There is no dispute that cannabis is a complex plant often used as a botanical drug, food, food ingredient, and textile. With no federal oversight, regulatory bodies of the now 29 United States and the District of Columbia where cannabis is legal in some form, are tasked with ensuring product safety to their constituents. Most states require finished product testing by the International Organization for Standardization and the International Electrotechnical Commission (ISO/IEC) 17025 accredited laboratories. Laboratory accreditation to ISO/IEC 17025 represents a laboratory’s commitment to develop protocols to ensure quality practices are implemented and includes the attestation of their competence by an independent third party. Whenever possible or when mandated, analytical labs rely on published consensus and standard test methods or to validate their modifications to such methods to perform the necessary work. Although standard methods are in development by scientific organizations such as AOAC International and ASTM, as of this writing there is not a single published compendial or consensus method for the most typical assays used in the cannabis industry. This article discusses basic principles of quality assurance and laboratory accreditation, and the current status of voluntary methods in development. A final intent of this article is to provide unique insight into the challenges associated with testing cannabis amidst the federal prohibition.
The origins of cannabis appear to be rooted in Central Asia, with evidence of fiber use dating to 10,000 BC (1) and medicinal use dating to 3000 BC (2-4). For centuries, this robust plant has been purposed and repurposed in textiles, foods, medicines, and agricultural crop remediation around the globe (1,3-5). The medicinal utility of the plant eventually made its way to the West around 1839, largely from the clinical work and advocacy of William O’Shaughnessy (3,6). Recognizing the beneficial contributions in medicine, cannabis was formally introduced to the United States around 1850 and was included in the United States Pharmacopeia (USP) from 1851 to 1942 (7). Physicians and researchers supported the use of cannabis for myriad diseases and disorders. For example, in 1860 the Ohio State Medical Society’s Committee on Cannabis Indica reported efficacy of cannabis for treatment of stomach cramps, post-partum depression, and venereal diseases (1). Cannabis, however, wasn’t the only “medicinal” agent in use during the latter half of the 19th century—opium-containing products were commonplace for treatment of nearly any malady. With no requirement for labeling, products were marketed as “cure-alls” with the result being an accidental, or at least incidental, opium-addicted population (8). Although physicians recognized the deleterious effects, they were not able to contain or reverse the problem, thus leading the way for regulatory intervention.
In the interest of consumer safety, the US Congress enacted the Pure Foods and Drugs Act in 1906 (reorganized to the US Food and Drug Administration [FDA] in 1930) as a mechanism to ensure the quality and safety of food and drug products. Established laws required specific labeling for certain products known to contain designated “poisons” such as alcohol, morphine, and cannabis (9). The Harrison Act of 1914, which declared cannabis use illegal, and the Marihuana Tax Act of 1937, essentially banned cannabis from further medical use and halted relevant research (3). Federal controls over drugs and food were further tightened when the Pure Foods and Drugs Act was subsequently replaced by the Federal Food, Drug, and Cosmetic Act in 1938 (9). The Controlled Substances Act in 1970 established a classification system for certain drugs and maintained the earlier declarations of the dangers of cannabis. The ensuing drug scheduling system continues to classify a substance based on its potential for abuse and medical value. Since 1970 cannabis has been designated on the most restrictive level, Schedule I, implicating it as a substance with potential for abuse, and no medicinal value (11) and by federal law, illegal to possess or distribute. Even with the Schedule I classification of cannabis, science has been moving forward (and succeeding) to characterize cannabis and empirically elucidating potential contributions for its use in medical applications (12) including the identification of an endogenous cannabinoid system (13).
