SAN FRANCISCO — As more states embrace legalized marijuana, the drug’s growing medicinal use has highlighted a disturbing fact for doctors: scant research exists to support marijuana’s health benefits.

Smoked, eaten or brewed as a tea, marijuana has been used as a medication for centuries, including in the United States, where Eli Lilly sold it until 1915. The drug was declared illegal in 1937, though its long history has provided ample anecdotal evidence of the plant’s potential medicinal use. Still, modern scientific studies are lacking.





What’s more, the federal government is scaling back its research funding. U.S. spending has dropped 31 percent since 2007 when it peaked at $131 million, according to a National Institutes of Health research database. Last year, 235 projects received $91 million of public funds, according to NIH data.

That’s left the medical community in a bind: current literature on the effects of medical cannabis is contradictory at best, providing little guidance for prescribing doctors.

“What’s happening in the states is not related to science at all,” said Donald Vereen, a former adviser to the last three directors of the National Institute on Drug Abuse.

“It’s difficult to get good information,” said Beau Kilmer, co-director of RAND Corp.’s drug policy research center. Kilmer is also part of a group selected to advise the state of Washington on its legalization effort.

Two states, Washington and Colorado, have fully legalized the drug. A bill in the Maine Legislature calls for a statewide referendum to fully legalized and tax marijuana use for other than medical reasons.

A federal bill, co-sponsored by U.S. Rep. Chellie Pingree, a Democrat who represents Maine’s 1st District, would no longer define marijuana use as a federal crime.

Eighteen states, including Maine allow its use for medical reasons and 17, including New York, have legislation pending to legalize it.

Vereen, the NIDA adviser, says that most doctors’ and policymakers’ knowledge on the subject stems from a 1999 report from the Institute of Medicine, an independent nonprofit that serves to provide information about health science for the government. The group summed up its findings saying cannabis appeared to have benefits, though the drug’s role was unclear.

The IOM report recommended clinical trials of cannabinoid drugs for anxiety reduction, appetite stimulation, nausea reduction and pain relief. It also found that the brain develops tolerance to marijuana though the withdrawal symptoms are “mild compared to opiates and benzodiazapines.”

“We don’t know that much more than what’s in that report,” said Vereen.

Vereen, for one, says marijuana’s effects on pain without the withdrawal symptoms associated with other medications are deserving of further study to develop better pain drugs.

Subsequent research suggests marijuana may help stimulate appetite in chemotherapy and AIDS patients, help improve muscle spasms in multiple sclerosis patients, mitigate nerve pain in those with HIV-related nerve damage and reduce depression and anxiety. It’s even been suggested that an active ingredient, THC, may prevent plaques in the brain associated with Alzheimer’s, according to a 2006 study by the Scripps Research Institute.

Still, fewer than 20 randomized controlled trials, the gold standard for clinical research, involving only about 300 patients have been conducted on smoked marijuana over the last 35 years, according to the American Medical Association, the U.S.’s largest doctor group.

A few small companies are trying to tap into an emerging market for marijuana therapies, which could exceed $1 billion in California alone, according to Mickey Martin, director of T-Comp Consulting in Oakland, Calif., which advises people who want to set up their own cannabis businesses.

His model of about 750,000 cannabis patients found that the estimated spending from California’s patient population is $1.1 billion, including $56 million in doctors’ fees and about $1 billion in medicine. That assumes roughly two-thirds of the patient population will pay $40 a week for medication, Martin said. Cannabis Science Inc., CannaVest Corp., and Medical Marijuana Inc. are among a handful of companies developing drugs based on cannabis research or medical marijuana itself.

Until more laws change, it will be difficult to study an illegal substance with the goal of turning it into a medication, researchers say. And since it’s illegal to grow, marijuana isn’t subjected to the rigorous quality control most medicines are, raising concerns patients may be at risk from contaminants, said Vereen.

