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FOUR

Reefer Research

Dr. Donald Abrams knew what he was in for. He knew his partner, Mark Henry, was going to die. Two years before he met the security officer from the Maui-Intercontinental Hotel, Abrams had been treating more patients with AIDS than any other physician in San Francisco. His experiences told him Henry’s deterioration from the disease would be rapid and excruciating. Yet that knowledge didn’t stop him from developing a relationship with Henry after the security officer sought him out at a lecture in Hawaii in 1986. It didn’t stop them from drawing close, from vacationing together, from laughing together, from reflecting together, or from smoking pot together.

Abrams was a Stanford University–educated hematologist and oncologist drawn by life-affecting events into the research and treatment of AIDS and HIV. It started for him after an unexplainable progression of young gay men with swollen glands began showing up at the Kaiser Foundation Hospital in San Francisco in 1979. Dr. Lee Wilkinson, the hospital’s chief hematologist, summoned Abrams, a twenty-nine-year-old openly gay medical resident. “Hey, Duck,” Wilkinson said, invoking the Disney character nickname he had bestowed on the promising young doctor. “Can you take a look at this?”

Abrams ordered lab tests on the men’s lymph nodes, seeking a cause for the symptoms. The results offered nothing from which to draw conclusions. So Abrams found himself cautioning the men on unhealthy lifestyles. “Stop having so many sexual partners,” he lectured. “Stop taking drugs. Move out of the fast lane.”

At the urging of Wilkinson, his mentor, Abrams moved on to the hematology and oncology training program at the University of California, San Francisco. There, he started encountering more young gay men with new, more severe symptoms. By 1981, doctors at the university were seeing the first cases of Kaposi’s sarcoma, a haunting, systemic affliction that left them splotched with lesions. Abrams began focusing on a strange “gay cancer” that would become known as acquired immune deficiency syndrome. He noticed many of the men had swollen glands. “How long have you had those?” Abrams asked. About two years, they told him, suggesting a troubling progression of the symptoms Abrams had noted in 1979.

Abrams applied for a grant to study lymphadenopathy syndrome, hoping to find clues about the first symptoms of illnesses leading to diagnoses of AIDS. As a research fellow treating the first-known AIDS patients in San Francisco, Abrams examined two hundred gay men with swollen glands who had yet to develop Kaposi’s sarcoma or pneumocystis, the ravaging pneumonia that would signal their rapid decline. He took lymph node specimens to the UC San Francisco laboratory of Dr. Harold Varmus, a Nobel prize–winning researcher for work on cancer-causing genes. They began studying what would be identified as a retrovirus that attacked cells and altered the body’s DNA and its ability to fend off disease.

In 1983, Abrams moved to San Francisco General Hospital, where oncologist Dr. Paul Volberding and infectious disease specialist Dr. Connie Wofsy established the world’s first AIDS inpatient ward, Ward 5B, with Abrams as their protégé. For a time, the trio knew every AIDS patient in San Francisco. That year, a French researcher, Dr. Luc Montagnier, would be widely credited with discovering the virus that led to AIDS. Abrams later became one of three researchers to name it the human immunodeficiency virus, or HIV. Soon the rate of HIV diagnoses and the number of AIDS patients were skyrocketing. All too soon, Abrams recalled, “we didn’t know everybody anymore.” San Francisco became a death camp for men wasting away, disfigured, stigmatized with a gay disease. Over twenty years, nineteen thousand city residents would perish from AIDS.

Still Abrams let himself fall in love with Mark Henry after Henry sought him out. His lectures in Maui had been initiated after Henry’s previous partner became the first person on the island to die of the disease. When the two men met, Henry had just had an episode of AIDS-related pneumonia. Abrams knew nearly everyone with the disease died within twelve months after a pneumocystis outbreak. Since early in his life, Abrams had had an ingrained fear of losing people he loved, going back to when he lost three grandparents as a small child and his “probably neurotic Jewish mother” took to raising him with a decided anxiety about death. Yet remarkably, Abrams’s upbringing had inspired his work in oncology and his desire to treat—and learn from—cancer patients in the transition from living to dying. And after he met Henry, Abrams realized there must be something in his makeup “that allowed me to go, eyes wide open, into a relationship with a man who was going to die.”

