What enzymes are affected by CBD and what is the impact?

CBD and its primary active metabolite, 7-hydroxy CBD (7-OH-CBD) affect several enzymes, such as the CYP450 enzymes, which are implicated both in primary metabolism and in the biotransformation of most therapeutic agents and xenobiotics.6

There are 3 different aspects of enzyme interaction that can be impacted by the presence of CBD, leading to potential DDIs: substrates, inhibitors, and inducers. (Table 1) CBD can also interact with secondary metabolism or transport proteins. (Table 2)

The effect of CBD can sometimes be inhibitory, or it may increase levels of other drugs in patients, thereby increasing the potential for ADEs.

This leads to a major concern, which is that many of these drugs are used in patients with complex health conditions, like immunosuppressants for people who have had organ transplants or chemotherapy for people with cancer. These agents already have toxicity and increasing their levels can increase adverse events.

Other common drugs, such as opioids, antipsychotics, benzodiazepines, and some sleep medications can likewise have risks if their levels are increased, including excess sedation, drowsiness, and potential dangers in terms of driving. Additionally, CBD itself has similar effects, such as causing sedation and we do not truly know how serious it is because there are no sufficient clinical studies.

You mentioned chemotherapy. Are there not cannabis derivatives used to treat side effects of chemotherapy, such as nausea?

Because cancer is such a serious condition, and people who undergo chemotherapy have such adverse effects, there is a unique risk-benefit analysis, where most people would likely err on the side of permitting its use to manage the severe side effects of chemotherapy like nausea and vomiting rather than withhold potentially effective treatment.

How should physicians and pharmacists address CBD-related issues in patients?

While it would be ideal if physicians and pharmacists could screen all patients for possible use of CBD and other cannabis products, it might be difficult to do so. As a first step, then, at least individuals who have a high risk of ADEs and DDIs should be screened—typically, people who are being treated with 5 or more medications, people who are frail, older adults, people with cognitive disorders, and people who generally have conditions such as multiple sclerosis, cancer, insomnia, and pain. Physicians can ask, for example, “Are you using anything beyond what I’m prescribing to manage your pain?”

Ideally, physicians and pharmacists should consider asking the same questions regarding patients’ use of any herbal medications or supplements because this is important to know when prescribing new medications, changing dosages, or trying to get a more complete picture of what is going on with the patient.

Moreover, since CBD can be used without medical supervision, it may signal to the physician or pharmacist that the patient has a given condition—such as insomnia—which may not be apparent until it emerges that the patient is using CBD to treat that condition.

Does the delivery route of CBD have an impact on ADEs and DDIs?

The delivery route has a profound impact. “Edibles” are absorbed more slowly than inhaled products, with no effect until 2 hours and onward, and a peak that will likely be lower than via the inhaled route. On the other hand, when inhaled, the concentration peaks very quickly—in roughly 15 to 30 minutes—so the acute effects, such as sedation and confusion, would be much higher during that peak period.

Although topical formulations such as lotions are available, there is little information on what type of systemic exposure they might cause. The likelihood is that they have a more localized effect, so it might be used to treat pain in a given area, such as knee pain. But for broader symptoms, like widespread arthritis, a topical cream will likely not absorb sufficiently nor be at high enough levels to cause adverse drug events.