Short-Term Effects of Cannabinoids in Patients with HIV-1 Infection: A Randomized, Placebo-Controlled Clinical Trial

University of California, San Francisco, and Gladstone Institute of Virology and Immunology, San Francisco, California 94110, USA.
Annals of internal medicine (Impact Factor: 17.81). 09/2003; 139(4):258-66. DOI: 10.7326/0003-4819-139-4-200308190-00008
Source: PubMed


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).
To determine the short-term effects of smoked marijuana on the viral load in HIV-infected patients.
Randomized, placebo-controlled, 21-day intervention trial.
The inpatient General Clinical Research Center at the San Francisco General Hospital, San Francisco, California.
67 patients with HIV-1 infection.
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.
HIV RNA levels, CD4+ and CD8+ cell subsets, and pharmacokinetic analyses of the protease inhibitors.
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.
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.

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    • "They suggested, based on studies by Baldwin et al, that cocaine inhibits the effector function of neutrophils and macrophages, as well as reduces cytokine production, decreasing the immune response [27]. In two cohorts that aimed to assess the effect of marijuana on the immune response of patients living with HIV, there was no statistically significant association between the two variables [24], [29], in contrast to our findings in the univariate analysis. However, Chao, et al. concluded that their results did not exclude the possibility that drug use could negatively affect T-cell function, as previously mentioned [24]. "
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    ABSTRACT: The measurement of CD4+ T-cell (CD4) counts is a strong predictor of progression to AIDS and a means of monitoring antiviral therapy (ART). The success or failure of controlling virus levels in untreated patients or those taking ART may be associated with treatment adherence, habits, correlated infections unrelated to HIV, cancer, immunosuppressive drugs; as well as socio-economic and psychosocial aspects and access to healthcare. The aim of the present study was to identify, using a multilevel model, the factors related to the variations of CD4 counts over time, in patients living with HIV. A cohort study was conducted with patients living with HIV, selected from July 2007 to December 2010. Patients were monitored from records of their first CD4 count after being diagnosed with HIV. A multilevel model with 3 levels of aggregation was applied to analyze the associations of predictor variables and the behavior of CD4 over time. A total of 1870 patients were enrolled. The mean number of CD4 at the beginning of the cohort was 393.1 cells/mm(3), and there was a mean increase of 1.529 cells/mm(3) per month. Patient's age, smoking, use of illicit drugs, hospital treatment, changing doctors and the use of ART, were factors that affected the kinetics of the CD4 count during the follow-up period. The results of this study indicated increased levels of CD4 over time in a cohort of patients living with HIV/AIDS and identified factors that may influence this increase and are liable to intervention.
    PLoS ONE 02/2014; 9(2):e84276. DOI:10.1371/journal.pone.0084276 · 3.23 Impact Factor
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    • "Concern has been expressed that the immunosuppressive effects of THC might prove deleterious in AIDS, but investigation has revealed no impairment of the drug on T cell levels or activation or any other aspect of immune function, nor any evidence of increased viral load. [78] [79] [80] The evidence supporting THC use in cancer-related weight loss is less clear cut. Exploratory trials suggested a positive effect on appetite and weight, [72] [81] [82] but a larger trial indicated that THC (2.5 mg twice daily) was significantly inferior to megestrol for improving appetite and weight, and did not improve the outcome if added to megestrol. "
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    ABSTRACT: Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines. The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology. In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders. Copyright © 2013 John Wiley & Sons, Ltd.
    Drug Testing and Analysis 02/2014; 6(1-2). DOI:10.1002/dta.1529 · 2.51 Impact Factor
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    • "Given the high prevalence of elevated marijuana use in this population and the use of marijuana among other groups of persons living with HIV/ AIDS, it will become increasingly important to study the long-term effects of marijuana use among persons living with HIV/AIDS. While marijuana use has been shown to not have an adverse effect on viral load or CD4 (Abrams et al., 2003), long-term effects of chronic marijuana use have been shown to include increased risk for depression and anxiety (Patton et al., 2002), pulmonary diseases (Wu et al., 1988), and cognitive dysfunction including decreased memory and attention (Solowij et al., 2002). Long-term effects of chronic marijuana use among persons living with HIV are not well documented. "
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    ABSTRACT: Marijuana use has been documented to be higher among emerging adults than among other age groups in the United States. Persons living with HIV may use marijuana as a method for alleviating symptoms and side effects associated with treatment as well as a coping or mood adjustment strategy. The authors analyzed data from a two-phase mixed methods study of young HIV-positive gay/bisexual men to explore motivations for heavy marijuana use. Phase I consisted of semi structured qualitative interviews with 54 young gay/bisexual HIV-positive men (mean age 21.0 years) conducted at four geographically and demographically diverse sites. Phase II consisted of a computer-assisted quantitative survey administered to 200 young gay/bisexual HIV-positive men (mean age 21.1 years) across 14 clinical sites within the ATN. Phase I participants described marijuana use chiefly within the contexts of responses to initial HIV diagnosis, stress relief, and relaxation, including active and avoidant coping techniques. Phase II results revealed that almost one-quarter (23%) of the sample reported smoking marijuana every day, and another 16% said they smoked at least weekly but not daily. Logistic regression analysis determined significant predictors of at least weekly marijuana use to be using substances to relieve the stress of living with HIV (β = 1.04, p < .01),using substances alone (β = 2.05, p < .01), and using substances to reduce side effects of medication (β = 2.44, p < .01). Heavy marijuana use in our quantitative sample greatly exceeded rates reported in population-based studies of emerging adults and in previous studies of medicinal marijuana among persons living with HIV. These data have implications for self-care strategies among young persons living with HIV and intervention development for this population.
    Journal of HIV/AIDS & Social Services 03/2013; 12(1):26-48. DOI:10.1080/15381501.2012.735171
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