By 1986, physicians were prescribing a new antiviral drug for the treatment of AIDS. But Abrams believed the toxicity of azidothymidine, or AZT, outweighed its therapeutic benefits. Mark Henry didn’t take the drug. Yet Abrams watched his partner survive through 1986, then 1987, then 1988 and into 1989, when he entered hospice care. Throughout the three years before he reached death’s door, Henry smoked marijuana. Abrams, who as an undergrad at Brown University preferred pot to booze, joined him. Ultimately, the weed made the doctor feel paranoid, too in touch with his deepening sadness over his lover’s pending death. So Abrams curtailed his use, but Henry did not. He went on to outlive fellow AIDS patients in one support group, then a second, then a third. When he died, Henry had survived three times longer after pneumocystis than the average for AIDS patients.

Abrams didn’t know for sure if there was a medical benefit to the marijuana Henry used. The doctor also had no inkling when Henry passed away that, years later, he would become California’s most renowned researcher on medical marijuana, and that clinical trials in the Golden State would challenge the federal government and medical research orthodoxy by helping establish the medical efficacy of pot. But one thing that struck Abrams at the time was that Henry had outlived most every other AIDS patient—and he used cannabis “every freakin’ day.”

• • •

By 1990, anguish over the unsolved epidemic of AIDS and HIV was exploding into rage in San Francisco. That year the city hosted the International Conference on AIDS, only to have the event disrupted by activists from ACT UP, the AIDS Coalition To Unleash Power. Wearing “Silence = Death” shirts, they blew piercing whistles, threw chairs, and directed shouts of “Shame!” at conference participants, including Donald Abrams and other AIDS doctors and researchers. According to the activists, people were dying because of a conspiracy of government obstruction, because of a heartless ban on immigration to the United States for people with AIDS and HIV, because of a lack of funding for AIDS treatments, and from the continued failure of researchers to find a cure.

By then, another movement was attaching itself to the cause of AIDS and gay rights—marijuana. That same year, narcotics officers raided the apartment of Dennis Peron, targeting the pot dealer who supplied weed to sick people in the gay community. Police roughed up Peron’s lover, lesion-wracked and skeletal-thin AIDS sufferer Jonathan West. An enraged Peron would later describe an officer putting a boot on West’s neck and taunting him: “Know what AIDS means? Asshole in Deep Shit.” In 1991, Peron marshaled his fury to win 80 percent voter support for San Francisco’s Measure P, an advisory measure calling on the state to legalize marijuana as medicine. It launched his political march toward passing the California medical marijuana initiative, Proposition 215, five years later. Peron also found an ally in Mary Jane Rathbun, an eccentric Irish Catholic septuagenarian with a passion for baking and for pot. She partnered with him to set up the San Francisco Cannabis Buyers Club, which went on to provide marijuana to thousands of gay men with AIDS. They would later cowrite a book, Brownie Mary’s Marijuana Cookbook and Dennis Peron’s Recipe for Social Change.

The people wanting in on that change would include the likes of Richard Lee and Steve DeAngelo, lured by Proposition 215 and the progressive pot politics and medical cannabis opportunities in Oakland. They would include suburban Chicago seeker Stephen Gasparas and other new marijuana migrants drawn to the north coast Emerald Triangle. But as the AIDS epidemic extended into the early 1990s, with antiretroviral treatments still evolving, the social movement around marijuana remained focused on pot as a still-forbidden alternative that could relieve suffering and perhaps instill hope for better days. So in the years before California voters legalized marijuana for medical use, profoundly ill people risked seeking fellowship and comfort in places such as the Santa Cruz garden of the Wo/Men’s Alliance for Medical Marijuana; many others turned to cannabis to soothe their nausea, loss of appetite, and pain and maybe extend their lives in the frightened landscape of San Francisco.

