HHS FACT SHEET
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

INVESTIGATING POSSIBLE MEDICAL USES OF MARIJUANA

Overview: The National Institutes of Health held a workshop in February 1997 to discuss research in the field of possible therapeutic uses for smoked marijuana. Non-federal experts in fields such as cancer treatment, infectious diseases, neurology, and ophthalmology reviewed research published to date and heard presentations. The studies discussed were gathered through a search of the peer-reviewed literature, including both NIH-supported research as well as case reports and studies conducted independently of NIH.

The invited experts assessed what is known about marijuana's possible therapeutic potential, and discussed the major scientific questions that remain unanswered; the indications that might hold promise for future research; and factors to be taken into account in undertaking clinical research on this subject.

The workshop concluded that there are too few scientific studies to determine marijuana's therapeutic utility, but that research is justified into marijuana's use for certain conditions or diseases: pain; neurological and movement disorders; the nausea of patients who are undergoing chemotherapy for cancer; loss of appetite and weight (cachexia) related to AIDS; and glaucoma. The experts also called for peer-reviewed research to provide clear answers about marijuana's effects in the most promising applications. They also stressed that clinical trials to determine any therapeutic effects of marijuana would have to be well-designed and carefully conducted to produce reliable results. The written summary of the panel's conclusions was provided to the NIH director in August 1997.

As in other research areas, NIH will review grant applications on the medical utility of marijuana and is prepared to fund those applications that meet the accepted standards of scientific design and that, on the basis of peer review, are competitive with other applications that qualify for funding.

On May 21,1999, HHS announced new steps to help facilitate research into the medical uses of marijuana and its constituents. The Department created a new process for providing research-grade marijuana on a reimbursable basis for approved clinical research, including projects other than those funded by NIH.

On July 2, 1999, the U.S. Drug Enforcement Agency (DEA) reclassified Marinol®–the synthetic oral form of the major active ingredient in marijuana, delta-9-tetrahydrocannabinol (THC)–so that the drug will be more widely available to patients. Marinol® has been approved by FDA for many years for use by patients undergoing chemotherapy and by patients with AIDS.

PAST RESEARCH

The NIH workshop reviewed independently sponsored studies as well as research that has been federally supported. In the past, NIH's research on the therapeutic aspects of marijuana has focused primarily on a synthetic form of the major active ingredient in marijuana, delta-9-tetrahydrocannabinol (THC).

In the late 1970s, two NCI pilot studies were performed with smoked marijuana as well as oral THC. These small studies suggested that the utility of smoked and oral THC varied in part by the type of cancer chemotherapy being administered. As information developed regarding the potential benefit of THC as an antiemetic for patients undergoing chemotherapy, the National Cancer Institute (NCI) supported the development of the drug dronabinol--synthetic THC--as an oral antinausea drug for such patients. In 1985, the Food and Drug Administration (FDA) approved dronabinol (Marinol®), for treatment of nausea and vomiting associated with cancer chemotherapy in patients who have not responded to conventional antinausea (antiemetic) therapy. FDA also approved dronabinol in 1992 for use in loss of appetite and weight loss related to AIDS.

Since 1986, Marinol® had been classified by the DEA as a Schedule II drug, which placed certain restrictions on the prescribing of it. In July 1999, in accord with the scientific and medical evaluation and recommendations of HHS, DEA lowered Marinol® to a Schedule III drug. One of the results of this change is that physicians will be allowed to write prescriptions with as many as five refills in six months. The change also reduces record-keeping requirements and distribution restrictions.

Other NIH institutes have conducted or supported some research--beginning over 20 years ago and into the present--aimed at evaluating the potential of synthetic THC in the management of conditions that include pain, muscle spasms, and HIV-associated cachexia. In particular, the National Eye Institute supported research studies from 1978 to 1984 in an effort to determine whether marijuana, or drugs derived from marijuana, might be effective as a treatment for glaucoma (elevated intraocular pressure). These studies demonstrated that some derivatives of marijuana lowered intraocular pressure when administered orally, intravenously, or by smoking, but not when topically applied to the eye.

However, none of these studies demonstrated that marijuana--or any of its components--could safely and effectively lower intraocular pressure any more than a variety of drugs on the market. As research with other potential glaucoma drugs has shown, simply lowering intraocular pressure does not necessarily control the disease. In addition, some potentially serious side effects were noted, including an increased heart rate and a decrease in blood pressure in studies using smoked marijuana.

EXISTING THERAPIES

In assessing possibilities for future research, the experts attending the February 1997 workshop weighed the potential of smoked marijuana as a medicine as compared with existing approved therapies for conditions where smoked marijuana has been suggested.

In glaucoma and nausea associated with cancer chemotherapy, for example, safe and effective treatments other than marijuana now exist for these conditions. Glaucoma can usually be effectively controlled with several existing medical and surgical treatments. These include a variety of prescription eye drops and pills used for glaucoma treatment that either enhance the drainage of fluid from the eye or decrease its production. Treatment with an argon laser has proved beneficial in NEI-sponsored clinical trials and is usually used in conjunction with drops or pills. Finally, several procedures that employ incisional surgery may be performed to improve drainage flow. Although these procedures have a fairly high success rate, they are generally reserved until medical therapy is no longer effective.

