As of January 2019, 33 states have medical cannabis programs. The first medical program started in 1996 with the passage of California’s Proposition 215, and has continued to be adopted and remodeled by other states, some requiring doctor recommendations for approval. That figure is still climbing steadily, up from 28 states in January 2017. Also climbing is the rate of states that have fully legalized cannabis and approved its recreational use, currently numbered at 10. Until now, the medical field has been more or less preoccupied with THC, the psychotropic component of cannabis. But two important moments in 2018 led to a massive expansion of awareness of another cannabinoid, CBD. First, in June the FDA approved Epidiolex, the first drug based on an active cannabis ingredient to get such approval. Second, the December passage of the 2018 Farm Bill update, which removed hemp (a strain of the Cannabis sativa plant species containing less than 0.03% THC) from the Schedule I list of controlled substances, allowing its legal industrial production and cultivation.
Studies like the 2008 paper published by researcher Ethan Russo indicate that CBD can have therapeutic properties for hard to treat pain relief, and others indicate its treatment for conditions like anxiety, autism spectrum disorder, and PTSD and OCD (no longer classified as anxiety disorders). It is also being studied for its role in treating substance abuse disorders, with a 2017 study supported by the National Center for Complementary and Integrative Health suggesting that “emerging data suggest that use and abuse of prescription drugs may be decreasing in states where medical cannabis is legal.“
The manifold internal and external applications of this broad-spectrum compound may seem unlikely, but the trajectory is clear, and the curiosity around the compound’s use in people’s lives has led to a boom in availability of CBD. It’s an expected correlation — news of a powerful, if little studied, multi-target compound will attract people who seek to improve or enhance their lives. That last point is precisely why adequate, broadly satisfying regulations and guidelines remain elusive, a complication for both consumers and producers of CBD. A 2017 Penn study funded by the Institute for Research on Cannabinoids found that nearly 70 percent of CBD extracts online were mislabeled, which can present a dire problem for patients who attempt to integrate products into existing pharmaceutical regimens without clear information. This startling figure informs Standard Dose’s education-based position in the CBD space, and emphasizes why transparency — and lab results— are so central to the company mission.
The Endocannabinoid System
Cannabis compounds including CBD interact with our naturally present endocannabinoid system (eCS) to play a role in diverse nervous system actions from mood to sleep. According to a 2015 study published by Neurotherapeutics, “The eCB system is also integral to regulation of emotional behavior, being essential to forms of synaptic plasticity that determine learning and response to emotionally salient, particularly highly aversive events.” Regulation of the triggering of different receptors in the eCS is being associated with treating anxiety and related mood disorders. There is a bell-shaped curve when it comes to efficacy, with 10mg/kg being “too low” for absorption, and 100mg/kg “too high,” indicating a moderate dose over time could have the most effective impact on the eCB. The overall regulatory effect of the eCB on has researchers seeking the barriers to be lifted. Speaking to the Senate Caucus on International Narcotics Control in 2015, National Institute on Drug Abuse Director Nora D. Volkow asked that barriers be lifted from study in support of the compounds anti-seizure effects, neuroprotective and anti-inflammatory effects, analgesic effects, anti-tumor and anti-anxiety effects, as well as its indications for use in treatment of substance use disorders.
Epidiolex and pipeline candidates for study
To date, the only FDA-approved drug containing a cannabis-derived compound is the oral solution Epidiolex, for the treatment of two rare forms of epilepsy. Dravet Syndrome and Lennox-Gastaut Syndrome are forms of epilepsy that develop in the first years of a child’s life, which CBD was shown to treat. Both syndromes have high rates of early mortality, and can cause upwards of 50-75 seizures a day for those afflicted. There are three approved cannabis-related drugs, Marinol, Syndros, and Cesamet, used for treating anorexia and weight loss in people living with AIDS.
In 2018, Epidiolex was approved via Fast Track Designation by the Food and Drug Administration under former commissioner Scott Gottlieb for the treatment of rare forms of childhood epilepsy. The drug was developed by GW Pharmaceuticals and is represented in the USA under its subsidiary Greenwich Biosciences. The Greenwich Biosciences has been studying cannabinoids since 1998, and began the preclinical investigations into CBD’s antiseizure properties in 2007.
During the announcement of its approval, there was an awareness that the information would trigger other areas of market interest, with Gottlieb indicating that the FDA would “continue to support rigorous scientific research on the potential medical uses of marijuana-derived products and work with product developers who are interested in bringing patients safe and effective, high quality products.” The FDA itself supports the clinical study of cannabis for medical use.