It was at San Francisco General Hospital where Donald Abrams and fellow AIDS doctors got to know Mary Rathbun as “Brownie Mary.” It was there where her presence would ultimately serve to inspire social change through the clinical research of marijuana. For years, Brownie Mary was an ever-present volunteer in an outpatient clinic in a converted pediatrics ward on the sixth floor of the hospital’s building number 80. “Ward 86” became America’s most famous AIDS clinic. There, Rathbun shuttled sick young men she dubbed her “kids” from the clinic to radiology. She also brought them fresh-baked goods infused with marijuana, becoming a media darling for her compassion for people destined to perish from the disease. Abrams and other doctors in Ward 86, most of them products of the sixties who had smoked a joint or more in college, welcomed Mary’s presence. They didn’t worry much about her medicinal brownies. They just appreciated that pot offered some relief despite patients’ overwhelming medical challenges.

In 1992, Abrams arrived in Amsterdam for another International AIDS Conference. He flipped on the television in his hotel room. CNN International was broadcasting a breaking story from the San Francisco Bay Area: Brownie Mary had been arrested with two and a half pounds of weed, raided by police as she was crafting her confections at a friend’s home in Sonoma County. Soon the City of San Francisco, which under the voter-approved Measure P now officially considered marijuana as a legitimate source of symptom relief for AIDS, cancer, and other illnesses, staged a “Brownie Mary Day.” The star of the show let loose with a stream of profanity unfit for airtime. “If the narcs think I’m going to stop baking pot brownies for my kids with AIDS, they can go fuck themselves in Macy’s window!” Brownie Mary let it be known. The Sonoma County district attorney later dropped the charges.

Brownie Mary’s message—even scrubbed of profanity—elevated AIDS and pot as an international story, not only affecting Abrams as he watched in Amsterdam but also reaching a frustrated medical marijuana research advocate named Rick Doblin in North Carolina. Doblin, a graduate of New College of Florida, was preparing to resume his doctorate studies in public policy at Harvard after completing his Harvard master’s degree with a thesis on medical marijuana. Doblin had founded a group called the Multidisciplinary Association for Psychedelic Studies, which advocated research on alternative medicines, including marijuana and the drug known as Ecstasy.

Doblin had no medical degree. But for two years he had shopped around a research protocol for studying marijuana’s effectiveness in reversing the nausea and loss of appetite that led to wasting syndrome and starved AIDS patients into hollow-eyed human forms. After Doblin saw Brownie Mary on television, he wrote a letter “to whom it may concern” at the AIDS program at San Francisco General Hospital. The letter, urging someone there to take on the research project, was routed to Donald Abrams. The doctor followed up, and Doblin made an instant impression. Doblin insisted that groundbreaking marijuana research “should come from Brownie Mary’s institution.” Abrams was bemused by the thought of becoming the Brownie Mary Research Institute. But he was inspired by the study idea. Doblin’s idea made him think of Henry. It reminded him of how pot had seemed to keep his lover alive and functioning for so long.

By 1992, Abrams was working with San Francisco’s Community Consortium, a group of physicians setting up community-based clinical trials to explore treatments with AIDS and HIV patients. Despite being intrigued, Abrams was skeptical of Doblin’s plan to investigate the medicinal effectiveness of marijuana brownies. He didn’t see a way to standardize cannabis doses in brownies, particularly over a multiweek clinical research trial. But Doblin insisted that some kind of study of marijuana’s effect on wasting syndrome needed to happen. Doblin contacted the Food and Drug Administration about supporting a clinical trial and got a positive response. He arranged with a Dutch medical marijuana firm to grow cannabis for the research.

The same year, the prescription drug Marinol, containing a synthetically produced version of marijuana’s psychoactive delta 9-tetrahydrocannabinol (THC) constituent, had been approved for treatment of people with HIV wasting syndrome. But patients of Community Consortium physicians reported that swallowing Marinol left them zoned out for hours. Many reported they preferred smoking pot because they could regulate their dose through the number and spacing of hits from a joint. The Community Consortium’s board decided to back a study to assess separate groups of wasting patients—who either smoked marijuana or took Marinol—for changes in HIV immune system levels, body weight, and body composition. Research review boards from UC San Francisco and the State of California signed off on the study. Soon multiple government entities appeared determined to stop it from happening.

