By Mark Gold, MD
Cannabidiol (CBD) is a “phytocannabinoid” part of cannabis, or an element created from the cannabis plant. According to a recent New York Times article, “The CBD industry is flourishing, conservatively projected to hit $16 billion in the United States by 2025. Already, the plant extract is being added to cheeseburgers, toothpicks and breath sprays."1 The FDA has approved Epidiolex, a CBD oral solution, for prescriptions to patients two years of age and older to treat certain intense forms of epilepsy, Lennox-Gastaut syndrome or Dravet syndrome, marking the first official go-ahead for a marijuana-derived substance.2 CBD, in short, makes headlines. Yet some consumers buying a CBD product sold over-the-counter have had difficulty finding a label and knowing what they’re actually getting.3 For other potential consumers, the biggest questions aren’t about a buzzy new wellness trend—they’re about failing a drug test after acquiring impure CBD or THC in a purchase.4
Consumers try to balance these fears with the purported benefits CBD. It is true that Epidiolex has been life-changing for the seizures associated with Lennox-Gastaut syndrome and Dravet syndrome. For parents and children coping with these conditions, all other treatments have failed. CBD may have benefits for other patients with rare or difficult-to-treat neurological diseases. In a recent study, researchers at the University of North Carolina wondered if CBD might help treat individuals with another condition involving severe seizures, Angelman syndrome.
What did this study find about CBD and Angelman syndrome?
Angelman syndrome is a neurodevelopmental disorder, in part involving powerful epileptic seizures this study describes as “common” and not responsive to current medications. This study found that in mice, CBD considerably reduced the intensity of seizures brought on by certain stimuli. Research You Can Use has previously looked at peer-reviewed research evidence on using CBD to help manage cravings from opioid use disorder (OUD). As a refresher, pure CBD is a nonintoxicating compound that does not produce a high for individuals using it, or lead to dependence. THC, by contrast, is a psychoactive compound linked to vaping-related lung disease5, produces a high, can produce dependence, and is linked to the negative consequences of marijuana use. CBD and THC are not approved or recommended for use by nursing, pregnant or soon-to-be pregnant women. In this study, researchers tested the effects of CBD on mice with some genetic similarities to humans with Angelman syndrome. They found that acute CBD doses—or 100 mg—reduced seizures in the mice brought on by loud noises and fluctuating body temperature. The study also found that this acute, anticonvulsant CBD caused a “mild sedation” effect in the mice, but did not significantly alter balance or motor function. CBD did not, however, stop the epilepsy-producing “plasticity” in the tested mice.
These results may still bode well for individuals with Angelman syndrome and their loved ones. CBD also helped stabilize brain pulses in the mice linked to EEG deficits in brain activity. Previous research has indicated that CBD may be beneficial in treating other health conditions that produce seizures, as well as certain related behaviors, such as anxiety. These results have held in preclinical and clinical trials, and this study’s authors are hopeful that more research will advance their findings on CBD. The usual caveats about the differences between human and animal studies apply—this study notes, for example, that it is hard to compare the effects of relative CBD dose levels in humans and mice when CBD has a different half-life in each—and the researchers call for future studies to examine administration routes for the substance.
Why is this important?
In addition to epilepsy and brain wave irregularities, as the study observes, Angelman syndrome also involves diminished speech, intellectual disability, and impaired coordination. On one level, this study is important because its findings are promising for individuals with Angelman syndrome, and their families, friends, and loved ones, who may find managing severe seizures an understandably taxing experience. Any advances in treatment for rare pediatric neurological diseases are great news. More broadly, this study also suggests that additional research on CBD may be warranted, especially for neuropsychiatric or neurodevelopmental diseases without a cure or viable treatments. We can’t know right now exactly which claims about CBD will be proved in FDA quality trials. We can’t know right now which related medications will subsequently be approved for a specific use. CBD’s health effects are not easily understood, given the magnitude and variety of claims about them. The FDA is likely to weigh in on CBD, and soon.6 It is logical that sound, random assignment double blind research trials on health effects will depend in large part on the CBD substance in question and the disease for which it is offered as a treatment. And so far, it appears that pediatric seizures are a reasonable target.
