relationship.22
As a professional community, we need to shift our stance to from “THC is toxic” to perhaps the more qualified position of “THC, if used inappropriately, can result in signs of toxicity…just like any powerful pharmaceutical.” In order to move forward and embrace the potential of THC, changing our attitude is the first step in initiating meaningful, productive discussion on its effective use in our patients.
After all, THC should not be demonized, if used in a safe, judicious manner, it holds the potential for profound medicinal benefits, for all species.