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1. Cannabis testing and research: An overview

If you're reading this guide, you most likely believe that data management software and laboratories make for a good marriage, and you want to know what the next steps are. Know that you're not alone in that belief. At its heart, this guide has the informed conviction that a flexible laboratory informatics solution like a laboratory information management system (LIMS), when properly implemented and maintained, has the potential to improve cannabis testing workflows, reduce long-term operational costs, and support standards- and regulations-based compliance. But before be we can begin talking about what makes for a well-designed and implemented cannabis testing LIMS, we have to first understand what drives cannabis testing, as well as the workflow involved.

This first chapter begins with a brief overview of the cannabis industry in the United States, giving a quick and concise review of where cannabis use, regulation, testing, and research have been and where they are now. It also argues the value of analytical testing of cannabis, not only from the standpoint of ensuring quality products for patients turning to cannabis products but also research and development (R&D) labs creating or improving those products marketed for both medical and recreational use. The next chapters will then get into the specifics of analyzing and reporting on the myriad constituents and substrates/matrices that make up cannabis products; determining the informatics requirements of cannabis testing; and acquiring, implementing, and maintaining an informatics product like a LIMS in a cannabis testing laboratory. But first, a little historical background ...

1.1 Cannabis legalization, use, and research

1.1.1 History and legalization

Drug bottle containing cannabis.jpg

Cannabis is a rapid-growing, flowering plant that has been used for centuries for industrial, medicinal, and recreational purposes. The plant includes three species or subspecies: indica, ruderalis, and sativa.[1] Broadly speaking, both "industrial hemp" and "recreational marijuana" are scientifically similar in that they both refer to the Cannabis plant. The important difference between the two is how they've been bred by humans, particularly in regards to their biochemical composition. Hemp—which has historically been used to create clothing, food and feed, paper, textiles, and other industrial items—tends to be bred to have lower levels of the psychoactive component tetrahydrocannabinol (THC) and higher levels of the non-psychoactive component cannabidiol (CBD).[2][3] However, some cannabis strains have intentionally been bred to maximize the psychoactive component THC; this is often referred to as marijuana (or the older term "marihuana"), a change arguably driven by newspaper reporters post-1900.[4][5]

Cannabis cultivation began in England's Jamestown colony of America in earnest around 1611, via formal orders. Several years later those orders turned into a royal decree, enacted by the Virginia Company, asking colonists to each grow 100 hemp plants for export to England.[3] Colonial America continued its growth, use, and exportation of hemp, even beyond the formal founding of the United States. During that time, growers undoubtedly were using the female plant (which flowers and has higher levels of THC) to treat aches and pains, as well as enjoy it recreationally. By the time the U.S. Civil War arrived in the 1860s, however, the growth and use of industrial hemp declined as increased cotton and wood use took away much of the profitability of hemp.[3] Around the same time, local governments began recognizing tonics, tinctures, and extracts from cannabis plants as potentially dangerous substances, labeling them as hypnotics, narcotics, or even poisons.[6] In the early twentieth century, U.S. labeling and prescription laws—such as the the Pure Food and Drug Act of 1906 at the federal level, as well as various state laws—saw further restrictions put on cannabis, effectively culminating in the Marihuana Tax Act of 1937 and the Federal Food, Drug, and Cosmetic Act of 1938. With the passage of those acts, hemp and marijuana essentially became illegal, controlled substances.[7][8][9]

State efforts to decriminalize marijuana were somewhat successful in the early 1970s, though progress towards that goal slowed again with the Reagan Administration's war on drugs.[10] Progress picked up steam again in the late 1990s into the 2000s, particularly in states such as California, Massachusetts, Connecticut, Washington, and Colorado.

