Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Exploring cannabidiol effects on inflammatory markers in individuals with cocaine use disorder: a randomized controlled trial

Abstract

Cocaine use disorder (CUD) is a major public health issue associated with physical, social, and psychological problems. Excessive and repeated cocaine use induces oxidative stress leading to a systemic inflammatory response. Cannabidiol (CBD) has gained substantial interest for its anti-inflammatory properties, safety, and tolerability profile. However, CBD anti-inflammatory properties have yet to be confirmed in humans. This exploratory study is based on a single-site randomized controlled trial that enrolled participants with CUD between 18 and 65 years, randomized (1:1) to daily receive either CBD (800 mg) or placebo for 92 days. The trial was divided into a 10-day detoxification (phase I) followed by a 12-week outpatient follow-up (phase II). Blood samples were collected from 48 participants at baseline, day 8, week 4, and week 12 and were analyzed to determine monocytes and lymphocytes phenotypes, and concentrations of various inflammatory markers such as cytokines. We used generalized estimating equations to detect group differences. Participants treated with CBD had lower levels of interleukin-6 (p = 0.017), vascular endothelial growth factor (p = 0.032), intermediate monocytes CD14+CD16+ (p = 0.024), and natural killer CD56negCD16hi (p = 0.000) compared with participants receiving placebo. CD25+CD4+T cells were higher in the CBD group (p = 0.007). No significant group difference was observed for B lymphocytes. This study suggests that CBD may exert anti-inflammatory effects in individuals with CUD.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Consolidated Standards of Reporting Trials (CONSORT) flowchart of participants (adapted with permission from Mongeau-Pérusse et al. [33]).
Fig. 2: Cytokines profile of the cannabidiol group compared with the placebo group at baseline (day 2), day 8, week 4, and week 12.
Fig. 3: Monocytes profile of the cannabidiol group compared with the placebo group at baseline (day 2), day 8, week 4, and week 12.
Fig. 4: Lymphocytes profile of the cannabidiol group compared with the placebo group at baseline (day 2), day 8, week 4, and week 12.

References

  1. 1.

    United Nations Office on Drugs and Crime. World drug report 2019. Vienna, Austria: United Nations Publications; 2019. Sales No. E.19.XI.8.

  2. 2.

    Florez-Salamanca L, Secades-Villa R, Hasin DS, Cottler L, Wang S, Grant BF, et al. Probability and predictors of transition from abuse to dependence on alcohol, cannabis, and cocaine: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Am J Drug Alcohol Abus. 2013;39:168–79. https://doi.org/10.3109/00952990.2013.772618.

    Article  Google Scholar 

  3. 3.

    Farrell M, Martin NK, Stockings E, Bórquez A, Cepeda JA, Degenhardt L, et al. Responding to global stimulant use: challenges and opportunities. Lancet 2019;394:1652–67. https://doi.org/10.1016/s0140-6736(19)32230-5.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Zaparte A, Schuch JB, Viola TW, Baptista TAS, Beidacki AS, do Prado CH, et al. Cocaine use disorder is associated with changes in Th1/Th2/Th17 cytokines and lymphocytes subsets. Front Immunol. 2019;10:2435. https://doi.org/10.3389/fimmu.2019.02435.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Narvaez JC, Magalhaes PV, Fries GR, Colpo GD, Czepielewski LS, Vianna P, et al. Peripheral toxicity in crack cocaine use disorders. Neurosci Lett. 2013;544:80–4. https://doi.org/10.1016/j.neulet.2013.03.045.

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Moreira FP, Medeiros JR, Lhullier AC, Souza LD, Jansen K, Portela LV, et al. Cocaine abuse and effects in the serum levels of cytokines IL-6 and IL-10. Drug Alcohol Depend. 2016;158:181–5. https://doi.org/10.1016/j.drugalcdep.2015.11.024.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Fox HC, D’Sa C, Kimmerling A, Siedlarz KM, Tuit KL, Stowe R, et al. Immune system inflammation in cocaine dependent individuals: implications for medications development. Hum Psychopharmacol. 2012;27:156–66. https://doi.org/10.1002/hup.1251.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Levandowski ML, Viola TW, Wearick-Silva LE, Wieck A, Tractenberg SG, Brietzke E, et al. Early life stress and tumor necrosis factor superfamily in crack cocaine withdrawal. J Psychiatr Res. 2014;53:180–6. https://doi.org/10.1016/j.jpsychires.2014.02.017.

