Short-Term Effects of Cannabinoids in Patients with HIV-1 Infection

A Randomized, Placebo-Controlled Clinical Trial

19 August 2003 | Volume 139 Issue 4 | Pages 258-266

Background: Cannabinoid use could potentially alter HIV RNA levels by two mechanisms: immune modulation or cannabinoid–protease inhibitor interactions (because both share cytochrome P-450 metabolic pathways).

Objective: To determine the short-term effects of smoked marijuana on the viral load in HIV-infected patients.

Design: Randomized, placebo-controlled, 21-day intervention trial.

Setting: The inpatient General Clinical Research Center at the San Francisco General Hospital, San Francisco, California.

Participants: 67 patients with HIV-1 infection.

Intervention: Participants were randomly assigned to a 3.95%-tetrahydrocannabinol marijuana cigarette, a 2.5-mg dronabinol (delta-9-tetrahydrocannabinol) capsule, or a placebo capsule three times daily before meals.

Measurements: HIV RNA levels, CD4⁺ and CD8⁺ cell subsets, and pharmacokinetic analyses of the protease inhibitors.

Results: 62 study participants were eligible for the primary end point (marijuana group, 20 patients; dronabinol group, 22 patients; and placebo group, 20 patients). Baseline HIV RNA level was less than 50 copies/mL for 36 participants (58%), and the median CD4⁺ cell count was 340 x 10⁹ cells/L. When adjusted for baseline variables, the estimated average effect versus placebo on change in log₁₀ viral load from baseline to day 21 was –0.07 (95% CI, –0.30 to 0.13) for marijuana and –0.04 (CI, –0.20 to 0.14) for dronabinol. The adjusted average changes in viral load in marijuana and dronabinol relative to placebo were –15% (CI, –50% to 34%) and –8% (CI, –37% to 37%), respectively. Neither CD4⁺ nor CD8⁺ cell counts appeared to be adversely affected by the cannabinoids.

Conclusions: Smoked and oral cannabinoids did not seem to be unsafe in people with HIV infection with respect to HIV RNA levels, CD4⁺ and CD8⁺ cell counts, or protease inhibitor levels over a 21-day treatment.

Editors' Notes Context Because the same systems metabolize cannabinoids and protease inhibitors, cannabinoids might alter viral loads in HIV-infected patients taking protease inhibitors. Contribution In this randomized trial, 62 HIV-infected patients taking indinavir or nelfinavir received a marijuana cigarette, dronabinol capsule, or placebo capsule three times daily for 21 days. Half of the patients in all three groups had undetectable viral loads during the study, and average changes in viral load with marijuana and dronabinol, relative to placebo, were small. Cautions The findings of no large harmful effects on viral loads with either smoked or oral cannabinoids need to be confirmed in larger and longer trials. –The Editors

 

Author and Article Information

From the University of California, San Francisco, and Gladstone Institute of Virology and Immunology, San Francisco, California; and the Washington University School of Medicine, St. Louis, Missouri.

Acknowledgments: The authors thank the research nursing and dietary staff at the San Francisco General Hospital General Clinical Research Center for the professionalism and compassion with which they conducted the trial. They also appreciate the efforts of the San Francisco General Hospital inpatient research pharmacy staff and are deeply indebted to the committed study participants. The authors also thank Bayer Diagnostics for providing the VERSANT HIV-1 RNA 3.0 Assays and disposables and Roxane Laboratories for the dronabinol and placebo capsules. Finally, the authors thank Dr. Jag H. Khalsa of the Center on AIDS and Other Medical Consequences of Drug Abuse at the National Institute on Drug Abuse for his thoughtful guidance and constant support, and Rick Doblin, PhD, for his inspiration and persistence.

Grant Support: By National Institutes of Health grants 1RO1 DA/MH11607, 5-MO1-RR00083, and P30-MH59037.