The Drug Enforcement Administration refused to allow the marijuana for the study, then being cultivated in Amsterdam, to be imported into the United States unless the Dutch government would send the DEA a letter saying it was okay for the company to export it. The Dutch government wouldn’t send the letter unless the DEA said it was okay to import it. So the Food and Drug Administration told Abrams to get in touch with the National Institute on Drug Abuse, which had access to government-grown marijuana, cultivated since 1970 under a closely supervised program at the University of Mississippi. Since 1976, the five-acre government pot farm had produced monthly tins of three hundred marijuana cigarettes, which were sent to about a dozen patients in the little-known Compassionate Investigational New Drug program of the FDA. The program was created after a lawsuit by glaucoma patient Robert Randall, who sued the government after a raid on his pot garden in 1975. A U.S. District Court in Washington ruled Randall’s use of marijuana was a medical necessity—pot helped keep him from going blind—and ordered the government to provide Randall with the drug. A dozen more people were later added to the Compassionate IND program. Otherwise, getting weed out of Uncle Sam’s pot garden was all but impossible—especially so for medical research that might show the benefits of cannabis.

The fact that Donald Abrams was working on the front lines of the AIDS epidemic, in which people were starving and dying with wasting syndrome, wasn’t enough to force the hand of the National Institute on Drug Abuse or its director, Alan I. Leshner. NIDA rejected Abrams’s plan for a community-based, outpatient study. The agency contended the study protocol didn’t provide adequate supervision of patients’ diets. It also suggested that research subjects with AIDS wasting syndrome might deal the government’s pot to their friends.

Leshner told Abrams he needed to go to the National Institutes of Health to have his study peer reviewed. Abrams reworked the study as a supervised, inpatient clinical trial at San Francisco General Hospital, in which subjects admitted for two fifteen-day evaluation periods would smoke marijuana or placebo joints with the psychoactive THC removed. The National Institutes of Health reviewed the study but effectively killed it, because the agency didn’t bother to attach a research score, an action critical to ranking the trial for potential government funding. Two peer reviewers questioned why researchers wanted to test a “toxic” substance such as pot. Another suggested that wasting patients rediscovering their appetites might develop high cholesterol, clogged arteries, and reduced suppression of tumor cells. Abrams was incredulous. People with wasting syndrome didn’t live remotely long enough for any of that to occur. These people obviously don’t see the same patients I do, he thought.

In 1995, Leshner wrote Abrams, formally notifying him that the study idea was flawed and not worth the government’s resources. Rick Doblin and fellow board members of the Multidisciplinary Association for Psychedelic Studies went to the National Conference on Marijuana Use, Prevention, Treatment and Research in Washington, D.C. In a silent protest, they unfurled banners charging that NIDA was blocking critical medical marijuana studies. Abrams, a clinician perpetually calm and cerebral with a wry humor, went off on Leshner in a furious missive.

“To receive the first communication from your office nine months after we sent the initial submission is offensive and insulting,” Abrams wrote. His letter rose in intensity as he challenged the NIDA director’s purported concern for wasting patients. “Finally, the sincerity in which you share my ‘hope that new treatments will be found swiftly’ feels so hypocritical that it makes me cringe,” Abrams wrote. He went on: “You and your institution had an opportunity to do a service to the community of people living with AIDS. You and your institution failed. In the words of the AIDS activist community: SHAME!”

By November 1996, when California voters passed Proposition 215, the prospects for research still remained uncertain at best. Three months earlier, the National Institutes of Health had joined in rejecting Abrams’s wasting syndrome study. Yet there was new hope in San Francisco and its gay community. Improved protease inhibitor drugs and other new antiretroviral medications were ending the death sentence of AIDS. Far fewer people were afflicted with wasting syndrome. And, though it made no reference to medical research, California’s historic medical marijuana vote seemed to cry out for studies on pot’s effectiveness in conditions such as AIDS/HIV, cancer, anorexia, spasticity, and pain.