    Article  PubMed  Google Scholar 

  9. 9.

    Manetti L, Cavagnini F, Martino E, Ambrogio A. Effects of cocaine on the hypothalamic–pituitary–adrenal axis. J Endocrinol Invest. 2014;37:701–8. https://doi.org/10.1007/s40618-014-0091-8.

    CAS  Article  PubMed  Google Scholar 

  10. 10.

    Sholar MB, Mendelson JH, Mello NK, Siegel AJ, Kaufman MJ, Levin JM, et al. Concurrent pharmacokinetic analysis of plasma cocaine and adrenocorticotropic hormone in men. J Clin Endocrinol Metab. 1998;83:966–8. https://doi.org/10.1210/jcem.83.3.4654.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Riezzo I, Fiore C, De Carlo D, Pascale N, Neri M, Turillazzi E, et al. Side effects of cocaine abuse: multiorgan toxicity and pathological consequences. Curr Med Chem. 2012;19:5624–46. https://doi.org/10.2174/092986712803988893.

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Loftis JM, Huckans M. Substance use disorders: psychoneuroimmunological mechanisms and new targets for therapy. Pharm Ther. 2013;139:289–300. https://doi.org/10.1016/j.pharmthera.2013.04.011.

    CAS  Article  Google Scholar 

  13. 13.

    Lopez-Pedrajas R, Ramirez-Lamelas DT, Muriach B, Sanchez-Villarejo MV, Almansa I, Vidal-Gil L, et al. Cocaine promotes oxidative stress and microglial-macrophage activation in rat cerebellum. Front Cell Neurosci. 2015;9:279. https://doi.org/10.3389/fncel.2015.00279.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Cisneros IE, Erdenizmenli M, Cunningham KA, Paessler S, Dineley KT. Cocaine evokes a profile of oxidative stress and impacts innate antiviral response pathways in astrocytes. Neuropharmacology 2018;135:431–43. https://doi.org/10.1016/j.neuropharm.2018.03.019.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Picard M, Juster RP, McEwen BS. Mitochondrial allostatic load puts the ‘gluc’ back in glucocorticoids. Nat Rev Endocrinol. 2014;10:303–10. https://doi.org/10.1038/nrendo.2014.22.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Kovacic P. Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer. Med Hypotheses. 2005;64:350–6. https://doi.org/10.1016/j.mehy.2004.06.028.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Sajja RK, Rahman S, Cucullo L. Drugs of abuse and blood–brain barrier endothelial dysfunction: a focus on the role of oxidative stress. J Cereb Blood Flow Metab. 2016;36:539–54. https://doi.org/10.1177/0271678X15616978.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Dhillon NK, Peng F, Bokhari S, Callen S, Shin SH, Zhu X, et al. Cocaine-mediated alteration in tight junction protein expression and modulation of CCL2/CCR2 axis across the blood–brain barrier: implications for HIV-dementia. J Neuroimmune Pharmacol. 2008;3:52–6. https://doi.org/10.1007/s11481-007-9091-1.

    Article  PubMed  Google Scholar 

  19. 19.

    Pimentel E, Sivalingam K, Doke M, Samikkannu T. Effects of drugs of abuse on the blood–brain barrier: a brief overview. Front Neurosci. 2020;14:513. https://doi.org/10.3389/fnins.2020.00513.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Kousik SM, Napier TC, Carvey PM. The effects of psychostimulant drugs on blood brain barrier function and neuroinflammation. Front Pharmacol. 2012;3:121. https://doi.org/10.3389/fphar.2012.00121.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Clark KH, Wiley CA, Bradberry CW. Psychostimulant abuse and neuroinflammation: emerging evidence of their interconnection. Neurotox Res. 2013;23:174–88. https://doi.org/10.1007/s12640-012-9334-7.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Moretti M, Belli G, Morini L, Monti MC, Osculati AMM, Visona SD. Drug abuse-related neuroinflammation in human postmortem brains: an immunohistochemical approach. J Neuropathol Exp Neurol. 2019;78:1059–65. https://doi.org/10.1093/jnen/nlz084.

    CAS  Article  PubMed  Google Scholar 

  23. 23.

    Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25:1822–32. https://doi.org/10.1038/s41591-019-0675-0.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Barron H, Hafizi S, Andreazza AC, Mizrahi R. Neuroinflammation and oxidative stress in psychosis and psychosis risk. Int J Mol Sci. 2017;18:651. https://doi.org/10.3390/ijms18030651.

    CAS  Article  PubMed Central  Google Scholar 

  25. 25.

    Nichols JM, Kaplan BLF. Immune responses regulated by cannabidiol. Cannabis Cannabinoid Res. 2020;5:12–31. https://doi.org/10.1089/can.2018.0073.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  26. 26.

    McKenna M, McDougall JJ. Cannabinoid control of neurogenic inflammation. Br J Pharmacol. 2020;177:4386–99. https://doi.org/10.1111/bph.15208.

    CAS  Article  PubMed  Google Scholar 

  27. 27.

    Atalay S, Jarocka-Karpowicz I, Skrzydlewska E. Antioxidative and anti-inflammatory properties of cannabidiol. Antioxidants. 2019;9:21. https://doi.org/10.3390/antiox9010021.

    CAS  Article  PubMed Central  Google Scholar 

  28. 28.

    Lattanzi S, Brigo F, Trinka E, Zaccara G, Cagnetti C, Del Giovane C, et al. Efficacy and safety of cannabidiol in epilepsy: a systematic review and meta-analysis. Drugs 2018;78:1791–804. https://doi.org/10.1007/s40265-018-0992-5.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Bonaccorso S, Ricciardi A, Zangani C, Chiappini S, Schifano F, Cannabidiol CBD. use in psychiatric disorders: a systematic review. Neurotoxicology 2019;74:282–98. https://doi.org/10.1016/j.neuro.2019.08.002.

    CAS  Article  PubMed  Google Scholar 

  30. 30.

    Larsen C, Shahinas J. Dosage, efficacy and safety of cannabidiol administration in adults: a systematic review of human trials. J Clin Med Res. 2020;12:129–41. https://doi.org/10.14740/jocmr4090.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    de Almeida DL, Devi LA. Diversity of molecular targets and signaling pathways for CBD. Pharm Res Perspect. 2020;8:e00682. https://doi.org/10.1002/prp2.682.

    CAS  Article  Google Scholar 

  32. 32.

    Jadoon KA, Ratcliffe SH, Barrett DA, Thomas EL, Stott C, Bell JD, et al. Efficacy and safety of cannabidiol and tetrahydrocannabivarin on glycemic and lipid parameters in patients with type 2 diabetes: a Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study. Diabetes Care. 2016;39:1777–86. https://doi.org/10.2337/dc16-0650.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Mongeau-Perusse V, Brissette S, Bruneau J, Conrod P, Dubreucq S, Gazil G, et al. Cannabidiol as a treatment for craving and relapse in individuals with cocaine use disorder: a Randomized Placebo-Controlled Trial. Addiction 2021. https://doi.org/10.1111/add.15417.

    Article  PubMed  Google Scholar 

  34. 34.

    Fox HC, Garcia M Jr, Kemp K, Milivojevic V, Kreek MJ, Sinha R. Gender differences in cardiovascular and corticoadrenal response to stress and drug cues in cocaine dependent individuals. Psychopharmacology. 2006;185:348–57. https://doi.org/10.1007/s00213-005-0303-1.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Ferri CP, Dunn J, Gossop M, Laranjeira R. Factors associated with adverse reactions to cocaine among a sample of long-term, high-dose users in Sao Paulo, Brazil. Addict Behav. 2004;29:365–74. https://doi.org/10.1016/j.addbeh.2003.08.029.

    Article  PubMed  Google Scholar 

  36. 36.

    Iffland K, Grotenhermen F. An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2017;2:139–54. https://doi.org/10.1089/can.2016.0034.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  37. 37.

    Cui C, Shurtleff D, Harris RA. Neuroimmune mechanisms of alcohol and drug addiction. Int Rev Neurobiol. 2014;118:1–12. https://doi.org/10.1016/B978-0-12-801284-0.00001-4.

    Article  PubMed  PubMed Central  Google Scholar 

  38. 38.

