There has definitely been a rapid cultural change over the last decade. Cannabis products have become more generally accepted, first for medicinal use and increasingly for recreational use. Cannabidiol (CBD) use in particular has taken off – CBD is a component of cannabis that does not contain the psychoactive properties of THC. It has become popular as an “herbal supplement”. On most city streets you will see signs advertising CBD products. But the rapid popularity of CBD may be premature.

As I have written before, “herbal supplements” are not supplements, and the fact that they are herbal is entirely inconsequential. They are, in fact, drugs, by any reasonable definition. In essence we have two parallel systems for selling drugs in the US (and many other countries). In one system drugs go through a highly regulated research protocol where they are purified and tested for safety and efficacy. Their pharmacokinetics and pharmacodynamics are characterized, proper dosing is established, drug-drug interactions are studied, and side effects are carefully tracked. Most drugs do not make it through this process, and those that do come with a detailed description of their pharmacological profile. Drugs are also classified based on their potential for harm, with many requiring a doctor’s prescription. This does not mean they are risk free, but at least there is a transparent process for minimizing harm and maximizing the benefit to risk ratio.

In the parallel drug market, however, drugs can be sold direct to the consumer with literally zero requirement for any prior study. They can be sold in combination with other ingredients, at unknown and highly variable doses, without any information about their pharmacology or safety, and with claims that have not been adequately scientifically demonstrated. Unsurprisingly, they have demonstrably high levels of ingredient substitution, contamination, and adulteration. But even when pure, there is simply no way to know the risks and benefits and therefore make rational decisions regarding their use. Fortunately (from one perspective) most products in this category have low bioavailability and overall dosing, which reduces both the potential for direct harm and benefit.

This second category of essentially unregulated drugs are called herbal supplements. They are regulated more like food than drugs, with general use being considered as adequate evidence of safety, and no mind paid to claims of efficacy. The one stipulation is that sellers cannot make disease claims regarding their products, but this is easily side-stepped and often ignored.

CBD is simply another pharmacologically interesting chemical. It may turn out to be, in one form or another, a useful drug. There is preliminary evidence that it may be useful in treating anxiety and other mood disorders, and have antiemetic properties. Actually, one form of CBD has been purified, studied, and FDA approved as a prescription drug for certain kinds of epilepsy, Epidiolex. It is a bit strange that a drug is available simultaneously in a prescription and “herbal” form.

This dual life of CBD shows how thin the justification for the current lack of regulations for herbal drugs is. The primary justification is that herbs are “natural”, but this is a meaningless term. It is not clearly defined, and there is no reason to think that being “natural” in any way conveys safety. The most deadly poisons on the planet are all natural, by any definition.

Another justification is that herbal supplements have “traditional use” which gives us a long history of safety. This is flawed reasoning on multiple levels. First, anecdotal evidence, no matter how extensive, will only tell you about obvious immediate side effects. It will not provide information about statistical risks, complex interactions, rare but deadly side effects, and subtle effects such as organ toxicity (see, for example, Aristolochia and kidney damage). Further, many herbal products do not have a long history of traditional use, even when claimed. This is more of a marketing tool than reality. In short, traditional use is no substitute for scientific evidence.

But as I said, there is an FDA approved form of CBD, which we cannot assume has identity risks of every herbal version out there, but does give us some information on safety. As is almost always the case, any drug that is pharmacologically active enough to have a demonstrable benefit likely also has potential risks and interactions. CBD, it turns out, has a safety profile that is fairly typical for a prescription drug, and in fact is worse than many drugs on the market.

A 2019 review found:

Nearly one-half of CBD users experienced [adverse drug events, ADEs], which displayed a general dose-response relationship. Common ADEs include transaminase elevations, sedation, sleep disturbances, infection, and anemia.

“Transaminase elevations” means effects on the liver while anemia could mean bone marrow suppression. These are concerning side effects because they can indicate organ toxicity. Also, just as with any drug, controlled trials are limited in their ability to detect rarer side effects. These tend to come out only when the drug is in wide use, which is why drugs are monitored after they are on the market. As an example, there is a recent case report of a patient who had a severe cardiac reaction to herbal CBD. She had prolonged QT intervals, which indicates an adverse effect on electrical conduction in the heart. This led to a life-threatening cardiac arrhythmia. No other cause was found, and the abnormal rhythm resolved when she stopped the CBD supplement.

In this case the patient was taking high doses of CBD, but that is part of the point – she was taking it without a prescription, without any physician advice or supervision, and was lulled into a false sense of safety because CBD is a “natural herb”.

CBD also has a relatively high potential for drug-drug interactions (DDI). What this means is that one drug alters the pharmacology of another, but increasing or decreasing its effective blood level, for example. The same 2019 review above found:

Given CBD effects on common biological targets implicated in drug metabolism (e.g., CYP3A4/2C19) and excretion (e.g., P-glycoprotein), the potential for DDIs with commonly used medication is high.

In other words, relative to other prescription drugs, the DDI potential of CBD is high. Taking CBD without supervision, therefore, results in a potential that it can affect other medications, resulting in a host of possible other risks.

CBD, in short, is a drug, and it behaves like a drug, and not a particularly clean one. The reviewers above concluded:

General clinical recommendations of reducing substrate doses, monitoring for ADEs, and finding alternative therapy should be considered, especially in medically complex patients. CBD is implicated as both a victim and perpetrator of DDIs and has its own ADE profile. These effects should be considered in the risk-benefit assessment of CBD therapy and patients and consumers made aware of potential safety issues with CBD use.

Of course, none of this can happen if consumers are taking CBD products over the counter without any supervision, and under the false impression that CBD is natural and therefore perfectly safe. To be clear, I am not against CBD itself. My criticism is of the current regulatory framework that creates a false dichotomy between drugs and supplements. CBD should be studied and regulated like any other drug, because that’s what it is.

Author

  • Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.

Posted by Steven Novella

Founder and currently Executive Editor of Science-Based Medicine Steven Novella, MD is an academic clinical neurologist at the Yale University School of Medicine. He is also the host and producer of the popular weekly science podcast, The Skeptics’ Guide to the Universe, and the author of the NeuroLogicaBlog, a daily blog that covers news and issues in neuroscience, but also general science, scientific skepticism, philosophy of science, critical thinking, and the intersection of science with the media and society. Dr. Novella also has produced two courses with The Great Courses, and published a book on critical thinking - also called The Skeptics Guide to the Universe.