Medical Marijuana: AIDS-Related Information in the New Federal Report

Marijuana and Medicine: Assessing the Science Base, the major report of the prestigious Institute of Medicine (IOM) of the U.S. National Academy of Sciences, was released on March 17. The conclusions and recommendations were a major news story, but the details received less attention--partly, we suspect, because the version released on the Web is hard to use, while the printed book is expensive and may have been difficult to obtain immediately when the national media spotlight was on.

The Institute found substantial consensus that certain cannabinoids (a class of chemicals found in marijuana) may have important symptom-management uses for some patients--but that marijuana smoke, like tobacco smoke, is harmful. The report found no reason to believe that medical use of marijuana would increase non-medical use, or that marijuana makes people more likely to use other drugs. The IOM made six recommendations: more research into the physiological effects of cannabinoids (a class of chemicals which includes THC, the main active ingredient of marijuana); development of rapid-onset, reliable, and safe delivery systems; studies of psychological effects such as anxiety reduction and sedation; studies of the health risk of smoking marijuana; clinical trials of marijuana use for medical purposes under certain conditions (including that efficacy data should be collected); and that use of smoked marijuana for patients with debilitating symptoms should meet certain conditions.


Inhalers, Vaporizers

One theme of the report which has become influential on both sides of the debate that the main danger of marijuana is from non-drug substances in the smoke--which studies have suggested may cause respiratory disease. While marijuana or its components can be taken orally, the oral route does not provide the rapid effect which is important both for relief, and to allow the patient to adjust the dose. There is now considerable interest in vaporizers for smokeless inhalation--especially for medical use, as patients may be especially vulnerable to harm from the smoke.

The report sees the future of marijuana as isolated chemicals (whether from the plant or synthetic), not crude plant materials. It recognizes that the development of these drugs and associated delivery systems (probably inhalers) will take years and may never happen due to the politics and economics of this issue, and that some patients need relief now.

"If there is any future for marijuana as a medicine, it lies in its isolated components, the cannabinoids and their synthetic derivatives. Isolated cannabinoids will provide more reliable effects than crude plant mixtures. Therefore, the purpose of clinical trials of smoked marijuana would not be to develop marijuana as a licensed drug, but such trials could be a first step towards the development of rapid-onset, nonsmoked cannabinoid delivery systems." (from the executive summary).

"It will likely be many years before a safe and effective cannabinoid delivery system, such as an inhaler, will be available for patients. In the meantime, there are patients with debilitating symptoms for whom smoked marijuana might provide relief. The use of smoked marijuana for those patients should weigh both the expected efficacy of marijuana and ethical issues in patient care, including providing information about the known and suspected risks of smoked marijuana use." (from the executive summary).

Meanwhile--not noted in the IOM report--vaporizers are now readily available for smokeless inhalation of cannabinoids from the plant material. These devices heat marijuana to a controlled temperature, enough to release active ingredients, but not enough to cause combustion. Early results seem positive, but laboratory testing is needed to see how well these vaporizers are actually working. (Incidentally, "hash oil," a traditional purified extract of the marijuana plant, has generally been heated and inhaled, not burned--showing that heating can indeed deliver active ingredients of marijuana.) We are researching vaporizers now available and the current state of knowledge about them, and plan to publish a report in a future issue of AIDS Treatment News.

Note: The quoted text in this article is from the "Prepublication Copy, Uncorrected Proofs," the only version available when this article went to press. The changes to the final edition are expected to be minor, though the page numbers may be different.


AIDS-Related Clinical Information

Most of the AIDS-relevant information is in Chapter IV, "The Medical Value of Marijuana and Related Substances," pages 4.9 to 4.22, and the summary, pages 4.42 and 4.43 (see below for instructions on how to obtain this information either in print, or on the Web).

Major sections are:

Nausea and vomiting, pages 4.9 to 4.17.

While not about HIV in particular, this discussion is relevant because these are side effects of antiretroviral medications for many patients.

The report notes that in recent years there has been much improvement in standard treatments for nausea and vomiting due to cancer chemotherapy--for example, serotonin receptor antagonists such as ondansetron or granisetron, sometimes used with dexamethasone, and given prior to chemotherapy. But control of delayed nausea and vomiting (occurring more than 24 hours after chemotherapy) is still a problem. (This writer does not know how feasible it is to use the new antiemetics--treatments for nausea and vomiting--with antiretrovirals, which must be taken continuously.)

It is clear that marijuana does relieve nausea and vomiting in some patients, although not as well, on the average, as the modern antiemetics. But these approved drugs cannot be used by all patients, or in all situations.

"Until the development of rapid onset antiemetic drug delivery systems, there will likely remain a subpopulation of patients for whom standard antiemetic therapy is ineffective and who suffer from debilitating emesis. It is possible that the harmful effects of smoking marijuana for a limited period of time might be outweighed by the antiemetic benefits of marijuana, at least for patients for whom standard antiemetic therapy is ineffective and who suffer from debilitating emesis. Such patients should be evaluated on a case by case basis and treated under close medical supervision. (page 4.17)

Wasting syndrome and appetite stimulation, page 4.17-4.22

"The profile of cannabinoid drug effects suggests that they are promising for treating wasting syndrome in AIDS patients. Nausea, appetite loss, pain, and anxiety are all afflictions of wasting and all can be mitigated by marijuana. Although there are medications that are more effective than marijuana for these problems, they are not equally effective for all patients. Thus we recommend the development and clinical testing of a rapid onset (that is, within minutes) form of THC for such patients. We do not recommend smoking. The long-term harms from smoking make it a poor drug delivery system, particularly for patients with chronic illnesses.

