This Article  • Extract  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citing articles on HighWire  • Citing articles on ISI (13)  • Contact me when this article is cited  Related Content  • Related letter  • Similar articles in JAMA  Topic Collections  • Immunology, Other  • Alert me on articles by topic

To the Editor: In vitro studies and experiments in animal models have found that cannabinoids modulate immune cell function.¹ However, investigations of immune effects in human subjects are scarce and contradictory. Gene expression of cannabinoid receptors in peripheral blood mononuclear cells may be altered among marijuana users.² Experimental data in healthy persons have found abnormalities in T lymphocyte and natural killer (NK) cell function, but have not confirmed that these alterations might affect susceptibility to infections.³ We sought to investigate cell-mediated immune response and cytokine release in cannabis users.

Methods. Participants were recruited by word of mouth and gave written consent to participate in the study, which was approved by our institutional ethical committee and conducted in accordance with the Declaration of Helsinki. Volunteers were deemed healthy after a full medical history and examination. They were then interviewed about their recent use of illicit drugs, and their statements were confirmed by urine testing. A psychiatric screening excluded drug abuse or dependence (except for cannabis or nicotine) or psychiatric disorders according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.

A blood sample was obtained between the hours of 8 and 11 AM to determine blood cell count and differential, lymphocyte immunophenotyping, lymphocyte proliferative response to mitogenic stimulation (stimulation index with phytohemoagglutinine [SI-PHA] or concanavaline A [SI-ConA]), and levels of interleukin 2 (IL-2), interleukin 10 (IL-10), and transforming growth factor -1 (TGF1), as described previously.⁴ Comparisons between cannabis exposure categories were performed using ² tests or analysis of variance. Multivariate linear regression models were fitted for each immune parameter to analyze the effects of cannabis consumption after adjusting for sex, as well as consumption of coffee, tobacco, and alcohol.

Results. According to total cannabis consumption and frequency of use during the previous 6 months, participants were classified as controls (n = 32), occasional users (eventual to monthly use, n = 13) and regular users (weekly to daily use, n = 16). Sex, tobacco smoking, and alcohol consumption were unequally distributed between groups (Table 1).

View this table: [in this window] [in a new window] Table. Group Characteristics and Immune Parameters in Controls and Cannabis Users

Cannabis use was associated with a decrease in NK counts, lymphocyte proliferative response by SI-PHA and SI-ConA, and levels of IL-2, and an increase in levels of IL-10 and TGF1. No differences were found in counts of total lymphocytes or CD4, CD8, and CD19 cells (TABLE). The significant effect of cannabis consumption on immune measures persisted after multivariate analysis controlling for the possible confounding effects of sex and use of coffee, tobacco, and alcohol. A significant dose-response relationship was found between cannabis exposure (total life consumption, as the log-transformed number of cannabis "joints") and the decrease in counts of total lymphocytes, CD4 or NK cells, and IL-2 levels, or the increase in IL-10 levels.

Comment. Cannabis use was associated with a decrease in levels of IL-2, a T_H1-type cytokine related to cell-mediated immunity, and an increase in levels of IL-10, a T_H2-type cytokine related to humoral immunity. The decrease of proinflammatory (IL-2) cytokines and the augment of anti-inflammatory (IL-10 and TGF1) cytokines was associated with a marked reduction in lymphocyte functionality, and a decrease in the number of NK cells. The suppression of immediate and innate responses of the immune system together with the disruption of T_H1/T_H2 balance might increase the susceptibility and promote the progression of infectious diseases and tumors, although the clinical relevance of these findings has not been clearly demonstrated in humans.^{3, 5} It also has been suggested that immunomodulatory effects of cannabinoids on inflammatory and autoimmune disorders could lead to new therapeutic interventions.⁶

AUTHOR INFORMATION
Funding/Support: This study was supported in part by Progetto No. 1 "Area Progetto Droga" from Istituto Superiore di Sanità, Rome, Italy; Generalitat de Catalunya (2001SGR00407); and Fondo de Investigaciones Sanitarias (FIS-00/00777), Spain.

Roberta Pacifici, PhD; Piergiorgio Zuccaro, PhD; Simona Pichini, PhD
Laboratorio Biochimica Clinica
Istituto Superiore di Sanitá (ISS)
Rome, Italy

Pere N. Roset, MD, PhD; Sandra Poudevida, PhD; Magí Farré, MD, PhD
Unit of Pharmacology
Institut Municipal d'Investigació Mèdica (IMIM)
Autonomous University of Barcelona
Barcelona, Spain

Jordi Segura, PhD; Rafael de la Torre, PharmD, PhD
Unit of Pharmacology
Institut Municipal d'Investigació Mèdica (IMIM)
Pompeu Fabra University
Barcelona

1. Klein TW, Newton C, Friedman H. Cannabinoids receptors and immunity. Immunol Today. 1998;19:373-381. FULL TEXT | ISI | PUBMED 2. Nong L, Newton C, Cheng Q, Friedman H, Roth MD, Klein TW. Altered cannabinoid receptor mRNA expression in peripheral blood mononuclear cells from marijuana smokers. J Neuroimmunol. 2002;127:169-176. FULL TEXT | PUBMED 3. Kaslow RA, Blackwelder WC, Ostrow DG, et al. No evidence for a role of alcohol or other psychoactive drugs in accelerating immunodeficiency in HIV-1-positive individuals: a report from the Multicenter AIDS Cohort Study. JAMA. 1989;261:3424-3429. ABSTRACT 4. Pacifici R, Zuccaro P, Hernández-López, et al. Acute effects of 3,4-methylenedioxymethamphetamine alone and in combination with ethanol on the immune system in humans. J Pharmacol Exp Ther. 2001;296:207-215. FREE FULL TEXT 5. Roth MD, Baldwin GC, Tashkin DP. Effects of delta-9-tetrahydrocannabinol on human immune function and host defense. Chem Phys Lipids. 2002;121:229-239. FULL TEXT | ISI | PUBMED 6. Zurier RB. Prospects for cannabinoids as anti-inflammatory agents. J Cell Biochem. 2003;88:462-466. FULL TEXT | ISI | PUBMED

Letters Section Editor: Stephen J. Lurie, MD, PhD, Senior Editor.

JAMA. 2003;289:1929-1931.

RELATED LETTER

Cannabinoids and Immune Function
Joep Killestein, Bernard M. J. Uitdehaag, and Chris H. Polman
JAMA. 2003;290(6):754.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Cannabinoids and Immune Function
Killestein et al.
JAMA 2003;290:754-754.
FULL TEXT