Treatment With Lorcaserin for Cocaine Use: The TLC Study

Summary

This project is a placebo-controlled, double-blind randomized trial evaluating the feasibility, tolerability, acceptability and adherence for lorcaserin among actively using, men who have sex with men (MSM) with cocaine use disorders.The study will enroll 45 individuals who will randomly be assigned to either the treatment (lorcaserin) arm or the placebo arm, to be taken twice a day for 12 weeks.

Timeline

Start

2018-01-01

Primary completion

2020-02-28

Completion

2020-06-30

Publications

• Background Riezzo I, Fiore C, De Carlo D, Pascale N, Neri M, Turillazzi E, Fineschi V. Side effects of cocaine abuse: multiorgan toxicity and pathological consequences. Curr Med Chem. 2012;19(33):5624-46. doi: 10.2174/092986712803988893.
• Background Karila L, Petit A, Lowenstein W, Reynaud M. Diagnosis and consequences of cocaine addiction. Curr Med Chem. 2012;19(33):5612-8. doi: 10.2174/092986712803988839.
• Background Crane EH. Highlights of the 2011 Drug Abuse Warning Network (DAWN) Findings on Drug-Related Emergency Department Visits. 2013 Feb 22. In: The CBHSQ Report. Rockville (MD): Substance Abuse and Mental Health Services Administration (US); 2013-. Available from http://www.ncbi.nlm.nih.gov/books/NBK384680/
• Background Degenhardt L, Baxter AJ, Lee YY, Hall W, Sara GE, Johns N, Flaxman A, Whiteford HA, Vos T. The global epidemiology and burden of psychostimulant dependence: findings from the Global Burden of Disease Study 2010. Drug Alcohol Depend. 2014 Apr 1;137:36-47. doi: 10.1016/j.drugalcdep.2013.12.025. Epub 2014 Jan 27.
• Background Vandhuick O, Pistorius MA, Jousse S, Ferreira-Maldent N, Guilmot JL, Guias B, Bressollette L. [Drug addiction and cardiovascular pathologies]. J Mal Vasc. 2004 Dec;29(5):243-8. doi: 10.1016/s0398-0499(04)96768-6. French.
• Background Kloner RA, Hale S, Alker K, Rezkalla S. The effects of acute and chronic cocaine use on the heart. Circulation. 1992 Feb;85(2):407-19. doi: 10.1161/01.cir.85.2.407.
• Background McCord J, Jneid H, Hollander JE, de Lemos JA, Cercek B, Hsue P, Gibler WB, Ohman EM, Drew B, Philippides G, Newby LK; American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Management of cocaine-associated chest pain and myocardial infarction: a scientific statement from the American Heart Association Acute Cardiac Care Committee of the Council on Clinical Cardiology. Circulation. 2008 Apr 8;117(14):1897-907. doi: 10.1161/CIRCULATIONAHA.107.188950. Epub 2008 Mar 17. No abstract available.
• Background Phillips K, Luk A, Soor GS, Abraham JR, Leong S, Butany J. Cocaine cardiotoxicity: a review of the pathophysiology, pathology, and treatment options. Am J Cardiovasc Drugs. 2009;9(3):177-96. doi: 10.2165/00129784-200909030-00005.
• Background Steinhauer JR, Caulfield JB. Spontaneous coronary artery dissection associated with cocaine use: a case report and brief review. Cardiovasc Pathol. 2001 May-Jun;10(3):141-5. doi: 10.1016/s1054-8807(01)00074-6.
• Background Sanchez T, Finlayson T, Drake A, Behel S, Cribbin M, Dinenno E, Hall T, Kramer S, Lansky A; Centers for Disease Control and Prevention (CDC). Human immunodeficiency virus (HIV) risk, prevention, and testing behaviors--United States, National HIV Behavioral Surveillance System: men who have sex with men, November 2003-April 2005. MMWR Surveill Summ. 2006 Jul 7;55(6):1-16.