An insurgence against the federal prohibition of cannabis has been gaining momentum for more than three decades and shows no signs of slowing. As of this writing, 29 states in the United States plus the District of Columbia have sanctioned cannabis use for medically compromised or recreational (adult) consumers. A memo issued by Deputy Attorney General James M. Cole (also known as the “Cole Memo”) in 2013 provided guidance to indicate that federal enforcement agencies would be unlikely to prosecute “individuals with cancer or other serious illnesses who use marijuana as part of a recommended treatment regimen consistent with applicable state law” (14). This memo essentially positioned the governing states with responsibility to ensure consumer safety. Paradoxically, where states were one day prosecuting individuals for cannabis possession, they immediately became guardians and regulatory bodies for this federally illicit substance.
For cannabis consumers, particularly those who are medically compromised, product safety is exceptionally important. Before we can discuss the merits of how to ensure safety, we must first define safety, as it can have different applications. Measures of safety are bifurcated along different, yet parallel paths (refer to Figure 1). (See upper right for Figure 1, click to enlarge.) Along the first path “safe” refers to, for example, the product’s effectiveness as a drug to treat medical specified conditions, determination of its toxicology, and opportunities to mitigate known contraindications. These elements are generally part of product or drug development schemes that typically require International Conference of Harmonization (ICH) quality guidelines (15), which are also subject to short and long-term monitoring programs. Along the second path, the regulation of safe products refers to assurance that products are correctly labeled and prohibitive additives or adulterants are absent. This “truth in labeling” was a prime intent of the Pure Foods and Drug Act of 1906 and is an element of the FDA’s Food Safety Modernization Act of 2011 (16). Although these two paths toward safety are parallel and critically important, they do not contradict each other and should be routinely implemented as part of good laboratory practices (GLP), good management practices (GMP), or good clinical practices (GCP) quality systems. These are typically referred to as “GxP” quality processes. GLP establishes a quality system framework used to support a laboratory research plan and performance of nonclinical health and safety studies in food, drug, biological products, and medical devices. These are regulations published in the Code of Federal Regulations, 21CFR part 58, and are enforced by the FDA (17). GMP, however, represent quality system requirements to ensure pharmaceutical products are consistently manufactured to product specification (18). Finally, GCP refers to a system of internationally accepted guidelines, also adopted by the FDA, for scientific quality standards relative to clinical studies involving human subjects (19).
- M. Booth, Cannabis: A History (St. Martin’s Press, New York, 2005).
- E. Russo, H.E. Jiang, X. Li, A. Sutton, A. Carboni, F. del Bianco, G. Mandolino, D.J. Potter, Y. Zhao, S. Bera, Y. Zhang, E. Lu, D.K. Ferguson, F. Hueber, L. Zhao, C. Liu, Y. Wang, and C. Li, J. Exp. Bot. 59(15), 4171-4182 (2008).
- L.L. Iversen, The Science of Marijuana (Oxford University Press, New York, 2008).
- E.B. Russo, in Handbook of Cannabis, R.G. Pertwee, Ed. (Oxford University Press, New York, 2014), pp. 23-43.
- V. Angelova, R. Ivanova, V. Delibaltova, and K. Ivanov, Industrial Crops and Products 19(3), 197-205 (2004).
- S. Mukherjee, The Public Domain Review, Retrieved January 15, 2018 from https://publicdomainreview.org/2017/04/19.
- US Pharmacopeia, 3rd Edition. Retrieved January 15, 2018, from http:antiquecannabisbook.com/view.timeline.php.
- D.F. Musto, Scientific American 20-27 (July 1991). Retrieved from https://faculty.unlv.edu.
- Federal Food and Drugs Act of 1906 (The “Wiley Act”), Public Law Number 59-384, 34 STAT.768 (1906), 21 USC Sec 1-15 (1934). Retrieved from www.fda.gov/regulatoryinformation/lawsenforcedbyFDA/ucm148690.
- H.R. 18583, 91st Congress of the United States (1970).
- United States Drug Enforcement Administration. Drug Scheduling. Retrieved from www.dea.gov/druginfo/ds.
- National Academies of Sciences, Engineering, and Medicine, The Health Effects of Cannabis and Cannabinoids: The Current State of Evidence and Recommendations for Research (The National Academies of Press, Washington, DC, 2017). Doi:10.17226/24625.