Publisher of Neurology Reviews Elizabeth Katz, who works directly with Greenwich Biosciences, is watching the conversation closely. “I don’t want to sound like a cynic, but there’s a lot of misinformation. Most people making claims about CBD don’t know what they are talking about. The first drug that was approved was for rare, severe forms of epilepsy Dravet and Lennox-Gastaut, and so it’s just the natural progression to go into other conditions.” Other pipeline candidates for investigation regarding CBD, according to information presented to the American Epilepsy Society Annual Meeting in 2016, include other forms of epilepsy, autism spectrum disorders, schizophrenia, and glioma (a form of brain tumor).
But what is the FDA waiting for in approving more cannabis-derived compounds for medical use? According to their Public Health Focus brief: [The] “FDA relies on applicants and scientific investigators to conduct research. The agency’s role, as laid out in the FD&C Act, is to review data submitted to the FDA in an application for approval to ensure that the drug product meets the statutory standards for approval.” Again, the waiting game, the onus being on researchers to submit proposals and participate in the rigorous processing the FDA maintains is the only way forward. Waiting for the research to catch up to its common usage, and then waiting for the research to turn into functional, useful products and medicine.
“It’s there, it works, people don’t know how it works, but it has a lot of potential. We’re waiting for more clinical trials.” But when it comes to extreme health issues, the waiting part gets complicated. Katz recalls one colleague, a neuroscientist whose pregnancy revealed her baby had Dravet Syndrome with in-utero seizures. When she was unable to get into the Greenwich Clinical trials for CBD because they had already been closed, she and other parents began making their own CBD, a less-than-ideal situation for any new parent. But as Katz observes, “Do you know what 100 seizures a day will do to your children, and what you’re willing to try?”
It was a similar story with Sam Vogelstein, the first patient in the world to try Epidiolex. As a young boy suffering with symptoms so extreme, his mother sought out any way she could get access to the drug that had been shown to help with epilepsy in rodents. Sam ended up being part of a one-person clinical trial at UCSF when his mother first heard about the research GW Pharmaceuticals was doing, although they still didn’t have much research about epilepsy. Sam, who is a teenager now, had been seizure-free for over two years using Epidiolex by the FDA’s 2018 approval of the drug. The significance of his role in the studies and the subsequent approval was described in Wired by his father like so: “It’s a big deal for 3 million people in the US who have epilepsy, and, if approved elsewhere, 73 million people worldwide. Epilepsy affects about one percent of the world’s population, more than Parkinson’s and Multiple Sclerosis combined.”
In January of this year, Consumer Reports surveyed 4,000 Americans nationwide about their interest in and use of CBD. More than 25% indicated they had tried CBD, and one in seven of those respondents report daily use for issues from anxiety, pain, stress, and sleep. Which makes one thing abundantly, redundantly clear: The need for accurately labeled, safely produced, and effective CBD products is acute. And the market is going forward, the science is trying to catch up, and in the meantime, we’re listening closely. To learn more about Standard Dose’s commitment to curating the best CBD products on the market, visit our Education page and ongoing coverage on The Drop.
Alger B.Getting High on the Endocannabinoid System. Cerebrum: The Dana Forum on Brain Science (2013): 14.
Birnbaum L. CBD: A Patient’s Guide to Medicinal Cannabis. 2017.
Bourgeois B, Douglass L, Sankar R. Lennox-Gaustat syndrome: a consensus approach to differential diagnosis, Epilepsia. 2014;55(Suppl. 4):4-9.
Corroon J, Mischley L, and Sexton M. Cannabis as a substitute for prescription drugs – a cross-sectional study. J Pain Res. 2017; 10: 989–998.
Kelly M, Lehmann C, Zhou J. The Endocannabinoid System in Local and Systemic Inflammation. (Colloquium Series on Integrated Systems Physiology: From Molecule to Function). 2017.
Nguyen J, Kravtsova I. Brief Report: Cannabidiol Approved for Treating Rare Epilepsies. Rare Neurological Disease Special Report, Supplement to Neurology Reviews. 2019; 52-53.
Epidiolex [package insert]. Carlsbad, CA: Greenwich Biosciences, Inc.; 2018.
Russo E. Cannabinoids in the management of difficult to treat pain. 2008.