Marijuana advocates point out inherent obstacles to conducting research: the National Institute on Drug Abuse controls all the cannabis used in approved trials, but the agency’s mandate is to study abuse of drugs, not health benefits.

This creates dilemmas. The Food and Drug Administration, for instance, has approved a clinical trial studying whether marijuana can relieve symptoms of post-traumatic stress disorder. The trial, however, which is in the second of three stages of clinical testing, is blocked. NIDA, which controls the legal testing supply of the drug grown at a University of Mississippi farm, has refused to supply the researchers with marijuana.

“NIDA is under a mandate from Congress to find problems with marijuana,” said Bob Melamede, CEO of Cannabis Science Inc., a Colorado Springs, Colo.-based company that develops medicines derived from marijuana. “If you want to run a study to show it cures cancer, they will not provide you with marijuana,” he said. “What you cannot do are the clinical studies that are necessary.”

Attempts to expand licensed facilities beyond the University of Mississippi farm, have been denied, including a petition from University of Massachusetts agronomist Lyle Craker. The Drug Enforcement Administration denied that request in 2011, reversing a 2007 recommendation from its own administrative law judge, Mary Ellen Bittner.

NIDA also administered the most projects from 2003 to 2012, overseeing $713 million split among 1,837 research efforts. The bulk of the funding in the past decade was devoted to evaluating marijuana’s risks, potential negative impacts on the brain and developing prevention and treatment strategies, according to NIDA.

“There’s been a significant amount of study, but not clinical research,” said Brad Burge, a spokesman for the Multidisciplinary Association for Psychedelic Studies, a non- profit research and advocacy group. What’s lacking, says Burge, is “research intended to move marijuana, the plant, through the path to prescription approval by the FDA.”

For now, the research that does exist is often contradictory. A survey of 4,400 people found that those who consumed marijuana daily or at least once a week reported less depressed mood than non-users, according to a 2005 report in the journal Addictive Behaviors. A 2010, however, study in the American Journal of Drug and Alcohol Abuse of 14,000 found that anxiety and mood disorders were more common in those who smoked almost every day or daily.

Still, people continue to swear by medical marijuana. Cathy Jordan, 63, was diagnosed with amyotrophic lateral sclerosis at 36 and given 3 to 5 years to live. She smoked marijuana, a strain called Myakka Gold, on a Florida beach with friends, and from that day “the disease just stopped,” said her husband Bob, 65.

“All cannabis seems to work, and it’s slowed the progression,” he said in a telephone interview. They think marijuana may interfere with a neurotransmitter, glutamate, that can have harmful effects in the disease “but we’re just guessing here. All we know is when she doesn’t have it, she gets sick and when she does have it, she doesn’t get sick.”

On Feb. 25, they were raided for growing 23 plants for Cathy’s use. Bob was charged, though the prosecutors declined to press charges because of the medical records the couple supplied, he said. Currently, Cathy is the president of FL CAN, an advocacy group meant to generate support for changing marijuana policies.

Doctors’ attitudes are also shifting in favor of easing marijuana restrictions. The American Medical Association, the nation’s biggest doctor organization has called for a review of marijuana’s Schedule I status, a designation that declares it has no accepted medical use.

The American College of Physicians, the second-largest U.S. doctor organization with 133,000 members, also wants criminal penalties waived for doctors who prescribe marijuana and patients who smoke it. The drug could be useful to treat multiple sclerosis, nausea and pain, based on preliminary studies and pre-clinical lab work, the group said in a 2008 position paper calling for more research.

For the first time, a majority of Americans say they support legalization, according to a survey released April 4 by the Pew Research Center.

As those views trickle up to law makers, there’s little doubt that the easing of marijuana restrictions on the state level will continue.

“We are in the middle of the river,” said Roger Roffman, a professor emeritus at the University of Washington’s school of social work who has studied marijuana use more than 20 years. “Change is happening so rapidly with both medical marijuana and non-medical marijuana, that it is too early to know what’s likely happening in terms of the effect.”