Abstract
Popular support for legalization of recreational and medicinal marijuana and marijuana derivatives is on the rise. Because marijuana is a schedule 1 substance, the official position of the federal government is that there is no medical application for marijuana. However, there are claims that marijuana is a reasonable treatment for a number of disorders. In this paper, I systematically review the literature around CBD oil (a marijuana derivative) and its relationship to pathology. I explore potential pathological side effects of using CBD oil, and disorders for which CBD oil could serve as a treatment. I focus specifically on the use of CBD oil as a treatment for epileptic seizures. I find that there is substantial evidence supporting the use of CBD oil as an epilepsy treatment, though there are potentially serious side effects. I conclude that CBD oil can be used as a treatment, and that the classification of marijuana and its derivatives as a schedule 1 substance is not tenable.
The Benefits of CBD Oil for Epilepsy
Level 1 research question: What are the pathological issues related to CBD oil?
There has been a recent surge of interest in the potential health benefits of marijuana and its derivatives, including cannabidiol (CBD) oil. In the past several years, political campaigns have been launched across the country to legalize these products either medicinally or recreationally, often with the justification that these drugs offer a health benefit or treatment option for patients with various ailments. However, marijuana is listed as a schedule 1 substance by the federal government, which explicitly stipulates that there is no medical use for marijuana. Clearly there is a disconnect between the stance of the federal government and the beliefs of people who are campaigning for the legalization of marijuana. This paper explores the pathological issues related to one of marijuana’s more abundant chemicals, CBD in oil extract form (CBD oil).
There are two major branches to be considered in this question. First, there is the question of whether or not CBD is related to or the cause of any pathology. The second is whether CBD or CBD oil is useful in the treatment of any pathology. In the first case, a 2015 review published in Neurotherapeutics (Sachs, McGlade, & Yurgelun-Todd, 2015) attempted to summarize current findings. Though the commentary was on cannabinoids generally and not on CBD oil specifically, the review highlights several potential negative health effects, many related to pathology. The major concerns were acute and long-term cardiovascular and respiratory effects, potential increase in cancer rates (largely related to smoking cannabis rather than use of CBD oil), and the promotion of manic episodes or schizophrenic breaks in bipolar individuals and people with predisposition to schizophrenia, respectively. The evidence is clear that cannabis use generally is not risk-free, though the use of CBD oil in particular may not have any of these individual risks. Based on the biology of CBD and its interaction with G-protein-coupled receptors in the brain (Welty, 2014), it’s reasonable to be concerned that CBD oil might play a role in at least the psychiatric risks, but more specific and extensive research is needed.
Regarding the second question, whether CBD oil can be used in the treatment of any pathologies, there is substantial research here. While Sachs and colleagues (2015) review potential therapeutic uses of cannabinoids, including CBD oil. They mention that cannabinoids can act as an immunosuppressant, that they may be useful for treatment of multiple sclerosis (MS), that oral CBD use may reduce anxiety, and that cannabis can generally be used in treatment of pain. Another review by Dr. Timothy Welty (2014) comments more specifically on the use of CBD oil, particularly with regard to treating epilepsy. The author reports that animal models have reduced convulsions when given CBD, though various drugs can increase or decrease this effect. The authors also review several findings in humans, specifically that people with epilepsy report a high use of marijuana and a belief that marijuana helped their seizures. Authors note that in one controlled study, there did appear to be a reduction of seizures in the treated group, but there is commentary on the small numbers and poor quality of the studies.
These findings lead me to believe that there are potential therapeutic benefits to CBD oil use, though they are not without risk. I was particularly interested in the use of CBD oil for the treatment of epilepsy. However, the studies referenced in the above reviews seemed poorly-designed and underpowered. This lead me to me Level 2 research question: Is there evidence that CBD or CBD oil is an effective treatment for epilepsy?
Level 2 research question: Is there evidence that CBD or CBD oil is an effective treatment for epilepsy?
