Exploring questions surrounding THC (trans-Δ9-tetrahydrocannabinol), the “other” cannabinoid, its safety, legality and place in the veterinary field.
In the last issue, we looked at veterinary indications for CBD and the complex regulatory picture affecting its use. While CBD products for both humans and animals have already taken over your local farmer’s market, coffee shop and feed store, the “other” cannabinoid, THC (trans-Δ9-tetrahydrocannabinol), is another can of worms altogether. Many federal, state and local cannabis regulations conflict with each other and are in flux, so if you are confused, join the club! Here are the big questions most vets are wondering about:
- Does THC have useful indications in veterinary medicine?
- Is it safe for pets?
- Is it legal for veterinarians to recommend or dispense THC-containing products?
This article will help provide answers to these questions.
1. Is this THC a useful medicine for pets?
There is considerable overlap in the effects of THC and CBD, the principle compounds found in the Cannabis sativa plant (see chart below). THC-rich compounds can be an important clinical adjunct to treating severe pain and neurologic disorders,2-4 in the treatment of cancer,5-10 and in complex gastrointestinal imbalances.11-13 Because of the decades-old prohibition of cannabis research, we are only just learning the many roles of the endocannabinoid system (ECS), which includes CB1 and CB2 receptors as well as their endocannabinoid ligands and the ligands’ synthesizing/degrading enzymes. Broadly speaking, the ECS is the mechanism through which the nervous system and immune system (inflammatory reactions) communicate and balance each other.
It is probable that many chronic neurologic syndromes, such as multiple sclerosis, refractory epilepsy, brain tumors, Parkinson’s disease, Alzheimer’s disease, traumatic brain injury/chronic traumatic encephalopathy,2 amyotrophic lateral sclerosis (ALS) and its canine analogue, degenerative myelopathy,3 have their origins in ECS dysfunction. THC is a partial agonist of both CB1 and CB2 receptors in the CNS, and is a phyto-mimetic for the neurotransmitter AEA (anandamide, also known as N-arachidonoylethanolamine).
While the psychoactive properties of THC are legendary, its analgesic properties are in large part mediated outside the endocannabinoid system: THC is a positive allosteric modulator of mu and delta opioid receptors, so it enhances the endogenous enkephalin response and potentiates any exogenous opioid medications.4 Because of this phenomenon, compassionate “medical marijuana” use has long been approved for severe chronic pain conditions.
In human medicine, THC has been used to alleviate the side effects of oncology treatments in addition to pain management, and as an anti-emetic and appetite stimulant to address cancer cachexia. However, growing research indicates that phytocannabinoids, both CBD and THC, also have direct anti-tumor effects. The National Cancer Institute states as follows:
“Cannabinoids may cause antitumor effects by various mechanisms, including induction of cell death, inhibition of cell growth, and inhibition of tumor angiogenesis invasion and metastasis.5-8 Two reviews summarize the molecular mechanisms of action of cannabinoids as antitumor agents.9,10 Cannabinoids appear to kill tumor cells but do not affect their non-transformed counterparts and may even protect them from cell death.”
Some of the more exciting recent research trends concern the role of the ECS in the gastrointestinal tract,11-13 leading to applications for phytocannabinoids in managing chronic disorders like inflammatory bowel disease. Cannabinoid receptors are fundamentally involved in all aspects of intestinal physiology, such as motility, secretion, and epithelial barrier function. The ECS has a strong impact on the pathophysiology of the gastrointestinal tract, and is believed to maintain homeostasis in the gut by controlling hypercontractility and promoting regeneration after injury.
2. Is THC safe?
3. Is it legal for you to prescribe or even discuss cannabis for pets?
1Silver R. Veterinary Medical Cannabis: Part One. NYS Veterinary Conference, Cornell University, October 2018.
2Russo EB (2018). “Cannabis Therapeutics and the Future of Neurology”. Front Integr Neurosci. 12: 51.
3Fernández-Trapero M, Espejo-Porras F, Rodríguez-Cueto C, Coates JR, Pérez-Díaz C, de Lago E, Fernández-Ruiz J (2017). “Upregulation of CB2 receptors in reactive astrocytes in canine degenerative myelopathy, a disease model of amyotrophic lateral sclerosis”. Dis Model Mech. 10 (5):551-558.
4Kathmann M, Flau K, Redmer A, Tränkle C, Schlicker E (February 2006). “Cannabidiol is an allosteric modulator at mu- and delta-opioid receptors”. Naunyn-Schmiedeberg’s Archives of Pharmacology. 372 (5): 354–61.
5Guzmán M (2003). “Cannabinoids: potential anticancer agents”. Nat Rev Cancer. 3 (10): 745-55.
6Blázquez C, Casanova ML, Planas A, et al (2003). “Inhibition of tumor angiogenesis by cannabinoids”. FASEB J 17 (3): 529-31.
7Vaccani A, Massi P, Colombo A, et al (2005). “Cannabidiol inhibits human glioma cell migration through a cannabinoid receptor-independent mechanism”. Br J Pharmacol 144 (8): 1032-6.
8Ramer R, Bublitz K, Freimuth N, et al (2012). “Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1”. FASEB J 26 (4): 1535-48.
9Velasco G, Sánchez C, Guzmán M (2012). “Towards the use of cannabinoids as antitumour agents”. Nat Rev Cancer 12 (6): 436-44.
10Cridge BJ, Rosengren RJ (2013). “Critical appraisal of the potential use of cannabinoids in cancer management”. Cancer Manag Res 5: 301-13.
11Taschler U, Hasenoehrl C, Storr M, Schicho R (2016). “Cannabinoid Receptors in Regulating the GI Tract: Experimental Evidence and Therapeutic Relevance”. In: Greenwood-Van Meerveld B. (eds) Gastrointestinal Pharmacology. Handbook of Experimental Pharmacology, vol 239. Springer, Cham.
12Hasenoehrl C, Taschler U, Storr M, Schicho R (2016). “The gastrointestinal tract – a central organ of cannabinoid signaling in health and disease”. Neurogastroenterol Motil Dec; 28(12): 1765–1780.
13Uranga JA, Vera G, Abalo R (2018). “Cannabinoid pharmacology and therapy in gut disorders”. Biochem Pharmaco Nov;157:134-147.
14Thompson GR, Rosenkrantz H, Schaeppi UH, Braude MC (1973). “Comparison of acute oral toxicity of cannabinoids in rats, dogs and monkeys”. Toxicology and Applied Pharmacology 25(3), 363-372.
15Meola SD, Tearney CC, Haas SA, Hackett TB, Mazzaferro EM (2012). “Evaluation of trends in marijuana toxicosis in dogs living in a state with legalized medical marijuana: 125 dogs (2005-2010)”. J Vet Emerg Crit Care (San Antonio) Dec;22(6):690-6.
16Freundt-Revilla J, Kegler K, Baumgärtner W, Tipold A (2017). “Spatial distribution of cannabinoid receptor type 1 (CB1) in normal canine central and peripheral nervous system”. PLoS One Jul 10;12(7):e0181064.
17Richter G, DVM. Personal communication.