Cannabinoid Drugs May Offer Symptom Relief

WASHINGTON—During the past 16 years, researchers have developed data that suggest cannabinoid-based drugs may be effective for a variety of medical uses, including pain relief, antiemesis, and appetite stimulation in cancer patients, an Institute of Medicine (IOM) committee has concluded. It warned, however, that such medical uses carry some risks, particularly the harmful effects of smoking marijuana, which it discouraged as a means of delivering medications.

In its report, “Marijuana and Medicine: Assessing the Science Base,” the 11-member advisory panel urged rigorous testing of marijuana’s active components, particularly against pain, nausea, the anorexia of AIDS and cancer, and muscle spasms in multiple sclerosis. It also called for the development of safer, fast-acting delivery systems, such as specialized inhalers, so patients would not have to smoke marijuana.

Currently, Marinol is the only cannabinoid-based drug marketed in the United States. It is a pill form of THC, the primary psychoactive ingredient of marijuana, which the FDA has approved for treating nausea and vomiting associated with chemotherapy and for anorexia and weight loss in AIDS.

“Marijuana’s medical effects are generally modest, and for most symptoms, there are more effective medicines already available on the market,” said John A. Benson, Jr., MD, professor of medicine and dean emeritus of the Oregon Health Sciences University School of Medicine. “For patients who do not respond well to other medications, however, short-term marijuana use appears to be suitable in treating conditions like chemotherapy-induced nausea and vomiting or the wasting caused by AIDS.”

Dr. Benson and Stanley J. Watson, Jr., MD, PhD, co-director of the University of Michigan’s Mental Health Research Institute, served as the panel’s principal investigators.

Since 1996, seven states have approved referenda that would legally allow the smoking of marijuana as a medical treatment. However, their implementation has been thwarted because of threats by the federal government to yank the narcotics-prescribing powers of physicians who prescribe marijuana.

The IOM report recommended avoiding smoked marijuana whenever possible because of its health risks. In addition to its common effect of euphoria, marijuana can adversely affect a user’s control over movement and can cause occasional disorientation and sometimes dependence, although withdrawal symptoms are generally mild and short-lived, the committee noted. Worse, smoking marijuana increases a person’s risk of cancer, lung damage, and pregnancy problems, including low birthweight.

Although the panel found marijuana may be useful to treat the muscle spasms of multiple sclerosis, it found little evidence for using marijuana to treat other movement disorders such as Parkinson’s or Huntington’s disease.

It also rejected marijuana’s usefulness in treating glaucoma, because smoking it only lowers eye pressure slightly and only for a short time. Thus, the benefit does not outweigh the long-term risk of inhaling the drug’s smoke.

Although marijuana use often precedes the use of harder drugs, the panel said no conclusive evidence exists that marijuana is a gateway drug, one that actually causes people to move up to harder drugs such as heroin and cocaine. Nor is there evidence that approving the medical use of marijuana would increase its use among the general population, particularly if it is regulated as closely as other drugs with the potential for abuse.

The IOM advisory group took an evidence-based approach to its assessment, commissioning 14 background papers and 8 technical commentaries, and had its work reviewed by 13 qualified experts.

Among the panel’s observations:

The most encouraging clinical data supporting the use of cannabinoids against chronic pain come from three methodologically sound studies on cancer pain. In one study, researchers found that the analgesic effect of 10 mg of THC was equivalent to 60 mg of codeine, and 20 mg of THC was equivalent to 120 mg of codeine.

Many cannabinoid receptors exist in the nucleus of the solitary tract, the brain center important to the control of emesis. Most reports of marijuana’s or THC’s use against nausea and vomiting come from chemotherapy-induced emesis, and these indicate that the degree of efficacy is not high.

In patients with nausea and vomiting, treatment with pills is generally ineffective because of the difficulty of swallowing or keeping the drug down. “Thus an inhalation (but preferably not smoking) cannabinoid drug delivery system would be advantageous for treating chemotherapy-induced nausea.”

Cachexia and anorexia are common in end-stage AIDS and metastatic cancers. However, despite widespread use by AIDS patients, there is little scientific evidence that marijuana or cannabinoids effectively counter malnutrition and wasting syndrome.

 Oncologists’ Attitudes Toward Marijuana

Two research teams have surveyed the attitudes of clinical oncologists in this decade toward prescribing marijuana as an antiemetic and reached contradictory conclusions, the IOM reported. A 1991 study concluded that great interest existed in such prescribing, and a 1994 survey, taken after serotonin receptor antagonists had become available, found little interest.

The studies warrant attention “because they are still frequently cited as evidence for or against the use of marijuana as an antiemetic,” the panel said. It noted that since 1994, the two teams have debated which view truly represents the prescribing sentiment among oncologists.

“There are numerous methodological differences between the two studies that might explain the different results,” the report said. “Nonetheless, ultimately these studies are irrelevant. Both studies deal with perceptions rather than pharmacological realities based on well-designed outcome studies.”

A 6-week study and a 1-year study both found that participants taking THC experienced an increase in appetite. But cannabinoids may modulate the immune system, the report said, which might be a problem in immunologically compromised patients.

In cancer patients, Marinol has been shown to improve appetite and promote weight gain.

Finally, a cannabinoid such as THC might prove useful as part of a combination therapy as an appetite stimulant, antiemetic, analgesic, and anxiolytic, especially for patients in the late stages of cancer.