In January 1997, after attending President Bill Clinton’s inauguration for his second term, Abrams got an audience at the National Institute on Drug Abuse in Bethesda, Maryland, with Alan Leshner. Abrams wanted to know what it would take for the government to support cannabis studies. Their meeting was both cordial and revealing.

“You know, I have better things to do than to continue to write grants to study marijuana,” Abrams began. He argued to Leshner that people were still going to smoke pot if studies showed it was harmful. He also suggested it was unlikely that more people would use marijuana if it was proven beneficial and safe.

“That’s where you may be wrong,” Leshner answered.

It was a year before the United States government would file civil actions to close Jeff Jones’s Oakland Cannabis Buyers Cooperative, declaring that the facility, which purported to offer medicinal comfort for sufferers of AIDS, cancer, and other serious illnesses, was drug trafficking under federal law. And the director of the National Institute on Drug Abuse told Abrams that proving pot’s medical efficacy could be problematic. Leshner suggested that it might challenge the government to rethink marijuana’s legal status as a prohibited Schedule I drug deemed to have no medical benefits and a high potential for abuse. He informed him that NIDA’s congressional mandate was to study substances of abuse or addiction. Leshner said the agency wasn’t intent on blocking all medical cannabis studies, particularly those with favorable peer review. But he made it clear that research protocols designed to establish marijuana’s medical benefits were unlikely to get agency backing or funding.

“We are the National Institute on Drug Abuse, not for drug abuse,” Abrams reported Leshner told him. The director denied using the phrase.

After Proposition 215’s passage, Abrams attended meetings with the San Francisco Department of Public Health in 1997 to discuss how to make the law operational for people who needed cannabis. At one meeting, he met an ACT UP member worried about the recent death of an AIDS patient who had been taking Ecstasy. The drug had blocked the liver’s metabolism of protease inhibitor drugs, heightening the patient’s vulnerability to the disease. By then, an estimated eleven thousand gay men in San Francisco were using marijuana for AIDS or HIV. The ACT UP activist wanted to know whether pot, too, could interfere with lifesaving antiretroviral drugs. Abrams had an epiphany. He could study the risk of pot for patients on protease inhibitors. He wrote up a research protocol for a clinical trial on the potential interaction between marijuana and the AIDS-fighting medications, arguing the connection “is worrisome since many HIV-infected patients continue to smoke marijuana as an appetite stimulant or to decrease nausea.”

On April Fools Day in 1997, Abrams attended a planning conference for the Office of AIDS Research in Washington, D.C. During a morning break, a colleague told Abrams there was a man from the National Institute on Drug Abuse who wanted to talk with him. Abrams found himself discussing his research aspirations with Dr. Jag Khalsa, a program officer with NIDA’s Center on AIDS and Other Medical Consequences. Khalsa told Abrams he funded studies on health and medical effects of substances of abuse. He said a study into whether marijuana interfered with protease inhibitor drugs might fit the bill.

“Send it to me,” he said of Abrams’s research plan.

“Do you know who I am?” Abrams asked, convinced this must be an April Fools joke.

“I know who you are,” Khalsa replied. “Send it to me.”

In August 1997, after a peer review by specialists whom Abrams had suggested—in clinical pharmacology, immunology, virology, endocrinology, and HIV medicine—NIDA and other government agencies signed off on the project. With $1 million in funding awarded for the research, Abrams accepted delivery from NIDA of fourteen hundred government-rolled joints from the University of Mississippi, plus a research supply of the synthetic THC drug Marinol from the pharmaceutical manufacturer Roxane Laboratories, of Columbus, Ohio. The pot was stored at San Francisco General Hospital in a locked freezer equipped with a burglar alarm.

On May 12, 1998, the first patients were enrolled for the study. In total, 67 confirmed HIV patients—89 percent men—who used protease inhibitors were selected for the study from 603 research volunteers. Five dropped out within two weeks. For twenty-one days, the others were kept in the hospital without visitors. One group smoked three marijuana joints daily that had been prepped in a humidifier and which contained 3.95 percent THC. Another group smoked cannabis-fragrant placebo joints with the THC removed. A third group took oral applications of Marinol. The sixteen-member research team led by Abrams monitored the weight, cell counts, and viral health of the patients.

