Elsevier

Mayo Clinic Proceedings

Volume 87, Issue 2, February 2012, Pages 172-186
Mayo Clinic Proceedings

Special article
Blurred Boundaries: The Therapeutics and Politics of Medical Marijuana

https://doi.org/10.1016/j.mayocp.2011.10.003Get rights and content

Abstract

For 5 millennia, Cannabis sativa has been used throughout the world medically, recreationally, and spiritually. From the mid-19th century to the 1930s, American physicians prescribed it for a plethora of indications, until the federal government started imposing restrictions on its use, culminating in 1970 with the US Congress classifying it as a Schedule I substance, illegal, and without medical value. Simultaneous with this prohibition, marijuana became the United States' most widely used illicit recreational drug, a substance generally regarded as pleasurable and relaxing without the addictive dangers of opioids or stimulants. Meanwhile, cannabis never lost its cachet in alternative medicine circles, going mainstream in 1995 when California became the first of 16 states to date to legalize its medical use, despite the federal ban. Little about cannabis is straightforward. Its main active ingredient, δ-9-tetrahydrocannabinol, was not isolated until 1964, and not until the 1990s were the far-reaching modulatory activities of the endocannabinoid system in the human body appreciated. This system's elucidation raises the possibility of many promising pharmaceutical applications, even as draconian federal restrictions that hamstring research show no signs of softening. Recreational use continues unabated, despite growing evidence of marijuana's addictive potential, particularly in the young, and its propensity for inducing and exacerbating psychotic illness in the susceptible. Public approval drives medical marijuana legalization efforts without the scientific data normally required to justify a new medication's introduction. This article explores each of these controversies, with the intent of educating physicians to decide for themselves whether marijuana is panacea, scourge, or both. PubMed searches were conducted using the following keywords: medical marijuana, medical cannabis, endocannabinoid system, CB1 receptors, CB2 receptors, THC, cannabidiol, nabilone, dronabinol, nabiximols, rimonabant, marijuana legislation, marijuana abuse, marijuana dependence, and marijuana and schizophrenia. Bibliographies were hand searched for additional references relevant to clarifying the relationships between medical and recreational marijuana use and abuse.

Section snippets

What is Medical Marijuana?

For 5 millennia, Cannabis sativa has been used throughout the world medically, recreationally, and spiritually.6 As a folk medicine marijuana has been “used to treat an endless variety of human miseries,” although typically under the aegis of strict cultural controls, according to DuPont.7 The first medical use probably occurred in Central Asia and later spread to China and India. The Chinese emperor Shen-Nung is known to have prescribed it nearly 5 millennia ago. Between 2000 and 1400 bc, it

Recreational Use Blends Into Medical Use

For recreational users, access to marijuana has always been about getting intoxicated. In the 21st century, cannabis is the most widely used illicit drug in the world,22 with the United Nations estimating that up to 190 million people consumed cannabis in 2007.23, 24, 25 Alice B. Toklas's legendary brownies notwithstanding, smoke inhalation is the preferred method of ingestion.20 Unlike eaten botanical cannabis, smoked botanical cannabis affords high bioavailability, rapid and predictable

The Relationship Between Psychosis and Marijuana

Marijuana continues to have the reputation among the general public as being benign, non–habit-forming, and incapable of inducing true addiction.39, 48 For most users this may be so. Experimentation with marijuana has become an adolescent rite of passage, with the prevalence of use peaking in the late teens and early 20s, then decreasing significantly as youths settle into the adult business of establishing careers and families. With a lifetime dependence risk of 9% in marijuana users vs 32%

Dangers of Early Use

Whereas adult users appear comparatively immune to cannabis-induced behavioral and brain morphologic changes, the same cannot be said of individuals initiating use during their early teens, when effects are both more severe and more long-lasting than in adults.66 During puberty, a period characterized by significant cerebral reorganization, particularly of the frontal lobes implicated in behavior, the brain is especially vulnerable to adverse effects from exogenous cannabinoids.58, 67 How they

Dangers of Medical Marijuana

Those skeptical of botanical cannabis do not argue that it is necessarily bad. Rather they contend that the benefits of cannabis—particularly when smoked—remain scientifically unproven, not only on its own merits but also compared with other available treatments. They contend that the usual standards for evaluating pharmacotherapies have been largely side-stepped.17 They want legitimate research. In a 2008 position paper, the American College of Physicians trod a middle ground between praising

The Endocannabinoid System

Although cannabis has been part of the world's herbal pharmacopoeia for millennia, next to nothing about its mechanisms of action was known until the last half century. As with all folk medicines, practitioners established the therapeutic benefits and risks of their plant-derived remedies through careful observation. In this respect, the cannabis story mirrors that of the Oriental poppy, Papaver somniferum, the source of opium, which was appreciated both as a renowned painkiller and a

Promising Pharmaceutical Applications

In the rapidly growing field of endocannabinoid pharmacology, the potential for designing pharmacologic interventions is as broad as the endocannabinoid system's bodily distribution.91 “Perhaps no other signaling system discovered during the past 15 years is raising as many expectations for the development of new therapeutic drugs, encompassing such a wide range of potential strategies for treatments,” Di Marzo92 writes. Describing the endocannabinoid system as “having pleiotropic homeostatic

Currently Available Pharmaceuticals

To date, only 4 pharmaceutical cannabinoids have been marketed. The first and second (dronabinol and nabilone) have been available in the United States since 1985 and a third one (nabiximols) in Canada since 2005.36 A fourth (rimonabant) has shown promise treating nicotine dependence and reducing appetite in obese individuals. Available in Europe since 2006, the FDA failed to approve its release in the United States over concerns it can induce depression and suicidal behavior.56, 84, 90

The 2 US

Federal Barriers to Cannabis Research

For nearly a century, cannabis was a part of the American pharmacopeia,83 but by the 1930s, its days as a legitimate treatment were numbered. The flames of popular fear had been fanned for decades by the popular press102 and by the likes of such high-camp films as the 1936 Reefer Madness, which hysterically portrayed “marihuana” as a threat to Western civilization through its purported capacity to induce user insanity and incite societal mayhem. In a standoff foreshadowing the current

States' Defiance of Federal Law

Meanwhile, in the legal arena, the federal government pits itself against increasing numbers of states—16 plus the District of Columbia—with regulations permitting botanical cannabis use for certain chronically or critically ill patients that contradict federal law.10 A consequence of the discrepancies between federal and state statutes is that users and purveyors of botanical cannabis for any purpose can be arrested and charged with federal crimes, even in states where possessing small

Conclusions

Given cannabis' worldwide use for thousands of years for medical and spiritual purposes, the contemporary American tumult over medical marijuana seems peculiar and misguided. Despite cannabis being part of the US pharmacopeia through much of the 19th and early 20th centuries, a federal government deeply suspicious of mind-altering substances began imposing restrictions on its prescription in the late 1930s, culminating in 1970 when the US Congress classified it as a Schedule I substance,

Acknowledgments

For Gabe, whose ongoing recovery from chemical dependence inspired me to write this article.

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