REPORT 04.15.19 Marijuana as Medicine William Martin, Ph.D., Director, Drug Policy Program Katharine Neill Harris, Ph.D., Alfred C. Glassell, III, Fellow in Drug Policy Several of these bills follow a recent INTRODUCTION trend of laws that allow for access to strains Thirty-four states have laws permiting of marijuana that are high in CBD, the the use of marijuana—properly called nonpsychoactive compound touted for its cannabis—for specified medical purposes. medical properties, but with little or no THC, Currently more than half the U.S. the component that causes the “high.” These population has access to marijuana for laws have attracted support, particularly in medical use, and an estimated 2.6 million southern states, because they are seen as people are using it for relief.1 States differ a way to provide patients with some of the in stipulating what medical cannabis is, main medicinal qualities of the marijuana who can use it, and how they can get it. plant but without any psychoactive effects. Most states with legal medical cannabis As one observer put it, “They don’t mind authorize licensed dispensaries. States that if you take medicine, as long as it doesn’t do not have dispensaries—as well as many make you happy.” A key drawback of CBD- that do—allow patients to grow their own only laws is that they typically place strict marijuana plants. limits on the number and types of qualifying A June 2018 University of Texas/Texas medical conditions. In 2015, Texas passed the Tribune poll indicated that 53 percent of Compassionate Use Act (CUA), which allows Texans would legalize it for any purpose, at Texans with intractable epilepsy to access It is necessary to least in small amounts, and 31 percent would low-THC (less than .5 percent) CBD oil, but understand what legalize it for medical purposes only. Only 16 that law has been criticized for its narrow makes cannabis serious scope (see below). Several bills introduced percent say marijuana should remain illegal medicine, not just a under any circumstance.2 this session are attempts to expand the CUA. In the summer of 2018, both The two drawing most attention are House stage on the road to major Texas political parties passed by Bill 1365,4 authored by Rep. Eddie Lucio III, full legalization of a overwhelming majorities platform planks D-Brownsville, and Senate Bill 90,5 authored recreational drug. that reflect these views. The Republican by Sen. José Menéndez, D-San Antonio. version calls on legislators “to allow doctors Though differing in some respects, both add to determine the appropriate use of cannabis substantially to the number of diseases or to certified patients” and its Democratic conditions that qualify for treatment, remove counterpart urges “the immediate the cap on the amount of THC than can be legalization of medical cannabis use.”3 legally dispensed or possessed, and provide Texas legislators have heard the call detailed regulation of dispensaries and testing and are considering 64 cannabis bills facilities, and myriad other details that are in the current session, 17 dealing only necessary parts of the lawmaking process. with medical cannabis, so many that To appreciate what these bills can Rep. Senfronia Thompson, D-Houston, accomplish, it is necessary to understand chairwoman of the Public Health Committee, what makes cannabis serious medicine, not has created a Subcommittee on Medical just a stage on the road to full legalization of a Marijuana just to deal with these bills. recreational drug. BAKER INSTITUTE REPORT // 04.15.19 receptor is not formed in the brain for the THE ENDOCANNABINOID SYSTEM sake of a plant constituent.”8 Therefore, they The chemical structure of cocaine, derived inferred and through careful experimentation from the coca plant, was understood and demonstrated that the human body produces described in the 1890s; that of morphine, its own (endogenous) cannabinoids, derived from opium, came in the 1920s. The molecules that act as “ligands” (from the first serious attempt to analyze the structure Latin legere, to bind) that activate and bind to and components of cannabis did not begin appropriate bimolecular receptors to produce until the early 1960s, when Dr. Raphael physiological effects. They called this happy Mechoulam, then an organic chemist bond anandamide, from the Sanskrit word at the Weizmann Institute of Science in for “bliss” or “supreme joy.” Less spiritually, Rehovot, Israel, applied to the U.S. National the scientific literature often uses images of a Institutes of Health for a grant to isolate key (the “endocannabinoid”) and a lock (the and identify the psychoactive component CB receptor) or a bullet and a target. “Essentially every of the marijuana plant. That first attempt Five years later (1993), a second