The FDA recently announced the publication of an article reviewing 50 years of the FDA’s experience with clinical research related to the use of cannabis in drug development. The article was written by Cassandra L. Taylor of the Office of the Center Director, Center for Drug Evaluation and Research (CDER), and Schuyler A. Pruyn of the Office of Executive Programs, CDER, and is titled “A U.S. FDA Perspective on Cannabis Research and Drug Development.” It was published online on October 31, 2023, in the journal Exploration of Medicine as part of its special issue, “Beyond Weed: Clinical Applications of Cannabis and Cannabinoids.”
Since the early 1970s, the FDA has received >800 investigational new drug (IND) or pre-IND applications related to cannabis and cannabis-derived agents.
According to Taylor and Pruyn, the FDA has long been reviewing clinical research for cannabis (eg, marijuana and hemp) and cannabis-derived products, such as cannabidiol (CBD). Since the early 1970s, the FDA has received >800 investigational new drug (IND) or pre-IND applications related to cannabis and cannabis-derived agents. During the past 10 years, there has been a significant increase in research focused on cannabis and cannabis-derived agents for medical treatments and on increased clinical research about new types of cannabis agents and new routes of administration.
The current IND applications for cannabis-derived therapies submitted by academic researchers and commercial developers focus on 4 key clinical areas: addiction and pain medicine (53%), neurology (19%), immunology and inflammation (14%), and psychiatry (9%).
This growing research effort is based on Title II of the Controlled Substances Act (CSA) of 1970, which established the policy on the manufacturing, distributing, importing, exporting, and use of regulated substances and placed all substances that were regulated under existing federal law into 1 of 5 schedules, depending on their abuse potential. Certain parts of the Cannabis sativa L. plant have been controlled under the CSA since 1970 under the drug class Marihuana.
Taylor and Pruyn broke down cannabis and cannabis-derived product (CCDP) applications in human clinical trials that the FDA has received over the past 50 years and summarized their experience and challenges in reviewing CCDP research applications; they also provided recommendations and resources for those interested in studying CCDPs in human clinical trials, dispelling misconceptions about the types of CCDP research reviewed by the FDA and offering a window into the research involving CCDPs in the United States, with the goal that this will assist researchers in developing new CCDP clinical research programs.
Pre-INDs and INDs provide the mechanism to conduct clinical trials for the research and development of any new drugs, including cannabis-related agents. The CDER reviews any pre-IND and IND applications for CCDPs in the same way that it reviews any application for other treatments that will be regulated as a drug.
Cannabis-based therapies are complex mixtures that often have >1 active ingredient with a therapeutic effect. The CDER review teams consider the complexity of these agents when evaluating the validity of an IND, regardless of the source of cannabis or of any other plant-based substance. Currently, the FDA is reviewing >150 active INDs for CCDPs, including related synthetic substances that produce effects that are similar to those produced by natural cannabis-derived substances.
The FDA supports sound, scientifically based research into the therapeutic uses of CCDPs and will continue to work with companies interested in bringing safe drug products to market.
So far, the FDA has not approved any marketing drug application for cannabis for the treatment of medical conditions, but research on botanicals has led to the isolation of many natural compounds or derivatives of botanical compounds (including those derived from cannabis) that have become well-known drugs: 4 examples of such drugs that are currently approved by the FDA include the 3 synthetic cannabis-related drugs dronabinol (Marinol, approved 1985), nabinol (Cesamet, 1985), and dronabinol (Syndros, 2016), which are synthetic forms of a cannabinoid (delta-9 THC), which is a botanical compound in the Cannabis sativa L. plant. In addition, the FDA approved the cannabis-derived drug cannabidiol (Epidiolex, 2018), which is a natural CBD that has been isolated from the cannabis plant; unlike other cannabis-related formulations that represent a mix of complex compounds, cannabidiol has a single molecule.
Taylor and Pruyn suggest that the preferences of consumers have led researchers to use different routes of administration for drugs to be tailored to the participants of clinical trials, but there is still significant complexity in developing cannabis-based drugs for use in clinical trials. These challenges include a lack of or inadequate quality and manufacturing information, unknown safety and risk-benefit profiles for emerging compounds (eg, hexahydrocannabinol and THC acetate), and the effects of a complex matrix on testing final drug formulations.
Taylor and Pruyn conclude, the FDA “supports sound, scientifically based research into the therapeutic uses of CCDPs and will continue to work with companies interested in bringing safe, effective, and quality drug products to market. The FDA believes the drug development and approval process represents the best way to ensure that safe and effective new medicines are available to patients in need of appropriate medical therapy. This includes drugs that contain cannabis and cannabis-derived compounds.”
You Might Also Like:
Medical Marijuana and Cancer Care
Penny Daugherty, RN, MS, OCN, ONN-CG
Chemotherapy-induced nausea and vomiting can be a terrible problem for people in active chemotherapy. Medical marijuana may help.