The Complexities of CBD Study Evaluations

At first glance, this comprehensive systematic review on the effectiveness and safety of cannabidiol (CBD) as a treatment for anxiety and anxiety-related disorders appears straightforward. In their search, the authors included cases reports, case series, and randomized controlled trials (RCTs) on humans that used standardized dosing and placebo protocols and well-established tools to measure anxiety and the effects of treatment with CBD. Findings from the cases and RCTs included in the review indicated reduced symptoms of anxiety in patients treated with CBD, with fewer side effects than standard therapies.¹

However, an in-depth critical look at the review article itself raises important questions and concerns about how study evaluations on CBD are presented with regard to accuracy and clarity. The large amount of misinformation and lack of understanding on the part of the clinicians involved in much of the discussion regarding cannabis-related studies continues to be a concern, and findings from this particular review are no exception.

Misleading Statements Perpetuate Misinformation

The review by Skelley et al. states, “[Delta-9-tetrahydrocannabinol] THC is the most abundant psychoactive chemical and is primarily responsible for the well-known hallucinogenic effects of [Cannabis] sativa. In contrast, CBD is not psychoactive.”¹ This statement is false, as CBD is in fact psychoactive, and has shown potential for treating multiple psychological-related disorders such as chronic psychosis and substance use disorder, as well as anxiety.^2,3

Although this may seem like an argument of semantics, the authors’ comment that CBD is not psychoactive—in a systematic review discussing its use for the treatment of psychological disorders—makes the remark not only misleading but wholly inaccurate. Such contradictory information causes further confusion among clinicians regarding cannabinoid medicine. A better description of CBD may be to call it non-intoxicating as it does affect brain activity without causing impairment. Therefore, it is essential that authors make every effort to ensure statements are carefully and accurately worded to avoid additional misunderstanding within the medical community.

Classification and Legality of CBD Products

The review is also misleading in its discussion of the classification and legality of CBD products, stating that “in the United States, there is only 1 Food and Drug Administration (FDA)-approved CBD product, Epidiolex and all other cannabis-derived CBD products remain under the purview of the FDA regulation under the 2018 Farm Bill.”¹ In actuality, CBD products derived from cannabis are either classified as hemp-derived CBD (ie, derived from cannabis containing <0.3% THC), or medical/recreational cannabis-derived CBD (ie, derived from cannabis containing >0.3% THC).

Although the resultant composition of the derived CBD oil may be the same, technically the hemp-derived CBD is the only product under FDA purview through the 2018 Farm Bill; any CBD product derived from non-hemp cannabis is federally illegal and only can be sold and purchased in states with legal medical or recreational cannabis programs.^3,4

Although this distinction may seem superfluous, when discussing CBD, it is important that authors explain clearly and accurately such nuanced bits of information to prevent clinicians from relating misinformation to patients about the legality, accessibility, and use of CBD products.

Source and Composition of CBD

The source and composition of the type of CBD used in the various cases and RCTs reviewed by Skelley et al. is another complex issue. This distinction often is overlooked in discussions on the therapeutic use of CBD. Even if one assumes that the CBD derived from hemp was used in all of the cases and studies reviewed (this information was not clearly stated in the article), there are 3 main types of CBD formulations (Figure).

The first type is CBD isolate, which as the name suggests is CBD that has been isolated from the plant in its purest form. The second type is broad-spectrum CBD, which contains CBD along with other naturally occurring terpenes and cannabinoids found in the plant, but with all traces of THC removed. The final form is full-spectrum CBD, which contains all naturally occurring terpenes and cannabinoids found in the plant, including THC at levels <0.3%.^3,5

Given the large amount of diversity found in the type and amount of terpenes found within cannabis,⁶ as well as the different clinical effects between CBD isolate and full-spectrum CBD products,⁷ it is clear that the type of CBD used in each of the studies reviewed has great bearing on the evaluation of outcomes and utilization of study data—not to mention the application of that data to patients and further studies.

Conclusion

There have been promising trends in the manner in which cannabinoids are being evaluated for their effectiveness and safety in treating various medical conditions. However, it is extremely important that one critically appraise the information presented in such reviews for accuracy and integrity. By doing so, efforts can be made to address the gaps in knowledge and the widespread incorrect use and confusion over terminology. This in turn will facilitate the growth of more accurate, usable, and credible data.

For more on the nuances of CBD formulations, listen to AJEM’s Founding Editor in Chief, Jahan Marcu, PhD, discuss with Stacia Woodcock, PharmD, a clinical cannabis pharmacist.