Akhmetshina A, Dees C, Busch N, Beer J, Sarter K, Zwerina J, Zimmer A, Distler O, Schett G, Distler JH (2009) The cannabinoid receptor CB2 exerts antifibrotic effects in experimental dermal fibrosis. Arthritis Rheum 60:1129–1136

Baczynsky WO, Zimmerman AM (1983) Effects of Δ9-tetrahydrocannabinol, cannabinol and cannabidiol on the immune system of mice. I. in vivo investigation of the primary and secondary immune response. Pharmacology 26:1–11

Basu S, Dittel BN (2011) Unraveling the complexities of cannabinoid receptor 2 (CB2) immune regulation in health and disease. Immunol Res 51:26–38

Börner C, Höllt V, Kraus J (2007) Activation of human T cells induces upregulation of cannabinoid receptor type 1 transcription. Neuroimmunemodulation 14:281–286

Börner C, Smida M, Höllt V, Schraven B, Kraus J (2009) Cannabinoid receptor type 1- and 2-mediated increase in cyclic AMP inhibits T cell receptor-triggered signaling. J Biol Chem 284:35450–35460

Bouaboula M, Rinaldi M, Carayon P, Carillon C, Delpech B, Shire D, Le Fur G, Casellas P (1993) Cannabinoid-receptor expression in human leukocytes. Eur J Biochem 214:173–180

Buchweitz JP, Karmaus PWF, Harkema JR, Williams KJ, Kaminski N (2007) Modulation of airway responses to influenza A/PR/8/34 by Δ9-tetrahydrocannabinol in C57BL/6 mice. J Pharmacol Exp Ther 323:675–683

Buchweitz JP, Karmaus PW, Williams KJ, Harkema JR, Kaminski NE (2008) Targeted deletion of cannabinoid receptors CB1 and CB2 produced enhanced inflammatory responses to influenza A/PR/8/34 in the absence and presence of Δ9-tetrahydrocannabinol. J Leukoc Biol 83:785–796

Buckley NE, McCoy KL, Mezey E, Bonner T, Zimmer A, Felder CC, Glass M (2000) Immunomodulation by cannabinoids is absent in mice deficient for the cannabinoid CB(2) receptor. Eur J Pharmacol 396:141–149

Cabral GA, Marciano-Cabral F (2004) Cannabinoid-mediated exacerbation of brain infection by opportunistic amebae. J Neuroimmunol 147:127–130

Cabral GA, Mishkin EM, Marciano-Cabral F, Coleman P, Harris L, Munson AE (1986) Effect of delta-9-tetrahydrocannabinol on herpes simplex virus type 2 vaginal infections in the guinea pig. Proc Soc Exp Biol Med 182:181–186

Castaneda JT, Harui A, Kiertscher SM, Roth JD, Roth MD (2013) Differential expression of intracellular and extracellular CB2 cannabinoid receptor protein by human peripheral blood leukocytes. J Neuroimm Pharmacol 8:323–332

Cencioni MT, Chiurchiu V, Catanzaro G, Borsellino G, Bernardi G, Battistini L, Maccarrone M (2010) Anandamide suppresses proliferation and cytokine release from primary human T-lymphocytes mainly via CB2 receptors. PLoS ONE 5:e8688 [Electronic Resource]

Condie R, Herring A, Koh WS, Lee M, Kaminski NE (1996) Cannabinoid inhibition of adenlate cyclase-mediated signal transduction and IL-2 expression in the murine T-cell line, EL4.IL-2. J Biol Chem 271:13175–13183

Coopman K, Smith LD, Wright KL, Ward SG (2007) Temporal variation in CB2R levels following T lymphocyte activation: evidence that cannabinoids modulate CXCL12-induced chemotaxis. Int Immunopharmacol 7:360–371

Costantino CM, Gupta A, Yewdall AW, Dale BM, Devi LA, Chen BK (2012) Cannabinoid receptor 2-mediated attenuation of CXCR4-tropic HIV infection in primary CD4+ T cells. PLoS ONE 7:e33961 [Electronic Resource]

Croxford JL, Yamamura T (2005) Cannabinoids and the immune system: potential for the treatment of inflammatory diseases? J Neuroimmunol 166:3–18