receptor (CB2), different from the one in the brain physiological system was rejected, with the explanation that marijuana was used mostly in Mexico and and central nervous system, was found identified in our South America and was not a problem in the throughout the immune and gastrointestinal bodies is in some way United States. A year later, as the buds of the systems. In 1995, the Mechoulam team modulated by eCBs 1960s began to flower in profusion, the NIH reported a new endocannabinoid, 2-arachidonoyl glycerol (2-AG), similar to [endocannabinoids].” called back, beginning decades of support that would enable Mechoulam to gain anandamide. Over the past quarter century, the unofficial title of “Father of Cannabis they have identified at least 100 others. Research.” More than 50 years later, at Together, these receptors and age 88, he is still on the case and under his cannabinoids constitute the leadership Israel has been called “The Holy “endocannabinoid system” (ECS). Though Land of Medical Marijuana,” attracting a much is still to be learned, a key reason concentration of cannabis research and top- the ECS exists is to maintain homeostasis— level researchers unmatched anywhere else keeping things on an even keel by offering in the world.6 relief from pain, reduction of inflammation, In fewer than five years, Mechoulam control of nausea, uplift from depression and his colleagues isolated many of the and anxiety, and preventing, moderating, more than 100 of the plant’s components, or curing some diseases. As one article put which they dubbed “cannabinoids” after it, “Essentially every physiological system marijuana’s scientific name, Cannabis sativa. identified in our bodies is in some way The most notable of these was Delta-9- modulated by eCBs [endocannabinoids].”9 Tetrahydrocannabinol (THC), responsible for The Scientist, the Canadian magazine the “high” that made marijuana famous. for life science professionals, put it more The other headliner, currently drawing even breezily: “Your Body is Teeming with Weed more public attention, was cannabidiol Receptors.”10 When the endogenous system (CBD), a substance capable of controlling or is not strong enough to handle such tasks on reducing inflammation, anxiety, epileptic its own, the use of exogenous cannabinoids— seizures, and pain, among numerous other extracted from cannabis plants or produced known or plausible beneficial effects.7 synthetically—can bind with CB1 or CB2 to Two decades later, Mechoulam’s team help restore order. gained a breakthrough understanding of Not surprisingly, pharmaceutical how and why cannabinoids do their work. companies have sought to meet these In 1988 came evidence that a type of needs by producing synthetic chemical cannabinoid receptor (CB1) exists in the brain equivalents of key cannabinoids or “limited and throughout the central nervous system, editions” of extracts from cannabis plants. ready for the appropriate cannabinoid to bind Prominent examples include dronabinol with it to produce its effect. As Mechoulam (trade name Marinol), a synthetic THC put it, “We assumed that a cannabinoid developed to control nausea produced by 2 MARIJUANA AS MEDICINE chemotherapy. Its popularity has been sclerosis, and control or significantly limited because it lacks CBD and other ease neuropathic pain associated with chemicals that modulate the unpleasant migraines, diabetes, traumatic nerve injury, effects of the “high.” Nabiximols (trade chemotherapy, and other conditions. name Sativex), produced by the UK company Clearly, scientific research regarding GW Pharmaceuticals, combines THC and CBD cannabinoids is not being done to provide extracted from cannabis plants in a 1-to- healthy 20-somethings with justification 1 ratio, and works to reduce neuropathic for using an alleged knee pain as a way pain, spasticity, and other symptoms of to obtain legal pot. For additional proof multiple sclerosis and related conditions. of that, visit the website of the National Sativex has been moderately well received Cancer Institute15 for brief descriptions and in Canada and most European countries, but links to hundreds of research investigations is not available legally in the United States. of the demonstrated or potential effects Mechoulam places greater confidence in of cannabis and cannabinoids for cancer what he calls the “Entourage Effect”—the development and treatment, appetite many components of this complex plant stimulation, analgesia, anxiety, and sleep. work better together than in isolation of Much of the research involves rodents or only one or two ingredients.11 monkeys, but clinical studies and trials Increased understanding of the ECS with humans, long blocked by the Food and has generated an explosion of research Drug Administration