• Background Raymond HF, Chen YH, Ick T, Scheer S, Bernstein K, Liska S, Louie B, Pandori M, McFarland W. A new trend in the HIV epidemic among men who have sex with men, San Francisco, 2004-2011. J Acquir Immune Defic Syndr. 2013 Apr 15;62(5):584-9. doi: 10.1097/QAI.0b013e318285febf.
• Background Mimiaga MJ, Reisner SL, Fontaine YM, Bland SE, Driscoll MA, Isenberg D, Cranston K, Skeer MR, Mayer KH. Walking the line: stimulant use during sex and HIV risk behavior among Black urban MSM. Drug Alcohol Depend. 2010 Jul 1;110(1-2):30-7. doi: 10.1016/j.drugalcdep.2010.01.017. Epub 2010 Mar 23.
• Background Colfax G, Vittinghoff E, Husnik MJ, McKirnan D, Buchbinder S, Koblin B, Celum C, Chesney M, Huang Y, Mayer K, Bozeman S, Judson FN, Bryant KJ, Coates TJ; EXPLORE Study Team. Substance use and sexual risk: a participant- and episode-level analysis among a cohort of men who have sex with men. Am J Epidemiol. 2004 May 15;159(10):1002-12. doi: 10.1093/aje/kwh135.
• Background Ober A, Shoptaw S, Wang PC, Gorbach P, Weiss RE. Factors associated with event-level stimulant use during sex in a sample of older, low-income men who have sex with men in Los Angeles. Drug Alcohol Depend. 2009 Jun 1;102(1-3):123-9. doi: 10.1016/j.drugalcdep.2009.02.002. Epub 2009 Mar 26.
• Background Mackesy-Amiti ME, Fendrich M, Johnson TP. Symptoms of substance dependence and risky sexual behavior in a probability sample of HIV-negative men who have sex with men in Chicago. Drug Alcohol Depend. 2010 Jul 1;110(1-2):38-43. doi: 10.1016/j.drugalcdep.2010.01.016. Epub 2010 Mar 9.
• Background Lambert G, Cox J, Hottes TS, Tremblay C, Frigault LR, Alary M, Otis J, Remis RS; M-Track Study Group. Correlates of unprotected anal sex at last sexual episode: analysis from a surveillance study of men who have sex with men in Montreal. AIDS Behav. 2011 Apr;15(3):584-95. doi: 10.1007/s10461-009-9605-3.
• Background Bowers JR, Branson CM, Fletcher JB, Reback CJ. Predictors of HIV Sexual Risk Behavior among Men Who Have Sex with Men, Men Who Have Sex with Men and Women, and Transgender Women. Int J Sex Health. 2012;24(4):290-302. doi: 10.1080/19317611.2012.715120.
• Background Santos GM, Coffin PO, Das M, Matheson T, DeMicco E, Raiford JL, Vittinghoff E, Dilley JW, Colfax G, Herbst JH. Dose-response associations between number and frequency of substance use and high-risk sexual behaviors among HIV-negative substance-using men who have sex with men (SUMSM) in San Francisco. J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):540-4. doi: 10.1097/QAI.0b013e318293f10b.
• Background Tyndall MW, Currie S, Spittal P, Li K, Wood E, O'Shaughnessy MV, Schechter MT. Intensive injection cocaine use as the primary risk factor in the Vancouver HIV-1 epidemic. AIDS. 2003 Apr 11;17(6):887-93. doi: 10.1097/00002030-200304110-00014.
• Background Cepeda JA, Vickerman P, Bruneau J, Zang G, Borquez A, Farrell M, Degenhardt L, Martin NK. Estimating the contribution of stimulant injection to HIV and HCV epidemics among people who inject drugs and implications for harm reduction: A modeling analysis. Drug Alcohol Depend. 2020 Aug 1;213:108135. doi: 10.1016/j.drugalcdep.2020.108135. Epub 2020 Jun 24.
• Background Ostrow DG, Plankey MW, Cox C, Li X, Shoptaw S, Jacobson LP, Stall RC. Specific sex drug combinations contribute to the majority of recent HIV seroconversions among MSM in the MACS. J Acquir Immune Defic Syndr. 2009 Jul 1;51(3):349-55. doi: 10.1097/QAI.0b013e3181a24b20.