As of July 2022, thirty-eight U.S. states and the District of Columbia (D.C.) have approved broad legalization of medicinal marijuana, with 19 U.S. states and D.C. also approving recreational marijuana.[11] Additionally, neighboring Canada has legalized the purchase, growth, and consumption of marijuana in small amounts across the country[12], while Mexico's Supreme Court has legalized "all forms of non-commercial adult use" of the plant[13], though, as of July 2022, fully implementing the decision continues to be an ongoing process.[14][15][16]

Industrial hemp has also been addressed in a more serious fashion in the U.S., with 47 states having introduced some sort of hemp cultivation and production programs, and the federal government making certain concessions on it (Cannabis sativa containing no more than 0.3 percent THC, grown under a state-sanctioned agricultural pilot program).[17][18] In December 2018, those concessions seemingly transformed into what became outright legalization of industrial hemp in the United States (with significant shared state-federal regulator restrictions[19]) via the full passage and reconciliation of the 2018 Farm Bill.[17][20][21][22] However, marijuana remains a Schedule I controlled substance, as determined by the U.S. Food and Drug Administration (FDA)[23], including extracts and other derivatives such as CBD that come from cannabis.[24] (However, the U.S. Drug Enforcement Administration [DEA] moved CBD-based prescription drugs with a THC content below 0.01 percent to Schedule V classification in September 2018.[25] The status of CBD extracted from industrial hemp appears to be in a legal quagmire with the passage of the 2018 Farm Bill; see The National Law Review from late 2018[22], the FDA's consumer update from late 2019[26], and it's most recent regulatory news[27] for further details.) This federal classification continues to clash with changing state laws and regulations at an increasing pace, creating both opportunities and difficulties for involved citizens at all points along the industrial, economic, and social chain.

1.1.2 Use

In its 2022 World Drug Report, the United Nations Office on Drugs and Crime estimated that more than four percent of the global population—roughly 209 million people—used cannabis in 2020.[28] Focusing in on the United States, the Substance Abuse and Mental Health Services Administration (SAMHSA) estimated that in 2020 the country had 49.6 million past-year marijuana users.[29] It's not clear if that total includes legal medical marijuana users, which numbered roughly 4.3 million by the end of December 2020 according to non-profit Marijuana Policy Project (MPP).[30] When compared to SAMHSA's estimate of 11.1 million users in 1997[31], it becomes clear that reported marijuana use has increased in the United States over the past few decades, whether it's through legalization efforts or otherwise. Some have pointed to the expansion of medical marijuana laws acting as gateways for increased adolescent use; however, multiple studies have tried but failed to find such a cause and effect relationship.[32][33][34] Regardless, with 38 U.S. states and D.C. now having some type of legalization law on the books[11], the number of marijuana users isn't likely to decrease any time soon in the U.S.

1.1.3 Research and analysis

Marihuana Test.jpg

One area that continues to expand—while taking advantage of new scientific research and techniques—is the laboratory sphere, particularly in research, regulation, and standardization activities. According to July 2016 testimony from Susan R.B. Weiss, Division Director at NIDA, the National Institutes of Health (NIH) alone supported 281 cannabinoid research projects totaling more than $111 million in 2015.[35] By the end of 2021, that number had risen to $198 million.[36]

While the research, analysis, and processing of cannabis has been ongoing for centuries[3], it wasn't until 1896 that Wood et al. conducted one of the first documented chemical experiments to determine the constituents of cannabis. Several years later, the researchers were able to correctly identify the extracted and isolated cannabinol from the exuded resin of Indian hemp as C21H26O2.[37] As of mid-2018, somewhere between 104 upwards to more than 140 of the more than 750 constituents of Cannabis sativa have been identified as cannabinoids[38][39][40], "a class of diverse chemical compounds that act on cannabinoid receptors in cells that modulate neurotransmitter release in the brain."[41]

Yet in the United States, when it comes to 1. enacting the broad level of testing required to ensure public safety—whether it be medical, recreational, or industrial use of cannabis—and 2. researching and better understanding the pharmacokinetics and pharmacodynamics (medical use and benefit) of cannabinoids in the human population, many have argued that laboratory testing of cannabis is still in its infancy[42][43][44][45][46][47] and evidence-based research of marijuana continues to be slow and bogged down in regulation.[48][49][35][50][51] In regards to the first issue, as some form of legalization continues to sweep across states, regulators, users, and industry are recognizing the need for improved standardization of the production and testing of medical and recreational marijuana; the current state of improper labeling and potentially harmful contaminants[42][43][44][47] will only serve to hinder the industry. To the second issue, in 2016, some within the federal government seemed to recognize the roadblocks to improved evidence-based research and began working to slowly improve how researchers can legally acquire and test marijuana in the U.S.[35][50][52] Those attempts were largely rebuffed by the Justice Department, however.[53][54]