    Szekely Y, Ingbir M, Bentur OS, Hochner O, Porat R. Natural cannabinoids suppress the cytokine storm in sepsis-like in vitro model. Eur Cytokine Netw. 2020;31:50–8. https://doi.org/10.1684/ecn.2020.0445.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Yeisley DJ, Arabiyat AS, Hahn MS. Cannabidiol-driven alterations to inflammatory protein landscape of lipopolysaccharide-activated macrophages in vitro may be mediated by autophagy and oxidative stress. Cannabis Cannabinoid Res. 2021. https://doi.org/10.1089/can.2020.0109.

    Article  PubMed  Google Scholar 

  40. 40.

    Lowin T, Tingting R, Zurmahr J, Classen T, Schneider M, Pongratz G. Cannabidiol (CBD): a killer for inflammatory rheumatoid arthritis synovial fibroblasts. Cell Death Dis. 2020;11:714. https://doi.org/10.1038/s41419-020-02892-1.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  41. 41.

    Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6:a016295. https://doi.org/10.1101/cshperspect.a016295.

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    El-Remessy AB, Al-Shabrawey M, Khalifa Y, Tsai NT, Caldwell RB, Liou GI. Neuroprotective and blood-retinal barrier-preserving effects of cannabidiol in experimental diabetes. Am J Pathol. 2006;168:235–44. https://doi.org/10.2353/ajpath.2006.050500.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Maor Y, Yu J, Kuzontkoski PM, Dezube BJ, Zhang X, Groopman JE. Cannabidiol inhibits growth and induces programmed cell death in kaposi sarcoma-associated herpesvirus-infected endothelium. Genes Cancer. 2012;3:512–20. https://doi.org/10.1177/1947601912466556.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Weis SM, Cheresh DA. Pathophysiological consequences of VEGF-induced vascular permeability. Nature 2005;437:497–504. https://doi.org/10.1038/nature03987.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Argaw AT, Asp L, Zhang J, Navrazhina K, Pham T, Mariani JN, et al. Astrocyte-derived VEGF-A drives blood-brain barrier disruption in CNS inflammatory disease. J Clin Invest. 2012;122:2454–68. https://doi.org/10.1172/JCI60842.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Petty MA, Lo EH. Junctional complexes of the blood–brain barrier: permeability changes in neuroinflammation. Prog Neurobiol. 2002;68:311–23. https://doi.org/10.1016/s0301-0082(02)00128-4.

    CAS  Article  PubMed  Google Scholar 

  47. 47.

    Suzuki Y, Nagai N, Umemura K. A review of the mechanisms of blood–brain barrier permeability by tissue-type plasminogen activator treatment for cerebral ischemia. Front Cell Neurosci. 2016;10:2 https://doi.org/10.3389/fncel.2016.00002.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Lurie DI. An integrative approach to neuroinflammation in psychiatric disorders and neuropathic pain. J Exp Neurosci. 2018;12:1179069518793639. https://doi.org/10.1177/1179069518793639.

    Article  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Fourrier C, Singhal G, Baune BT. Neuroinflammation and cognition across psychiatric conditions. CNS Spectr. 2019;24:4–15. https://doi.org/10.1017/S1092852918001499.

    Article  PubMed  Google Scholar 

  50. 50.

    Chen WW, Zhang X, Huang WJ. Role of neuroinflammation in neurodegenerative diseases (Review). Mol Med Rep. 2016;13:3391–6. https://doi.org/10.3892/mmr.2016.4948.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Zhang HT, Zhang P, Gao Y, Li CL, Wang HJ, Chen LC, et al. Early VEGF inhibition attenuates blood–brain barrier disruption in ischemic rat brains by regulating the expression of MMPs. Mol Med Rep. 2017;15:57–64. https://doi.org/10.3892/mmr.2016.5974.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Chi OZ, Hunter C, Liu X, Weiss HR. Effects of anti-VEGF antibody on blood–brain barrier disruption in focal cerebral ischemia. Exp Neurol. 2007;204:283–7. https://doi.org/10.1016/j.expneurol.2006.11.001.

    CAS  Article  PubMed  Google Scholar 

  53. 53.

    Wu HY, Huang CH, Lin YH, Wang CC, Jan TR. Cannabidiol induced apoptosis in human monocytes through mitochondrial permeability transition pore-mediated ROS production. Free Radic Biol Med. 2018;124:311–8. https://doi.org/10.1016/j.freeradbiomed.2018.06.023.

