iven its legal status as a restricted, often prohibited, narcotic, cannabis’ place in US society has been complicated over the last century. While using cannabis and cannabis-related products for medical purposes predates the American Civil War, stringent restrictions at the federal and state levels made it difficult to explore their therapeutic potential. These restrictions have relaxed considerably in recent years, resulting in the rapid development and growth of a nascent industry in cannabis and cannabis-related products. Despite this thaw, researchers, producers, and developers still must be aware of a considerable number of regulatory guidelines and practices governing the cannabis industry.
What is the Legal Definition?
At present, “marihuana” is defined as “all parts of the plant Cannabis sativa L., whether growing or not; the seeds thereof; the resin extracted from any part of such plant; and every compound, manufacture, salt, derivative, mixture, or preparation of such plant, its seeds or resin” in the United States legal code1,2. It is also designated as a Schedule I substance by the Controlled Substances Act, meaning that it is considered to have a high potential for abuse, has no currently accepted medical use in treatment in the United States, and that there is a lack of accepted safety for use of the drug or other substance under medical supervision3.
Notably, this definition of marihuana excludes hemp, "the plant Cannabis sativa L. and any part of that plant, including the seeds thereof and all derivatives, extracts, cannabinoids, isomers, acids, salts, and salts of isomers, whether growing or not, with a delta-9 tetrahydrocannabinol [THC] concentration of not more than 0.3 percent on a dry weight basis,” included in the Agriculture Improvement Act of 2018 (a.k.a. the 2018 “Farm Bill”)1,4.
Working with Cannabis for Research and Manufacturing
Because of its status as a Schedule I controlled substance, all researchers who work with cannabis or cannabis-derived products must obtain a Schedule I research registration, per 21 CFR section 1301.185. They must also obtain a Schedule I research licenses from state-level drug authorities. Moreover, all cannabis to be used for research/experimental purposes must also be obtained from a cultivator who is registered with the US Drug Enforcement Administration (DEA) as a Schedule I manufacturer.
At present, the only federally lawful source of research-grade cannabis in the United States is the University of Mississippi, which contracted with the National Institute on Drug Abuse (NIDA) to produce research-grade cannabis4. This poses a considerable challenge for manufacturers, as research targeting new drug applications requires a large amount of cannabis under consistent conditions. The production facility at the University of Mississippi consists of a 12-acre farm. In comparison, a 45-acre glasshouse was required to produce enough material for Phase 3 clinical trials and commercialization of the product Epidiolex®4. This problem can be alleviated by manufacturing investigational cannabis products outside of the United States and importing them for research purposes under an investigational new drug designation4.
Quality Control During and Post-Production
All products containing cannabis or cannabis-derived compounds, including those classified as “hemp,” are subject to FDA regulations under both the Federal Food, Drug, and Cosmetic Act as well as Section 351 of the Public Health Service Act1. As such, current Good Manufacturing Practices must be adhered to during both plant cultivation and post-harvest refinement and processing workflows. FDA inspections will be conducted for all manufacturing sites, as they would be for any pharmaceutical product. Finally, cannabis-related products, whether botanical in nature or a processed extract, must undergo the full range of safety and efficacy testing, as well as a battery of tests to evaluate its abuse potential4.
A Rapidly Shifting Landscape
The evolving legal status of cannabis means that understanding and adhering to regulations concerning the plant and products derived from the plant is a continuous process. Scientists need to be aware of the additional legal hurdles facing research involving a controlled substance, and pay attention to the resources provided by regulatory and law enforcement agencies in order to become compliant and stay compliant. Alternatively, they can seek out well-established third party manufacturers such as Elite Molecular, who already understand and are compliant with laws and regulations, for their cannabis extraction and manufacturing needs.
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