Las Vegas—Despite federal laws to the contrary, 18 states and the District of Columbia have legalized medical marijuana for a range of indications, including cancer, glaucoma, epilepsy, nausea, chronic pain, muscle spasms and appetite stimulation. Countless users swear that medical marijuana improves their health and quality of life.

But as access to marijuana eases due to its increasing decriminalization, evaluation of its health benefits and risks still presents unique challenges for pharmacists and other members of the patient care team—challenges that simply don’t exist for any other prescription drug, according to Lawrence J. Cohen, PharmD, associate dean for clinical programs at the University of North Texas System College of Pharmacy, in Fort Worth.

“I believe there are disorders where medical marijuana has efficacy. But there are a large number of cannabinoids in marijuana, and there’s no way to predict if the particular sample of marijuana acquired will have the desired effect or if a patient is going to have a misadventure because of unknown contaminants and unpredictable amounts of various cannabinoids with different pharmacologic properties,” Dr. Cohen told Pharmacy Practice News. “Will it control nausea without causing excessive sedation or disorientation? Are there contaminants in the plant material that may be very harmful, particularly for immunocompromised individuals? You can’t predict that type of thing nearly as well as you can for most prescription drugs.”

A number of his patients have told him that marijuana has been the only treatment that has offered relief from their maladies, added Dr. Cohen, who was one of several speakers to tackle these issues during a session at the 2012 Midyear Clinical Meeting of the American Society of Health-System Pharmacists (ASHP). The session was titled “Medical Marijuana: Rational Medicine or Potential Medication Misadventure?”

A Hazy Picture

Attempts to corroborate such anecdotal reports with clinical research have yielded mixed results on safety and efficacy, according to the speakers. That is partly due, they noted, to the difficulty of determining just what compounds and forms of marijuana should be studied. In its most commonly used form—the flower buds of the female marijuana plant—there is no dose standardization, no meaningful way to compare samples from different plants or hybrids, and no way to ascertain if the product is free of potentially dangerous contaminants, such as mold, bacteria and pesticides, all of which have been identified in marijuana. No other prescription drug is burned and smoked—an act that, in and of itself, is comparable to (and maybe worse than) smoking cigarettes. Some users bake marijuana into food and eat it, or vaporize it with special devices, all of which further confounds assessment of the drug’s value and dangers, the speakers noted.

For pharmacists who want to drill a bit deeper and understand the pharmacodynamics of marijuana, the picture gets even murkier. The cannabinoid tetrahydrocannabinol (THC), marijuana’s most psychoactive compound, is also believed by proponents to be the drug’s most therapeutically active constituent, particularly for pain, nausea, glaucoma and spasticity associated with multiple sclerosis. Yet there is another cannabinoid—cannabidiol (CBD)—to keep in mind. Although CBD has far weaker pharmacologic properties than THC but is still considered an anti-inflammatory and anxiolytic. Complicating the picture even further are altered forms of medical marijuana, which include nabiximols (Sativex), a derivative delivered as an oral-mucosal spray and approved in several European countries and Canada; and the oral synthetic cannabinoids, nabilone (Cesamet, Meda Pharmaceuticals) and dronabinol (Marinol, Abbott Laboratories).

A Mixed Bag of Research

Researchers have completed dozens of peer-reviewed clinical studies of marijuana in its various forms. Results are mixed, according to Laura Borgelt, PharmD, BCPS, FCCP, an associate professor in the Departments of Clinical Pharmacy and Family Medicine at the University of Colorado, in Aurora, who also spoke at the ASHP session.

“If you look for evidence that medical marijuana is effective, you can probably find that information, and if you look for it to be ineffective you can probably find that too,” Dr. Borgelt said in an interview. Like Dr. Cohen, Dr. Borgelt added that many of her patients have reported health-related benefits from using marijuana.

Based on her review of clinical research, the most frequently reported medicinal uses for marijuana are treating pain, muscle spasms related to multiple sclerosis and nausea. “Those are all indications for which data supporting the beneficial effects reach statistical significance, although there’s always the caveat that the studies that don’t show efficacy are less likely to be published,” she said. “Many patients get significant benefits, but some have none at all.”

Dr. Borgelt made her case primarily with meta-analyses or systematic study reviews. While acknowledging such compilations aren’t ideal, she deemed them most useful for portraying a broad picture of the medical marijuana landscape (see resource box, page 4). Many individual studies are small and sometimes of dubious methodology, she added. “It’s very difficult to establish well-designed, controlled clinical trials in this environment with varied marijuana dosages and formulations used.”

The most appropriate patients, in her opinion, are those whose conditions are refractory to more orthodox medications, and who experience either inadequate response to, or intolerance of, second- or third-line drugs. “Having said that, most primary care physicians are not the ones recommending marijuana to patients,” Dr. Borgelt continued. “Patients typically get the prescription from physicians who specialize in medical marijuana. That’s not ideal, because patients are essentially self-medicating when other treatments don’t work, or even before they try more conventional treatments.”

Side effects are pretty much inevitable when smoking marijuana, and most notably—and of no great surprise—are euphoria, confusion, disorientation, and impaired memory and perceptions of time, to name a few.

Dr. Cohen agreed that, as with any medication, the potential risks associated with marijuana must be weighed against potential benefits. Marijuana has been linked to a range of adverse cardiovascular, respiratory and nervous system effects.

Medical Marijuana Studies and Resources

For comprehensive listings of medical marijuana studies, visit the International Association for Cannabinoid Medicines (http://www.cannabis-med.org/​), and ProCon.org (http://medicalmarijuana.​procon.org/​view.​resource.php?​resourceID=000884).