Smoking or vaping CBD is not the same as taking an FDA-approved solution or pill. Naturally, those offering over-the-counter forms of CBD are currently lobbying to have their products deemed dietary supplements.7 They hope to see such products, like vitamins or other substances, whether taken orally or applied as ointments, selling on the market. Experts still have to answer many questions about CBD, its current manufacturing process, and claims of efficacy routinely asserted without evidence. At the same time, scientific analysis has found particular health benefits from CBD, which is why certain forms are approved as medical treatments. CBD, being relatively safe, has started to undergo testing for use in treating a variety of psychiatric problems. While it has failed in some recent rigorous trials8, it is unlikely to fail in all trials.
THC and the future of CBD
This public health situation contrasts interestingly with THC, which has not gone through the rigors of FDA trials to demonstrate safety, efficacy, dose-purity, and duration. Yet for some health conditions, THC has been approved—by consumers and voters. Many seem to believe that, if nothing else, surely “medical marijuana” is entirely harmless, less dangerous than alcohol, and maybe even helpful. A well-controlled study9 found that recent cannabis use was associated with memory problems and poor psychomotor function. Here, we have to give credit to CBD manufacturers for proving that the substance, in a specific dose, for a specified duration, was equal to or better than the existing treatments for 2 rare forms of pediatric epilepsy. This new Angelman syndrome study is a hopeful sign for some families and individuals. After more time and study, FDA approval of CBD for sleep problems10 and Autism spectrum disorders may be next.
CBD is different from THC, and that by itself is a good reason for public health officials and researchers to continue to study THC, CBD, and Epidiolex independently. But in the meantime, we need FDA guidelines, controlled clinical trials, and manufacturing and testing standards so consumers know how much CBD is in a product and how much THC is hidden in it as well.
One expert neatly summed up the health context of CBD products in the recent Times’ article11:
"'CBD is not a scam,' said Yasmin Hurd, director of the Addiction Institute of Mount Sinai in New York City who led a double-blind study of 42 recovering heroin addicts and found that CBD reduced both cravings and cue-based anxiety, both of which can cycle people back into using. 'It has a potential medicinal value, but when we are putting it into mascara and putting it into tampons, for God’s sake, to me, that’s a scam.'"
MacKeen, D. (October 16, 2019) What Are the Benefits of CBD? New York Times
FDA News Release. (June 25, 2018) FDA approves first drug comprised of an active ingredient derived from marijuana to treat rare, severe forms of epilepsy. fda.gov
Bonn-Miller, M.O., et al. (2017) Labeling Accuracy of Cannabidiol Extracts Sold Online. JAMA
Lewis, A.C. (October 15, 2019) CBD or THC? Common Drug Test Can't Tell the Difference. New York Times
FDA Statement. (October 4, 2019) Statement on consumer warning to stop using THC vaping products amid ongoing investigation into lung illnesses. fda.gov
Abernethy, A., Schiller, L. (2019) FDA is Committed to Sound, Science-based Policy on CBD. FDA Voices: Perspectives From FDA Leadership and Experts
Jaeger, K. (October 14, 2019) Dietary Supplement Industry Pushes Congress To Allow CBD Product Sales. Marijuana Moment
Arndt, D.L., de Wit, H. (2017) Cannabidiol Does Not Dampen Responses to Emotional Stimuli in Healthy Adults. Cannabis Cannabinoid Res.
Parker, T., Owens, M.M., Amlung, M.T., Oshri, A., Sweet, L.H., MacKillop, J. (2019) Cannabis involvement and neuropsychological performance: findings from the Human Connectome Project. J. Psychiatry Neurosci.
Kuhathasan, N., Dufort, A., MacKillop, J., Gottschalk, R., Minuzzi, L., Frey, B.N. (2019) The use of cannabinoids for sleep: A critical review on clinical trials. Exp Clin Psychopharmacol
MacKeen, D. (October 16, 2019) What Are the Benefits of CBD? New York Times
1. Gu, B., Zhu, M., Glass, M.R., Rougie, M., Nikolova, V.D., Moy, S.S., Carney, P.R., Philpot, B.D. (2019). Cannabidiol attenuates seizures and EEG abnormalities in Angelman syndrome model mice. The Journal of Clinical Investigation
Dr. Mark S. Gold is a teacher of the year, translational researcher, author, mentor and inventor best known for his work on the brain systems underlying the effects of opiate drugs, cocaine and food. Read more by Dr. Gold here.