The study concluded that use of cannabinoids, the natural THC in pot or synthetic THC in Marinol, neither increased the viral load of individuals with HIV infection nor interfered with their protease inhibitor drugs. Anecdotally, the researchers noted that patients given Marinol were more lethargic and spent more time in bed, while those smoking pot were more active. The research, Abrams wrote, failed to demonstrate “clinically significant interactions with cannabinoids that would warrant dose adjustments of protease inhibitors.” He delivered the conclusion that marijuana was a safe medicine for people with HIV. It didn’t interfere with anti-AIDS drugs. And there was something more. Patients using marijuana and Marinol saw increased production of healthy cells, with marginally higher levels for the pot smokers. People in the marijuana group also put on an average of 7.7 pounds in twenty-one days, compared to 7 pounds for the Marinol group and 2.9 pounds for the placebo group. Though there were no wasting patients in the study, the clinical trial signaled that pot could boost the immune system for people with HIV and AIDS.

Despite the results, no leading medical research journal was eager to publish a medical marijuana study. Abrams was rejected by the prestigious medical journal Lancet, by the New England Journal of Medicine, and by the Journal of the American Medical Association. Ultimately, after an initial denial, the Annals of Internal Medicine of the American College of Physicians interviewed Abrams on his study. In 2003, it published his research. Clinical evidence of the efficacy of cannabis with HIV patients was now part of accepted medical literature. In the study and with the media, Abrams was politic about the conclusions. He wrote that the findings meant “placebo-controlled studies of the efficacy of smoked marijuana could be considered in the future.” He called for more research.

After the death of Mark Henry, Abrams had found a new life partner in Clint Werner, with whom he began a relationship in 1994 and later married. Years after Abrams’s clinical trial on cannabis and patients with HIV infection, Werner revealed the doctor’s internal sense of triumph. What Abrams mostly refrained from broadcasting, Werner, a natural-foods chef devoted to the dietary prevention of disease, all but shouted out. “The clinical trial was a Trojan horse, finally allowing researchers to get the data they had been seeking for years,” Werner wrote in his book Marijuana Gateway to Health. Abrams’s “true purpose” in the study, Werner wrote, “had been to ascertain whether marijuana helped improve the appetite of AIDS patients—and it did.” Abrams’s husband concluded with a flourish: “Science had spoken. THC really did cause the munchies.”

• • •

After Donald Abrams’s breakthrough clinical trial, state assemblyman John Vasconcellos sought to make medical cannabis research a fully funded priority of the state. Vasconcellos championed legislation calling for creation of a California “Center for Medicinal Cannabis Research.” Its mission would be to provide answers—affirmative, negative, or both—to the question “Does marijuana have therapeutic value?”

Vasconcellos set out to develop the concept in consultation with some of the top medical and research professionals in the University of California system. One of them was Dr. Igor Grant, a renowned neuropsychiatrist at the University of California, San Diego. Grant directed the UC San Diego HIV neurobehavioral program, which used brain imaging and neuropsychological studies to research the effects of HIV and AIDS on the brain. Grant also had a long-standing interest in the impacts of alcohol and drug abuse, going back to when, as a young faculty member at the University of Pennsylvania in the 1970s, he analyzed literature on whether long-term marijuana use could cause brain dysfunction. Grant looked at rodent studies suggesting that high-dose exposure to THC in young rats could produce learning and performance deficits. He extrapolated the data to humans. To achieve the same effect, Grant would later conclude, a 154-pound man or woman would have to smoke 420 joints day.

