The Complex Conundrum of Cannabis

Humans have been using cannabis (Cannabis sativa) for over 12,000 years. It likely originated in Central Asia, where it grew wild, providing early hunter gatherers with fiber used for ropes and nets and with seeds for oil. At some point, our ancestors realized that the distinctive female plant contained psychoactive substances and they began using it for healing and spiritual ceremonies. It is unclear exactly when humans began to cultivate it, but as they migrated across the continents, they evidently took their cannabis seeds with them. The Scythians of the Central Eurasian steppes are credited with bringing cannabis to Europe around 1000 to 500 B.C., and from there it rapidly disseminated across the globe to Africa and the New World. Spain introduced the cultivation of hemp in central Chile within the first decade of their invasion and colonization in the 16th century and Louis Hébert, an apothecary with a practice in Paris, is said to have been the first colonist to grow cannabis in North America in 1606 in Acadia, today’s Nova Scotia

In the U.S., cannabis was widely used as a patent medicine during the 19th and early 20th centuries, having been described in the United States Pharmacopoeia (USP) for the first time in 1850. Federal restrictions on the use and sale of cannabis first occurred in 1937 with the passage of the Marihuana Tax Act. While not an outright ban, the act essentially criminalized the non-medical sale and use of the plant through excessive taxation and stringent regulations. In 1942, cannabis was dropped from the USP, and legal penalties for its use or possession increased over the following decades. The culmination of these changes was the passage in 1970 of the Controlled Substances Act (CSA) that criminalized the manufacture, distribution, and possession of cannabis. In 2018, the CSA was amended to exclude cannabis plants that contain no more than 0.3% THC (Delta-9-tetrahydrocannabinol), the cannabinoid responsible for the characteristic psychoactive effects. These low-THC cannabis plants are known as hemp, and the amendment was intended to permit their cultivation and processing for industrial uses such as fiber and rope production. Although it may not have been the intent of the amendment, its passage also allowed for the creation of the hemp-based supplement industry which in 2025 had an estimated value in the U.S. of $10B.

The hemp-based industry produces products that contain active ingredients extracted from the plant including CBD (cannabidiol), CBN (cannabinol) and CBG (cannabigerol). Some products also add THC, though as noted above under the CSA its concentration in the product must be less than 0.3%. To further complicate the matter, although these products may be compliant with the CSA, they are not considered legal dietary supplements under Food and Drug Administration (FDA) regulations. This is because both CBD and THC have been approved as prescription drug products, and therefore they are excluded from the definition of a dietary supplement as defined in the Dietary Supplement Health and Education Act of 1994 (DSHEA). CBD is approved to treat rare severe seizure disorders in children (Epidiolex; Jazz Pharmaceuticals) and a synthetic form of THC (dronabinol) is approved to treat chemotherapy-induced nausea and vomiting (Marinol; AbbieVie) and to stimulate appetite in patients with HIV/AIDS (Syndros; Benuvia Manufacturing). Nevertheless, although products containing CBD and THC cannot technically be sold as dietary supplements, these products are not hard to find online and in many retail stores. To avoid the attention of the Drug Enforcement Agency (DEA), most retailers label these products as being consistent with the 2018 Farm bill, (i.e., containing less than 0.3% THC).

While the legalities of hemp-based dietary supplements are murky, regulations around cannabis-based products, (i.e., plants containing > 0.3% THC, commonly referred to as marijuana) are even more convoluted. In fact, in some states, federal and state laws are in direct conflict. For example, federally, cannabis is still classified as a Schedule I controlled substance under the CSA, meaning it has no accepted medical use and high potential for abuse. There have been proposals to change its classification to a Schedule III substance, which would indicate that it does have legitimate medical uses, but that process is ongoing. Regulation of cannabis at the state level varies tremendously. For example, roughly 24 states and Washington D.C. have legalized the recreational use of cannabis for adults, and another 13-14 states permit cannabis for qualifying medical conditions with a physician's recommendation. Only a handful of states, concentrated in the South, still ban all cannabis use. The patchwork nature of regulations around cannabis create complexity and uncertainty for manufacturers, distributors, retailers, and consumers of cannabis and cannabis-derived products. For example, because cannabis businesses are illegal under federal law, banks are reluctant to serve them, and they can't deduct normal business expenses from their federal taxes. Consumers should also be aware that products they can legally purchase in one state may be illegal in another.

Legal ambiguities aside, consumers and pet owners should question whether cannabis and hemp-based products are safe and effective for themselves and their pets. In humans and pets, cannabinoids have been touted as having positive effects on everything from pain, cancer, nausea, inappetence, and inflammatory bowel disease, to name but a few. The evidence supporting their use for any specific condition, however, is extremely variable. For example, there is some positive data around their use in cancer. A recent metanalysis found that in humans cannabinoids may enhance the efficacy of chemotherapeutic agents, particularly in glioblastoma and breast cancer. Another metanalysis found that in dogs CBD consistently showed antiproliferative and proapoptotic effects but acknowledged that most of the studies were pre-clinical, limiting the significance of the findings. In terms of pain a metanalysis, examining cancer pain in humans, found that cannabinoids were not associated with consistent or clinically meaningful opioid-sparing effects. And in a similar manner, a meta-analysis found little to no evidence to support the use of cannabinoids to alleviate pain in pets with osteoarthritis (OA). Most of these studies were conducted using formulations that contained little to no THC. Several studies have evaluated the effects of full-spectrum Cannabis sativa oil, which would be expected to have relatively high concentrations of cannabinoids including THC, on pain associated with OA in dogs, and some, but not all found the oil to produce significant analgesia.

While CBD has demonstrated anti-seizure benefits and THC can help reduce nausea and stimulate appetite, evidence for the broader health claims made about these and other cannabinoids remains limited. In addition, the formulation found most efficacious, full spectrum sativa oil, would likely be considered illegal under federal law as well as in some states. Pet owners should approach cannabidiol-containing products with caution and be skeptical of claims made for both human and animal use.

Beyond questions of efficacy, pet owners should understand that dogs and cats are generally more sensitive than humans to cannabinoids, particularly THC. For example, in one retrospective study conducted in a state where medical cannabis was legal, researchers found a significant positive correlation between the number of medical cannabis licenses issued and the number of known or suspected cases of THC toxicosis in dogs. The consequences can be severe. In that study, two dogs died after ingesting baked products made with cannabis butter. The conundrum is that THC is likely responsible for the efficacy of many cannabis-derived products, but it’s therapeutic margin is narrow.

Cannabis and hemp-based products are becoming commonplace as the regulations around the use of cannabis have been relaxed in many states. As more research is conducted on this ancient plant and its derivatives, we may identify new molecules derived from these plants that have positive effects on any number of diseases, but currently apart from the FDA-approved formulations of CBD and THC there is little to support their use as therapeutic medications in humans or pets. Products containing THC also present a toxicity risk to dogs and cats. Pet owners should be cautious when using these products on themselves and their pets.

– Cindy Cole, DVM, PhD, DACVCP

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