Regardless, an excerpt from the previously mentioned testimony of NIDA's Dr. Weiss illustrates the sentiment still felt by many researchers today[35]:

The current state of the research on marijuana and its constituent cannabinoids suggests the potential for therapeutic value for a number of conditions; however, more evidence is needed before marijuana or cannabinoid products (beyond those already approved through the FDA) are ready for medical use. Promising preclinical findings do not always prove to be clinically relevant, and even fewer lead to new treatments. Moreover, clinical studies of sufficient quality to meet FDA standards for drug approval are currently lacking for most conditions. Among the factors that impact this research are the specific statutory requirements and treaty obligations that govern research on marijuana. NIH is working closely with the Office of National Drug Control Policy (ONDCP), the Drug Enforcement Administration (DEA), and FDA to explore ways to streamline these processes to facilitate research.

In the meantime, government entities such as the NIH and non-profits such as jCanna have continued to push forward with scientific conferences, summits, and roundtables that bring scientists and interested parties together to share existing knowledge and testing techniques.[55][56] Some U.S. lawmakers have since further discussed the issue of cannabis research; an official hearing scheduled for January 2020 provided an opportunity to further highlight to Congress the "catch-22" of regulation and medical research: "Research is restricted because cannabis is currently considered a Schedule I drug under the Controlled Substances Act, yet more research would better determine if marijuana should be rescheduled or descheduled."[57]

Encouragingly, the DEA finalized its amended "21 Code of Federal Regulations 1318 to facilitate the cultivation of marihuana for research purpose and other licit purposes to ensure compliance with the Controlled Substances Act (CSA) and treaty obligations" in December 2020[58] This added an additional five grow-ops to support researchers[58][59], though the impact of this change on research organizations is unclear at this early juncture.


1.2 Regulation and standardization of cannabis testing

Dea color logo.svg

On October 27, 1970, the Controlled Substances Act put into place five schedules or classifications of drugs that would be regulated in some fashion, and drugs were initially classified into those schedules, followed by annual reviews and updates.[60] Marijuana was initially placed under Schedule I[60] and remains there today.[23][50][61] As a Schedule I drug, the federal government is indicating marijuana has[60]:

  • "a high potential for abuse";
  • "no currently accepted medical use in treatment in the United States"; and
  • "a lack of accepted safety for use of the drug or other substance under medical supervision".

Then came the Reorganization Plan No. 2 of 1973, which took existing enforcement entities such as the Bureau of Narcotics and Dangerous Drugs and placed them into a new, unified entity called the Drug Enforcement Administration (DEA).[62][63] Then President Richard Nixon said of the transition[62]:

The enforcement work could benefit significantly, however, from consolidation of our anti-drug forces under a single unified command. Right now the Federal Government is fighting the war on drug abuse under a distinct handicap, for its efforts are those of a loosely confederated alliance facing a resourceful, elusive, worldwide enemy.

The DEA was given numerous responsibilities, including but not limited to the development of enforcement strategy; investigation and prosecution preparation of suspects violating federal law; regulation of drugs and other controlled substances; and coordination and cooperation with state and local government drug enforcement efforts.[62] Since then the DEA has taken various steps—with guidance from the Food and Drug Administration (FDA)[64]—to regulate and enforce the availability and use of controlled substances such as marijuana. As the decriminalization and legalization efforts of states have increased in past decades, this has brought federal regulation and enforcement conflicts to those states that have decriminalized and legalized, largely due to the federal government's insistence on maintaining marijuana as a Schedule I drug.[52][65]

Numerous changes in federal policy, as well as a few controversies, have occurred since the Controlled Substance Act and DEA were implemented. This includes:

