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Patients, caregivers, and scientists offered diverse testimony regarding the medical properties of marijuana and its components during a two-day hearing in Washington, D.C., last month for the National Academy of Sciences' Institute of Medicine (IOM).
The hearing was the last of three held by the IOM as part of a $1 million, 18-month study to evaluate the therapeutic value of marijuana and its chemical components, particularly cannabinoids. The study was commissioned by the Office of National Drug Control Policy in response to the November 1996 passage of Proposition 215 in California and a similar referendum in Arizona legalizing medical marijuana use. The referenda created exceptions to the general prohibition on cultivation and possession of marijuana, provided that the plant is cultivated and possessed for medical purposes upon the recommendation of a physician.
The Arizona referendum was never implemented due to a series of legal challenges, but the California initiative has resulted in the emergence of an undetermined number of medical marijuana dispensaries that operate openly with the approval of local officials. The study was not designed to address the legal status of marijuana, however. The I0M plans to release its report on the topic later this year.
One cannabinoid, tetra-hydrocannabinol (THC), has been available as Marinol in an FDA-approved pill for more than a decade, and a substantial part of last month's hearing was devoted to testimony from pharmaceutical companies interested in developing drugs based on marijuana's active components. The interest suggests that cannabinoids, if not marijuana, are gaining acceptance as therapeutic agents.
Proponents of use of whole marijuana have argued that the whole plant, particularly smoked, has properties that render it superior to an isolated or synthesized single-component drug. No one questions that the active components of marijuana, including THC, are more easily absorbed through smoking than orally. Defenders of whole marijuana use also argue that smoking allows the user to self-titrate the dosage. It is possible that the synergy of different compounds in whole marijuana alters the therapeutic effect, some advocates contend.
The anecdotal evidence sparked a number of states to launch FDA-approved clinical trials with marijuana over the last three decades, and some of those trials progressed to Phase III, the final step prior to FDA approval, attorney Kevin Zeese, J.D., told the IOM committee. But the trials were aborted after the federal government ended its compassionate-use program in March 1992. The program had provided a mechanism by which patients could apply for a legal supply of federally grown marijuana; it also provided a rationale for clinical trials. When the program was terminated, 13 people were enrolled. Eight people continue to receive government marijuana, and two of those testified at the IOM hearing. The clinical trials found evidence for marijuana's efficacy in a variety of conditions, particularly those involving pain, nausea, and muscle spasm, said Zeese. Another panelist pointed out that the medical use of marijuana is nothing new, and that there is a record of such use going back to antiquity.
For reasons cultural, political, and legal, however, the use of marijuana in contemporary medicine has sparked extraordinary controversy. Extremists have emerged on both sides, with a few proponents claiming that virtually any use of marijuana is medicinal, and some opponents arguing, in the words of one participant at last month's hearing, that "marijuana is good for nothing." It was in this volatile environment that the IOM was asked to sift fact from fancy, the known from the speculative.
In addition to frequent reports from AIDS patients that marijuana has antidepressant properties, a number of psychiatric patients have emerged to testify that it is effective as a stabilizing agent in bipolar disorder. During last month's hearing, two patients who have used marijuana successfully for that purpose testified to the IOM committee. Most psychiatrists advise patients with psychiatric disorders to avoid non-prescribed, psychoactive drugs, and there is evidence that such drugs may exacerbate psychiatric disorders in some patients.
Although the IOM study will not address the drug's legal status, the sweeping prohibition of marijuana as a Schedule I drug under the federal Controlled Substances Act (CSA) has created tremendous obstacles to good clinical research on its therapeutic risks and benefits. Earlier recommendations that marijuana be rescheduled to a less-restrictive category, including a recommendation by the administrative law judge of the federal Drug Enforcement Administration (DEA) in September 1988, have been ignored. Whether the findings of the IOM-whatever their nature-will have an impact on clinical research or medical availability of marijuana remains to be seen.
The overwhelming majority of the public testimony at last month's hearing came from people affirming marijuana's medical value. The testimony was often passionate, and despite the IOM's stated intent to avoid legal and political issues, the IOM heard from people who have suffered, directly or indirectly, from the harsh legal sanctions that surround the cultivation and use of the marijuana plant.