Potential Financial Conflicts of Interest:Consultancies: N.L. Benowitz (Alexza Molecular Delivery Corp.); Honoraria: D.I. Abrams (Solvay Pharmaceuticals), T.A. Elbeik (Bayer Diagnostics), F.T. Aweeka (Merck & Co.); Stock ownership or options (other than mutual funds): N.L. Benowitz (Alexza Molecular Delivery Corp.); Grants received: T.A. Elbeik (Bayer Diagnostics, Cellestics Ltd., Roche Molecular Systems), F.T. Aweeka (Agouron Pharmaceuticals).

Requests for Single Reprints: Donald I. Abrams, MD, University of California, San Francisco, Positive Health Program, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110.

Current Author Addresses: Drs. Abrams and Deeks: University of California, San Francisco, Positive Health Program, Ward 84, 995 Potrero Avenue, San Francisco, CA 94110.

Dr. Hilton: 500 Parnassus Avenue, San Francisco, CA 94143-0560.

Ms. Leiser: University of California, San Francisco, 143 Stillings Avenue, San Francisco, CA 94131.

Mr. Shade and Mr. Mitchell: University of California, San Francisco, 3180 18th Street, Suite 201, San Francisco, CA 94110.

Drs. Elbeik and Benowitz and Mr. Bredt: University of California, San Francisco, 1001 Potrero Avenue, San Francisco, CA 94110.

Dr. Aweeka: University of California, San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0622.

Dr. Kosel: University of Washington, 325 9th Avenue, Seattle, WA 98104.

Dr. Aberg: Washington University, 4511 Forest Park, St. Louis, MO 63108.

Dr. Mulligan: San Francisco General Hospital, 1001 Potrero Avenue, Building 30, R3501D, San Francisco, CA 94110.

Dr. Bacchetti: University of California, San Francisco, 500 Parnassus Avenue, Room 423A West, San Francisco, CA 94143-0560.

Dr. McCune: Gladstone Institute, PO Box 419100, San Francisco, CA 94141-9100.

Dr. Schambelan: San Francisco General Hospital, Building 5, 5B6, San Francisco, CA 94110.

Author Contributions: Conception and design: D.I. Abrams, J.F. Hilton, R.J. Leiser, S.B. Shade, T.A. Elbeik, F.T. Aweeka, N.L. Benowitz, T.F. Mitchell, K. Mulligan, J.M. McCune, M. Schambelan.

Analysis and interpretation of the data: D.I. Abrams, J.F. Hilton, S.B. Shade, T.A. Elbeik, F.T. Aweeka, N.L. Benowitz, B.M. Bredt, B. Kosel, K. Mulligan, P. Bacchetti, J.M. McCune, M. Schambelan.

Drafting of the article: D.I. Abrams, J.F. Hilton, T.A. Elbeik, S.G. Deeks, T.F. Mitchell, J.M. McCune.

Critical revision of the article for important intellectual content: D.I. Abrams, J.F. Hilton, R.J. Leiser, S.B. Shade, T.A. Elbeik, F.T. Aweeka, N.L. Benowitz, B.M. Bredt, B. Kosel, J.A. Aberg, S.G. Deeks, T.F. Mitchell, K. Mulligan, P. Bacchetti, J.M. McCune, M. Schambelan.

Final approval of the article: D.I. Abrams, S.B. Shade, F.T. Aweeka, N.L. Benowitz, B.M. Bredt, J.A. Aberg, S.G. Deeks, T.F. Mitchell, K. Mulligan, P. Bacchetti, J.M. McCune, M. Schambelan.

Provision of study materials or patients: D.I. Abrams, R.J. Leiser, T.A. Elbeik, J.A. Aberg, S.G. Deeks.

Statistical expertise: J.F. Hilton, S.B. Shade, P. Bacchetti.

Obtaining of funding: D.I. Abrams, J.F. Hilton, T.A. Elbeik, T.F. Mitchell.

Administrative, technical, or logistic support: R.J. Leiser, S.B. Shade, T.A. Elbeik, B.M. Bredt, J.A. Aberg, S.G. Deeks, T.F. Mitchell, M. Schambelan.

Collection and assembly of data: R.J. Leiser, T.A. Elbeik, F.T. Aweeka, B.M. Bredt, B. Kosel, S.G. Deeks, K. Mulligan, M. Schambelan.