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Effects of Cannabinoids on T-cell Function and Resistance to Infection

Abstract

This review examines the effects of cannabinoids on immune function, with a focus on effects on T-cells, as well as on resistance to infection. The paper considers the immune modulating capacity of marijuana, of ∆9-THC extracted from the marijuana plant, and synthetic cannabinoids. Of particular interest are synthetic compounds that are CB2 receptor (CB2R) selective agonists. As the CB2R is principally expressed on cells of the immune system, agonists that target this receptor, and not CB1 (which is mainly expressed on neurons), have the possibility of altering immune function without psychoactive effects. The overall conclusion of the studies discussed in this review is that cannabinoids that bind to the CB2 receptor, including ∆9-THC and CB2 selective agonists are immunosuppressive. The studies provide objective evidence for potentially beneficial effects of marijuana and ∆9-THC on the immune system in conditions where it is desirable to dampen immune responses. Evidence is also reviewed supporting the conclusion that these same compounds can sensitize to some infections through their immunosuppressive activities, but not to others. An emerging area of investigation that is reviewed is evidence to support the conclusion that CB2 selective agonists are a new class of immunosuppressive and anti-inflammatory compounds that may have exceptional beneficial effects in a variety of conditions, such as autoimmune diseases and graft rejection, where it is desirable to dampen the immune response without psychoactive effects.

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Abbreviations

BMDC:

bone marrow-derived dendritic cells

ConA:

concanavalin A

9-THC:

9-tetrahydrocannabinol

HPA:

Hypothalamic-Pituitary-Adrenal Axis

Io:

Ionomycin

K/O:

Knock-out

Lck:

Lymphocyte-specific protein tyrosine kinase

MLR:

Mixed Lymphcyte Reaction

PHA:

Phytohemaggluttinin

PKA:

Protein Kinase A

PMA:

Phorbol Myristic Acid

SCID:

Severe Combined Immunodeficiency

SRBC:

Sheep Red Blood Cells

WT:

Wild Type

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Acknowledgments

This work was supported by grant DA013429 from the National Institute on Drug Abuse and a grant from the Pennsylvania Department of Health as part of the Tobacco Settlement funds to Temple University.

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The author declares that she has no conflict of interest.

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Correspondence to Toby K. Eisenstein.

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Eisenstein, T.K., Meissler, J.J. Effects of Cannabinoids on T-cell Function and Resistance to Infection. J Neuroimmune Pharmacol 10, 204–216 (2015). https://doi.org/10.1007/s11481-015-9603-3

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Keywords

  • CB2 agonist
  • 9-THC
  • T-cells
  • Infection