• Background Koblin BA, Husnik MJ, Colfax G, Huang Y, Madison M, Mayer K, Barresi PJ, Coates TJ, Chesney MA, Buchbinder S. Risk factors for HIV infection among men who have sex with men. AIDS. 2006 Mar 21;20(5):731-9. doi: 10.1097/01.aids.0000216374.61442.55.
• Background Ostrow DG, DiFranceisco WJ, Chmiel JS, Wagstaff DA, Wesch J. A case-control study of human immunodeficiency virus type 1 seroconversion and risk-related behaviors in the Chicago MACS/CCS Cohort, 1984-1992. Multicenter AIDS Cohort Study. Coping and Change Study. Am J Epidemiol. 1995 Oct 15;142(8):875-83. doi: 10.1093/oxfordjournals.aje.a117727.
• Background Hinkin CH, Barclay TR, Castellon SA, Levine AJ, Durvasula RS, Marion SD, Myers HF, Longshore D. Drug use and medication adherence among HIV-1 infected individuals. AIDS Behav. 2007 Mar;11(2):185-94. doi: 10.1007/s10461-006-9152-0.
• Background Carrico AW. Substance use and HIV disease progression in the HAART era: implications for the primary prevention of HIV. Life Sci. 2011 May 23;88(21-22):940-7. doi: 10.1016/j.lfs.2010.10.002. Epub 2010 Oct 8.
• Background Shoptaw S, Stall R, Bordon J, Kao U, Cox C, Li X, Ostrow DG, Plankey MW. Cumulative exposure to stimulants and immune function outcomes among HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study. Int J STD AIDS. 2012 Aug;23(8):576-80. doi: 10.1258/ijsa.2012.011322.
• Background Cook JA, Burke-Miller JK, Cohen MH, Cook RL, Vlahov D, Wilson TE, Golub ET, Schwartz RM, Howard AA, Ponath C, Plankey MW, Levine AM, Grey DD. Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women. AIDS. 2008 Jul 11;22(11):1355-63. doi: 10.1097/QAD.0b013e32830507f2.
• Background 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 Dec;34(12):2858-2873. doi: 10.1007/s11606-019-05074-8. Epub 2019 Jun 10.
• Background Higgins GA, Fletcher PJ, Shanahan WR. Lorcaserin: A review of its preclinical and clinical pharmacology and therapeutic potential. Pharmacol Ther. 2020 Jan;205:107417. doi: 10.1016/j.pharmthera.2019.107417. Epub 2019 Oct 16.
• Background Rothman RB, Blough BE, Baumann MH. Dopamine/serotonin releasers as medications for stimulant addictions. Prog Brain Res. 2008;172:385-406. doi: 10.1016/S0079-6123(08)00919-9.
• Background Higgins GA, Sellers EM, Fletcher PJ. From obesity to substance abuse: therapeutic opportunities for 5-HT2C receptor agonists. Trends Pharmacol Sci. 2013 Oct;34(10):560-70. doi: 10.1016/j.tips.2013.08.001. Epub 2013 Sep 13.
• Background Alex KD, Pehek EA. Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission. Pharmacol Ther. 2007 Feb;113(2):296-320. doi: 10.1016/j.pharmthera.2006.08.004. Epub 2006 Oct 17.
• Background Bubar MJ, Cunningham KA. Serotonin 5-HT2A and 5-HT2C receptors as potential targets for modulation of psychostimulant use and dependence. Curr Top Med Chem. 2006;6(18):1971-85. doi: 10.2174/156802606778522131.
• Background Bubar MJ, Cunningham KA. Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse. Prog Brain Res. 2008;172:319-46. doi: 10.1016/S0079-6123(08)00916-3.
• Background Burton CL, Rizos Z, Diwan M, Nobrega JN, Fletcher PJ. Antagonizing 5-HT(2)A receptors with M100907 and stimulating 5-HT(2)C receptors with Ro60-0175 blocks cocaine-induced locomotion and zif268 mRNA expression in Sprague-Dawley rats. Behav Brain Res. 2013 Mar 1;240:171-81. doi: 10.1016/j.bbr.2012.11.030. Epub 2012 Nov 28.
