Inhibition of Cellular Mediated Immunity in Marihuana Smokers

Nahas, Gabriel G.; Suciu‐Foca, Nicole; Armand, Jean‐Pierre; Morishima, Akira

doi:10.1126/science.183.4123.419

Cited by 228 publications

(54 citation statements)

References 11 publications

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“…Studies in the early 1970s using human peripheral blood mononuclear cells (PBMCs) from marijuana smokers showed a tendency for heavy use to result in suppression of lymphocyte proliferation in culture as well as alterations in PBMCs immune cell subsets (154). Serum immunoglobulin (Ig) levels were also modulated by marijuana use, with IgG protein levels decreasing and IgE protein levels increasing.…”

Section: Marijuana-induced Enhancement Of Susceptibility To Infectionmentioning

confidence: 99%

Microbial Infections, Immunomodulation, and Drugs of Abuse

2003

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The use of recreational drugs of abuse has generated serious health concerns. There is a long-recognized relationship between addictive drugs and increased levels of infections. Studies of the mechanisms of actions of these drugs became more urgent with the advent of AIDS and its correlation with abused substances. The nature and mechanisms of immunomodulation by marijuana, opiates, cocaine, nicotine, and alcohol are described in this review. Recent studies of the effects of opiates or marijuana on the immune system have demonstrated that they are receptor mediated, occurring both directly via specific receptors on immune cells and indirectly through similar receptors on cells of the nervous system. Findings are also discussed that demonstrate that cocaine and nicotine have similar immunomodulatory effects, which are also apparently receptor mediated. Finally, the nature and mechanisms of immunomodulation by alcohol are described. Although no specific alcohol receptors have been identified, it is widely recognized that alcohol enhances susceptibility to opportunistic microbes. The review covers recent studies of the effects of these drugs on immunity and on increased susceptibility to infectious diseases, including AIDS

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Section: Marijuana-induced Enhancement Of Susceptibility To Infectionmentioning

confidence: 99%

Microbial Infections, Immunomodulation, and Drugs of Abuse

2003

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“…The increase was abrogated by SR144528, L-NAME, indomethacin, and rofecoxib. Our results suggest that 2AG and CP55,940 decreased mast cell activation in a manner that is susceptible to a CB 2 receptor antagonist and to inhibition of nitric oxide and prostanoid pathways.The immunosuppressive effect of tetrahydrocannabinol (THC) was formerly reported both in humans (Nahas et al, 1974) and experimental animals (Coffey et al, 1996). More recently, the effects of THC on human immune functions and host defense have been reviewed, providing evidence that THC can suppress the human immune response in a host of leukocyte subsets and alveolar macrophages, further stressing the relationship between marijuana smoking and immunologically-related diseases (Klein et al, 1998).…”

mentioning

confidence: 99%

The Endocannabinoid 2-Arachidonylglycerol Decreases the Immunological Activation of Guinea Pig Mast Cells: Involvement of Nitric Oxide and Eicosanoids

Vannacci¹,

Giannini²,

Passani³

et al. 2004

J Pharmacol Exp Ther

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The antigen-induced release of histamine from sensitized guinea pig mast cells was dose-dependently reduced by endogenous (2-arachidonylglycerol; 2AG) and exogenous [(1R,3R,4R)-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl]-4-(3-hydroxypropyl)cyclohexan-1-ol (CP55,940)] cannabinoids. The inhibitory action afforded by 2AG and CP55,940 was reversed by N- [(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl]5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3-carboxamide (SR144528), a selective cannabinoid 2 (CB 2 ) receptor antagonist, and left unchanged by the selective CB 1 antagonistThe inhibitory action of 2AG and CP55,940 was reduced by the unselective nitric-oxide synthase (NOS) inhibitor N-monomethyl-L-arginine methylester (L-NAME) and reinstated by L-arginine, the physiological substrate. The inhibitory action of 2AG and CP55,940 was also reduced by the unselective cyclooxygenase (COX) inhibitor indomethacin and the selective COX-2 blocker rofecoxib. Both 2AG and CP55,940 significantly increased the production of nitrite from mast cells, which was abrogated by benzyl)acetamidine (1400W), a selective inducible NOS (iNOS) inhibitor. Nitrite production consistently paralleled a CP55,940-induced increase in the expression of iNOS protein in mast cells. Both 2AG and CP55,940 increased the generation of prostaglandin E 2 from mast cells, which was abrogated by indomethacin and rofecoxib and parallel to the CP55,940-induced expression of COX-2 protein.Mast cell challenge with antigen was accompanied by a net increase in intracellular calcium levels. Both cannabinoid receptor ligands decreased the intracellular calcium levels, which were reversed by SR144528 and L-NAME. In unstimulated mast cells, both ligands increased cGMP levels. The increase was abrogated by SR144528, L-NAME, indomethacin, and rofecoxib. Our results suggest that 2AG and CP55,940 decreased mast cell activation in a manner that is susceptible to a CB 2 receptor antagonist and to inhibition of nitric oxide and prostanoid pathways.The immunosuppressive effect of tetrahydrocannabinol (THC) was formerly reported both in humans (Nahas et al., 1974) and experimental animals (Coffey et al., 1996). More recently, the effects of THC on human immune functions and host defense have been reviewed, providing evidence that THC can suppress the human immune response in a host of leukocyte subsets and alveolar macrophages, further stressing the relationship between marijuana smoking and immunologically-related diseases (Klein et al., 1998).Of the immunocompetent cells, mast cells are strategically placed in tissues that interface with the external environment and vary in the way in which their activation is modified by endocannabinoids. In the rat ear pin, the degranulation of resident mast cells induced by substance P is fully abrogated by the endogenous ligands at cannabinoid (CB) receptors arachidonylethanolamide (anandamide; AEA) and palmitoylethanol-