"Terminal patients raise different issues. For those patients, the medical harms of smoking are of little consequence. For terminal patients suffering debilitating pain or nausea and for whom all indicated medications have failed to provide relief, the medical benefits of smoked marijuana might outweigh the harms." (page 4.22)

From the chapter summary (pages 4.42 and 4.43):

"Advances in cannabinoid science of the last 16 years have given rise to a wealth of new opportunities for the development of medically useful cannabinoid-based drugs. The accumulated data suggests a variety of indications, particularly for pain relief, antiemesis, and appetite stimulation. For patients, such as those with AIDS or undergoing chemotherapy, who suffer simultaneously from severe pain, nausea, and appetite loss, cannabinoid drugs might thus offer broad spectrum relief not found in any other single medication...

"Although marijuana smoke delivers THC and other cannabinoids to the body, it also delivers harmful substances, including most of those found in tobacco smoke. In addition, plants contain a variable mixture of biologically active compounds and cannot be expected to provide a precisely defined drug effect. For those reasons, there is little future in smoked marijuana as a medically-approved medication. If there is any future in cannabinoid drugs, it lies with agents of more certain, not less certain composition. While clinical trials are the route to developing approved medications, they are also valuable for other reasons. For example, the personal medical use of smoked marijuana--regardless of whether or not it is approved--to treat certain symptoms is reason enough to advocate clinical trials to assess the degree to which the symptoms or course of the disease are affected..."

"There are two caveats to following the traditional path of drug development for cannabinoids. The first is timing. Patients who are currently suffering from debilitating conditions unrelieved by legally available drugs, and who might find relief with smoked marijuana, will find little comfort in a promise of a better drug ten years from now. In terms of good medicine, marijuana should rarely be recommended unless all reasonable options had been eliminated. But what then? It is conceivable that medical and scientific opinion might find itself in conflict with drug regulations. This presents a policy issue that must weight--at least temporarily--the needs of individual patients against broader social issues. Our assessment of the scientific data on the medical value of marijuana and its constituent cannabinoids is but one component of attaining that balance.

"The second caveat is a practical one. Although most scientists who study cannabinoids would agree that the scientific pathways to cannabinoid drug development are clearly marked, there is no guarantee that the fruits of scientific research will be made available to the public. Cannabinoid-based drugs will only become available if either there is enough incentive for private enterprise to develop and market such drugs, or if there is sustained public investment in cannabinoid drug research and development. The perils along this pathway are discussed in chapter 5 [Development of Cannabinoid Drugs]. Although marijuana is an abused drug, the logical focus of research on the therapeutic value of cannabinoid-based drugs is the treatment of specific symptoms or diseases, not substance abuse. Thus, the most logical research sponsors would be the several institutes within the National Institutes of Health or organizations whose primary expertise lies in the relevant symptoms or diseases..."


Anti-Inflammatory Potential

The possible use of marijuana as an anti-inflammatory is a hot scientific topic, but much less is known than about the other potential medical uses. The following section appears in Chapter II, "Cannabinoids and Animal Physiology," page 4.42:

"Anti-inflammatory Effects

"As discussed above, cannabinoid drugs can modulate the production of cytokines, which are central to inflammatory processes in the body. In addition, several studies have shown directly that cannabinoids can be anti-inflammatory. For example, in rats with autoimmune encephalomyelitis (an experimental model used to study multiple sclerosis), cannabinoids were shown to attenuate the signs and the symptoms of central nervous system damage. (Some believe that nerve damage associated with multiple sclerosis is caused by an inflammatory reaction.) Likewise, the cannabinoid, HU-211, was shown to suppress brain inflammation that resulted from closed head injury or infectious meningitis in studies on rats. HU-211 is a synthetic cannabinoid that does not bind to cannabinoid receptors, and is not psychoactive; thus, without direct evidence, the effects of marijuana cannot be assumed to include those of HU-211. CT-3, another atypical cannabinoid, suppresses acute and chronic joint inflammation in animals. It is a nonpsychoactive, synthetic derivative of 11-THC-oic acid (a breakdown product of THC), and does not appear to bind to cannabinoid receptors. Cannabichromene, a cannabinoid found in marijuana, has also been reported to have anti-inflammatory properties. No mechanism of action for possible anti-inflammatory effects of cannabinoids has been identified and the effects of these atypical cannabinoids and effects of marijuana are not yet established.

"It is interesting to note that two reports of cannabinoid-induced analgesia are based on the ability of the endogenous cannabinoids, anandamide and PEA, to reduce pain associated with local inflammation that was experimentally induced by subcutaneous injections of dilute formalin. Both THC and anandamide can increase serum levels of ACTH and corticosterone in animals. Those hormones are involved in regulating many responses in the body, including those of inflammation. The possible link between experimental cannabinoid-induced analgesia and reported anti-inflammatory effects of cannabinoids is important for potential therapeutic uses of cannabinoid drugs, but has not yet been established."


For More Information

The report can be purchased as a printed copy, or read online without charge, at www.nap.edu, the Web site of the National Academy Press. (Note: the final version should be available in early June for $39.95, with a 20% discount for ordering it through the Web; until then only a "prepublication copy, uncorrected proofs" is available). Unfortunately the official site's online copy is hard to use, because the pages are on the Web as images, as if each page were photographed with a digital camera--and the pages are numbered differently than in the printed copies. We do not know if the format will be improved when the final version becomes available.

Thanks to private organizations and individuals, web copies which are much easier to use are currently available at: (website no longer available)

Each chapter has many references, sometimes hundreds, to scientific and medical articles.

To find other Web sites on the topic, search for "medical marijuana" using a search engine (for example, www.metacrawler.com).