  • 2009's Ogden Memorandum, "intended solely as a guide to the exercise of investigative and prosecutorial discretion" in regards to state-based laws allowing medical cannabis[66];
  • 2011's Cole Memorandum 1, underlining that while the stance of the Ogden Memo still stood, large grow-ops that didn't qualify as "caregivers" had sprung up since, requiring federal enforcement action[67];
  • 2013's Cole Memorandum 2, which sought to reduce the emphasis on the size of the grow-op and increase emphasis on—using a case-by-case basis—"whether the operation is demonstrably in compliance with a strong and effective state regulatory system"[68];
  • 2014 and onward's Rohrabacher-Farr/Joyce Amendments, prohibiting the DoJ from spending funds to prevent or enforce against state laws that allow for medical marijuana cultivation, distribution, and use, particularly when those actions are performed consistently with those state laws[69];
  • 2016's DEA denial of a petition to reschedule marijuana out of Schedule I, while recognizing the need for further research and the lack of legal marijuana sources for researchers[23][70];
  • 2018 Farm Bill, which removed industrial hemp from the Controlled Substance Act's definition of "marijuana" and struck it from Schedule I[71];
  • 2020's House Health Subcommittee meetings, the first of their kind, to discuss cannabis research and cannabis' current scheduling, as well as the problems that come from it[72]; and
  • 2020's MORE Act, a continuing effort which would decriminalize "marijuana at the federal level while enabling states to set their regulatory policies without the threat of federal intervention."[73]

At the state level, changing laws and regulation have continued to put pressure on cannabis law at the federal level. As of July 2021, thirty-seven U.S. states and the District of Columbia have put some sort of broad decriminalization or legalization laws for cannabis on the books.[11] In October 1973, Oregon became the first state to enact decriminalization laws for marijuana, imposing a $100 fine for possession of less than an ounce. Eleven other states followed a similar path within five years.[74] The next wave of changes began with the passage of medical marijuana legislation in California—the Compassionate Use Act—in November 1996, followed by similar legislation in Oregon and Alaska in 1998, Maine in 1999, and Colorado, Hawaii, and Nevada in 2000.[75][76] Other states continued to add decriminalization and medical marijuana laws in the 2000s. But it wasn't until 2012 that Colorado and Washington became the first states to make recreational marijuana legal, followed by Alaska, Oregon, and the District of Columbia in 2014.[75] Colorado, Maine, Massachusetts, and Nevada followed suit in 2016[77], with Michigan doing the same in 2018.[78]

As shown by Cambron et al. in 2016[75], dispensaries, possession limits, and interstate ID card acceptance can vary significantly among affected states. California, Colorado, Michigan, Oregon, and Washington led in number of dispensaries; Massachusetts, Oregon, and Washington in maximum possession limits; and Arizona plus five others allowed ID cards from other states. Yet the number of allowed dispensaries can be in the single digits, possession limits can be as low as one ounce, and numerous states still don't honor ID cards from other states.[75]

Then there's the matter of state differences in testing, enforcement, advertising allowances, etc. It helps to turn to professional associations and organizations—who often lead the charge for improved, more relevant standards—to sort through the variances. The Association of Public Health Laboratories (APHL), for example, has published its Guidance for State Medical Cannabis Testing Programs to help sort through the confusing tangle of existing testing laws, where they exist. They exemplify this variation of law in their document[79]:

As with most programs in the United States, every state takes a different approach. For example as of January 2016, New Jersey’s Public Health & Environmental Laboratories only test cannabis plant material. Just across the Hudson, however, New York’s Public Health Laboratory will not be testing any plant material, only cannabis extracts. In addition, the New York Department of Health will provide an oversight role for commercial cannabis laboratories that are licensed by the federal Drug Enforcement Administration (DEA) and approved for testing cannabis products. On the other hand, New Jersey state government does all testing in-house for the medical cannabis program.

This variation in law also largely mirrors the variation found in laboratory testing methods of cannabis and its constituents. Recognizing this variance in standards and methods, state officials from Colorado, New Mexico, Oregon, and Washington teamed up to give a presentation called "State Regulatory Approaches to Cannabis Testing, Operations and Product Logistics" at the July 2016 Cannabis Quality, Strategies and Solutions Summit. That presentation focused on the harmonization of regulatory standards and frameworks across states, as well as discussions of what scientific efforts are required to support those standards and frameworks.[80] Additionally, organizations such as Americans for Safe Access Foundation (ASAF), American Herbal Pharmacopoeia (AHP), American Herbal Products Association (AHPA), Association of Official Agricultural Chemists (AOAC), and the American Oil Chemists' Society (AOCS) have been developing standards, methods, and certifications for analysis, extraction, labeling, and laboratory operations surrounding medical (and recreational) marijuana.[81][82][83][84][85][86] More recent efforts from the Foundation of Cannabis Unified Standards (FOCUS), ASTM International, the AOAC's Cannabis Analytical Science Program (CASP), and the National Institute of Standards and Technology (NIST) have, however, furthered attempts to standardize cannabis laboratory testing.[87][88][89][90][91]