Grant believed the discovery, in the early 1990s, of receptors in the brain that reacted to marijuana had opened the door to new medical research for pot. Researchers looking at the effects of THC named the first of these molecular neurotransmitters anandamide, using the Sanskrit word for bliss. They discovered that THC would bind itself to these receptors, found on the surface of cells throughout the central nervous system. The receptors were later named cannabinoid receptors, after the cannabis plant. Natural compounds produced by the body and acted upon by marijuana were named endocannabinoids. For Grant, identifying a molecular signaling system for pot—a system that worked much like the different receptors in the body that reacted to opiate drugs such as morphine or codeine—meant researchers could look at pot’s potential for treating conditions such as multiple sclerosis, glaucoma, gastrointestinal disorders, cancer, and chronic pain.

Such research on pot was not possible in California unless Vasconcellos could get a marijuana research bill through the legislature. Vasconcellos, a self-described “old-time liberal,” found an unexpected ally during the 1998 election season in a law-and-order conservative, Dan Lungren, who was then attorney general. Lungren, who had been an ardent opponent of Proposition 215, ran for governor in 1998. He drew a Republican primary challenge from Dennis Peron, whose cannabis club had been targeted by the attorney general. With no shot at winning, Peron served as an antagonist to remind people that Lungren opposed the will of voters on medical marijuana. Looking to find middle ground on pot for the November general-election race against Democrat Gray Davis, Lungren endorsed research on the medical use of cannabis. Vasconcellos saw a political opportunity. He reached out to the attorney general. Their staffs began drafting legislation for unprecedented medical marijuana studies.

Lungren was gone from office, defeated in the governor’s election, and Vasconcellos had moved to the state senate when the pot legislation—Senate Bill 847—reached the floor in 1999. Lungren’s endorsement helped pry loose crucial Republican votes. Vasconcellos needed twenty-seven votes—a two-thirds majority of the forty-member senate—to pass the appropriation. With no votes to spare, Vasconcellos offered procedural cover to three Republican senators—Jim Brulte, Tim Leslie, and Pete Knight—who were skittish about being the twenty-seventh vote on a pro-marijuana bill. The GOP trio agreed to shout “aye” in unison so that no individual got the blame as California lawmakers voted to spend $8.7 million in state tax dollars to study weed.

The Center for Medicinal Cannabis Research was created in 2000 and headquartered at UC San Diego, with Dr. Igor Grant as its director. Research proposals began streaming in by 2001. Over the next decade, the center would approve and oversee fifteen California clinical studies, including seven trials directly testing pot’s effect on research subjects. The center established an exhaustive peer review process and used the legislative clout of the most populous state in the nation to win research approval from multiple federal agencies. Grant, who didn’t conduct any research himself, saw to it that the center handled all research applications and that his clinicians didn’t have to fight the government to do cannabis work. Meanwhile, Grant demanded rigorous, modern trials that could be published in medical research literature. He figured there was no point in wasting California tax money on studies “that wouldn’t see the light of day.”

One of those applying for a research grant, Dr. Barth Wilsey, a pain management physician at the University of California, Davis, sought funding for a study on whether cannabis provided relief for people with neuropathic pain from spinal cord injuries, diabetes, strokes, and other conditions causing life-disrupting discomfort from nerve damage or injury. Earlier in his career, Wilsey was a fellow in pain management at UC San Francisco, seeing patients in a small clinic in the city. People coming in would tell him they turned to marijuana when nothing else seemed to work. Wilsey, a licensed acupuncturist, was interested in alternative therapies. As a pain doctor, he figured that 40 to 60 percent of his patients didn’t get adequate relief from prescriptions he wrote. He saw cannabis as an alternative worth exploring.

Dr. Mark Wallace, an anesthesiologist and pain specialist at UC San Diego proposed a study in which healthy subjects would smoke marijuana and researchers would study the analgesic effects of cannabis after injecting capsaicin, the hot ingredient in chili peppers, into their skin. Dr. Jody Corey-Bloom, director of the UC San Diego Multiple Sclerosis Center, set out to see if marijuana could relieve spasticity in MS patients whose use of pharmaceuticals often failed to alleviate their suffering. Donald Abrams and Dr. Ron Ellis, a UC San Diego neurologist, worked to see if pot could quell tingling and shooting pains that would start in the feet of AIDS and HIV patients and move to their fingers and hands, disrupting their ability to sleep, to exercise, and, often, to cope.