Daaka Y, Friedman H, Klein TW (1996) Cannabinoid receptor proteins are increased in jurkat, human T-cell line after mitogen activation. J Pharmacol Exp Ther 276:776–783

Devane WA, Hanus L, Breuer A, Pertwee RG, Stevenson LA, Griffin G, Gibson D, Mandelbaum A, Etinger A, Mechoulam R (1992) Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 258:1946–1949

Eisenstein TK, Meissler JJ, Wilson Q, Gaughan JP, Adler MW (2007) Anandamide and Δ9-tetrahydrocannabinol directly inhibit cells of the immune system via CB2 receptors. J Neuroimmunol 189:17–22

Felder CC, Joyce KE, Briley EM, Mansouri J, Mackie K, Blond O, Lai Y, Ma AL, Mitchell RL (1995) Comparison of the pharmacology and signal transduction of the human cannabinoid CB1 and CB2 receptors. Mol Pharmacol 48:443–450

Friedman H, Newton C, Klein TW (2003) Microbial infections, immunomodulation, and drugs of abuse. Clin Micro Rev 16:209–219

Galiegue S, Mary S, Marchand J, Dussossoy D, Carriere D, Carayon P, Bouaboula M, Shire D, Le Fur G, Casellas P (1995) Expression of central and peripheral cannabinoid receptors in human immune tissues and leukocyte subpopulations. Eur J Biochem 232:54–61

Gardner B, Zu LX, Sharma S, Liu Q, Makriyannis A, Tashkin DP, Dubinett SM (2002) Autocrine and paracrine regulation of lymphcyte CB2 receptor expression by TGF-β. Biochem Biophys Res Comm 290:91–96

Ghosh S, Preet A, Groopman JE, Ganju RK (2006) Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes. Mol Immunol 43:2169–2179

Gorantla S, Makarov E, Roy D, Finke-Dwyer J, Murrin LC, Gendelman HE, Poluektova L (2010) Immunoregulation of a CB2 receptor agonist in a murine model of neuroAIDS. J Neuroimmune Pharmacol 5:456–468

Hanuš L, Breuer A, Tchilibon S, Shiloah S, Goldenberg D, Horowitz M, Pertwee RG, Ross RA, Mechoulam R, Fride E (1999) HU-308: a specific agonist for CB2, a peripheral cannabinoid receptor. Proc Natl Acad Sci 96:14228–14233. doi:10.1073/pnas.96.25.14228:

Hegde VL, Hegde S, Cravatt BF, Hofseth LJ, Nagarkatti M, Nagarkatti PS (2008) Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: Involvement of regulatory T cells. Mol Pharmacol 74:20–33

Huemer HP, Lassnig C, Bernhard D, Sturm S, Nowotny N, Kitchen M, Pavlic M (2011) Cannabinoids lead to enhanced virulence of the smallpox vaccine (vaccinia) virus. Immunobiology 216:670–677

Huffman JW, Yu S, Showalter V, Abood ME, Wiley JL, Compton DR, Martin BR, Bramblett RD, Reggio PH (1996) Synthesis and pharmacology of a very potent cannabinoid lacking a phenolic hydroxyl with high affinity for the CB2 receptor. J Med Chem 39:3875–3877

Huffman JW, Liddle J, Yu S, Aung MM, Abood ME, Wiley JL, Martin BR (1999) 3-(1′,1′-dimethylbutyl)-1-deoxy-delta8-THC and related compounds: synthesis of selective ligands for the CB2 receptor. Bioorg Med Chem 7:2905–2914

Kaminski NE (1996) Immune regulation by cannabinoid compounds through the inhibition of the cyclic AMP signaling cascade and altered gene expression. Biochem Pharmacol 52:1133–1140

Kaminski NE, Abood ME, Kessler FK, Martin BR, Schatz AR (1992) Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation. Mol Pharmacol 42:736–742

Karmaus PWF, Chen W, Crawford RB, Harkema JR, Kaplan BLF, Kaminski NE (2011) Deletion of cannabinoid receptors 1 and 2 exacerbates APC function to increase inflammation and cellular immunity during influenza infection. J Leukoc Biol 90:983–995

Karmaus PW, Chen W, Kaplan BL, Kaminski NE (2012) Δ9-tetrahydrocannabinol suppresses cytotoxic T lymphocyte function independent of CB1 and CB 2, disrupting early activation events. J Neuroimmune Pharmacol 7:843–855