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“…3,4 In addition, we found an upregulation of hepatic CB2 receptor but not CB1 receptor expression in a mouse model of CCl 4 -induced hepatic fibrosis (Fig. 1).…”

Section: Potential Role Of Cb2 Receptors In Cannabis Smokers With Chrmentioning

confidence: 81%

“…Indeed, we previously showed by both RT-PCR and immunohistochemistry that CB1 and CB2 receptors are markedly upregulated in human liver samples with cirrhosis compared with normal liver, predominantly in hepatic myofibroblasts. [2][3][4] In addition, we found that CB1 knockout (KO) mice showed reduced liver fibrosis following chronic CCl4 intoxication, an effect related to reduced accumulation of hepatic myofibroblasts (Grenard et al 2 and Teixeira-Clerc et al, personal results). These results therefore strongly suggest that activation of CB1 receptors enhances liver fibrogenesis.…”

Section: Replymentioning

confidence: 98%

Potential Role of CB2 Receptors in Cannabis Smokers With Chronic Hepatitis C *

Schwabe

Siegmund

2005

Hepatology

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should alert to the possible coexistence of multiple underlying cardiovascular risk factors warranting evaluation and treatment as much as the risk for advancing liver disease.Prospective studies are clearly needed to validate these findings and better estimate the individual cardiovascular risks associated with the presence of MetS and NAFLD. Reply:The above letter is very timely. It presents data demonstrating that subjects with nonalcoholic fatty liver disease have increased atheroma mass, as demonstrated by an increased carotid intima-medial thickness (IMT) when compared to controls. Carotid IMT is another marker of atheroma progression. While abnormalities of flow-mediated vasodilation identify early mechanical abnormalities in the arterial wall, IMT tends to demonstrate later atherosclerotic structural abnormalities. Interestingly, an IMT Ͻ 0.87 mm carries a low odds ratio of coronary heart disease, and an IMT Ն 1.10 carries a high odds ratio of coronary heart disease: IMTs found by these authors in their controls and subjects with NAFLD. 1 Although no specific structural characterization of the increased IMT (fatty infiltration, fibrofatty disease, or fibrocalcific) is made by the authors, it would seem that these patients most likely will have fatty and fibrofatty infiltrates. The fatty atheroma components are amenable to therapy.Therefore, patients with nonalcoholic fatty liver disease having either altered flow-mediated vasodilation or increased carotid IMT could be candidates for aggressive treatment of the liver disease, cholesterol lowering, and treatment of any related metabolic syndromes. This would help to modify and potentially decrease atheroma mass and progression.These findings emphasize the importance of evaluating cardiovascular risk and cardiovascular disease in patients diagnosed with nonalcoholic fatty liver disease. DAVID MCPHERSON Potential Role of CB2 Receptors in Cannabis Smokers With Chronic Hepatitis CTo the Editor:We read with great interest the recent study by Hezode et al. 1 on the effects of daily cannabis smoking on fibrogenesis in chronic hepatitis C, and we completely agree with the authors that patients with chronic hepatitis C should abstain from using cannabis based on the results of this study. In previous studies the authors have shown an upregulation of CB1 receptor expression in liver with fibrosis. 2 Based on these results, Hezode et al. proposed that cannabis ingredients act through CB1 receptors to enhance hepatic fibrogenesis in patients with chronic hepatitis C, and they discussed CB1 receptor antagonists as potential treatment options for liver fibrosis. We suggest CB2-mediated immunomodulation as an alternative mechanism by which cannabis ingredients might enhance fibrogenesis in this specific set of patients.There is overwhelming evidence that Cannabis sativa, including the most active ingredient ⌬-9-tetrahydrocannibol (THC) exerts powerful immunosuppressive effects. 3,4 In addition, we found an upregulation of hepatic CB2 receptor but not CB1 receptor expre...

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Inhibition of Cellular Mediated Immunity in Marihuana Smokers

Cited by 228 publications

References 11 publications

Microbial Infections, Immunomodulation, and Drugs of Abuse

Microbial Infections, Immunomodulation, and Drugs of Abuse

The Endocannabinoid 2-Arachidonylglycerol Decreases the Immunological Activation of Guinea Pig Mast Cells: Involvement of Nitric Oxide and Eicosanoids

Potential Role of CB2 Receptors in Cannabis Smokers With Chronic Hepatitis C *

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