Potential for Abuse: Cannabis and Dronabinol

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There is growing evidence that there is no relevant difference in subjective effects between (Schedule III) dronabinol and cannabis. Thus, it can be expected that the abuse liability is similar for both agents.

In 1999, the Drug Enforcement Administration (DEA) reclassified Marinol™ from a “Schedule II” drug to the less restrictive “Schedule III” category according to the Controlled Substances Act. This essentially means that instead of being classified with drugs like morphine, Marinol™ is now classified with more widely used drugs like codeine. According to the Associated Press of July 3, 1999, Barry McCaffrey, director of the White House Office of National Drug Control Policy, said the capsule form of Marinol™ is the “safe and proper way” to make components of marijuana available to the public. “This action will make Marinol™, which is scientifically proven to be safe and effective for medical use, more widely available,” he said. Geoff Sugerman, a medical marijuana advocate in Oregon, said “Here is more proof that the properties in marijuana really do work as medicine.” Oregon along with other states approved the use of marijuana with a doctor’s consent, an action McCaffrey has opposed.

There are not many direct comparisons of the subjective and medicinal effects of cannabis and dronabinol (THC, Marinol™). Recent experimental research has shown that the subjective effects of cannabis and THC are very similar (Wachtel et al. 2002). Authors write:

“There has been controversy about whether the subjective, behavioral or therapeutic effects of whole plant marijuana differ from the effects of its primary active ingredient, Delta(9)-tetrahydrocannabinol (THC). However, few studies have directly compared the effects of marijuana and THC using matched doses administered either by the smoked or the oral form. (…)

Two studies were conducted to compare the subjective effects of pure THC to whole-plant marijuana containing an equivalent amount of THC in normal healthy volunteers. In one study the drugs were administered orally and in the other they were administered by smoking. (…)

In each study, marijuana users (oral study: n=12, smoking study: n=13) participated in a double-blind, crossover design with five experimental conditions: a low and a high dose of THC-only, a low and a high dose of whole-plant marijuana, and placebo. In the oral study, the drugs were administered in brownies, in the smoking study the drugs were smoked. Dependent measures included the Addiction Research Center Inventory, the Profile of Mood States, visual analog items, vital signs, and plasma levels of THC and 11-nor-9-carboxy-THC. (…)

In both the oral study and the smoking study, THC-only and whole plant marijuana produced similar subjective effects, with only minor differences.

CONCLUSION: These results support the idea that the psychoactive effects of marijuana in healthy volunteers are due primarily to THC” (Wachtel et al. 2002).

Since the abuse potential of a drug is mainly attributed to its subjective effects it can be assumed that the the abuse potential of THC and cannabis are quite similar.

Clinical research has also demonstrated similar properties of THC and cannabis with regard to therapeutic effects. This is shown in the data from marijuana research programs on the anti-emetic effects of marijuana in 6 states (Musty & Rossi 2001, see above), where patients who smoked marijuana experienced 70-100% relief from nausea and vomiting, and those who used the THC capsule experienced 76-88% relief. In the study by Abrams et al. (2002) that investigated the interaction of smoked cannabis and Marinol™ (THC) with HIV medication, very similar effects were observed with regard to weight gain. The participants had been divided into three groups, with one set smoking marijuana (3.95% THC), another taking oral dronabinol capsules (3×2.5 mg daily), and a third taking oral placebo capsules. Researchers found that those using dronabinol (THC) or marijuana experienced significant increases in caloric intake and gained an average of 3.5 kg (marijuana group) and 3.2 kg. (THC group) compared to 1.3 kg in the placebo group. There was no significant difference between marijuana and THC with regard to side effects and benefits.

Leo Hollister stated in a recent review on the medical use of marijuana:

“Marinol™ or dronabinol, is available for treating nausea and vomiting associated with cancer chemotherapy and as an adjunct to weight loss in patients with wasting syndrome associated with AIDS. Although such approval currently applies only to orally administered THC, for practical purposes smoked marijuana should also be expected to be equally effective. Promising leads, also often fragile, suggest possible uses for treating chronic pain syndromes, neurological disease with spasticity and other causes of weight loss. These indications require more study.”

The American public notes that the difference between cannabis and dronabinol with regard to classification is hypocritical and political. Journalist Cynthia Cotts commented the reclassification of Marinol™ from Schedule II to Schedule III in the Nation on September 20, 1999:

“For more than half a century, the U.S. government has maintained a hard line on marijuana, denying that the plant has any medical value at all. But in the period since 1996, during which voters in several states have approved the medical use of marijuana and the Institute of Medicine has hailed the therapeutic effects of THC (one of the cannabinoids found in the natural plant), the Feds have scrambled to revise their position. Now, the drug warriors’ line goes something like this: Who needs pot, an illegal substance that burns up your lungs, when you can take Marinol™, a little white pill that contains synthetic THC?

The government threw its weight behind Marinol™ this past July, when the Drug Enforcement Administration moved the drug into Schedule III, lifting its dangerous stigma and making it easier for doctors to prescribe. While drug czar Barry McCaffrey insisted the move was based on “pure science,” a review of the players involved suggests that the rise of Marinol™ is more the result of politics and profiteering” (Cotts 1999).

References

Abrams DI, et al. Short-Term Effects of Cannabinoids In Patients With HIV Infection. J Cannabis Ther 2002;2(2):92-93.
Cotts C. Marijuana made easy. The Nation, September 20, 1999.
Hollister L. Marijuana (cannabis) as medicine. J Cannabis Ther 2001;1(1):5-27.
Musty RE, Rossi R. Effects of smoked cannabis and oral ?9-tetrahydrocannabinol on nausea and emesis after cancer chemotherapy: a review of state clinical trials. J Cannabis Ther 2001;1(1):29-42.
Wachtel SR, ElSohly MA, Ross SA, Ambre J, De Wit H. Comparison of the subjective effects of Delta(9)-tetrahydrocannabinol and marijuana in humans. Psychopharmacology (Berl) 2002;161(4):331-9.