Based on the above findings, I searched for more recent research on CBD and epilepsy treatment. Several studies have been performed since the 2014 piece by Dr. Welty (2014), but there have been mixed results. One report (Tazdok et al., 2016) specifically dealt with medical cannabis oil enriched for CBD. Of 74 children with epilepsy, 66 reported a reduction in frequency of seizures. This study had the advantage of involving a large cohort, but was disadvantaged in that it dealt largely with self-reports, and was therefore less controlled. Another article published issue of the journal had an alternative finding (Rosemergy, Adler, & Psirides, 2016). In this study, it was found that CBD oil was not effective in reducing the frequency or intensity of seizures of a patient with a severe condition. This report was only a single case study, meaning that it may not be widely applicable. But it had the advantage of being in a controlled environment with well-documented pathology and treatment standards. It is possible that the severity of the situation made it an edge case, and that CBD oil is more useful for less severe conditions. These studies revealed that there is a spectrum of response to CBD oil in epilepsy, depending on the particular situation.
These two studies provide a small window into the world of CBD oil use for the treatment of epilepsy, but a review of the field is more useful for synthesizing all of the research. A recent review (Perucca, 2017) analyzed 107 articles on the subject of cannabis and epilepsy published in the past decade. The review comments that cannabis has been a candidate treatment for epilepsy for over 150 years, but that research was stifled due to illegalization of the drug. There is also a discussion of modern experiments, largely in animal model systems, that demonstrate the effectiveness of CBD for treatment of seizures. Two major points were the usefulness of CBD versus another molecule, CBDV, and that the mechanism of action for CBD in seizure reduction is unknown. Of more interest was the review of clinical trials. The authors comment that most of the research before 2015 was poor, and few conclusions could be drawn. But one large study performed in 2016 involved 214 patients with seizures. It was found that nearly 80% had adverse effects from using CBD oil, including somnolence (sleepiness), diarrhea, and loss of appetite. However, it was found that there was a decrease of 35% in the total number of seizures patients experienced, and a small number of patients had long-term benefits after discontinuing CBD oil use. Similar results were found for well-controlled, double-blind trials of CBD oil use for reduction of seizures in Dravet syndrome and Lennox-Gastaut syndrome, two disorders characterized by seizures.
In all, my research found that CBD oil is effective for treatment of seizures in many cases. However, the treatment is not without risks or side-effects. Sleepiness, diarrhea, and loss of appetite were frequent, and in rare cases they were severe enough to require discontinuing of the treatment for patients. This implies that the treatment may only be viable for cases where other treatments are ineffective. Still, this is a promising avenue that suggests CBD oil does have legitimate medical applications for a treatment-resistant disorder.
- Sachs, J., McGlade, E., and Yurgelun-Todd, D. (2015). Safety and toxicology of cannabinoids. Neurotherapeutics 12(4), 735-746. doi: 10.1007/s13311-015-0380-8
- Perucca, E. (2017). Cannabinoids in the treatment of epilepsy: Hard evidence at last? Journal of Epilepsy Research 7(2), 61-76. doi: 10.14581/jer.17012
- Rosemergy, I., Adler, J., and Psirides, A. (2016). Cannabidiol oil in the treatment of super refractory status epilepticus. A case report. Seizure 35, 56-58. doi: https://doi.org/10.1016/j.seizure.2016.01.009
- Tazdok, M., Uliel-Siboni, S., Linder, I., Kramer, U., Epstein, O., Menascu, S., … Ben-Zeev, B. (2016). CBD-enriched medical cannabis for intractable pediatric epilepsy: The current Isreali experience. Seizure 35, 41-44. doi:10.1016/j.seizure.2016.01.004
- Welty, T.E. (2014). Cannabidiol: Promise and pitfalls. Epilepst Currents 14(5), 250-252. doi:10.5698/1535-7597-14.5.250