    CAS  Article  PubMed  Google Scholar 

  54. 54.

    Rajesh M, Mukhopadhyay P, Batkai S, Hasko G, Liaudet L, Drel VR, et al. Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruption. Am J Physiol Heart Circ Physiol. 2007;293:H610–9. https://doi.org/10.1152/ajpheart.00236.2007.

    CAS  Article  PubMed  Google Scholar 

  55. 55.

    Dhanda AD, Williams EL, Yates E, Lait PJP, Schewitz-Bowers LP, Hegazy D, et al. Intermediate monocytes in acute alcoholic hepatitis are functionally activated and induce IL-17 expression in CD4(+) T cells. J Immunol. 2019;203:3190–8. https://doi.org/10.4049/jimmunol.1800742.

    CAS  Article  PubMed  Google Scholar 

  56. 56.

    Gaur P, Myles A, Misra R, Aggarwal A. Intermediate monocytes are increased in enthesitis-related arthritis, a category of juvenile idiopathic arthritis. Clin Exp Immunol. 2017;187:234–41. https://doi.org/10.1111/cei.12880.

    CAS  Article  PubMed  Google Scholar 

  57. 57.

    O’Brien EC, Abdulahad WH, Rutgers A, Huitema MG, O’Reilly VP, Coughlan AM, et al. Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1beta secretion in response to anti-MPO antibodies. Sci Rep. 2015;5:11888. https://doi.org/10.1038/srep11888.

    Article  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Franca CN, Izar MCO, Hortencio MNS, do Amaral JB, Ferreira CES, Tuleta ID, et al. Monocyte subtypes and the CCR2 chemokine receptor in cardiovascular disease. Clin Sci. 2017;131:1215–24. https://doi.org/10.1042/CS20170009.

    CAS  Article  Google Scholar 

  59. 59.

    Wolf AA, Yanez A, Barman PK, Goodridge HS. The ontogeny of monocyte subsets. Front Immunol. 2019;10:1642 https://doi.org/10.3389/fimmu.2019.01642.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Ignatowska-Jankowska B, Jankowski M, Glac W, Swiergel AH. Cannabidiol-induced lymphopenia does not involve NKT and NK cells. J Physiol Pharmacol. 2009;60 Suppl 3:99–103.

    PubMed  Google Scholar 

  61. 61.

    Jan TR, Su ST, Wu HY, Liao MH. Suppressive effects of cannabidiol on antigen-specific antibody production and functional activity of splenocytes in ovalbumin-sensitized BALB/c mice. Int Immunopharmacol. 2007;7:773–80. https://doi.org/10.1016/j.intimp.2007.01.015.

    CAS  Article  PubMed  Google Scholar 

  62. 62.

    Wu HY, Chu RM, Wang CC, Lee CY, Lin SH, Jan TR. Cannabidiol-induced apoptosis in primary lymphocytes is associated with oxidative stress-dependent activation of caspase-8. Toxicol Appl Pharmacol. 2008;226:260–70. https://doi.org/10.1016/j.taap.2007.09.012.

    CAS  Article  PubMed  Google Scholar 

  63. 63.

    Dhital S, Stokes JV, Park N, Seo KS, Kaplan BL. Cannabidiol (CBD) induces functional Tregs in response to low-level T cell activation. Cell Immunol. 2017;312:25–34. https://doi.org/10.1016/j.cellimm.2016.11.006.

    CAS  Article  PubMed  Google Scholar 

  64. 64.

    Bahador A, Hadjati J, Hassannejad N, Ghazanfari H, Maracy M, Jafari S, et al. Frequencies of CD4+ T regulatory cells and their CD25(high) and FoxP3(high) subsets augment in peripheral blood of patients with acute and chronic Brucellosis. Osong Public Health Res Perspect. 2014;5:161–8. https://doi.org/10.1016/j.phrp.2014.04.008.

    Article  PubMed  PubMed Central  Google Scholar 

  65. 65.

    Santegoets SJ, Dijkgraaf EM, Battaglia A, Beckhove P, Britten CM, Gallimore A, et al. Monitoring regulatory T cells in clinical samples: consensus on an essential marker set and gating strategy for regulatory T cell analysis by flow cytometry. Cancer Immunol Immunother. 2015;64:1271–86. https://doi.org/10.1007/s00262-015-1729-x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  66. 66.