- V. DiMarzo, D. Melck, T. Bisogno, and L. De Petrocellis, Trends in Neurosciences 21, 521-528 (1998).
- J.M. Cole, Deputy Attorney General. Memorandum for all United States Attorneys (August 29, 2013). Retrieved January 10, 2018 from www.mpp.org/federal/cole-memo.
- B.T. Yeh, The Controlled Substances Act: Regulatory Requirements (2012). Retrieved January 15, 2018 from https://fas.org/sgp/crc/mis.
- Federal Drug Administration Food Safety Modernization Act of 2011. Retrieved January 15, 2018 from https://www.fda.gov/food/guidanceregulations/fsma.
- US Food and Drug Administration, Good Laboratory Practices. Retrieved January 30, 2018: www.fda-glp.com (FDA, Rockville, Maryland).
- US Food and Drug Administration, Facts about Current Good Manufacturing Practices. Retrieved January 30, 2018: www.fda.gov/drugs/development/approvalprocess/manufacturing (FDA, Rockville, Maryland).
- International Conference on Harmonization, Harmonised Tripartite Guideline, Guideline for Good Clinical Practice, E6(R1) (ICH, Geneva, Switzerland, 1996).
- US Food and Drug Administration, FDA and Marijuana: Questions and Answers. Retrieved January 30, 2018: www.fda.gov/newsevents/publichealthfocus (FDA, Rockville, Maryland).
- H.R. 2642, 130th Congress of the United States, 2nd Session (2014).
- M.A. ElSohly, and D. Slade, Life Sciences 78, 539-548 (2005).
- G.A. Cabral, E.S. Raborn, and G.A. Ferreira, “Phytocannabinoids and the Immune System,” in Handbook of Cannabis, R.G. Pertwee, Ed. (Oxford University Press, New York, 2014), pp. 261-274.
- U. Pagotto, G. Marsicano, D. Cota, B. Lutz, and R. Pasquali, Endocrine Reviews 27(1), 73-100 (2006).
- M.A. ElSohly, in Emerging Issues in Analytical Chemistry, B.F. Thomas, Ed. (Elsevier, Amsterdam, The Netherlands, 2016).
- A. Thompson and V. Langfield, in Handbook of Cannabis, R.G. Pertwee, Ed. (Oxford University Press, New York, 2014), pp. 356-372.
- M. Backes, Cannabis Pharmacy (Black Dog & Leventhal Publishers, New York, 2014).
- M. Starks, Marijuana Chemistry (Ronin Publishing, Inc., Berkeley, California, 1990).
- A. Hazecamp, A. Peltenburg, R. Verpoorte, and C. Giroud, Journal of Liquid Chromatography & Related Technologies 28, 2361-2382 (2005).
- International Laboratory Accreditation Cooperation (ILAC). Retrieved January 20, 2018 from www.ILAC.gov.
- International Organization for Standardization. (1994). Quality management and quality assurance - vocabulary (ISO Standard No. 8402).
- E. Pritchard and V. Barwick, Quality Assurance in Analytical Chemistry (Wiley Publishers, West Sussex, UK, 2007).
- M.E. Swartz and I.S. Krull, Handbook of Analytical Validation (CRC Press, Boca Raton, Florida, 2012).
- AOAC International. Retrieved January 29, 2018: www.aoac.org/aoac_prod_imis/APAC/AB/AOAC.
- ASTM International, The History of ASTM International. Retrieved January 29, 2018: www.astm.org/about/history_book.
- American Oil Chemists’ Society, History of AOCS. Retrieved January 29, 2018: www.aocs.org/info/about-aocs/history-of-aocs.
- US Pharmacopeia, Our History. Retrieved January 29, 2018: www.usp.org/about.
How to Cite This Article
S. Audino, Cannabis Science and Technology 1(1), 14-20 (2018),