CBD, which initially started as a grassroots movement, is quickly becoming a thing everyone knows or has heard about. The industry is exploding amidst the appeal of CBD as a natural, well tolerated medical-supplement hybrid. However, while CBD is generally well tolerated, its wide range of pharmacological actions demand air of care, and it’s certainly not the walk in the park it’s often made out to be.
Like many hot and trendy consumable products before it (a notable recent example being vape products), the market is outpacing the research. To fill the gap, companies and the lay community relies on a limited body of research, much of which is difficult to understand in full context without an appropriate background. This not only leaves room for misinterpretation but also leaves out research which is not accessible to the general public.
But science is slowly catching up. Today we’re focusing on a publication from last month which addresses two major concerns in the CBD community: adverse effects and drug interactions. The paper is a review of clinical data from two pharmaceutical formulations, Sativex (CBD and THC) and Epidiolex (CBD only).
The authors showcase Epidiolex’s reported adverse effects profile, which ranges from sedation, diarrhea, decreased appetite, weight loss, and insomnia to more serious effects such as weight loss, infection and increased liver activity. It’s worth mentioning that the doses in these clinical trials are much larger than what is commercially affordable, and the patients involved are epilepsy patients who continue taking their medications throughout the trial.
The authors acknowledge the narrow context here. There is a lot of variation among consumers in terms of how much CBD they take, how often they take it and how they take it (vaping, tinctures, etc). So, while the numbers may not fully reflect the casual market, they nevertheless warrant vigilance.
Drug Interactions: Cytochrome P450 and Beyond
The adverse effects reported are also common to other drugs, including antidepressants, chemotherapy drugs, anti-inflammatories and many others that are commonplace among the general population. People using CBD for therapeutic effect may be taking one or more of these common drugs regularly, and joint use of CBD may increase the risk of and/or aggravate potential side effects.
Your body is full of enzymes – molecules that speed up chemical reactions. Some are responsible for helping to create chemicals in your body, while others are responsible for breaking them down. Most drugs, including pharmaceuticals, are broken down by a family of enzymes known as cytochrome P450 (or CYP450 for short). Different chemicals can heighten or lower the activity of certain CYP450 enzymes, which affects your body’s ability to break down chemicals that are normally broken down by those enzymes. As a common example, you may have seen warnings on some bottles of medication to avoid drinking grapefruit juice. Some cholesterol medications, called statins, are like this. This is because one of the chemicals in grapefruit juice lowers the activity of the CYP450 enzyme 3A4, which is responsible for breaking down statins (among other things). As a result, your body will not break down the medication as quickly, leading to higher levels of the drug in your system. This is potentially dangerous and can increase the risk of adverse effects.
CBD has been shown to inhibit (lower the activity) of many of the CYP450 enzymes responsible for breaking down drugs, notably CYP3A4 and CYP2C19, which break down many different drugs such as antidepressants, blood thinners (warfarin) and chemotherapy medications, to name just a few (the paper includes a large list of examples). Furthermore, when CBD is broken down in the body, it is converted to other chemicals (called metabolites) which also affect bodily enzymes, some of them outside CYP450, responsible for breaking down drugs including ibuprofen and acetaminophen, both of which are very common over-the-counter medications. As a result, the authors of the paper note an increased risk of side effects related to medication taken along with CBD, and recommend that doctors monitor patients taking CBD in conjunction with medication, watching for adverse effects and toxicity.
To drive the point home, we quote the authors’ conclusion at length:
“Contrary to popular belief and anecdotal evidence, CBD is not a biologically inert compound. Rather, CBD has a complex pharmacokinetic and pharmacodynamic profile similar to any other medication with the potential to interact with other medications and medical conditions.”
From all of us here at Calyx, we wish you good health: be mindful, be safe, and most of all, enjoy life!