A Prospective Study of Humoral and Cellular Immune Responses to Hepatitis B Vaccination in Habitual Marijuana Smokers.

Exposure to Δ9-tetrahydrocannabinol (THC) in vitro and in animal models can significantly impair the differentiation, activation and function of dendritic cells, T cells and B cells. However, studies directly assessing the impact of marijuana smoking on human immunity are lacking. A prospective study of immune responses to a standard hepatitis B vaccination was therefore carried out in a matched cohort of 9 marijuana smokers (MS) and 9 nonsmokers (NS). In addition to their regular marijuana use, MS smoked four marijuana cigarettes in a monitored setting on the day of each vaccination. Blood samples were collected over time to assess the development of hepatitis B-specific immunity. The majority of subjects from both the NS (8) and MS (6) groups developed positive hepatitis B surface antibody titers (>10 IU/L) and of these 6 NS and 5 MS were classified as high antibody (good) responders (>100 IU/L). The development of a good response correlated with the presence of hepatitis B-specific T cell proliferation and cytokine production, resulting in a clear distinction regarding the immune status of good responders versus non-responders. However, even though there were slighter more non-responders in the MS cohort, there were no significant differences between MS and NS with respect to peripheral blood cell phenotypes or vaccination-related changes in hepatitis B responses. While a larger cohort may be required to rule out a small suppressive effect, our findings do not suggest that habitual marijuana smoking exerts a major impact on the development of systemic immunity to hepatitis B vaccination.

A pilot study of all-trans-retinoic acid for the treatment of human emphysema.

Emphysema results from progressive destruction of alveolar septae and was considered irreversible until all-trans-retinoic acid (ATRA) was shown to reverse anatomic and physiologic signs of emphysema in a rat model. To evaluate the feasibility of ATRA as a clinical therapy, 20 patients with severe emphysema were enrolled into a randomized, double-blind, placebo-controlled pilot study. Participants included 16 male and 4 female former smokers, two with alpha(1)-antitrypsin deficiency. Patients were treated with either 3 mo of ATRA (50 mg/m(2)/d) or 3 mo of placebo, followed by a 3-mo crossover phase. Plasma drug levels were followed and outcome measures included serial pulmonary function tests, blood gases, lung compliance, computed tomography (CT) imaging, and quality of life questionnaires. In general, treatment was well tolerated and associated with only mild side effects including skin changes, transient headache, hyperlipidemia, transaminites, and musculoskeletal pains. Plasma drug levels varied considerably between subjects and decreased significantly over time in 35% of the participants. Physiologic and CT measurements did not change appreciably in response to therapy. We conclude that ATRA is well tolerated in patients with emphysema, and trials evaluating higher doses, longer treatment, or different dosing schedules are feasible.