Klein TW (2005) Cannabinoid-based drugs as anti-inflammatory therapeutics. Nat Rev Immunol 5:400–411

Klein TW, Newton CA, Widen R, Friedman H (1985) The effect of delta-9-tetrahydrocannabinol and 11-hydroxy-delta-9-tetrahydrocannabinol on T-lymphocyte and B-lymphocyte mitogen responses. J Immunopharmacol 7:451–466

Klein TW, Kawakami Y, Newton C, Friedman H (1991) Marijuana components suppress inducion and cytolytic function of murine cytotoxic T-cells in vitro and in vivo. J Toxicol Environ Health 32:465–477

Klein TW, Friedman H, Specter S (1998) Marijuana, immunity and infection. J Neuroimmunol 83:102–115

Klein TW, Newton CA, Nakachi N, Friedman H (2000) Δ9-tetrahydrocannabinol treatment suppresses immunity and early IFN-γ, IL-12 and IL-12 receptor β2 responses to legionella pneumophila infection. J Immunol 164:6461–6466

LeCapitaine NJ, Zhang P, Winsauer P, Walker E, Stouwe CV, Porretta C, Molina PE (2011) Chronic Δ9-tetrahydrocannabinol administration increases lymphocyte CXCR4 expression in rhesus macaques. J Neuroimmune Pharmacol 6:540–545

Lee SF, Newton C, Widen R, Friedman H, Klein TW (2001) Differential expression of cannabinoid CB2 receptor mRNA in mouse immune cells subpopulations and following B cell stimulation. Eur J Pharmacol 423:235–241

Lefkowitz S, Klager K (1978) Effect of Δ9-tetrahydrocannabinol on in vitro sensitization of mouse splenic lymphocytes. Immunol Commun 7:557–566

Li X, Kaminsky NE, Fischer LJ (2001) Examination of the immunosuppressive effect of Δ9-tetrahydrocannabinol in streptozotocin-induced autoimmune diabetes. Int Immunopharmacol 1:699–712

Lombard C, Nagarkatti M, Nagarkatti P (2007) CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents. Clin Immunol 122:259–270

Lombard C, Hegde VL, Nagarkatti M, Nagarkatti PS (2011) Perinatal exposure to Δ9-tetrahydorcannabinol triggers profound defects in T cell differentiation and function in fetal and postnatal stages of life, including decreased responsiveness to HIV antigens. J Pharmacol Exp Ther 339:607–317

Lu H, Kaplan BL, Ngaotepprutaram T, Kaminski NE (2009) Suppression of T cell costimulator ICOS by Delta9-tetrahydrocannabinol. J Leukoc Biol 85:322–329

Luo YD, Patel MK, Wiederhold MD, Ou DW (1992) Effects of cannabinoids and cocaine on the mitogen-induced transformations of lymphocytes of human and mouse origins. Int J Immunopharmacol 14:49–56

Maresz K, Pryce G, Ponomarev ED, Marsicano G, Croxford JL, Shriver LP, Ledent C, Cheng X, Carrier EJ, Mann MK, Giovannoni G, Pertwee RG, Yamamura T, Buckley NE, Hillard CJ, Lutz B, Baker D, Dittel BN (2007) Direct suppression of CNS autoimmune inflammation via the cannabinoid receptor CB1 on neurons and CB2 on autoreactive T cells. Nat Med 13:492–497

Massi P, Sacerdote P, Ponti W, Fuzio D, Manfredi B, Viganó D, Rubino T, Bardotti M, Parolaro D (1998) Immune function alterations in mice tolerant to Δ9-tetrahydrocannabinol: functional and biochemical parameters. J Neuroimmunol 92:60–66

Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI (1990) Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346:561–564

McKallip RJ, Lombard C, Martin BR, Nagarkatti M, Nagarkatti PS (2002) Δ9-tetrahydrocannabinol-induced apoptosis in the thymus and spleen as a mechanism of immunosuppression in vitro and in vivo. J Pharmacol Exp Ther 302:451–465

Mechoulam R, Ben-Shabat S, Hanus L, Ligumsky M, Kaminski NE, Schatz AR, Gopher A, Almog S, Martin BR, Compton DR, Pertwee RG, Griffin G, Bayewitch M, Barg J, Vogel Z (1995) Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem Pharmacol 50:83–90