In separate, overlapping studies between 2002 and 2006, patients with neuropathic pain from HIV smoked pot under the supervision of Abrams’s nine-member research team at UC San Francisco’s General Clinical Research Center and Ellis’s eight-member team at the UC San Diego Medical Center. In San Francisco, fifty-five patients, mostly men with HIV infection for fourteen years, smoked three marijuana cigarettes or placebo joints a day in five-day trials. In surveys for chronic pain during the trials, cannabis was found to reduce the subjects’ pain by an average of 34 percent—double the rate of the marijuana placebo. Tests in which brushes were stroked against the subjects’ skin showed pot could quell shooting pain sensations in HIV patients, for whom things as benign as pulling a bedsheet over their toes could trigger lightning bolts of agony. Yet in tests involving applying heat to HIV patients’ shoulders, Abrams’s team failed to show similar benefits of marijuana in cases of acute pain such as might be experienced after an injury or surgery.

In San Diego, research subjects were given placebo joints or three potency levels of marijuana. Ellis’s team monitored twenty-eight HIV subjects as they toked on marijuana or the pot placebos over two-week periods, with a two-week break with no marijuana use allowed between each new research stage. Notably, Ellis also had all subjects continue taking their pharmaceutical pain medications during the study. He found they still got a boost from cannabis, with the pot group reporting pain relief at two and a half times the frequency of the placebo group. Ellis also measured impairment. He tested people’s ability to connect random letters and numbers on a page, and he had them operate a driving machine, in which they were to avoid simulated traffic obstacles and follow lights and signs. In both tests, patients scored worse after smoking cannabis than before.

One of Ellis’s original thirty-four enrolled research subjects had to be excused when he developed an intractable cough from smoking pot. Another subject, who had never before used marijuana, gave researchers a scare. After smoking his first joint, he started staring into space. He stopped responding to questions. The man was in a catatonic state, “attending to what was going on in his head,” Ellis observed. Doctors and nurses watching from outside the study room rushed in. They checked his vitals. His heartbeat was normal. He was fine. He came to in a couple of hours with no memory of what happened. He was dropped from the study.

Afterward, University of California researchers enrolled only research subjects who had previously smoked cannabis. They also required drug testing to ensure that subjects were weed-free for thirty days before any clinical research. In every trial, subjects reported a degree of impairment. Pot, even at low, government-grade doses, got them high.

Dr. Corey-Bloom reported that MS patients given cannabis showed modest cognitive impairment. However, her study on thirty patients also demonstrated that smoking marijuana could reduce painful, often disabling symptoms of spasticity. At UC Davis, Dr. Wilsey found something he wasn’t counting on. In outpatient sessions of three to twenty-one days, Wilsey and his seven-member team monitored thirty-two patients with nerve injuries as they smoked marijuana with 7 percent or 3.5 percent THC or toked on THC-free placebo joints in a university research center at the Veterans Administration Hospital in Sacramento County. Subjects in both marijuana groups found significant relief from chronic pain. What surprised Wilsey is that they got the same relief with the lower cannabis dose as with the higher dose, only with less impairment. That set Wilsey on a new quest. He sought to find out if patients with painful neuropathy could get relief from marijuana that had further-reduced levels of THC—and without getting stoned.

By the end of Wilsey’s first study, Abrams had demonstrated the effectiveness of a healthier marijuana delivery system in another trial. Abrams brought fourteen healthy research volunteers to UC San Francisco and monitored them as they smoked joints or inhaled cannabis from a German-made Volcano Vaporizer, a smokeless delivery device that heated marijuana without lighting it. The heat released cannabis particles into a plastic bag, from which the subjects would breathe medicinal vapors. Abrams found that people using the vaporizer took in significantly reduced levels of carbon monoxide. THC detected in the blood after six hours was the same for people smoking joints and for those consuming cannabis by vaporizing, but vaporizing produced much higher THC levels for the first hour. Abrams’s study showed that the vaporizer delivered medicinal effects more efficiently. More important for political acceptance of cannabis research, the vaporizer also could deliver low-tar marijuana.