____________________________________________________ Medical Marijuana and Other Cannabinoids
• Analgesic: Headaches, migraine, eye strain, menopause, brain tumors, neuralgia, gastric ulcer, indigestion, mul- tiple neuritis, pain not due to lesions, dysmenorrhea, chronic inflammation, acute rheumatism, eczema and pruritus, tingling, numbness of gout, dental pain • Other uses: To improve appetite and digestion associ- ated with “pronounced anorexia following exhausting diseases,” dyspepsia, diarrhea, dysentery, cholera, nephritis, diabetes mellitus, vertigo Many indications are consistent with scientific confirma- tion, more than 90 years later, of analgesic, antispasmodic, antiemetic, sedative, anti-inflammatory, anticachexic, and antianorexic efficacy. THE 20TH CENTURY The psychoactive properties of cannabis were recognized thousands of years ago but were valued mainly as religious adjuncts. Before the mid-20th century, recreational cannabis use was restricted to “fringe” or marginalized groups and the impoverished, for whom it was considered “the opium of the poor” [19]. Its use became increasingly popular in African American and immigrant Hispanic neighborhoods in the United States before 1950. Cannabis prescribing in the United States significantly declined over the first three decades of the 20th century due to difficulty in developing reliable, standardized preparations; inability to isolate its active constituent; and introduction of effective medications in the areas of primary indication for cannabis. Medical cannabis use was burdened with severe taxa- tion by the Federal Marihuana Tax Act of 1937, and cannabis was removed from the U.S. Pharmacopoeia in 1942 [8]. The American Medical Association (AMA) opposed both acts and testified before Congress that nearly 100 years of medical expe- rience in the United States had demonstrated an irreplaceable therapeutic role for cannabis [23; 24]. Prohibition of medical marijuana culminated with the 1970 Controlled Substance Act (CSA) that categorized marijuana, along with heroin, as a Schedule I substance or CS-I. Drugs with CS-I listing are deemed highly addictive and devoid of medical value or safety. The CSA was a component of the “War on Drugs” launched in 1968, enforced and upheld by the newly established DEA. Possession of a CS-I substance potentially confers severe legal consequences, and possessing small amounts of cannabis has led to the lengthy incarceration of many. Black Americans have been disproportionately arrested and incarcerated for marijuana possession. Despite data showing that drug use is unaffected by severity (or leniency) in drug policy, harsh sen- tencing of marijuana possession has persisted in some jurisdic- tions [25]. Prominent groups have petitioned the government to review and reconsider its Schedule I status, including the IOM, the AMA, and the American College of Physicians [24].
Research and clinical interest in cannabis was re-ignited with identification of the chemical structure for THC in 1964, fol- lowed by discovery and cloning of cannabinoid receptors and isolation of the endogenous cannabinoid anandamide in the 1970s to early 1990s [24]. The first sporadic scientific reporting of medical marijuana benefit started in the 1970s, particularly with nausea and vomiting from chemotherapy. As the acquired immune deficiency syndrome (AIDS) epidemic spread through the 1980s, patients increasingly found that marijuana relieved many of their symptoms, particularly wasting symptoms associ- ated with AIDS. A landmark 1999 IOM report described the scientific and clinical basis for supporting medical marijuana use. There were increasing media reports of medical marijuana users subjected to criminal prosecution during this period [8]. These events stimulated media attention and growing public demand for medical access. Despite its illegal status at the federal level, cannabis was reintroduced into medical use in 1996 by popular vote and legislative acts in California. By 2023, 38 states and the District of Columbia had followed suit [1]. (For information on laws pertaining to medical marijuana in your state, visit https://medicalmarijuana.procon.org/legal- medical-marijuana-states-and-dc.) In addition, cannabis is used by millions of patients for medicinal purposes in jurisdictions where it remains illegal for medical use [11]. In opposition to federal law, state medical marijuana programs have received support by official federal statements of cooperative noninter- ference by the Veterans Health Administration and the U.S. Department of Justice in 2009 [24]. The DEA and National Institute on Drug Abuse (NIDA) are funded by the Office of National Drug Control Policy (ONDCP). Both agencies are guided by ONDCP’s agenda and explicit policy goal of a drug-free America. The NIDAs research priority on cannabis harms reinforces its CS-I status by DEA. This long-standing federal obstruction of cannabis efficacy research perpetuated criticism that cannabis lacked scientific evidence of clinical benefit [11]. However, since 2000, advances in research design and evaluation have finally been applied to cannabis research. There are now numerous well-controlled clinical trials that fulfill the highest contemporary standards of scientific evidence. This clinical data, and the findings of preclinical and population-level studies, have greatly clarified the risk/benefit profiles of cannabis in a number of indica- tions, addressed many long-standing safety concerns, defined patient contraindications, and identified the safety outcomes in recreational users that are inappropriate for generalization to medical users [11]. Contributing to this body of evidence was the 1999 founding of the Center for Medicinal Cannabis Research (CMCR) at the University of California, San Diego. The CMCR is the first comprehensive cannabis clinical research program in the United States and was launched with the goal of conducting randomized, placebo-controlled safety and efficacy trials of
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