Marijuana (Cannabis sp.) has been used as a medicine for more than 4,000 years. But in the eyes of the US federal government, cannabis is an illegal drug that has no place in the clinic. Biomedical researchers who would like to study cannabis in a medical setting are frustrated by the challenges of obtaining government clearance and funding. But some data pointing to medical benefits of smoking marijuana do exist.
In 1970, the US Congress voted to classify cannabis under Schedule I of the Controlled Substances Act. Marijuana joined heroin, LSD, and peyote on Schedule I, and according to the Act, it—along with all other Schedule I drugs—has a high potential for abuse, lacks safety, and has “no currently accepted medical use in treatment in the United States.”
Since then, 16 US states and the District of Columbia have legalized the use of medicinal cannabis for a variety of indications, from chronic pain to cancer- and HIV-related appetite and weight loss, nausea, and vomiting. But despite the recent wave of state-level legalization, and the enactment of similar laws in Canada and elsewhere around the globe, the US federal government still classifies marijuana as a Schedule I drug, a designation that makes studying the medical effects of the drug in the U.S. extremely difficult (requiring approval from the Drug Enforcement Administration in addition to the Department of Health and Human Services (HHS)). Therefore, it has been far more common (and easier) to get funding and clearance to study the negative impacts of marijuana as a substance of abuse than to investigate its positive effects as a therapeutic agent.
Nonetheless, some researchers have braved the bureaucratic obstacles to conduct a handful of randomized, placebo-controlled trials that point to benefits of smoking cannabis, though they acknowledge that smoking the plant comes with its own risks and drawbacks. A more extensive body of literature involves molecular components, extracts, or synthetic forms of marijuana, simply because studying these non-Schedule I substances is less fraught with regulatory obstacles than is studying the whole plant.
The strongest evidence of smoked marijuana’s benefit exists in patients who experience chronic pain. With funding from the University of California Center for Medicinal Cannabis Research (CMCR), researchers published studies in 2007, 2008, and 2009 that all suggested smoked cannabis possessed analgesic properties. A study published in 2007, for example, noted that HIV patients experiencing neurological pain, or neuropathy—a general name for burning pain, hypersensitivity to light touch, and other uncomfortable symptoms—experienced a dulling of that pain when they smoked a cannabis cigarette three times a day for 5 days.
Psychiatrist Igor Grant, director of the center and an HIV/AIDS researcher at the University of California, San Diego, says that patients suffering from neuropathy in particular seem to find relief in cannabis. “We don’t have terrific agents to treat it. There are agents [such as antiepileptics and antidepressants] and they are modestly effective in many people,” Grant says. “The bottom line is that [cannabis] seems to work, and the effects are comparable in strength to traditional agents.”
Other studies from the CMCR have probed new conditions the plant might be used to treat. For example, UC San Diego researchers reported in 2008 that smoked marijuana has the potential to reduce muscle spasticity in multiple sclerosis (MS) patients. That finding was bolstered by a randomized, double-blind, placebo-controlled study published last year on the liquid marijuana extract Sativex, which is approved for use in some European countries, Canada, and New Zealand. The results of that trial, conducted by European researchers, indicated that a 4-week course of Sativex, an oral spray that contains the cannabinoids cannabidiol (CBD) and delta-9 tetrahydrocannabinol (THC), was safe and effective at reducing spasticity in many MS patients.
US researchers are completing Phase III trials of Sativex for the treatment of pain associated with cancer, and Otsuka Pharmaceutical, the US licensing partner of UK drugmaker GW Pharmaceuticals, hopes to gain FDA approval soon.
Aside from the relative logistical ease of studying constituents, extracts, or synthetics due to the fact that they do not run afoul of the Controlled Substances Act, these compounds stimulate the endocannabinoid system, the body’s homegrown constellation of receptors that interact with the active components of cannabis in a more tractable way than does smoked cannabis. “Harnessing that system with medications is a potentially new avenue for therapeutics,” says Mark Ware, McGill University neurologist and pain physician.
For example, Marinol is a synthetic THC drug that is used by chemotherapy patients experiencing nausea and vomiting or AIDS patients who are rapidly losing weight. It is the only FDA-approved synthetic cannabinoid, and offers an alternative to conventional therapies for these patients, though results have been mixed when comparing its effects to those of smoked cannabis, with the herbal version usually outperforming the synthetic.
This highlights one problem with going the synthetic route in the eyes of some cannabis researchers. “We shouldn’t forget that the herbal product contains multiple other constituents which may add to the effects of any one single agent,” says Ware. Also problematic are isolated cannabinoids’ tendency to be rapidly broken down in the liver and the difficulty in determining optimal doses.
As the political and social storm around medical cannabis continues to brew, most researchers who have seriously tested the drug’s therapeutic properties lament their inability to freely study it in a medical context. “The [cannabis] laws date to a time when what we knew about marijuana was voodoo,” says Mayo Clinic psychiatrist Michael Bostwick. “[The drug] can’t be applied to humans and to therapeutics because the laws don’t permit it to be done. The whole attitude towards medical marijuana is just irrational.”
For its part, the NIH claims that studying smoked marijuana is fair game. “Research projects seeking to determine the therapeutic potential of smoked marijuana are considered under the same criteria as any other project submitted for NIH funding,” the agency wrote in an e-mail to The Scientist. “Investigator-initiated applications for NIH funding are evaluated by peer-review groups composed of scientists from outside the NIH. The peer-review group evaluates the scientific and technical merit of the proposed research.” That said, the NIH’s Research Portfolio online Reporting Tools (RePORT) database lists many more active projects focusing on molecular components of cannabis or marijuana as a harmful drug than it does projects seeking to probe the potential medical benefits of smoking cannabis. Still, officials at the HHS also claim that the US government is game to fund studies of medical marijuana. “We’re very open to people submitting applications and trying to make [evaluating medical marijuana study proposals] a transparent and efficient process,” says Sarah Wattenberg, senior advisor for substance abuse policy at HHS. “In order for us to move this forward at all, we have to take the politics and stigma away, deal with it as a therapeutic class, and give people what science there is,” says Ware.
Particularly vexing to Ware is that so many people all over the world are using marijuana either recreationally or for the treatment of some ailment, legally or more often illegally, while science is forced to sit idly by and miss out on all that potential data. “We have so many people who are already doing the drug in one form or another in some sort of legal framework, but they’re not being involved in any type of research,” he says. “There’s kind of a huge natural experiment going on right now, and we’re not learning from it.”