Mishkin EM, Cabral GA (1985) Delta-9-tetrahydrocannabinol decreases host resistance to herpes simplex virus type 2 vaginal infection in the B6C3F1 mouse. J Gen Virol 66:2539–2549

Molina PE, Amdee A, LeCapitaine NJ, Zabaleta J, Mohan M, Winsauer P, Stouwe CV (2011) Cannabinoid neuroimmune modulation of SIV disease. J Neuroimmune Pharmacol 6:516–527

Molina PE, Amedee AM, LeCapitaine NJ, Zabaleta J, Mohan M, Winsauer PJ, Stouwe CV, McGoey RR, Auten MW, LaMotte L, Chandra LC, Birke LL (2014) Modulation of gut-specific mechanisms by chronic D9-tetrahydrocannabinol administration in male rhesus macaques infected with simian immunodeficiency virus: a systems biology analysis. AIDS Res Hum Retrovir 30:567–578

Morahan PS, Klykken PC, Smith SH, Harris LS, Munson AE (1979) Effects of cannabinoids of host resistance to Listeria monocytogenes and herpes simples virus. Infect Immun 23:670–674

Munro S, Thomas KK, Abu-Shaar M (1993) Molecular characterization of a peripheral receptor for cannabinoids. Nature 365:61–65

Nakano Y, Pross S, Friedman H (1992) Contrasting effect of delta-9-tetrahydrocannabinol on IL-2 activity in spleen and lymph node cells of mice of different ages. Life Sci 52:41–51

Newton CA, Klein TW, Friedman H (1994) Secondary immunity to Legionella pneumophila and Th1 activity are suppressed by delta-9-tetrahydrocannabinol injection. Infect Immun 62:4015–4020

Newton CA, Chou P, Perkins I, Klein TW (2009) CB1 and CB2 cannabinoid receptors mediate different aspects of delta-9-tetrahydrocannabinol (THC)-induced T helper cell shift following immune activation by Legionella pneumophila infection. J Neuroimmune Pharmacol 4:92–102

Ngaotepprutaram T, Kaplan BL, Crawford RB, Kaminski NE (2012) Differential modulation by Δ9-tetrahydrocannabinol (Δ9-THC) of CD40 ligand (CD40L) expression in activated mouse splenic CD4+ T cells. J Neuroimmune Pharmacol 7:969–980

Pertwee RG (2008) The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: Δ9-tetrahydrocannabinol, cannabidiol, and Δ9-tetrahydrocannabivarin. Br J Pharmacol 153:199–215

Pross SH, Klein TW, Newton CA, Smith J, Widen R, Friedman H (1990) Differential suppression of T-cell subpopulations by THC (delta-9-tetrahydrocannabinol). Int J Immunopharmacol 12:539–544

Purohit V, Rapaka RS, Rutter J (2014) Cannabinoid receptor-2 and HIV-associated neurocognitive disorders. J Neuroimmune Pharmacol 9:447–453

Ramirez SH, Hasko J, Skuba A, Fan S, Dykstra H, McCormick R, Reichenbach N, Krizbai I, Mahedevan A, Zhang M, Tuma R, Son Y, Persidsky Y (2012) Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood–brain barrier dysfunction under inflammatory conditions. J Neurosci 32:4004–4016

Rieder SA, Chauhan A, Singh U, Nagarkatti M, Nagarkatti P (2010) Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression. Immunobiology 215:598–605

Robinson RH,Meisser JJ, Breslow-Deckman JM,Gaughan J,AdlerMW, Eisenstein TK (2013) Cannabinoids inhibit T-cells via cannabinoid receptor 2 in an in vitro assay for graft rejection, the mixed lymphocyte reaction. J Neuroimmune Pharmacol 8:1239–1250

Roth MD, Tashkin DP, Whittaker KM, Choi R, Baldwin GC (2005) Tetrahydrocannabinol suppresses immune function and enhances HIV replication in the huPBL-SCID mouse. Life Sci 77:1711–1722

Schatz AR, Koh WS, Kaminski NE (1993) Δ9-tetrahydrocannabinol selectively inhibits T-cell dependent humoral immune responses through direct inhibition of accessory T-cell function. Immunopharmacology 26:129–137