    Shevach EM. CD4+ CD25+ suppressor T cells: more questions than answers. Nat Rev Immunol. 2002;2:389–400. https://doi.org/10.1038/nri821.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Corthay A. How do regulatory T cells work? Scand J Immunol. 2009;70:326–36. https://doi.org/10.1111/j.1365-3083.2009.02308.x.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Romano M, Fanelli G, Tan N, Nova-Lamperti E, McGregor R, Lechler RI, et al. Expanded regulatory T cells induce alternatively activated monocytes with a reduced capacity to expand T helper-17 cells. Front Immunol. 2018;9:1625. https://doi.org/10.3389/fimmu.2018.01625.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Guo N, Liu L, Yang X, Song T, Li G, Li L, et al. Immunological changes in monocyte subsets and their association with Foxp3(+) regulatory T cells in HIV-1-infected individuals with syphilis: a brief research report. Front Immunol. 2019;10:714. https://doi.org/10.3389/fimmu.2019.00714.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  70. 70.

    Muller-Durovic B, Grahlert J, Devine OP, Akbar AN, Hess C. CD56-negative NK cells with impaired effector function expand in CMV and EBV co-infected healthy donors with age. Aging. 2019;11:724–40. https://doi.org/10.18632/aging.101774.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Melaiu O, Lucarini V, Cifaldi L, Fruci D. Influence of the tumor microenvironment on NK cell function in solid tumors. Front Immunol. 2019;10:3038. https://doi.org/10.3389/fimmu.2019.03038.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Chan B, Kondo K, Freeman M, Ayers C, Montgomery J, Kansagara D. Pharmacotherapy for cocaine use disorder—a systematic review and meta-analysis. J Gen Intern Med. 2019;34:2858–73. https://doi.org/10.1007/s11606-019-05074-8.

    Article  PubMed  PubMed Central  Google Scholar 

  73. 73.

    Haney M, Malcolm RJ, Babalonis S, Nuzzo PA, Cooper ZD, Bedi G, et al. Oral cannabidiol does not alter the subjective, reinforcing or cardiovascular effects of smoked cannabis. Neuropsychopharmacology 2016;41:1974–82. https://doi.org/10.1038/npp.2015.367.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank the CIHR (#125864), the Fonds de recherche du Québec en Santé, the Université de Montréal, the CRCHUM, the Institut du Cancer de Montréal, and the Institut universitaire sur les dépendances for their financial support. We thank the clinical immunomonitoring core facility of the CRCHUM for performing biobanking, immunophenotyping, and cytokine measurements. We are grateful to Léa Gagnon for reviewing and editing the manuscript, and Guillaume Gazil and his team (Unité de recherche clinique appliquée) for their support in data management and statistical analysis for the main trial. The study team also wants to extend special thanks to all participants for their engagement in this study.

Funding

The Canadian Institutes of Health Research (CIHR) funded this study (#125864). Insys Therapeutics provided the investigational product. DJ-A holds a scholar award from the Fonds de recherche du Québec en Santé. FM received scholarships from the CIHR, the Institut Universitaire sur les Dépendances, the Université de Montréal, and the CRCHUM. JB holds the Canada Research Chair in Addiction Medicine and receives investigator-driven grants from Gilead Sciences and AbbVie for work outside this study.

Author information

Affiliations

Authors

Contributions

FM, VM-P, ER, and PT wrote the original draft. FM and VM-P did the formal analysis. PT and SL performed biobanking, immunophenotyping, and cytokine measurements. FM and PT did the visualization. SB, JB, SD, ES, and DJ-A conceptualized the study. J-FC and DJ-A co-supervised the project. JB, ES, DJ-A obtained the funding. All authors reviewed the manuscript.

Corresponding author

Correspondence to Didier Jutras-Aswad.

Ethics declarations

Competing interests

VM-P, ER, PT, SL, SB, SD, ES, and J-FC declare no competing interests. The funders of the study and Insys Therapeutics had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to publish.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Morissette, F., Mongeau-Pérusse, V., Rizkallah, E. et al. Exploring cannabidiol effects on inflammatory markers in individuals with cocaine use disorder: a randomized controlled trial. Neuropsychopharmacol. (2021). https://doi.org/10.1038/s41386-021-01098-z

Download citation

Search

Quick links