Clinical Brief

Medicinal Uses of Cannabis-Derived Products

Rapidly evolving state and federal cannabis policies present countless challenges for employers across the country. Frequent changes in state law have significant impact on employers’ day-to-day operations, including substance and drug use policies, employee training, and hiring and firing practices. Just as employers address one challenge, another seems to surface.

This clinical brief provides an overview What is the legal status of of the legal status of cannabis in the cannabis in the United States? The FDA has approved United States, the Food and Drug At the federal level, most cannabis and Administration’s (FDA) approved uses cannabis derivatives are classified several pharmaceutical for cannabis-derived products in medical as Schedule I substances under the treatment, as well as employer workplace Controlled Substances Act (CSA), and it cannabis-based policy considerations regarding non-FDA medicines for the approved cannabis-derived products that purchase, possess or use these substances. may be available. Schedule I status means a substance is treatment of specific considered to have no currently accepted What is cannabis? medical use, high potential for abuse, and medical indications. Cannabis sativa L., or marijuana as lacks accepted safety for use even under it’s commonly called, is a flowering plant, medical supervision. Each formulation has has been cultivated for centuries and that However, the 2018 Farm Bill changed used for a variety of purposes, including how certain types of low-THC cannabis been subject to rigorous textile fiber, food, and recreation. are classified under the CSA, removing Cannabis is also the source of more than “hemp” from the CSA’s definition of medical and scientific 100 plant-derived chemical compounds marijuana, and therefore from the called cannabinoids. Th review. e two most well- schedules of controlled substances. Hemp known and commonly occurring is the cannabis plant and derivatives that cannabinoids are tetrahydrocannabinol contain no more than 0.3% THC on a dry (THC) and cannabidiol (CBD). THC weight basis. The Farm Bill also preserved causes the “high” associated with cannabis the authority of the FDA to regulate use. CBD does not produce an intoxicating products containing cannabis or cannabis eect and is increasingly used in products derivatives, regardless as to whether they with purported health and wellness are classified as marijuana or hemp. This benefits. is important because it is unlawful under the Federal Food, Drug & Cosmetic Act, Figure 1. CBD Oil and CBD Gummies enforced by the FDA, to include either THC or CBD in any food or dietary supplement.

