History of Cannabis Regulation and Medicinal Therapeutics: It’s Complicated

The use of medicinal cannabis (also called medical marijuana) has been a controversial topic among patients, clinicians, researchers, and policymakers across the world, growing more pronounced each year since the legalization of medicinal cannabis use in California in 1996. Notably, the legalization of cannabis use preceded most of what science currently understands about the substance and its therapeutic use, as an estimated 97% of research articles on cannabis have been published since 2000.4While both the science and regulation of cannabis continue to grow, they often operate in distinct silos. This lack of communication between researchers and regulators can obscure evidence-based policies (ie, laws and regulation) and lead to heterogeneity in policy design and health care practices among jurisdictions with legalized cannabis use. As such, the legalization of cannabis for medicinal or adult use continues to be complex, with diverse legal, ethical, and societal implications.⁵

Cannabis was used for its therapeutic properties by multiple ancient cultures since it was first documented in China in 2800 bc,^8,9and was later reintroduced in 1843 by Irish physician W.B. O’Shaughnessy.^10,11Around that time, the 19th century scientific revolution in medicine pivoted the collective understanding of disease and medicinal applications. This shift focused on embracing the use of drugs to prevent and cure disease¹²and shifted away from ancient understandings of disease that focused on divine manifestations. Despite the differences in philosophy on the origin of disease, early medicine discovered many plant extracts with therapeutic pharmacologic properties that are still used today, including cannabis.^12,13While cannabis is currently cultivated and used for varying purposes internationally,¹⁴its use for medicinal purposes remains contested and controversial¹⁵despite advancements in scientific knowledge in recent years.

Currently, public and health care policies and practices alike set the parameters on whether cannabis constitutes an accepted medicinal intervention.16This phenomenon has led to varying policies, health care practices, and drug therapeutics across varying jurisdictions and cultures worldwide.17,18More recently, multiple countries and other, localized jurisdictions have legalized the medicinal use of cannabis for the treatment of patients with specified illnesses and symptoms. However, as mentioned, these policies, including those of the 38 US states with legalized medicinal cannabis use,19often operate in silos external to the health care system, further complicating its usage and integration into conventional therapeutics.

Despite policy-related complexities, cannabis is a promising medicinal plant with increasing use in the treatment of patients with various medical conditions.20Legalization has introduced crucial medical and agricultural research21that have led to more effective analysis of the plant and its hundreds of chemical compositions compared to what had been possible previously.21,22Knowledge gained from the history of and different formulations for the administration of cannabis have informed research on cannabis-based treatments for patients with medical conditions that remain challenges in 21st century medicine, such as chronic pain, spasticity, cancer, seizure disorders, nausea, anorexia, and infectious diseases.15Changes in policies, scientific advances, and perceptions of cannabis may result in increasing patient inquiries about its medicinal usage, regardless of a clinician’s personal opinions or beliefs,23thus meriting education and training of clinicians.

All categories are important for a better understanding of the potential for cannabis in medicinal use.

Cannabis has been regulated internationally since the Second Opium Conference and the International Opium Convention signed in 1925.³⁹

Regulation eliminated the prior legalized and accepted medicinal therapeutics. In the United States, the 1970s’ federal Controlled Substances Act designated cannabis as a Schedule I drug—the most restrictive rank, on par with heroin, with the exception of specified synthetic pharmaceutical cannabinoids and hemp.³⁷

This scheduling, still in place today, states that cannabis has a high potential for abuse, no current accepted medicinal use in the United States, and a lack of accepted safety for use under medical supervision.⁴⁰

Despite federal law, modern efforts to legalize the use of medicinal cannabis in the United States began in 1996, when California voters approved Proposition 215 (the Compassionate Use Act).⁴¹

Since that landmark legislation was passed, 38 US states and territories (the District of Columbia, Guam, Puerto Rico, and the US Virgin Islands) have enacted varying policies to permit patients with specified illnesses to use cannabis for medicinal purposes as of April 2023.⁴²

US states are not alone in modern-day efforts to legalize cannabis for medicinal use. Canada has allowed access to cannabis for medicinal use since 2001.⁴³

Some countries in Europe, including Germany, Italy, and the United Kingdom, among others, have implemented comprehensive medicinal cannabis programs.^44,45

Even among countries that do not have a bona fide program in place, many have legalized the use of synthetic cannabinoid pharmaceuticals (eg, CBD, nabiximols).⁴⁶

Eight countries in Africa⁴⁷and five across the Asia-Pacific region, including Australia, New Zealand, and Thailand, have legalized the use of medicinal cannabis, with Singapore and South Korea allowing more limited access.⁴⁸

The example set in one Australian state is particularly noteworthy: New South Wales employs guidance on prescribing cannabinoids that provides medical practitioners with the latest scientific evidence to inform the prescribing of cannabis to patients.⁴⁹

Additionally, a recent review process conducted by the World Health Organization led to recommendations to the United Nations,⁵⁰which in turn resulted in the recognition of the medicinal value of cannabis, and the reclassification of cannabis in an international listing by the United Nations’ Commission on Narcotic Drugs in 2020.⁵¹

There is substantial heterogeneity among jurisdictions with legalized medicinal cannabis use, both internationally and within the United States.¹⁷

For example, in 10 of the 38 US states with legalized medicinal cannabis use, the laws allow for the use of only medicinal CBD and low-THC (ie, chemotype III) products.¹⁹

Beyond this specification, there are numerous other policy discrepancies that may influence the ways in which patients interact with programs. For example, as of January 2020, 35% of legalized states permit home cultivation and 70% permit home delivery.⁵²

Major discrepancies in permitted possession limits also exist, ranging from observable weights of 1 to 15 oz of flower, to more arbitrary values, such as a “30-day” or “90-day” supply.⁵²

The complexity of these state policies can make it difficult for patients to navigate programs and for research to determine the effects of cannabis-related programs.

Unlike other pharmaceutical therapies, cannabis has additionally been legalized for nonmedicinal use in adults (also called adult use or recreational use) in some jurisdictions internationally and across the United States. This unique status has resulted in complexities with regard to the ways in which policymakers regulate both medicinal- and adult-use cannabis to best protect medicinal cannabis programs and patients’ unique needs. Some states, such as Alaska, Nevada, and Oregon (1998) and Colorado (2000), have seen a decline in the use of medicinal cannabis programs, as evidenced by exponential decreases in cardholder registrations after the legalization of adult-use cannabis.^53,54

With more states legalizing cannabis for adult use each legislative cycle, more critics are questioning the efficacy of medicinal cannabis programs, leaving such programs effectively in a state of “identity crisis,” which may potentially negatively affect patients.