Book:LIMS Buyer’s Guide for Cannabis Testing Laboratories/Cannabis testing and research: An overview/Cannabis legalization, use, and research

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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

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. 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). 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.

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. 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. 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. 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.

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. 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. Additionally, neighboring Canada has legalized the purchase, growth, and consumption of marijuana in small amounts across the country, while Mexico's Supreme Court has legalized "all forms of non-commercial adult use" of the plant, though, as of July 2022, fully implementing the decision continues to be an ongoing process.

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). 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) via the full passage and reconciliation of the 2018 Farm Bill. However, marijuana remains a Schedule I controlled substance, as determined by the U.S. Food and Drug Administration (FDA), including extracts and other derivatives such as CBD that come from cannabis. (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. 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, the FDA's consumer update from late 2019, and it's most recent regulatory news 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. 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. 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). When compared to SAMHSA's estimate of 11.1 million users in 1997, 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. Regardless, with 38 U.S. states and D.C. now having some type of legalization law on the books, the number of marijuana users isn't likely to decrease any time soon in the U.S.

1.1.3 Research and analysis

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. By the end of 2021, that number had risen to $198 million.

While the research, analysis, and processing of cannabis has been ongoing for centuries, 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. 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, "a class of diverse chemical compounds that act on cannabinoid receptors in cells that modulate neurotransmitter release in the brain."

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 and evidence-based research of marijuana continues to be slow and bogged down in regulation. 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 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. Those attempts were largely rebuffed by the Justice Department, however.

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

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. 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."

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 This added an additional five grow-ops to support researchers, though the impact of this change on research organizations is unclear at this early juncture.