NIH may fund research into marijuana therapy
AIDS patients may benefit from research
For years, some AIDS patients and their treating physicians have believed that marijuana in its inhaled form could provide major therapeutic benefits. Now a federal panel is set to recommend that federal funds be used to conduct research to prove their hypothesis.
Following two days of scientific and medical testimony regarding what currently is known about the possible benefits of marijuana, members of a National Institutes of Health panel announced in mid-February that they would almost certainly authorize further research. "It looks promising enough for us to recommend that some new controlled studies be done," said William T. Beaver, MD, a professor of pharmacology and anesthesia from Georgetown University School of Medicine who chaired the panel. The panel will issue a report in late March.
For patients suffering from HIV and AIDS, the most likely research applications would be for control or reversal of wasting syndrome, relief of neuropathic pain, and management of spasticity and other movement disorders that can afflict AIDS patients.
Rapid acceptance of marijuana sought
Some attendees from the AIDS treatment community remain skeptical that federal research dollars will be targeted to this AIDS research soon, and sought more immediate acceptance of marijuana as a treatment regimen. "We still have to contend with wasting syndrome, and the nausea and appetite loss that come as side effects of some of the powerful and effective new antivirals," said Kiyoshi Kuromiya, director of the Critical Path AIDS Project in Philadelphia.
Others, however, point to three key reasons why the use of marijuana may be possible and politically acceptable for this patient population in the near future, and why Phase II clinical trials should be approved. These grounds are:
• Cannabinoid (marijuana) receptors recently have been identified and are abundant in areas of neuropathy, cognition, and motor coordination. "It would be very important to measure the effects of marijuana on neuropathic pain," says Richard Payne, MD, a neurologist and chief of the pain and symptoms management section at M.D. Anderson Cancer Center in Houston.
Despite expressing clear doubts about widespread efficacy of inhaled marijuana as an analgesic compared to other drugs, Payne testified before the panel that its neuropathic benefits may make the drug "a good adjunctive pain medication." Many AIDS patients with inflammatory neuropathy may benefit from this application.
• Inhaled marijuana has been anecdotally effective in controlling wasting syndrome in patients for whom no other therapy has proven more successful. The burden of proving it to be a "better" drug therapy than any other would be weighted against the fact that "wasting is not an inevitable complication of AIDS and it can be reversed," says Kathleen Mulligan, PhD, assistant professor of medicine and AIDS researcher at University of California in San Francisco.
Wasting correlates with development of AIDS
Mulligan told the panel that a much higher proportion of HIV patients go on to develop AIDS when wasting occurs. "Survival in AIDS patients is significantly related to the loss of weight and lean tissue," says Mulligan. The symptoms of a patient who suffers from wasting mirror those seen in patients who starve to death, she maintains, and the problem almost always occurs during periods of acute infection.
The importance of controlling wasting is critical, says Mulligan. There is clinical evidence that the synthetic pill form of marijuana, THC, controls wasting. There also is anecdotal evidence, including personal accounts from patients who testified at the hearing, that the inhaled version is even more effective.
Mulligan suggests that key research goals would be to determine if marijuana does increase total energy intake and expenditure, if resting metabolic rate increases, and if activity level also goes up.
The use of marijuana as a adjunctive therapy for AIDS patients with inflammatory neuropathy also would alleviate the common nausea-inducing side effect of other analgesics. In this respect, researchers said marijuana also could prevent wasting syndrome precipitated by nausea.
• The factors that may make inhaled marijuana more effective for patients (immediate entry into the blood stream, ability of patients to titrate the dosage based on need) may possibly be replicated in an alternative delivery system such as an inhaler or a transdermal patch. One of the major barriers to using marijuana for medical purposes has been the reluctance to legalize use of an inhaled substance, as well as concern about the possible side effects of smoking the plant.
Words of caution
Despite these positive prospects for treatment of AIDS patients, researchers at the meeting, along with an official of the Food and Drug Administration (FDA), caution that all clinical trials would be stringently scrutinized by the government and the public. "The FDA does not require it, but in this case researchers would have to prove that smoked marijuana is not just effective but also advantageous," says Robert Temple, MD, associate director for medical policy in the Center for Drug Evaluation and Research at the Rockville, MD-based FDA.
These advantages may include effectiveness in patients who do not respond to other therapy, more rapid response, better titration, or more efficacy than pill form, Temple states.
A good study design, and an appropriate placebo, will be necessary to make any clinical trial successful, Temple and others on the panel contend. Two study factors will be critical control groups and objective endpoints.
AIDS advocates should design the studies and then consider naming neutral investigators, says Temple. Monitor possible side effects, urges the panel. These include pulmonary infection, blood pressure changes, central nervous system response, and change in neuropsychological status. "This will be a difficult scientific task, but a possible enrichment of current therapy would be highly beneficial and welcome," says Avram Goldstein, MD, AIDS researcher and professor emeritus of pharmacology at Stanford University.