According to the National Cancer Institute, other antiemetic drugs or combinations of antiemetic drugs have been shown to be more useful than smoked marijuana or synthetic THC as "first-line therapy" for nausea and vomiting caused by anticancer drugs. Examples include drugs called serotonin antagonists, including ondansetron (Zofran) and granisetron (Kytril), used alone or combined with dexamethasone (a steroid hormone); metoclopramide (Reglan) with diphenhydramine and dexamethasone; high doses of methylprednisolone (a steroid hormone) combined with droperidol (Inapsine); and prochlorperazine (Compazine). Research withother agents and combinations is under way to determine their usefulness in controlling chemotherapy-induced nausea and vomiting.

A number of medications have been shown to be effective for pain control and for HIV-associated wasting, which are among the most frequently cited conditions for which marijuana has been proposed as potentially helpful. These medications include opiates and anti-inflammatory drugs for pain, while for HIV wasting, the synthetic hormone megestrol acetate, dronabinol and somatropin are FDA-approved. Researchers in government and the private sector are continuing to develop improved methods of treatment for each of these conditions.

To determine whether dronabinol might be of benefit for treating wasting or cachexia from cancer, NCI has a clinical trial under way comparing dronabinol with another drug, megestrol acetate, or Megace, for cancer cachexia.

RESEARCH CHALLENGES

Research involving smoked marijuana poses several challenges. For example, studies on smoked marijuana would have to take into account how to objectively measure a positive therapeutic effect, given the fact that a blind study, in which neither the doctor or patient knows which drug is being used, would be difficult. In addition, the psychoactive effects of marijuana limit its use in people who experience depression instead of euphoria from the drug and in those who find the intoxicating sensation disorienting and unpleasant.

NIH has focused its marijuana-related research on dronabinol because the orally-administered drug eliminates some of the known difficulties of using smoked marijuana as a drug-delivery system. These difficulties include the respiratory effects of smoking, exposure to a large mix of chemicals present in the marijuana plant (including about 60 cannabinoids) and to potential contamination with organisms that may be hazardous to someone whose immune system is impaired, and the variability of the dose that patients absorb when they smoke. Like smoked marijuana, dronabinol has psychoactive as well as therapeutic effects.

The immediate effects of marijuana include rapid heart beat, some loss of coordination, and impaired short-term memory. In addition, the drug adversely affects critical skills, including those necessary to drive a car safely, such as judgment of distance and reaction time.

The group of experts noted in their report from the workshop that the risks associated with marijuana, especially smoked marijuana, must be considered not only in terms of immediate adverse effects on the lung, but also the long-term effects in patients with chronic diseases. They also felt the possibility that frequent and prolonged marijuana use might lead to clinically significant impairments of immune function is great enough that studies on immune function should be part of any research project on the medical uses of marijuana. This is especially true in studies involving patients with compromised immune systems. Members of the group also were concerned about the effects of the dangerous combustion byproducts of smoked marijuana on patients with chronic diseases. So, they favored the development of a smoke-free inhaled delivery system that could deliver purer forms of marijuana's most active ingredient, THC, or its related compounds known as cannabinoids.

The full text of the report of the NIH workshop on the medical utility of marijuana is available on the Internet at <http://www.nih.gov/news/medmarijuana/MedicalMarijuana.htm> .

In addition to the NIH workshop, the Institute of Medicine, part of the National Academy of Sciences, carried out a separate assessment of the scientific knowledge of health effects and possible medical uses of marijuana. The IOM project was funded by the White House Office of National Drug Control Policy. The IOM released their report on March 17, 1999. Some of their conclusions were similar to those of the NIH panel. The full text of the IOM report is available at

<http://pompeii.nap.edu/books/0309071550/html/index.html>.

PROVIDING MARIJUANA FOR CLINICAL RESEARCH

In May 1999 HHS announced the creation of a new mechanism to provide research-grade marijuana not only for NIH-funded research but also for sound research that is funded by other sources.

An ad hoc Public Health Service (PHS) committee will review non-NIH funded clinical studies and assess them both for scientific quality and the likelihood that they will yield data capable of meeting the FDA standards for drug approval.

When a study is approved by the PHS committee, the researcher will have to apply for an Investigational New Drug (IND) license from the FDA and obtain a Drug Enforcement Administration (DEA) registration for Schedule I substances. When these are obtained, NIH will provide research-grade marijuana for the project on a reimbursable basis. Thus, researchers will be required to reimburse the contractor of the National Institute on Drug Abuse (NIDA) for the costs of growing and producing marijuana for research purposes. In this way, NIH will be able to produce and supply sufficient marijuana for a variety of additional clinical studies. Reimbursement requirements would also apply to projects funded by NIH institutes other than NIDA as well as to projects that do not have NIH funding. This new procedure does not signal any change in HHS' view on the therapeutic efficacy of marijuana but rather a way to enable more objective research to be done to evaluate the potential merits of marijuana for medical uses. Details of this new HHS procedure can be found in the NIH Guide for Grants and Contracts, May 21, 1999 at <http://www.nih.gov/grants/guide/notice-files/not99-091.html>.

###