• Background Craige CP, Unterwald EM. Serotonin (2C) receptor regulation of cocaine-induced conditioned place preference and locomotor sensitization. Behav Brain Res. 2013 Feb 1;238:206-10. doi: 10.1016/j.bbr.2012.10.034. Epub 2012 Oct 26.
• Background Cunningham KA, Fox RG, Anastasio NC, Bubar MJ, Stutz SJ, Moeller FG, Gilbertson SR, Rosenzweig-Lipson S. Selective serotonin 5-HT(2C) receptor activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues. Neuropharmacology. 2011 Sep;61(3):513-23. doi: 10.1016/j.neuropharm.2011.04.034. Epub 2011 May 11.
• Background Filip M, Alenina N, Bader M, Przegalinski E. Behavioral evidence for the significance of serotoninergic (5-HT) receptors in cocaine addiction. Addict Biol. 2010 Jul;15(3):227-49. doi: 10.1111/j.1369-1600.2010.00214.x. Epub 2010 Apr 29.
• Background Filip M, Spampinato U, McCreary AC, Przegalinski E. Pharmacological and genetic interventions in serotonin (5-HT)(2C) receptors to alter drug abuse and dependence processes. Brain Res. 2012 Oct 2;1476:132-53. doi: 10.1016/j.brainres.2012.03.035. Epub 2012 Mar 23.
• Background Katsidoni V, Apazoglou K, Panagis G. Role of serotonin 5-HT2A and 5-HT2C receptors on brain stimulation reward and the reward-facilitating effect of cocaine. Psychopharmacology (Berl). 2011 Feb;213(2-3):337-54. doi: 10.1007/s00213-010-1887-7. Epub 2010 Jun 25.
• Background Leggio GM, Cathala A, Moison D, Cunningham KA, Piazza PV, Spampinato U. Serotonin2C receptors in the medial prefrontal cortex facilitate cocaine-induced dopamine release in the rat nucleus accumbens. Neuropharmacology. 2009 Feb;56(2):507-13. doi: 10.1016/j.neuropharm.2008.10.005. Epub 2008 Oct 17.
• Background Manvich DF, Kimmel HL, Howell LL. Effects of serotonin 2C receptor agonists on the behavioral and neurochemical effects of cocaine in squirrel monkeys. J Pharmacol Exp Ther. 2012 May;341(2):424-34. doi: 10.1124/jpet.111.186981. Epub 2012 Feb 10.
• Background Pockros LA, Pentkowski NS, Conway SM, Ullman TE, Zwick KR, Neisewander JL. 5-HT(2A) receptor blockade and 5-HT(2C) receptor activation interact to reduce cocaine hyperlocomotion and Fos protein expression in the caudate-putamen. Synapse. 2012 Dec;66(12):989-1001. doi: 10.1002/syn.21592. Epub 2012 Sep 11.
• Background Grottick AJ, Fletcher PJ, Higgins GA. Studies to investigate the role of 5-HT(2C) receptors on cocaine- and food-maintained behavior. J Pharmacol Exp Ther. 2000 Dec;295(3):1183-91.
• Background Pelloux Y, Dilleen R, Economidou D, Theobald D, Everitt BJ. Reduced forebrain serotonin transmission is causally involved in the development of compulsive cocaine seeking in rats. Neuropsychopharmacology. 2012 Oct;37(11):2505-14. doi: 10.1038/npp.2012.111. Epub 2012 Jul 4.
• Background Pirtle JL, Hickman MD, Boinpelly VC, Surineni K, Thakur HK, Grasing KW. The serotonin-2C agonist Lorcaserin delays intravenous choice and modifies the subjective and cardiovascular effects of cocaine: A randomized, controlled human laboratory study. Pharmacol Biochem Behav. 2019 May;180:52-59. doi: 10.1016/j.pbb.2019.02.010. Epub 2019 Feb 24.
• Background Fletcher PJ, Rizos Z, Noble K, Higgins GA. Impulsive action induced by amphetamine, cocaine and MK801 is reduced by 5-HT(2C) receptor stimulation and 5-HT(2A) receptor blockade. Neuropharmacology. 2011 Sep;61(3):468-77. doi: 10.1016/j.neuropharm.2011.02.025. Epub 2011 Mar 21.
