Categories
Uncategorized

How do phytocannabinoids work?

A look at endocannabinoid support and the tricky therapeutic and regulatory landscape of using CBD for pets.
The cannabidiol (CBD) craze is in full swing all over North America. Recently, it was announced that even gas stations will be selling it, not to mention supermarkets, coffee
shops and health food stores. Big money is being invested in cannabis worldwide, and as with any trade bubble, there are plenty of players trying to get in, get rich, and get out before the bubble bursts — unfortunately, this “get rich quick” scheme has produced a plethora of unreliable products. Even companies specializing in human CBD products are jumping on the bandwagon and offering pet lines as an “extra” — despite lacking knowledge of veterinary applications, dosing or protocols.

But let’s not throw out the baby with the bathwater! This mania would not exist if utilizing CBD didn’t result in remarkable benefits. While most people are familiar with the marijuana plant’s “high” effects, mediated by tetrahydrocannabinol (THC), Cannabis sativa contains
hundreds of compounds, most of which, like CBD, are not psychoactive, and have untapped therapeutic potential. The native cannabis plant has abundant CBD and a small amount of THC; however, high THC strains have been bred for recreational use.

Is CBD legal, and what about my DEA license?
Unfortunately, this is highly variable state by state. To make things even more confusing, while federal law has declared industrial hemp (less than 0.3% CBD) to be lawful, cannabis has not yet been removed from the list of Schedule One drugs, leaving a lot of room for interpretation.

In some states, like https://bestcbdoilfordogs.org California, even though both medical and recreational marijuana products are legal, veterinarians are not allowed to discuss the medical use of cannabinoids with clients. However, all these laws are rapidly changing and adapting to the hemp industry’s exponential growth over the past 18 months. If you don’t like the regulations in your state, wait ten minutes!

Unfortunately, the legal gray area is preventing vets from giving their clients the expertise they need, which leads animal owners to rely on Dr. Google.

How do phytocannabinoids work?
The endocannabinoid system (ECS) helps the nervous system and immune system communicate. The ECS is suspected to be involved in neuroprotection, immunomodulation, the fighting of cancer, pain reduction, metabolic balance and gastrointestinal motility, with effects in and around the synaptic space.1 Phytocannabinoids (cannabinoids derived from hemp and other cannabis species) can act as partial agonists of the ECS, providing pain relief through coactivation with endogenous opioid receptors. They can also reduce excessive inflammatory responses involved in chronic diseases and aging. THC primarily interacts with the CB1 receptors on nerve endings, which function to regulate neurotransmitter turnover. CBD, on the other hand, has indirect effects throughout the body via CB2 receptors, which have widespread distribution in immune cells, muscles, joints, and organs.

Can my dog or cat get high from CBD?
CBD is not a psychoactive drug. However, in a quirk of physiology, dogs have an unusually high number of CB1 receptors in their cerebellum, making them highly susceptible to THC effects — a big health risk for dogs that accidentally ingest their human’s medical or recreational marijuana “edibles” or bud. While THC is not toxic to dogs, subsequent severe ataxia and dissociation make them susceptible to secondary dangers, such as falling or aspiration pneumonia.

Pharmacokinetics of cannabinoids
Preliminary data in dogs indicates that optimal therapeutic levels are most rapidly reached through trans-mucosal 2 dosing, which avoids interaction with the liver CYP450 detoxification system. However, cannabinoids may compete for CYP450 binding sites, possibly altering or affecting drug clearance time for other medications. This list3 of affected drugs includes, but is not limited to, certain anti-seizure medications and several classes of antibiotics and cytotoxic chemotherapy drugs, so it is critically important for people to seek the advice of their human or pet health professional before using these substances on themselves or their animals. Anecdotally, dosing with cannabinoids has not been found to alter phenobarbital serum levels (G. Richter, DVM, personal communication).

Purified cannabinoids have a bell-shaped dose-efficacy curve; clinical effects increase then fall off with doses exceeding the peak efficacy for that individual. For this reason, some trial and adaptation is advisable when adding CBD to a treatment plan, because dosage may increase or decrease. Occasionally, pets receiving micro-doses of CBD for anxiety may become disinhibited — forgetting about their house-training or failing to control their aggressive instincts. This usually resolves with a further reduction of the dose. Best results are achieved when checking the dosage after three to five days for effects. Desired CBD effects, whether for pain mitigation or soothing the nervous system, should be visible within a day or two, unlike many therapeutic regimens which take weeks to load.

Indications for use of exogenous cannabinoids in animals
There are many useful applications for CBD, the non-psychoactive cannabinoid. (THC is mainly used, where legal, for cancer and end-of-life care. CBD is used for reducing anxiety and phobias, treating arthritis pain and inflammation 4 as well as neurogenic pain, mitigating idiopathic and non-drug-responsive seizure activity,5 and regulating diabetes.6 While cannabinoid research is in its infancy in the US, researchers worldwide have speculated that some neurodegenerative conditions, such as Parkinson’s disease in humans and degenerative myelopathy7 in dogs, may have their etiology in dysregulated function of the endocannabinoid system (ECS). For clinicians who have incorporated CBD into their treatment plans, it is proving to be a useful adjunct in managing many common pet ailments, especially in geriatric pets (see CBD case studies at IVCJournal.com/CBD-case-studies).

Though each individual animal’s response may vary, four levels of CBD dosing are generally used in pets:

Dose (per kg body weight) indications

Micro (0.1 mg/kg) — anxiety, fear, stress, behavioral issues, mild pain, muscle tension
Medium (0.2-0.5 mg/kg) — osteoarthritis, moderate pain, muscle spasms
High (0.5-1.0 mg/kg) — moderate to severe pain, neurogenic pain, degenerative myelopathy, tremors, idiopathic epilepsy, diabetes regulation, IBD
Ultra (1.0-5.0 mg/kg) — refractory epilepsy, anti-neoplastic, refractory pain, hospice care
In a recent study at Colorado State University College of Veterinary Medicine,8 high dose CBD treatment was associated with mild transitory diarrhea upon initiation of treatment. After long-term high-dose usage, one third of dogs showed elevated alkaline phosphatase. However, this study lacked a control group to compare environmental and stress effects with the CBD-associated effects. It is also essential to note that these results were found at doses of 10 mg/kg to 20 mg/kg, compared with the dose range of 0.1 mg/kg to 1 mg/kg, administered trans-mucosally, recommended by veterinarians with extensive experience in CBD’s clinical applications in pets. (R. Silver, Cornell NYSVMS seminar, 2018; G. Richter, CIVT webinar, 2019).

A study conducted at Cornell University 4 showed similar elevations of alkaline phosphatase, but also involved dosing at 2 mg/kg to 8 mg/kg orally, rather than the lower doses using trans-mucosal delivery. Neither study showed evidence of hepatocellular damage, so it is difficult to interpret the meaning of the changes mentioned above. It is likely that lower dosing though an appropriate delivery method would prevent them. Preliminary research trials in horses suggest that pain and anxiety reduction can be achieved with as little as 20 mg to 25 mg CBD oil administered trans-mucosally, once or twice a day

Leave a Reply

Your email address will not be published. Required fields are marked *