Marinol—the brand name of dronabinol and a synthetic isomer of THC—is not a satisfactory treatment alternative for many patients for at least four reasons. First, while Marinol is approved by the Food and Drug Administration to treat nausea and vomiting associated with cancer chemotherapy and anorexia associated with weight loss in patients with AIDS, it paradoxically is often vomited before it can counteract the vomiting. 64 Fed. Reg. 35,928 (1999). Moreover, many patients suffering from the symptoms for which Marinol is approved, are unable to swallow the drug. As a result, patients are often unable to ingest a sufficient quantity of the drug to benefit from its effects. See Declaration of Dr. Howard Maccabee, SER 123 ¶ 9; Declaration of Dr. Marcus Conant, SER 61 ¶ 15. In contrast, neither vomiting nor the inability to swallow diminishes the efficacy of THC delivery by smoking marijuana. Second, Marinol delays relief to patients. Marinol is ingested while the active ingredients in smoked marijuana are inhaled. As a result, patients in need of immediate relief must often suffer for an extended period of time before Marinol takes effect. By contrast, smoking marijuana is a more efficient delivery mechanism that provides the blood stream with the therapeutic properties of marijuana almost instantaneously, resulting in prompt relief for patients:

smoking . . . delivers a rapid drug effect, whereas the THC capsule takes effect slowly, and its results are variable. There are many symptoms for which a quick-acting drug is ideal, such as pain, nausea, and vomiting.

Opening Statement of Stanley J. Watson, Jr., Institute Of Medicine News Conference Marijuana and Medicine: Assessing the Science Base (Mar. 17, 1999).(24)

Third, smoking marijuana has less debilitating psychoactive side effects than Marinol. After being swallowed, Marinol is delivered first to the stomach and then to the liver where it is metabolized into 11-hydroxy-delta 9-THC. This metabolite is three times more psychoactive than THC delivered to the lungs by smoked cannabis. IOM Report at 36. (25) Therefore, not only do patients on Marinol suffer a prolonged wait for relief, but they also often experience harsh psychoactive side effects from ingesting a full-dose of THC that they are unable to mitigate. By contrast, patients who smoke marijuana can regulate their dose of THC, achieving the desired therapeutic effect without experiencing the same intensity of psychoactive side effects.

[S]moking . . . is actually a very good route of administration, in some ways; it is very effective, there is a very rapid absorption, and the patients have a great deal of control over how much they take. They learn to titrate.(26)

Fourth, marijuana contains other effective active ingredients not contained in Marinol. Marinol is composed of only a single compound, THC. By contrast, marijuana is a complex botanical substance, containing over 400 constituents and approximately 66 cannabinoids, which fall into 10 groups of closely related cannabinoids. IOM Report at 24. The main cannabinoids include delta9-THC, delta8-THC, cannabidiol ("CBD"), cannabinol, cannabichromene, and cannabigerol. IOM Report at 24-25. Several of these cannabinoids—not just THC—have therapeutic applications, either alone or in combination with others.

Herbal cannabis contains a mixture of active compounds. It is too early to be certain if the therapeutic action [of cannabis] is limited to one compound. . . . Cannabis may contain a synergistic mixture of active compounds. This is particularly likely now that we know there are at least two receptor specified loci of action.(27)

For example, CBD, which is not psychoactive, has been shown to have potential neuroprotective and anti-inflammatory uses.(28)

24. The complete text is available at www4.nationalacademies.org (search for "Watson and Marijuana").
25. Citing Razdan, R., Structure-activity relationships in cannabinoids, 38 Pharmacology Rev. 75-149 (1986).
26. Select Committee on Science and Technology, House of Lords, Sess. 1997-98, Cannabis: The Scientific and Medical Evidence: Evidence (Nov. 4, 1998) ("Lords Evidence"). As an alternative to smoking, the therapeutic components of the cannabis plant can be inhaled using vaporizer devices. Vaporizers heat cannabis to 150-200 degrees Centigrade, evaporating the cannabinoids and other volatile oils. This temperature is below the burning point of combustible plant material, so smoke is not generated. This technology has been available for over 20 years. John M. McPartland & Patty L. Pruitt, Medical Marijuana and Its Use by the Immunocompromised, 3 Alternative Therapies 39, 43 (1997).
27. Lords Evidence at 32; see also John M. McPartland & Patty L. Pruitt, Side Effects of Pharmaceuticals Not Elicited by Comparable Herbal Medicines: The Case of Tetrahydrocannabinol and Marijuana, 5 Alternative Therapies 57, 60 (1999).
28. See A.J. Hampson et al., Cannabidiol and (-)delta-9-tetrahydrocannabinol are neuroprotective sntioxidants, 95 Proceedings of the National Academy of Sciences 8268 (July 1998) (addressing neuroprotection use); A.M. Malfait, et al., The nonpsychoactive cannabis constituent cannabidiol is an oral anti-arthritic therapeutic in murine collagen-induced arthritis, 97 Proceedings of the National Academy of Science 9561 (Aug. 2000) (addressing anti-inflammatory/anti-arthritic uses). These articles are available at http://www.pnas.org/all.shtml (search for the desired author).