Pets and pot: Highlights on therapeutic marijuana and cannabinoids

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Given the in-flux status of the legalization of marijuana across the United States, it's not surprising that veterinarians are being asked questions about marijuana use for clients' pets, says Dawn Boothe, DVM, MS, PhD, DACVIM, DACVCP, who lectured at a recent Fetch dvm360 conference.

To date, marijuana is a schedule 1 controlled substance in the United States, meaning it has no currently accepted medical use and has a high potential for abuse. With several states legalizing medicinal marijuana, advocates are pushing for a degradation to at most a schedule 2 status, indicating that although the potential of abuse is high, it has significant clinical indication, Dr. Boothe says. However, marijuana has been cultivated and used therapeutically in the world for more than 5,000 years. In fact, up until prohibition in the United States, it was the most commonly prescribed therapeutic intervention in human medicine.1

The marijuana, or hemp, plant contains over 450 unique chemicals, the most well-known of which are more than 70 cannabinoids. The most pharmacologically and toxicologically relevant as well as the most well-understood cannabinoid is tetrahydrocannabinol (THC), Dr. Boothe states. THC is responsible for most of the psychotropic or behavioral effects of the Cannabis plant, and it acts by binding to the CB-1 receptor in the brain. Another phytocannabinoid that is emerging as pharmacologically important is cannabidiol (CBD). This cannabinoid appears to retain many of the potentially therapeutically beneficial effects of THC but without the undesirable psychotropic effects. Further, CBD may antagonize some of the unpleasant side effects of THC, such as anxiousness.

In humans, the potential efficacy of marijuana for controlling pain has led several states to pass legislation allowing medical use. This has led the DEA and FDA to ask for scientific evidence for this and other medical uses of marijuana or its constituents, Dr. Boothe says. Other proposed indications for medical marijuana include behavioral issues, sleep and gastrointestinal disorders, anorexia, nausea, glaucoma, diabetes, immunosuppression and malaria, along with conditions helped by agents with neuroprotective, antispasmodic, prokinetic or anti-inflammatory properties.2

In pets, regulatory issues regarding the use of medical marijuana are unclear and likely to remain so for some time, Dr. Boothe notes. Legalization of marijuana is focused on human rather than veterinary use at this time.

The term “marijuana” generally refers to the dried leaves or flowering part of the Cannabis species plant. The cannabinoids found in the plant vary with the part of the plant. An animal's response to the cannabis plant will be much different if it is exposed to the flowering portion of the plant as compared with the stem, Dr. Boothe says. The stem contains very little THC but a high proportion of CBD and other nonpsychotropic cannabinoids as well as flavonoids, terpenoids and other potentially beneficial compounds, Dr. Boothe says. The DEA has clarified its regulation of marijuana, noting the products derived from the parts of the plant that have only a trace of cannabinoids are not considered marijuana and thus are not subject to schedule 1 regulation.

However, extractions from portions of the plant that do not contain high cannabinoid content often contain more than trace amounts of cannabinoids, rendering them subject to DEA regulation as a schedule 1 product. As such, the legality of products containing little THC but high amounts of CBD is not clear. Further, interstate transport of these products has not been addressed. Manufacturers of these supplements claim they are effective for analgesia without psychotropic effects. Currently, though, no data exists regarding the efficacy of any portion of the hemp plant as an analgesic or for other therapeutic indications in companion animals, Dr. Boothe notes.

Cannabinoids of medical significance appear to undergo first-pass metabolism and, as such, the risk of toxicity with inhalant products is much greater than with oral products, Dr. Boothe says. The implication for medical use, then, is that oral administration may not be cost-effective. The drug is eliminated by hepatic metabolism and biliary excretion in five days in dogs. Cannabinoids are very safe in dogs; indeed, a life-threatening dose of THC is hard to determine. “Toxicity” often reflects ingestion of another compound in the product eaten, such as chocolate.

The most common clinical signs of toxicosis following ingestion in dogs are extremely variable, but may include tachycardia or bradycardia, hypotension, depression, ataxia, vomiting (inducing emesis is not recommended in clinically depressed dogs because of the risk of aspiration), altered behavior, hypersalivation, weakness, hypothermia and seizures, Dr. Boothe says. In terms of treatment for toxicosis cases, care is largely supportive, with sedation with benzodiazepines or phenothiazines as needed-antiemetic therapy may also be indicated. Currently, no over-the-counter test for drugs of abuse in humans appears to be accurate or sensitive in the detection of marijuana toxicity.

As more research is done into the therapeutic effects of marijuana, the potential for wider legalization and more options for alternative therapies for patients may become a possibility.

References

1. Kreitzer FR, Stella N. The therapeutic potential of novel cannabinoid receptors. Pharm Ther 2009; 122:83-96

2. Izzo AA: Non-psychotropic plant cannabinoids: new therapeutic opportunities from an ancient herb. Cell Press 2009; 30(10):515-527.