At the state level, legalization of cannabis for medical and recreational purposes has accelerated over the past decade. Today, 33 states and the District of Columbia have legalized cannabis for medical use, and 11 of those states and the District have legalized recreational cannabis. These developments do not affect the legal status of cannabis at the federal level, which, as described above, imposes criminal penalties for the Despite high THC content, these products qualify as hemp under federal law, distribution, purchase, possession or use i.e., THC content is at or below 0.3%. of cannabis, and explicitly preserves these specific medical indications, and for rigorous evaluation of cannabis- FDA’s authorities to regulate all products that their expected benefits outweigh derived pharmacotherapies to secure containing cannabis or cannabis- potential risks to patients. On this point, FDA approval, employers already face derived compounds. the FDA has been very clear: challenges with the potential workplace consequences of cannabinoid- Cannabis-derived medical Cannabis and cannabis-derived therapies products claiming in their marketing containing products purchased at and promotional materials dispensaries or online. The FDA has approved several that they’re intended for use in pharmaceutical cannabis-based the diagnosis, cure, mitigation, Cognition and safety medicines for the treatment of specific treatment, or prevention of diseases concerns of THC/CBD medical indications. One of these (such as cancer, Alzheimer’s disease, products medicines, a highly purified CBD, is psychiatric disorders, and diabetes) Worker safety plant-derived, and approved for use in are considered new drugs or new THC in cannabis has an intoxicating treatment of two forms of childhood animal drugs and must go through the effect that can affect an individual’s onset epilepsy, Dravet Syndrome, and FDA drug approval process for human motor skills, reaction time, and Lennox Gastaut Syndrome. These rare, or animal use before they are marketed coordination at low levels (as little as 2.5 severe conditions comprise about in the US. Selling unapproved products to 5 mg). As a result, certain states with 5%-10% of epileptic patients and 1%-2% with unsubstantiated therapeutic recreational cannabis laws prohibit of all childhood epilepsies. The other claims is not only a violation of the law, but also can put patients at risk, as more than 5 mg of THC in a serving of three medicines, which are synthetic these products have not been proven to recreational cannabis edible products. THC, are used in the treatment of be safe or effective. THC intoxication can have serious anorexia associated with weight loss in consequences for employees with patients with AIDS, and nausea and While the current eligible population safety-focused roles such as operating vomiting associated with cancer for FDA-approved cannabis-derived machinery or driving a vehicle. chemotherapy in patients who have medications is quite small, there are failed to respond adequately to currently more than 200 clinical trials Studies indicate a link between cannabis conventional antiemetic treatments. evaluating cannabinoids for treatment use and adverse workplace of a broad array of conditions including consequences, including increased risk Each of these cannabis formulations autism, pain, behavioral health for injury or accidents. According to a has been subject to rigorous medical disorders, irritable bowel syndrome, study from the National Institute on and scientific review. Based on safety cognitive disorders, and multiple Drug Abuse, postal workers who tested and efficacy data derived from extensive sclerosis. In the face of expanding positive for THC use had 55% more preclinical and clinical evaluation, availability of recreational cannabis and industrial accidents, 85% more injuries, the FDA has determined that these associated CBD and THC-containing and 75% greater absenteeism compared drugs are effective for treatment of products, and the necessary time delays with those who tested negative. mislabeled (e.g., products labeled as For FDA-approved cannabis-derived It is important for THC-free contain high levels of THC; medicines, rigorous scientific and or products contain significantly medical review demonstrates that employers to understand lower levels of CBD than indicated the benefits of a specific formulation on the product label). In some cases, outweigh its known and potential risks that CBD products may such quality deficiencies have serious for each approved use. That is not the consequences for consumers. case with non-FDA approved cannabis also contain significant products (Figure 2). Implications for patients levels of THC, enough Why does FDA approval Employer considerations: matter?  Be mindful of current state to cause intoxication, In the US, the FDA drug approval regulations pertaining to process is the only way to clarify availability and use of non-FDA without the consumer’s questions about a drug’s efficacy, the approved cannabis products. These awareness. conditions it is intended to treat, and products are subject to varying and safety considerations unique to the inconsistent quality assurance patients who will take the drug. It is also standards, and therefore vary in the only way to assure standardization, identity, purity and consistency. It is important for employers to quality control, and batch to batch  Because certain companies have understand that CBD products may consistency; establish a reliable dosing invested in the comprehensive also contain significant levels of THC, range; and identify drug interactions. research necessary to obtain enough to cause intoxication, without A benefit-risk assessment is the drug approval from the FDA, there the consumer’s awareness. The 2018 cornerstone of the FDA approval are FDA-approved cannabis-derived Farm Bill de-scheduled hemp-derived process. Before a medicine can be medicines currently available. products containing no more than 0.3% approved for marketing, the FDA must However, due to permissive state THC. A 30-ml bottle of CBD oil determine that it is effective and that its cannabis laws, most cannabis (Figure 1), which is a common retail expected benefits outweigh its potential businesses have no need to pursue unit, could contain 82 milligrams of risks to patients. This assessment is FDA approval, thus potentially THC and still fall below the 0.3% THC informed by a body of evidence derived manufacturing and distributing limit established in the Farm Bill. A from comprehensive preclinical and unsafe and/or ineffective products. single 4-gram CBD gummy, commonly clinical study. sold in packages of 30, could contain 12  Acknowledge potential employee mg of THC and remain below the 0.3% Regarding cannabis products, most pressures for plan coverage for non- THC limit (remember, it may take only studies cited to support the therapeutic FDA approved products. 2.5 to 5 mg of THC to cause impairment). value of non-FDA approved cannabis  Understand that there are critical As a point of comparison, smoking an products are preclinical laboratory differences between FDA-approved entire marijuana joint delivers only about or animal studies, observational cannabis-derived medicines and 17 mg of THC. studies that do not control for bias or state-authorized, unapproved confounding factors, or surveys of people Finally, due to the varying and cannabis-derived products such as self-medicating with cannabis. While inconsistent state-level regulation of differences in federal legality levels such studies can help in generating non-FDA approved cannabis products, of scientific and medical rigor and hypotheses, there are important such products often go to market quality. For these reasons, coverage questions that must be addressed without assurances of standardization for non-FDA approved cannabis to reach conclusions regarding the for strength, identity, quality, and derived products is not appropriate. safety and efficacy of these products consistency. In certain cases, cannabis as medicine. FDA approval of specific products have been marketed  Understand workplace implications cannabis formulations is necessary containing harmful contaminants, for use of cannabis-derived products, before employers can have confidence such as synthetic cannabinoids (e.g., particularly non-FDA approved a cannabis-derived product is safe “spice”), pesticides, and heavy metals. products. These products often and effective for treating specific medical And products frequently go to market contain high levels of THC, conditions. Figure 2. FDA-approved versus non-FDA Approved Cannabinoid Products

