University of California medical researchers slipped an ingredient in chili peppers beneath the skin of marijuana smokers to see if pot could relieve acute pain. It could at certain doses.
They monitored patients with AIDS and HIV as they toked on joints or placebos to determine whether marijuana could quell agonizing pain from nerve damage. It provided relief.
They tested a "Volcano Vaporizer" to see whether inhaling smokeless pot delivered healthier, low-tar cannabis. It did.
Over a dozen years, California's historic experiment in medical marijuana research brought new science to the debate on marijuana's place in medicine. State-funded studies costing $8.7 million found pot may offer broad benefits for pain from nerve damage from injuries, HIV, strokes and other conditions.
California's famed Center for Medicinal Cannabis Research established by the Legislature to answer the question, "Does marijuana have therapeutic value?" has now all but completed America's most comprehensive studies into the efficacy of pot.
The money is gone. State-commissioned clinical trials totaling more than 300 research subjects are over. The last data are being crunched for medical journals. And it is unlikely that medicinal pot research on such a scale is going to be repeated any time soon.
Headquartered at UC San Diego with work also conducted in Sacramento County and San Francisco, the Center for Medical Cannabis Research challenged medical orthodoxy by undertaking the first clinical trials in decades looking at pot as medicine.
Now it survives in name only as an informational center and potential clearinghouse for grant applications for future cannabis studies.
Political frictions over pot remain volatile, and researchers say getting additional studies approved by federal agencies is as hard as ever. Despite findings of potential health benefits by California researchers, cannabis is no closer to winning federal acceptance as medicine.
Three years after California voters passed the nation's first medical marijuana law in 1996, the Legislature in 1999 approved funding for the nation's first sustained modern medical research for pot.
After seven completed trials between 2002 and 2012, with five studies published and two pending, California researchers say the research shows pot does, in fact, have therapeutic value.
"Every one of the studies showed a benefit," said Dr. Igor Grant, a neuropsychiatrist who served as director of the Center for Medicinal Cannabis Research. "The convergence of evidence makes me convinced there is a medical benefit here, and there may be a niche for cannabis."
The California researchers sought to avoid the politics of pot or advocacy of its use. But Grant said the research results suggest the U.S. government's listing of marijuana as a Schedule I drug with no medical use on par with heroin and LSD "is completely at odds with the existing science."
"It is intellectually dishonest to say it has no value whatsoever, because it's just not true," he said.
Trials with HIV patients
While doctors can recommend marijuana, and people buy it at California dispensaries, it is not available as a legal prescription drug.
So the challenge for California researchers was to try to determine if a plant with no uniform medical dose could be shown as effective.
In many cases, researchers took their cues from people already using marijuana.
Dr. Donald Abrams at UC San Francisco and Dr. Ronald Ellis at UC San Diego knew AIDS and HIV patients with nerve damage were treating themselves with cannabis to quell shooting pains from stimuli as benign as pulling a bed sheet over their toes.
In separate clinical trials between 2002 and 2006, Abrams and Ellis found that patients infected with HIV got marked pain relief from pot even on top of prescription pain medications.
In May, a published study by Jody Corey-Bloom, director of the Multiple Sclerosis Center at UC San Diego, reported that 30 patients smoking marijuana got noticeable relief from painful spasticity.
Through May, another research team led by UC Davis pain management physician Dr. Barth Wilsey worked to determine whether cannabis could relieve pain without getting people stoned.
Wilsey was surprised when research subjects with discomfort from nervous system damage found the same relief from marijuana cigarettes with 3.5 percent tetrahydrocannabinol the psychoactive ingredient in pot as from cigarettes with 7 percent THC. He commissioned a follow-up, in which patients breathed in vaporized pot with even smaller amounts of THC or with psychoactive elements extracted.
"I think we're traveling together," Wilsey said of the synergy between researchers and subjects using cannabis. "I want to be able to provide a suitable dose that doesn't impair people or impairs them minimally."
It was as part of that study that Sacramento County resident Gene Murphy, a multiple sclerosis patient, was driven to a UC Davis research center in Rancho Cordova over a three-week period so scientists could watch him inhale different potencies of cannabis from a vaporizer, check his pain and see if he was getting high.
Murphy found himself taking tokes of government pot, grown for research at the University of Mississippi, and complaining about the taste as the UC Davis team tried to find out if a minuscule dose of marijuana could help with his shooting pains.
"It was harsh on your throat and you didn't get high or nothing," Murphy said. "I asked them, 'Can't you get something better out of Humboldt County?' "
But Murphy also found his discomfort seemed to decrease with cannabis use in a way it didn't with his prescription of Vicodin alone. His impressions will be included in an upcoming study.
This month, Wilsey is enrolling research subjects for another study, funded under a $910,000 grant from the National Institutes of Health, on cannabis's effectiveness with spinal cord injury pain.
Conflicts over testing
Before the California research and still today federal agencies have preferred to support studies of marijuana as a drug of abuse, not as a potential medical benefit.
As U.S. authorities crack down on California marijuana dispensaries, some UC researchers question if medical cannabis research is any more acceptable today. "I don't think science drives the train here," Abrams said, adding. "It's a difficult environment at the current time to obtain funding."
Rick Doblin, director of the Multidisciplinary Association for Psychedelic Studies, a nonprofit group advocating alternative medical research, said he hoped the California studies would have kicked open the door to large, multistate trials that could evaluate marijuana as a prescription drug.
That didn't happen. Neither did a much-publicized study MAPS hoped to undertake in Arizona this year on whether pot could help Iraq and Afghanistan combat veterans with symptoms of post-traumatic stress disorder.
Doblin said the Food and Drug Administration supported the veterans study. But the National Institute on Drug Abuse, which controls access to the government's supply of marijuana for research, did not.
"With the fact that the Center for Medicinal Cannabis Research had all of these promising leads, you would think in a rational world that people would be studying marijuana to make it a (prescription) medicine," Doblin said.
In response to written questions from The Bee, Stephanie Older, a public affairs officer with the National Institutes of Health and the National Institute on Drug Abuse, wrote that the agencies "will continue to support research on the potential benefits of cannabis."
However, she added: "While there have been some small studies on the potential therapeutic benefits of smoked cannabis, the literature on its harms is much more well-established."
For now, Grant said, the Center for Medicinal Cannabis research suggests that pot is a promising secondary therapy for people for whom other treatments fail.
But Grant said he worries about a lack of standardization for medical marijuana. He suggests people buying pot at dispensaries offering products far more potent than used in state research is akin "to going to a flea market for an antibiotic."
And UC San Diego researcher Dr. Mark Wallace said finding proper dosing for marijuana is a challenge.
In a novel study, Wallace, an anesthesiologist and pain specialist, injected capsaicin, the hot ingredient in chili pepper, beneath the skin of healthy research subjects who smoked pot with different THC levels.
Five minutes after inhaling marijuana, none reported pain relief. After 45 minutes, those who smoked marijuana with 2 percent THC said they still hurt. But those who smoked pot with 4 percent THC said their pain was all but gone. And those who smoked marijuana with 8 percent THC reported their pain actually increased.
Wallace said the findings are significant because they showed "that cannabis has a therapeutic window."
But exactly what the proper marijuana dose is and how it may vary for different conditions will require much more research, Wallace said. He doesn't know when that may happen.