Barbara Sweeney of Fairfax, Calif., who suffers from AIDS cachexia, smokes marijuana to enhance her appetite. She was arrested by local police in 1992 for growing two marijuana plants. Since then her 8-year-old daughter hides whenever she sees a police officer, Sweeney said. After the arrest, Sweeney suffered from post-traumatic stress syndrome, for which she successfully sought compensation in a $10,000 civil suit against the Fairfax police department, she told the committee. But a cannabis dispensary she tried to operate was raided by federal agents last year, and she continues to fear further harassment.
"I don't know what to do," said Sweeney. "I don't know why the federal government is going after us. I don't want to die in vain, and I don't want to die in jail."
Meg Foster of Tulsa, Okla., testified on behalf of her husband, Will. He is serving a 93-year term for growing a little more than one pound of marijuana, which she said he used to treat severe arthritis.
Jeff Jones, executive director of the Oakland, Calif., Cannabis Buyers' Cooperative, described the discreetly run facility. It is one of an undetermined number of cooperatives that sprang up in response to the passage of Proposition 215. Despite federal opposition, the Oakland City Council has passed four resolutions in support of the cooperative, requesting the federal government to avoid any enforcement action against the facility, said Jones.
Given both local support and the overwhelming statewide support of voters who passed Proposition 215, it is incumbent upon the federal government either to allow the facilities to operate or to assist in the implementation of a "workable, regulated, medicinal marijuana distribution system," said Jones.
During the scientific session, George Koob, Ph.D., a professor of neuro-pharm-acology at Scripps Research Institute in La Jolla, Calif., discussed the neurobiology of cannabinoid dependence. He spoke with Psychiatric News. Popular conceptions notwithstanding, a small but substantial number of marijuana users do become dependent on the drug, said Koob. He estimated the incidence at about 9 percent of marijuana users, compared with about 14 percent of alcohol users, 25 percent of nonmedical opiate users, and 31 percent of tobacco users. The misconception with marijuana, as was initially the case with cocaine, was that since the withdrawal syndrome does not involve dramatic physical symptoms, the drug is nonaddictive, said Koob. But the hallmark of addiction is craving and dysphoria upon cessation, leading to compulsive use, said Koob. On this basis, some people are certainly addicted to marijuana, he said.
The neurochemical basis for THC's reinforcing effects is its capacity to stimulate dopamine release in the brain's nucleus accumbens, and this is something that THC shares with other drugs of abuse, said Koob.
There is "no rational policy on drug use and no coherent, balanced rational view on how drugs should be used, because there's no rational, scientific-based discussion of what drugs do to you," Koob commented. "It's all a horrible mess."
From a medical perspective, whether marijuana is addictive is almost irrelevant, according to Koob. Sick people rarely become addicted, said Koob, and it makes no sense to deprive people of a drug, even an addictive drug, if it can be shown to relieve suffering.
"We shouldn't deny people in pain morphine because it's addictive, so why should we deny sick people marijuana?," he remarked.
The three IOM hearings were held in geographically diverse locations, with each hearing devoted to a specific theme. The first was held last December in Irvine, Calif., on the theme "Perspectives on the Medical Use of Marijuana: Basic and Clinical Science." In January a hearing on the theme "Acute and Chronic Effects of Marijuana" was held in New Orleans. The final hearing last month in Washington was titled "Prospects for Cannabinoid Drug Development."
Each meeting has included both general public input and scientific sessions. In addition, IOM investigators made site visits to several medical marijuana facilities in California in conjunction with the December 1997 meeting, and to an AIDS clinic in New Orleans in conjunction with the January meeting. During the California site visits, IOM investigators observed and spoke with patients who used marijuana for conditions related to AIDS, including cachexia and depression, nausea related to chemotherapy or other medical treatments, arthritis pain, central nervous system inflammatory diseases, and muscle tremors due to multiple sclerosis or injury. During the visit to the New Orleans AIDS clinic, investigators heard from physicians, nurses, and scientists on their experiences treating patients for nausea, anorexia, and depression with Marinol.
At press time, a ruling by the California Supreme Court threatened to close down the state's medical marijuana facilities as a violation of state law. The facilities have asserted a right to operate under the terms of Proposition 215.
A similar referendum in Washington State last year failed to win approval. Proponents of legalizing marijuana for medical use have indicated they will try again in Washington State, and similar efforts are under way in other states.
-R.B.K.