1.3 Why test?

CCE by Draconis- laboratory work on plant essences and cannabinoid material.jpg

The attempts to legalize, regulate, and standardize cannabis, cannabis products, and all the activities surrounding the industry are apparent, but why is laboratory testing of cannabis important? Why test?

First, from a purely research-based perspective, analytical testing of cannabis helps society learn more about the plant and its constituents, and how they positively and negatively affect human health when ingested. Though research has been difficult to accomplish in the U.S. over the years[92], the long-term lack of understanding about the plant and its effects of use continues to push researchers forward to expand that societal understanding.[93][94] Granted, some countries such as Israel have been at the forefront of cannabis research and testing, with researchers there receiving funding from U.S. companies, as well as the U.S. government.[95][96] Studies and clinical trials from Israeli researchers on autism[97] and inflammatory bowel disease[98], as well as the agricultural[99][100], analytical[101], and broad medical aspects of the plant[102] continue to move the science forward for everyone. With a new administration steering the helm in the U.S. in 2021, a promise of prioritizing "the research needed to advance science-based federal policies related to the use of marijuana for medical conditions, chronic pain, and disabilities"[103] remains to be seen, though some in the cannabis industry appear to be cautiously optimistic.[104][105]

Second, similar to how we have mechanisms like laboratory testing in place to ensure the safety of medicines, foods, beverages, and cosmetics for human use, we should be performing similar testing for the human and animal use of cannabis and cannabis-related products. Microbes, heavy metals, pesticides, and solvents that are dangerous to consume—particularly for medical marijuana patients with fragile and weak immune systems—must be identified and quantified through quality control in order to protect public health.[106][107][108] Without quality testing and safety oversight, cannabis products can cause sickness or even death.[109]

Third, growers and sellers of cannabis and cannabis-related products should be held accountable for the claims they make about their products. When growers, sellers, and even the testing laboratories themselves are held accountable, consumer confidence can be gradually built.[108] This can be difficult, however, given a lack of a federal regulatory framework for both THC-containing and low-THC/high-CBD products. For example, independent testing in 2020 of CBD-containing products found an abysmally low 13 percent of products tested matched their label claims, findings similar to those of a 2020 FDA market survey.[110] Law firm Keller and Heckman warn that "buyers need to be cautious" concerning the purchase of largely unregulated CBD products[110], which highlights the difficulty of improving consumer confidence in the face of little regulation. However, most U.S. states that have legalized some form of cannabis have also mandated laboratory testing, not only for the two prior reasons but also to hold accountable those producers and sellers supplying the legal cannabis market with products containing specific cannabinoid amounts.[108][111]

When considering these three points, it's easier to understand the "why" of testing. But what gets tested and how? The next chapter addresses this question, as well as the workflows surrounding the "how."