• Background Higgins GA, Silenieks LB, Rossmann A, Rizos Z, Noble K, Soko AD, Fletcher PJ. The 5-HT2C receptor agonist lorcaserin reduces nicotine self-administration, discrimination, and reinstatement: relationship to feeding behavior and impulse control. Neuropsychopharmacology. 2012 Apr;37(5):1177-91. doi: 10.1038/npp.2011.303. Epub 2011 Dec 21.
• Background Colfax GN, Santos GM, Das M, Santos DM, Matheson T, Gasper J, Shoptaw S, Vittinghoff E. Mirtazapine to reduce methamphetamine use: a randomized controlled trial. Arch Gen Psychiatry. 2011 Nov;68(11):1168-75. doi: 10.1001/archgenpsychiatry.2011.124.
• Background Bohula EA, Wiviott SD, McGuire DK, Inzucchi SE, Kuder J, Im K, Fanola CL, Qamar A, Brown C, Budaj A, Garcia-Castillo A, Gupta M, Leiter LA, Weissman NJ, White HD, Patel T, Francis B, Miao W, Perdomo C, Dhadda S, Bonaca MP, Ruff CT, Keech AC, Smith SR, Sabatine MS, Scirica BM; CAMELLIA-TIMI 61 Steering Committee and Investigators. Cardiovascular Safety of Lorcaserin in Overweight or Obese Patients. N Engl J Med. 2018 Sep 20;379(12):1107-1117. doi: 10.1056/NEJMoa1808721. Epub 2018 Aug 26.
• Background de Andrade Mesquita L, Fagundes Piccoli G, Richter da Natividade G, Frison Spiazzi B, Colpani V, Gerchman F. Is lorcaserin really associated with increased risk of cancer? A systematic review and meta-analysis. Obes Rev. 2021 Mar;22(3):e13170. doi: 10.1111/obr.13170. Epub 2020 Dec 1.
• Background Centers for Disease Control and Prevention. Revised guidelines for HIV counseling, testing, and referral. MMWR Recomm Rep. 2001 Nov 9;50(RR-19):1-57; quiz CE1-19a1-CE6-19a1.
• Background Haberer JE, Kahane J, Kigozi I, Emenyonu N, Hunt P, Martin J, Bangsberg DR. Real-time adherence monitoring for HIV antiretroviral therapy. AIDS Behav. 2010 Dec;14(6):1340-6. doi: 10.1007/s10461-010-9799-4.
• Background Das M, Santos D, Matheson T, Santos GM, Chu P, Vittinghoff E, Shoptaw S, Colfax GN. Feasibility and acceptability of a phase II randomized pharmacologic intervention for methamphetamine dependence in high-risk men who have sex with men. AIDS. 2010 Apr 24;24(7):991-1000. doi: 10.1097/qad.0b013e328336e98b.
• Background Dunn C, Deroo L, Rivara FP. The use of brief interventions adapted from motivational interviewing across behavioral domains: a systematic review. Addiction. 2001 Dec;96(12):1725-42. doi: 10.1046/j.1360-0443.2001.961217253.x.
• Background Samet JH, Rollnick S, Barnes H. Beyond CAGE. A brief clinical approach after detection of substance abuse. Arch Intern Med. 1996 Nov 11;156(20):2287-93. doi: 10.1001/archinte.156.20.2287.
• Background Koblin B, Chesney M, Coates T; EXPLORE Study Team. Effects of a behavioural intervention to reduce acquisition of HIV infection among men who have sex with men: the EXPLORE randomised controlled study. Lancet. 2004 Jul 3-9;364(9428):41-50. doi: 10.1016/S0140-6736(04)16588-4.
• Background Macalino GE, Celentano DD, Latkin C, Strathdee SA, Vlahov D. Risk behaviors by audio computer-assisted self-interviews among HIV-seropositive and HIV-seronegative injection drug users. AIDS Educ Prev. 2002 Oct;14(5):367-78. doi: 10.1521/aeap.14.6.367.24075.
• Background Delucchi KL, Jones RT, Batki SL. Measurement properties of quantitative urine benzoylecgonine in clinical trials research. Addiction. 1997 Mar;92(3):297-302.
