Risk Versus Reality: Here's What The Current Research On CBD Tells Us
When it comes to CBD, perhaps the greatest consumer health risk is the lack of a sensible, science-backed regulatory framework.
CBD, once the underrated cousin of THC, now finds itself in the sociopolitical spotlight.
It is perceived as a "cure-all" by some and "snake oil" by others. In the age of misinformation and alternative facts, being quickly promulgated via social media and popular opinion, the reality of CBD’s potential risks and benefits have been exaggerated, manipulated, and misunderstood.
Amidst competing and vocal interests of various sectors within the US, the FDA is faced with the challenge of creating a rational regulatory scheme for CBD that protects public health. Consumers, farmers, and many politicians are pushing for the rapid implementation of regulations on CBD. The hemp industry naturally supports the production and sale of CBD products but offers no consensus on what regulations should be enacted. Many pharmaceutical companies insist that CBD, at doses with demonstrated benefit, should require FDA-approval and be managed by a health care provider.
Because the FDA is responsible for protecting public health, it is easy to understand its hesitancy. It has been reluctant to confirm a “safe dose” of a compound that, while sold in the US prior to corporate pharmaceutical involvement, was classified by the Drug Enforcement Administration as a Schedule I drug with no accepted medical use and a high potential for abuse. In fact, CBD still is classified this way if synthesized or derived from cannabis other than hemp.
Unfortunately, the regulatory void created by continued deliberation on the safety of CBD may pose more of a public health risk than CBD itself. Without regulation, consumers and patients are purchasing products that may contain heavy metals, pesticides, solvents, and other harmful substances. They may be using products that are mislabeled with regard to the presence of THC and that fail to inform consumers of their potential for intoxication.
In this federal vacuum, some states, such as New York, have rapidly implemented regulations to minimize public risk; many states, however, have done nothing.
Cannabis sativa L. contains over 120 cannabinoids, including delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). THC is the primary psychoactive cannabinoid found within cannabis, and its effects present a well-documented safety concern. Volkow and colleagues noted in a 2014 study that potential negative side effects associated with the use of THC as including intoxication, euphoria, driving impairments, the possible (yet highly debated) development of psychosis among those with genetic vulnerability, and mild-moderate short- and long-term cognitive impairment. These outcomes have been documented at doses as low as 10 milligrams of THC.
According to current research, CBD has been shown to confer little to no safety risk, even at high doses in healthy individuals. Doses of 6,000 milligrams CBD have been shown to be safe when administered acutely (i.e., single dose), and daily consumption of 3,000 milligrams CBD in healthy individuals and an equivalent of 3,500 milligrams CBD among individuals with tubular sclerosis have been shown to be safe. Documented adverse events (AEs) in the above-noted healthy volunteer studies were all mild or moderate; no deaths, severe or serious AEs, discontinuations due to AEs, or any clinically significant laboratory, vital sign, ECG, or physical examination findings were reported. Studies utilizing purified CBD preparations other than Epidiolex have found that doses of 1,500 milligrams taken daily were well tolerated (Bergamaschi et al., 2011).
A recent retrospective analysis of adverse event data from 40,460 patients in Canada who were using a high CBD/low THC formulation found only 0.38 percent (n=152) of these patients reported adverse events from January 2017 to November 2018, of which five were considered serious (Ware et al., 2019).
The evidence supporting the safety of CBD is strong. It is important to note that CBD, as with almost every known compound, is not completely benign. Studies of CBD in children have noted some drug-drug interactions at 5mg/kg. Larger studies have demonstrated elevated liver enzymes when CBD is taken in high doses of 20 mg/kg (equivalent adult dose of 1400 milligrams per day) with another drug known to cause liver toxicity, valproic acid. There are also reports of patients experiencing somnolence, typically an adult equivalent dose of 1400 mg per day while taking the benzodiazepine, clobazam, which has a known drug-drug interaction with CBD.
Many cite the “lack of research” on CBD’s safety as a reason to postpone regulation. Yet, in America, a broad range of dietary supplements and medications are available for sale over the counter (OTC) with little to no conclusive scientific evidence of their safety or efficacy. Readily available supplements such as St. John’s Wart, Kava and Yohimbe have been known to interact with other drugs or carry serious risks such as liver damage, rapid heartbeat, kidney failure, seizure, and heart attack. The supplement industry is only required to demonstrate safety among rodents, not humans, in order to market these products. If the same safety standards that are being considered for the sale of CBD as a supplement were applied to the market more broadly, the supplement market as we know it would not exist today.
In fact, many supplements and medications are marketed to Americans despite evidence that they can carry risks to consumers. The FDA collects safety data on most products (legal and illegal) in the US through the FDA Adverse Event Reporting System (FAERS). Calcium, a supplement, has a reported 2,624 adverse events, including 232 deaths, 129 reports of kidney. Acetaminophen (OTC generic Tylenol®) has 50,677 reports of adverse events including 10,518 deaths, 5,825 cases of toxicity, 1,110 case of kidney injury, and 841 reports of drug-drug interactions.
Meanwhile, a review of available safety data from Jan. 2014 to Aug. 2019 shows only 197 reports of adverse events associated with the use of non-pharmaceutical CBD, including 55 reports of somnolence (drowsiness) and 42 reports of drug-drug interactions.
When it comes to CBD, perhaps the greatest consumer health risk of all is the lack of a sensible, science-backed regulatory framework designed to protect us from the very real harms of contaminated, mislabeled, and irresponsibly marketed products.
Hunter Land, director of cannabinoid research at Canopy Growth Corporation, has devoted his career to researching cannabis-derived medicines and their application across a variety of conditions, leading the clinical development of the first FDA-approved CBD medication, Epidolex.