Food & Drug Administration (FDA)- Non-FDA Approved Cannabinoid Approved Cannabinoid Products Products Hemp-Derived Dispensary Plant-Based and Synthetic Medicines Products and Medical Marijuana

Study Evidence Placebo-controlled, publicly disclosed clinical trials Randomized clinical studies have not been & Requirements with large patient samples to determine efficacy, conducted. Public disclosure of smaller, informal safety, and recommended dosing studies not required.

FDA inspects to ensure adherence. Produced No federal testing standards, and variable from Manufacturing according to regulated current good state to state; some states require no testing. manufacturing practices (cGMP). FDA-approved FDA does not inspect manufacturing sites for medications must adhere to strict specifications adherence to cGMP. that ensure batch consistency and stable shelf life.

Quality Testing methods must be agreed upon with Non-prescription, non-FDA approved cannabinoid Standards FDA. Meets FDA standards for quality, stability, products are subject to inconsistent regulation at consistency Tested toe ensure they contain the the state level. There are non federal standards for consistent concentrations of cannabinoids and testing to ensure accuracy and consistency. other products ingredients listed on the label.

Only FDA-approved medicines with CBD or THC Healthcare providers can "recommend" but not Legality (e.g. Epidiolex) is federally legal under the Food, prescribe help-derived dispensary products or Drug and Cosmetic Act. marijuana, as they are illegal at the federal level

Eligible Not eligible Coverage

which can compromise employees’ content includes articles, information leaflets, 4. If Weed Is Medicine, So Is Budweiser https:// videos, policy statements, and more. www.wsj.com/articles/if-weed-is-medicine- safety and productivity. so-is-budweiser-11547770981 2. United States Surgeon General’s Advisory: Marijuana and the Developing Brain https:// 5. The Atlantic: The Pitfalls of Weed Legalization  Ensure existing policies related www.hhs.gov/about/news/2019/08/29/ (video) to employee use of mood-altering surgeon-general-releases-advisory- https://www.theatlantic.com/video/ marijuana-damaging-effects.html index/581044/marijuana-use/?utm_ substances take into consideration source=eb 3. Aimed Alliance (infographic). Reading the Tea cannabis-derived products. (or Hemp) Leaves: Post FDA Hearing. https:// 6. TakeOnEpilepsy.com is a unique online aimedalliance.org/wp-content/ community created by and for caregivers. uploads/2019/07/FDA-Hearing-Reading-the- The site provides expert advice and valuable Employer Resources Tea-or-Hemp-Leaves-Flyer_v13.pdf or https:// resources to help this resilient community. 1. CannabinoidClinical.com is an educational aimedalliance.org/aimed-alliance-submits- resource where readers can learn more about a-comment-to-the-fda-regarding-the- research on cannabinoids. Representative regulation-of-hemp-derived-cbd-products/

National Alliance acknowledges support from Greenwich Biosciences by way of clinical expertise and funding to produce this Clinical Brief.