References

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  2. ↑ Swanson, T.E. (2015). "Controlled Substances Chaos: The Department of Justice's New Policy Position on Marijuana and What It Means for Industrial Hemp Farming in North Dakota" (PDF). North Dakota Law Review 90 (3): 599–622. https://law.und.edu/_files/docs/ndlr/pdf/issues/90/3/90ndlr599.pdf. 
  3. ↑ 3.0 3.1 3.2 3.3 Deitch, R. (2003). Hemp – American History Revisited. New York City: Algora Publishing. pp. 232. ISBN 9780875862262. 
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  5. ↑ Thompson, M. (22 July 2013). "The Mysterious History Of 'Marijuana'". NPR. National Public Radio. https://www.npr.org/sections/codeswitch/2013/07/14/201981025/the-mysterious-history-of-marijuana. Retrieved 08 July 2022. 
  6. ↑ U.S. Senate (16 February 1860). "Senate". The New York Times. Archived from the original on 04 February 2018. https://web.archive.org/web/20180204001301/http://www.nytimes.com/1860/02/16/news/senate-88150825.html. Retrieved 08 July 2022. 
  7. ↑ Walton, R.F. (1938). Marijuana, America’s New Drug Problem. Philadelphia: B. Lippincott. p. 37. 
  8. ↑ Woodward, W.C.; House of Representatives, Committee on Ways and Means (4 May 1937). "Taxation of Marihuana". Schaffer Library of Drug Policy. https://www.druglibrary.org/schaffer/hemp/taxact/woodward.htm. Retrieved 08 July 2022. 
  9. ↑ Cavers, D.F. (1939). "The Food, Drug, and Cosmetic Act of 1938: Its Legislative History and its Substantive Provisions". Law and Contemporary Problems 6: 2–42. https://scholarship.law.duke.edu/lcp/vol6/iss1/2/. 
  10. ↑ Meier, K.J. (2016). The Politics of Sin: Drugs, Alcohol and Public Policy: Drugs, Alcohol and Public Policy. Taylor & Francis. p. 58. ISBN 9781315287270. https://books.google.com/books?id=J4wYDQAAQBAJ&pg=PT58. 
  11. ↑ 11.0 11.1 11.2 Berke, J.; Gal, S.; Lee, Y.J. (6 January 2021). "Marijuana legalization is sweeping the US. See every state where cannabis is legal". Business Insider. Insider, Inc. https://www.businessinsider.com/legal-marijuana-states-2018-1. Retrieved 08 July 2022.  Cite error: Invalid <ref> tag; name "BerkeMichigan18" defined multiple times with different content
  12. ↑ Porter, C. (11 November 2018). "Canada’s Message to Teenagers: Marijuana Is Legal Now. Please Don’t Smoke It". The New York Times. The New York Times Company. https://www.nytimes.com/2018/11/11/world/canada/marijuana-legalization-teenagers.html. Retrieved 08 July 2022. 
  13. ↑ Timmons, P. (31 October 2018). "Mexico's Supreme Court legalizes cannabis for recreational use". UPI. United Press International, Inc. https://www.upi.com/Top_News/World-News/2018/10/31/Mexicos-Supreme-Court-legalizes-cannabis-for-recreational-use/9621541024238/. Retrieved 07 July 2021. 
  14. ↑ Williams, S. (16 November 2019). "News Flash: Recreational Marijuana in Mexico Is Going to Have to Wait". The Motley Fool. https://www.fool.com/investing/2019/11/16/news-flash-recreational-marijuana-in-mexico-is-goi.aspx. Retrieved 07 July 2021. 
  15. ↑ Westfall, S. (29 June 2021). "Mexico’s top court rolls back marijuana prohibition, opening door to legalization". The Washington Post. https://www.washingtonpost.com/world/2021/06/29/marijuana-legalization-court-ruling-mexico/. Retrieved 07 July 2021. 
  16. ↑ Busby, M. (12 May 2022). "Mexico’s Supreme Court rules personal marijuana possession legal, again". Leafly. https://www.leafly.com/news/politics/mexicos-supreme-court-rules-personal-marijuana-possession-legal-again. Retrieved 08 July 2022. 
  17. ↑ 17.0 17.1 "State Industrial Hemp Statuses". National Conference of State Legislatures. 16 April 2020. https://www.ncsl.org/research/agriculture-and-rural-development/state-industrial-hemp-statutes.aspx. Retrieved 08 July 2022. 
  18. ↑ "Statement of Principles on Industrial Hemp". Federal Register 81 (156): 53395–6. 12 August 2016. https://www.federalregister.gov/documents/2016/08/12/2016-19146/statement-of-principles-on-industrial-hemp. Retrieved 08 July 2022. 