• Background Batki SL, Washburn AM, Delucchi K, Jones RT. A controlled trial of fluoxetine in crack cocaine dependence. Drug Alcohol Depend. 1996 Jun;41(2):137-42. doi: 10.1016/0376-8716(96)01233-1.
• Background Preston KL, Epstein DH, Cone EJ, Wtsadik AT, Huestis MA, Moolchan ET. Urinary elimination of cocaine metabolites in chronic cocaine users during cessation. J Anal Toxicol. 2002 Oct;26(7):393-400. doi: 10.1093/jat/26.7.393.
• Background Sobell LC, Brown J, Leo GI, Sobell MB. The reliability of the Alcohol Timeline Followback when administered by telephone and by computer. Drug Alcohol Depend. 1996 Sep;42(1):49-54. doi: 10.1016/0376-8716(96)01263-x.
• Background Tziortzis D, Mahoney JJ 3rd, Kalechstein AD, Newton TF, De La Garza R 2nd. The relationship between impulsivity and craving in cocaine- and methamphetamine-dependent volunteers. Pharmacol Biochem Behav. 2011 Apr;98(2):196-202. doi: 10.1016/j.pbb.2010.12.022. Epub 2011 Jan 6.
• Background Gonzalez-Saiz F, Domingo-Salvany A, Barrio G, Sanchez-Niubo A, Brugal MT, de la Fuente L, Alonso J. Severity of dependence scale as a diagnostic tool for heroin and cocaine dependence. Eur Addict Res. 2009;15(2):87-93. doi: 10.1159/000189787. Epub 2009 Jan 10.
• Background Hunt MK, Hopko DR, Bare R, Lejuez CW, Robinson EV. Construct validity of the Balloon Analog Risk Task (BART): associations with psychopathy and impulsivity. Assessment. 2005 Dec;12(4):416-28. doi: 10.1177/1073191105278740.
• Background Reise SP, Moore TM, Sabb FW, Brown AK, London ED. The Barratt Impulsiveness Scale-11: reassessment of its structure in a community sample. Psychol Assess. 2013 Jun;25(2):631-42. doi: 10.1037/a0032161. Epub 2013 Apr 1.
• Background McCann DJ, Li SH. A novel, nonbinary evaluation of success and failure reveals bupropion efficacy versus methamphetamine dependence: reanalysis of a multisite trial. CNS Neurosci Ther. 2012 May;18(5):414-8. doi: 10.1111/j.1755-5949.2011.00263.x. Epub 2011 Oct 18.
• Background Day SJ, Altman DG. Statistics notes: blinding in clinical trials and other studies. BMJ. 2000 Aug 19-26;321(7259):504. doi: 10.1136/bmj.321.7259.504. No abstract available.
• Background Lash TL, Ahern TP. Bias analysis to guide new data collection. Int J Biostat. 2012 Jan 6;8(2):/j/ijb.2012.8.issue-2/1557-4679.1345/1557-4679.1345.xml. doi: 10.2202/1557-4679.1345.
• Background Negus SS, Banks ML. Learning from lorcaserin: lessons from the negative clinical trial of lorcaserin to treat cocaine use disorder. Neuropsychopharmacology. 2020 Nov;45(12):1967-1973. doi: 10.1038/s41386-020-00815-4. Epub 2020 Aug 24. No abstract available.
• Background Palacios JM, Pazos A, Hoyer D. A short history of the 5-HT2C receptor: from the choroid plexus to depression, obesity and addiction treatment. Psychopharmacology (Berl). 2017 May;234(9-10):1395-1418. doi: 10.1007/s00213-017-4545-5. Epub 2017 Mar 7.
• Background Li SH, Chiang CN, Tai BC, Marschke CK, Hawks RL. Quantitative versus qualitative urinalysis for benzoylecgonine in clinical trials for the assessment of cocaine use. Psychopharmacol Bull. 1995;31(4):671-9.
• Results Santos GM, Ikeda J, Coffin P, Walker JE, Matheson T, McLaughlin M, Jain J, Vittinghoff E, Batki SL. Pilot study of extended-release lorcaserin for cocaine use disorder among men who have sex with men: A double-blind, placebo-controlled randomized trial. PLoS One. 2021 Jul 15;16(7):e0254724. doi: 10.1371/journal.pone.0254724. eCollection 2021.

Drugs

Indications