For lists of the states that have legalized medical marijuana and conditions for which it can be prescribed, visit http://medical​marijuana.​procon.org/​view.​resource.php?​resourceID=000881

—S.F.

Some things for pharmacists to keep an eye on:

  • Drug interactions. Marijuana interacts with a variety of drugs, including opioids, barbiturates, central nervous system depressants, hypnotics, sedatives and other sedating drugs, protease inhibitors, selective serotonin reuptake inhibitors and alcohol.
  • Drug–disease interactions. Marijuana may cause tachycardia and transient hypertension, and has been associated with syncope and palpitations. It also has been suspected of triggering myocardial infarction and transient ischemic attacks in patients at low risk for developing cardiac abnormalities, but such findings aren’t from controlled studies and the patients were taking other drugs, Dr. Cohen noted. “Most of this is based on case reports,” he said. “It’s difficult to weigh what the cardiac risks are.”
  • Central nervous system effects. Dry mouth, nausea, drowsiness, dizziness, sleep difficulties, memory impairment, euphoria, disorientation and confusion, and dose-related impairment of cognitive and behavioral functions are common. Some fear that the drug can cause psychosis, but the causal relationship between marijuana use and behavioral disorders in healthy individuals is weak, Dr. Cohen noted. “Right now, it’s just a matter of common sense to not use this drug in people at risk for behavioral disorders, like psychosis, bipolar disorder or depression,” he said. “I’m only certain of one thing: In an individual with depression or a family history of developing psychiatric disorders, medical marijuana should be used with caution.”
  • Respiratory. Marijuana smoke contains 50% to 70% more carcinogens than cigarette smoke and clearly irritates the respiratory tract. The smoke is considered a potential risk for lung cancer, although evidence is not definitive (Can Epidemiol Biomarkers Prev 2006;25:1829). Regular use is associated with chronic bronchitis (J Gen Intern Med 2005;20:33).
  • Addiction. Marijuana addiction is a risk, but a relatively small one—about 9% of users, according to the National Institute on Drug Abuse (http://www.drugabuse.gov/​publications/​drugfacts/​marijuana).

The bottom line is that “the data in the medical literature are truly conflicting on matters concerning marijuana’s health risks,” Dr. Cohen said.

Still, some knowledge is better than none, added Dr. Borgelt. “The more information we can get, however imperfect, then the more knowledgeable we become and the better prepared we can be to make decisions about whether marijuana will benefit or harm our patients.”



Drs. Borgelt and Cohen report no relevant conflicts of interest.

Don’t Be ‘the Ethics Police’

In Colorado alone, more than 105,000 people possess a valid medical marijuana registry ID card. Undoubtedly, many more in the state use the drug purportedly for medicinal purposes. Nationwide, the number of people who use medical marijuana runs easily into the millions. Sorting out who uses the drug medicinally and who uses it recreationally is a fool’s errand. But what is a near certainty is that clinical pharmacists can expect to encounter an increasing number of patients who acknowledge their marijuana use to health care providers. The enactment of more lenient laws and lax enforcement in some regions (and nationally) have given many users some comfort that law enforcement authorities will leave them alone.

Marijuana is a Schedule I substance. As defined by the Controlled Substances Act, Schedule I drugs have a high potential for abuse and have no currently accepted medical use in treatment in the United States. Additionally, there is a lack of accepted safety data for their use under medical supervision.

“People tend to frame this politically, but the reality is, especially in states where laws have been enacted, that a lot of patients are using marijuana, whether medicinally or recreationally, and they’re using it in combination with many other medications. So it’s important to understand how marijuana can be a player in a patient’s medical regimen,” Dr. Borgelt said.

Dr. Borgelt told Pharmacy Practice News that pharmacists, regardless of their personal stance on medical marijuana, are obligated to gain some understanding of the drug’s pharmacology and its unique set of potential benefits, risks, drug–drug interactions and drug–disease interactions.

Other than perhaps pointing out to patients that possession and sale of marijuana is illegal in the eyes of the federal government (and of many states), Dr. Borgelt advised pharmacists to detach themselves from the legal and moral arguments and approach patients with the same consideration they show to all. If anything, she added, these individuals deserve a pat on the back for stepping forward to provide their health care providers with important medical information, despite it making them uncomfortable.

“Please don’t judge the patient or be the ‘ethics police,’” she said. “It’s about keeping lines of communication open between patient and provider and giving patients the full picture of what they’re doing with regard to their health.” That means assessing and monitoring patients for side effects and adverse drug reactions and advising them accordingly, she noted.

“We have a responsibility to warn them about marijuana’s potential risk—the fact that there is a risk,” added Dr. Cohen. “I would also praise them for disclosing such sensitive information, but make sure they understand that there could be effects, beyond getting high, that may be undesirable, and that there’s no way to predict what problems it might cause when taken with other medications.”

With his own patients, Dr. Cohen tries to get information about when and how much marijuana they use, their perceptions of efficacy, and of course other medications they’re taking. He also encourages them to notify their other health care providers, as appropriate.

“A lot depends on the relationship you have with a patient,” Dr. Cohen said. “They’re usually uncomfortable talking about it unless they have no fear you’re not going to disclose it to a law enforcement agency, and I think that fear will continue for a while. There are some real benefits for some patients, and I suspect we will continue hearing from more people that they’ve found something that really improves their quality of life and allows them to feel better day to day.”

—S.F.