UCSF researchers found no harmful changes in HIV virus levels in patients on combination antretroiviral therapy in a safety study looking at both smoked marijuana and dronabinol, an oral medical cannabinoid.
“People with HIV are a vulnerable population, so successfully addressing the safety concerns allows us to move on to effectiveness studies, three of which are currently underway here,” said study author Donald Abrams, MD, professor of clinical medicine in the UCSF Positive Health Program at San Francisco General Hospital Medical Center (SFGHMC).
The findings, which appear in the August 19, 2003 issue of the Annals of Internal Medicine, mark the first publication of a randomized, controlled study involving medical marijuana in a major peer-reviewed journal in several years.
Sixty-two HIV-infected patients on antiretroviral regimens containing a protease inhibitor completed the 25 day inpatient study. Patients were randomized to three groups—20 received smoked marijuana, 22 received dronabinol, and 20 received an oral placebo.
The study measured changes in HIV virus levels in blood (rising levels tend to indicate disease progression) and CD 4 and CD 8 T lymphocyte cell counts. These
disease- fighting white blood cells are essential for defending against infections and are targeted and destroyed by the HIV virus.
The study investigated whether cannabinoids would alter the levels of the virus either by changing the levels of the protease inhibitor medication or by a direct effect on the immune system. Fifty-eight percent of the participants entered the study with levels of HIV virus circulating in their blood below the limit currently detectable by the usual tests. They ended the study with no change in their undetectable status. In all three arms, patients with detectable levels of virus saw no change in the levels of HIV in their blood over the three-week study period.
There was no significant change in CD 4 or CD 8 T-cell counts for the placebo group over the course of the study. CD 4 T-cell counts rose by about 20 percent for both the smoked marijuana and the dronabinol group. CD 8 T-cell counts rose by 20 percent in the smoked marijuana group and by 10 percent in the dronabinol group.
“The change in lymphocyte counts for the smoked marijuana group is intriguing. At a minimum, it contradicts findings from previous studies suggesting that smoked marijuana suppresses the immune system,” said Abrams.
While not the primary objective of the study, weight gain was observed in all three groups, possibly due to regularly scheduled meals and snacks. Statistically significant weight gain occurred in both the smoked marijuana and the dronabinol arms compared with the placebo arm, though the gain was fat, not in the desired lean body mass compartment.
Co-authors of the study are Joan F. Hilton, DSc, MPH, UCSF associate professor of epidemiology and biostatistics; Roslyn J. Leiser, RN, clinical nurse, Starley B. Shade, MPH, senior statistician, Steven G. Deeks, MD, UCSF associate professor of medicine, and Thomas F. Mitchell, MPH, program director, all in the UCSF Positive Health Program at SFGHMC; Tarek A. Elbeik, PhD, UCSF associate researcher in laboratory medicine at SFGHMC; Francesca T. Aweeka, PharmD, UCSF professor of clinical pharmacology; and Neal L. Benowitz, MD, UCSF chief of the division of clinical pharmacology and vice chair of the department of biopharmaceutical sciences.
Also, Barry M. Bredt, MA, specialist, and Morris Schambelan, MD, UCSF professor of medicine and director, General Clinical Research Center at SFGHMC; Bradley Kosel, PharmD, visiting postdoctoral scholar in clinical pharmacology at UCSF; Judith A. Aberg, MD, associate professor of medicine at Washington University, St. Louis, Mo.; Kathleen Mulligan, PhD, UCSF associate professor of medicine at SFGHMC; and Joseph M. McCune, MD, PhD, UCSF professor of medicine at the Gladstone Institute of Virology and Immunology.
The study was supported by a research grant from the National Institute on Drug Abuse, a part of the National Institutes of Health, which also supplied the marijuana cigarettes for the trial. The dronabinol and placebo were supplied by Roxane, Inc., Columbus, Ohio.