  19. ↑ Hudak, J. (14 December 2018). "The Farm Bill, hemp legalization and the status of CBD: An explainer". FIXGOV. The Brookings Institution. https://www.brookings.edu/blog/fixgov/2018/12/14/the-farm-bill-hemp-and-cbd-explainer/. Retrieved 08 July 2022. 
  20. ↑ Good, K. (20 December 2018). "Farm Bill Signed, SNAP Proposal Released, and Trade Aid Payments Approved". Farm Policy News. Board of Trustees of the University of Illinois. https://farmpolicynews.illinois.edu/2018/12/farm-bill-signed-snap-proposal-released-and-trade-aid-payments-approved/. Retrieved 08 July 2022. 
  21. ↑ Milligan, S. (4 December 2018). "Legalization of Hemp Could Be First Step for Federal Marijuana Protections". U.S. News and World Report. https://www.usnews.com/news/national-news/articles/2018-12-04/legalization-of-hemp-could-be-first-step-for-federal-marijuana-protections. Retrieved 08 July 2022. 
  22. ↑ 22.0 22.1 Stewart, I.A.; Kloss, J.M.; Willner, N.M. (4 December 2018). "Will Hemp-Derived CBD Be Fully Legal with Passage of the 2018 Farm Bill? Not Quite…". The National Law Review. https://www.natlawreview.com/article/will-hemp-derived-cbd-be-fully-legal-passage-2018-farm-bill-not-quite. Retrieved 08 July 2022. 
  23. ↑ 23.0 23.1 23.2 Leger, D.L. (11 August 2016). "Marijuana to remain illegal under federal law, DEA says". USA. Today. Gannett Company. https://www.usatoday.com/story/news/2016/08/11/dea-marijuana-remains-illegal-under-federal-law/88550804/. Retrieved 08 July 2022.  Cite error: Invalid <ref> tag; name "LegerMari16" defined multiple times with different content
  24. ↑ Wallace, A. (13 January 2017). "Legal challenge filed against DEA’s new marijuana extract rule". The Cannabist. The Denver Post. https://www.thecannabist.co/2017/01/13/hemp-dea-extracts-marijuana-cbd-judicial-review/71387/. Retrieved 08 July 2022. 
  25. ↑ Romza-Kutz, D. (1 October 2018). "CBD drugs moved to Schedule 5; no promises for cannabis". Thompson Coburn LLP. https://www.thompsoncoburn.com/insights/blogs/tracking-cannabis/post/2018-10-01/cbd-drugs-moved-to-schedule-5-no-promises-for-cannabis. Retrieved 08 July 2022. 
  26. ↑ U.S. Food and Drug Administration (5 March 2020). "What You Need to Know (And What We’re Working to Find Out) About Products Containing Cannabis or Cannabis-derived Compounds, Including CBD". Consumer Updates. https://www.fda.gov/consumers/consumer-updates/what-you-need-know-and-what-were-working-find-out-about-products-containing-cannabis-or-cannabis. Retrieved 08 July 2022. 
  27. ↑ U.S. Food and Drug Administration (22 January 2021). "FDA Regulation of Cannabis and Cannabis-Derived Products, Including Cannabidiol (CBD)". Public Health Focus. https://www.fda.gov/news-events/public-health-focus/fda-regulation-cannabis-and-cannabis-derived-products-including-cannabidiol-cbd#legaltosell. Retrieved 08 July 2022. 
  28. ↑ United Nations Office on Drugs and Crime (June 2022). "World Drug Report 2022: Global Overview of Drug Demand and Supply" (PDF). United Nations. https://www.unodc.org/res/wdr2022/MS/WDR22_Booklet_2.pdf. Retrieved 08 July 2022. 
  29. ↑ Substance Abuse and Mental Health Services Administration (October 2021). "Results from The 2020 National Survey on Drug Use And Health". In RTI International (PDF). p. 2. https://www.samhsa.gov/data/sites/default/files/reports/rpt35325/NSDUHFFRPDFWHTMLFiles2020/2020NSDUHFFR1PDFW102121.pdf. Retrieved 08 July 2022. 
  30. ↑ "Medical Marijuana Patient Numbers". Marijuana Policy Project. 2 December 2020. Archived from the original on 09 May 2021. https://web.archive.org/web/20210509095341/https://www.mpp.org/issues/medical-marijuana/state-by-state-medical-marijuana-laws/medical-marijuana-patient-numbers/. Retrieved 08 July 2022. 
  31. ↑ Rabkin, N.J. (July 1999). Drug Control: DEA's Strategies and Operations in the 1990s. U.S. General Accounting Office. pp. 172. ISBN 9780788184833. https://books.google.com/books?id=ZvzBdlolKrQC&pg=PA16. 
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Chapter: 1. Cannabis testing and research: An overview

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