Schwarz H, Blanco FJ, Lotz M (1994) Anandamide, an endogenous cannabinoid receptor agonist inhibits lymphocyte proliferation and induces apoptosis. J Neuroimmunol 55:107–115

Servettaz A, Kavian N, Nicco C, Deveaux V, Chereau C, Wang A, Zimmer A, Lotersztajn S, Weill B, Batteux F (2010) Targeting the cannabinoid pathway limits the development of fibrosis and autoimmunity in a mouse model of systemic sclerosis. Am J Pathol 177:187–196

Singh UP, Singh NP, Singh B, Price RL, Nagarkatti M, Nagarkatti PS (2012) Cannabinoid receptor-2 (CB2) agonist ameliorates colitis in IL-10(−/−) mice by attenuating the activation of T cells and promoting their apoptosis. Toxicol Appl Pharmacol 258:256–267

Smith SH, Harris LS, Uwayday IM, Munson AE (1978) Structure-activity relationships of natural and synthetic cannabinoids in suppression of humoral and cell-mediated immunity. J Pharmacol Exp Ther 207:165–170

Specter S, Lancz G, Westrich G, Friedman H (1991) Delta-9-tetrahydrocannabinol augments murine retroviral induced immunosuppression and infection. Int J Immunopharmacol 13:411–417

Springs AEB, Karmaus PWF, Crawford RB, Kaplan BLF, Kaminski NE (2008) Effects of targeted deletion of cannabinoid receptors CB1 and CB2 on immune competence and sensitivity to immune modulation by Δ9-tetrahydrocannabinol. J Leukoc Biol 84:1574–1584

Storr MA, Keenan CM, Zhang H, Patel KD, Makriyannis A, Sharkey KA (2009) Activation of the cannabinoid 2 receptor (CB 2 ) protects against experimental colitis. Inflamm Bowel Dis 15:1678–1685

Watson ES, Murphy JC, El Sohly HN, El Sohly MA, Turner CE (1983) Effects of the administration of coca alkaloids on the primary immune responses of mice: Interaction with Δ9-tetrahydrocannabinol and ethanol. Toxicol Appl Pharmacol 71:1–13

Winsauer PJ, Molina PE, Amedee AM, Filipeanu CM, McGoey RR, Troxclair DA, Walker EM, Birke LL, Stouwe CV, Howard JM, Leonard ST, Moerschbaecher JM, Lewis PB (2011) Tolerance to chronic delta-9-tetrahydrocannabinol (Δ9-THC) in rhesus macaques infected with simian immunodeficiency virus. Exp Clin Psychopharmacol 19:154–172

Xu H, Cheng CL, Chen M, Manivannan A, Cabay L, Pertwee RG, Coutts A, Forrester JV (2007) Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH-133 in a rodent model of autoimmune uveoretinitis. J Leukoc Biol 82:532–541

Yang X, Hegde VL, Rao R, Zhang J, Nagarkatti PS, Nagarkatti M (2014) Histone modifications are associated with Δ9-tetrahydrocannabinol-mediated alterations in antigen-specific T cell responses. J Biol Chem 289:18707–18718

Yuan M, Kiertscher SM, Cheng Q, Zoumalan R, Tashkin DP, Roth MD (2002) Δ9-tetrahydrocannabinol regulates Th1/Th2 cytokine balance in activated human T cells. J Neuroimmunol 133:124–131

Zhang M, Adler MW, Abood ME, Ganea D, Jallo J, Tuma RF (2009a) CB2 receptor activation attenuates microcirculatory dysfunction during cerebral ischemic/reperfusion injury. Microvasc Res 78:86–94

Zhang M, Martin BR, Adler MW, Razdan RJ, Kong W, Ganea D, Tuma RF (2009b) Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke. J Neuroimmune Pharmacol 4:249–259

Zhu W, Friedman H, Klein TW (1998) Δ9-tetrahydrocannabinol induces apoptosis in macrophages and lymphocytes: involvement of bcl-2 and capsase-1. J Pharmacol Exp Ther 286:1103–1109

Zhu LX, Sharma S, Stolina M, Gardner B, Roth MD, Tashkin DP, Dubinett SM (2000) Δ9-tetrahydrocannabinol inhibits antitumor immunity by a CB2 receptor-mediated, cytokine-dependent pathway. J Immunol 165:373–380