It's not that there isn't popular knowledge about marijuana's relative medicinal value for conditions such as glaucoma, chronic pain, lack of appetite and multiple sclerosis.
The problem is that findings — from folk medicine, anecdotal use or government-sponsored studies — aren't translating to agreement about marijuana's effectiveness and therefore its acceptance as a federally approved, physician-prescribed drug.
And without more consensus about marijuana's ability to bring something new to the treatment of such conditions — with limited side effects and an understood and controlled potential for abuse — cannabis is not going to enter the official governmental lexicon as medicine.
"There are a lot of hurdles you'd have to get over," says Diane Hoffman, an associate dean at the University Maryland School of Law who has written about marijuana law for the New England Journal of Medicine.
Not that the lack of consensus has prevented its popular use. Voters in 14 states have approved some legal medicinal marijuana applications. But politicians and policymakers, especially the feds, still treat the drug as an illegal substance ripe for abuse. Signs are that, in part due to that outlook, there won't be adequate research in the future. Yet with the growing number of state laws allowing people to medicate in varying amounts, by different methods and with sometimes mysterious, homegrown compounds, aren't the studies needed more than ever?
"You couldn't bypass a state law that would allow somebody to sell a new drug without having it go through the federal approval process," Hoffman says.
Still, the federal government — which doesn't officially recognize any therapeutic value to marijuana and its primary compound, THC — is reluctant to approve or fund studies of marijuana beyond those looking at its addictive properties, links to other problems, especially among teen populations, and its negative health effects.
"Some NIH Institutes and centers do fund a few projects on medical applications of marijuana," says Jenny Haliski, spokeswoman for the National Institutes of Health in Bethesda, Md. "The National Institute on Drug Abuse only studies the deleterious effects of drugs."
The vast majority of 271 active NIH-funded studies related to marijuana do not examine therapeutic elements of the drug. Given that such research is most often federally funded, that means state universities and other research centers across the country aren't generally doing such work.
"The federal government severely restricts what states can do and holds the cards because of the money the feds give to most states for research," says Greg Carter, professor of rehabilitation medicine and co-director of the Muscular Dystrophy Association/Amyotrophic Lateral Sclerosis Center at the University of Washington.
Some research advocates are calling for more funding and fewer restrictions, worried, in part, about patients consuming unregulated and untested medications and physicians who may be confused about how patients should take the drug and in what amount.
Carter, for example, co-authored a 2007 article calling for clarification of provider-related aspects of medicinal marijuana laws in the Pacific Northwest state. Twelve years ago, voters there approved a measure preventing "qualifying patients" from being found guilty of a crime for "possession and limited use" of marijuana.
But problems persist, Carter says. "The law does not protect patients (or their caregivers) from arrest or prosecution," Carter and the other authors wrote, "It only allows them to present a medical marijuana defense in court."
Carter is concerned about the lack of guidelines in state laws regarding dosing or the amount of marijuana reasonable for certified patients to have as a "supply." Specifically, he calls for a "scientifically grounded, logic-based framework to help states with a medical marijuana policy address the issue of dosing."
Such research would help physicians help their patients with more professional prescriptions. "I cannot say, 'Eat two brownies and call me in the morning,'" Carter says.
Part of marijuana's "lone wolf" status in the prescriptive drug research world is because, well, it is one.
"I think one of the most interesting aspects of marijuana is that it's dissimilar to so many other drugs that are classified as drugs of abuse," says Randy Commissaris, an associate professor of pharmaceutical science at Wayne State University. "Marijuana is in a chemical class by itself. Marijuana is the only compound there. It's not part of a family of drugs and it interacts with the body in a way that's unique to marijuana."
Opiates — for example, morphine and codeine — work as heroin does, interacting with the body's opiate receptors. Benzodiazepines — including Valium and Xanax — decrease abnormal excitement in the brain like barbiturates do as well. Both classes of drugs work with a protein molecule in the body. But THC has a unique pathway: The THC receptor is activated when cannabis is smoked, inhaled or orally ingested.
There is "a unique protein called a THC receptor in the brain, but also in other parts of the body, where it interacts and produces the effects," Commissaris says.
In its official materials, the NIH's National Institute on Drug Abuse finds that cannabinoids — compounds that bind to the same receptors as THC — "have great potential for treating a number of disorders, including addiction, obesity and pain, among others."
But the FDA still regards marijuana as having high abuse potential with no currently accepted medical use because marijuana is classified as a Schedule I drug under the Controlled Substances Act as passed by Congress. Until that's changed, the federal agency's hands are tied, and that means approval for therapeutic studies is limited. Still, the Center for Marijuana Research at the University of California-San Diego managed to get 15 clinical trials approved during the last decade. Funded by the state, the center oversaw experiments showing therapeutic benefits for pain control related to spinal cord injuries or nervous system diseases including HIV. People with multiple sclerosis also showed some benefit from marijuana in controlling muscle spasticity.
Some study participants experienced side effects, but researchers noted that these were not much different than what would be expected with other drugs.
J. Hampton Atkinson, a center co-director, says researchers realize the limits to their work. They didn't, for example, study long-term cannabis use, which he says other research has linked to bronchitis and upper respiratory tract ailments. Smoking marijuana, though, Atkinson says, doesn't have the same link to lung cancer.
"I'm not saying, 'There's something wonderful about cannabis, it won't give you lung cancer.' I can certainly believe that smoking any plant material, if you do it long enough, you're in for trouble," he says. "But there isn't that, for whatever reason, maybe the amount of exposure, maybe something else, there isn't that link with smoking marijuana as there is with tobacco."
Atkinson says the California studies, like others approved by the federal government, used marijuana cultivated at a federal research facility where joints' THC and other content is known and controlled.
That lack of regulation in most marijuana used medically worries some physicians. For one thing, homegrown weed can't necessarily guarantee its ingredients.
And unless patients observe their marijuana from seed to harvest, Michigan State Police Det. 1st Lt. Tim Gill says they should be worried about what's in it. Gill, who oversees drug enforcement units that have raided grow operations in eight central Michigan counties, has seen marijuana cultures that scare him: mold, chemical fertilizers, rodent and insect infestations and other substances he'd consider poisons.
And with dozens of strains of weed, varying strengths and no dosing schedule akin to "take one pill twice a day," marijuana is a medicine unlike other therapies.
Without parallel regulated studies into medicinal marijuana's use, the data about abuse potential and other side effects is inadequate, some researchers say.
"From a medical perspective, the effects of marijuana, the THC itself, are not as dangerous in terms of overdose risk as many other prescription drugs like painkillers. That doesn't mean it's absolutely safe. There is a risk of addiction that's a real risk and that's another area where more research needs to take place," says Commissaris, who teaches the "Recreational Drug Use and Drug Abuse" elective in Wayne State's pharmacy program.
Joint? Brownie? Vapor?
Another future issue might be how patients take marijuana. While prescription drugs such as the FDA-approved Marinol pill deliver THC, they don't provide it in the higher concentrations or produce the rapid effects that smoking marijuana does.
Research in California, Atkinson says, sought to determine if a safer delivery route — vaporized marijuana — would have the same benefits and reduce pain at the same efficiency as smoking. It just about did.
Another study seemed to show "medium to lowish doses are just as effective or more effective than higher potency cigarettes," Atkinson says.
The center is wrapping up this year as funding has run out. "We'll be a resource for investigators who wish to pursue these kinds of studies or we'll be a resource for policymakers," he says.
Assuming, of course, they have any interest in looking at research.