Marijuana, immunity and infection

Klein, Thomas; Friedman, Herman; Specter, Steven

doi:10.1016/s0165-5728(97)00226-9

Cited by 173 publications

(106 citation statements)

References 79 publications

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“…Cannabinoids, including THC, have been well recognized as modulators of host immunity (47), with most studies indicating that THC is immunosuppressive (48). Previous studies have indicated that THC can compromise the immune response and limit resistance to both bacterial and viral infections (47, 49 -54).…”

Section: Discussionmentioning

confidence: 99%

Δ-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway

Zhu

Sharma

Stolina³

et al. 2000

The Journal of Immunology

235

160

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In this study, we show that Δ-9-tetrahydrocannabinol (THC), the major psychoactive component of marijuana, suppresses host immune reactivity against lung cancer. In two different weakly immunogenic murine lung cancer models, intermittent administration of THC (5 mg/kg, four times/wk i.p. for 4 wk) led to accelerated growth of tumor implants compared with treatment with diluent alone. In contrast to our findings in immunocompetent mice, THC did not affect tumor growth in tumor-bearing SCID mice. The immune inhibitory cytokines, IL-10 and TGF-β, were augmented, while IFN-γ was down-regulated at both the tumor site and in the spleens of THC-treated mice. Administration of either anti-IL-10- or anti-TGF-β-neutralizing Abs prevented the THC-induced enhancement in tumor growth. Both APC and T cells from THC-treated mice showed limited capacities to generate alloreactivity. Furthermore, lymphocytes from THC-treated mice transferred the effect to normal mice, resulting in accelerated tumor growth similar to that seen in the THC-treated mice. THC decreased tumor immunogenicity, as indicated by the limited capacity for tumor-immunized, THC-treated mice to withstand tumor rechallenge. In vivo administration of a specific antagonist of the CB2 cannabinoid receptor also blocked the effects of THC. Our findings suggest the THC promotes tumor growth by inhibiting antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway.

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Section: Discussionmentioning

confidence: 99%

Δ-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway

Zhu

Sharma

Stolina³

et al. 2000

The Journal of Immunology

235

160

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“…The induced psychotropic and adverse effects of marijuana are attributable to THC acting at CB1 receptors expressed by neurons (Mallet and Beninger, 1998;Zimmer et al, 1999;Hampson and Deadwyler, 2000;Huestis et al, 2001), whereas the immunomodulatory effects are attributable to THC and CBN acting at CB2 receptors expressed by immune cells and to CBD acting on abn-CBD receptors (Kaminski, 1998;Klein et al, 1998;Buckley et al, 2000;Malfait et al, 2000). Because CBN and CBD do not have significant intrinsic activity on CB1 receptors (Felder et al, 1995;Showalter et al, 1996), these compounds do not produce psychotropic and adverse side effects (Perez-Reyes et al, 1973), which makes them promising candidates as anti-inflammatory therapeutics.…”

Section: Introductionmentioning

confidence: 99%

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Walter¹,

Franklin²,

Witting³

et al. 2003

J. Neurosci.

599

543

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During neuroinflammation, activated microglial cells migrate toward dying neurons, where they exacerbate local cell damage. The signaling molecules that trigger microglial cell migration are poorly understood. In this paper, we show that pathological overstimulation of neurons by glutamate plus carbachol dramatically increases the production of the endocannabinoid 2-arachidonylglycerol (2-AG) but only slightly increases the production of anandamide and does not affect the production of two putative endocannabinoids, homo-␥-linolenylethanolamide and docosatetraenylethanolamide. We further show that pathological stimulation of microglial cells with ATP also increases the production of 2-AG without affecting the amount of other endocannabinoids. Using a Boyden chamber assay, we provide evidence that 2-AG triggers microglial cell migration. This effect of 2-AG occurs through CB2 and abnormal-cannabidiolsensitive receptors, with subsequent activation of the extracellular signal-regulated kinase 1/2 signal transduction pathway. It is important to note that cannabinol and cannabidiol, two nonpsychotropic ingredients present in the marijuana plant, prevent the 2-AG-induced cell migration by antagonizing the CB2 and abnormal-cannabidiol-sensitive receptors, respectively. Finally, we show that microglial cells express CB2 receptors at the leading edge of lamellipodia, which is consistent with the involvement of microglial cells in cell migration. Our study identifies a cannabinoid signaling system regulating microglial cell migration. Because this signaling system is likely to be involved in recruiting microglial cells toward dying neurons, we propose that cannabinol and cannabidiol are promising nonpsychotropic therapeutics to prevent the recruitment of these cells at neuroinflammatory lesion sites.

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“…Experimental studies have shown that commonly used recreational drugs such as marijuana, cocaine, poppers, and amphetamines have immunomodulatory properties [Baldwin et al, 1998;Klein et al, 1998;Pellegrino and Bayer, 1998;Dax et al, 1991;James, 1999;Kubera et al, 2002;Nunez-Iglesias et al, 1996]. Altered T cell responses to immune challenges such as mitogens, alloantigens, and bacterial infections with exposure to these substances have been observed in vitro and in animal models [Domingues-Junior et al, 2000;Freire-Garabal et al, 1991;Klein et al, 1998;Klein et al, 2004;Kubera et al, 2002;Pellegrino and Bayer, 1998;Dax et al, 1991].…”

Section: Introductionmentioning

confidence: 99%

“…Altered T cell responses to immune challenges such as mitogens, alloantigens, and bacterial infections with exposure to these substances have been observed in vitro and in animal models [Domingues-Junior et al, 2000;Freire-Garabal et al, 1991;Klein et al, 1998;Klein et al, 2004;Kubera et al, 2002;Pellegrino and Bayer, 1998;Dax et al, 1991]. However, the impact of exposure to recreational drugs on the function and number of T cell subsets in humans remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men

Chao

Jacobson

Tashkin

et al. 2008

Drug and Alcohol Dependence

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The effects of recreational drugs on CD4 and CD8 T cells in humans are not well understood. We conducted a longitudinal analysis of men who have sex with men (MSM) enrolled in the Multicenter AIDS Cohort Study to define associations between self-reported use of marijuana, cocaine, poppers and amphetamines, and CD4 and CD8 T cell parameters in both HIV-uninfected and HIV-infected MSM. For the HIV-infected MSM, we used clinical and laboratory data collected semiannually before 1996 to avoid potential effects of antiretroviral treatment. A regression model that allowed random intercepts and slopes as well as autoregressive covariance structure for within subject errors was used. Potential confounders adjusted for included length of follow-up, demographics, tobacco smoking, alcohol use, risky sexual behaviors, history of sexually transmitted infections, and antiviral therapy. We found no clinically meaningful associations between use of marijuana, cocaine, poppers, or amphetamines and CD4 and CD8 T cell counts, percentages, or rates of change in either HIVuninfected or -infected men. The regression coefficients were of minimum magnitude despite some reaching statistical significance. No threshold effect was detected for frequent (at least weekly) or continuous substance use in the previous year. These results indicate that use of these substances Correspondence and reprint request should be addressed to:

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Marijuana, immunity and infection

Cited by 173 publications

References 79 publications

Δ-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway

Δ-9-Tetrahydrocannabinol Inhibits Antitumor Immunity by a CB2 Receptor-Mediated, Cytokine-Dependent Pathway

Nonpsychotropic Cannabinoid Receptors Regulate Microglial Cell Migration

Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men

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