The Rapidly Changing Composition of the Global Street Drug Supply and its Effects on High-risk Groups for COVID-19

Author(s): Thom Browne*, Mark S. Gold, David M. Martin

Journal Name: Current Psychopharmacology

Volume 10 , Issue 2 , 2021


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Graphical Abstract:


Abstract:

Background: Globally, an alarming number of pharmaceutically active compounds are now routinely added to the street drugs of abuse, cocaine and heroin. In some cases, seventeen (17) or more potentially toxic compounds are found in a single street purchased bag or block of cocaine or heroin. Pharmacologically active compounds, impurities, or breakdown products from drug manufacturing and industrial chemicals (collectively referred to as toxic adulterants) are now found in street drugs. They include, but are not limited to: antipsychotics, antidepressants, anxiolytics, antihistamines, anthelmintics, anesthetics, antiinflammatorys, antipyretics, analgesics, antispasmodics, antiarrhythmics, antimalarials, veterinary medications, bronchodilators, expectorants, sedatives, muscle relaxers, natural/synthetic hallucinogens, decongestants, new psychoactive substances (NPS), industrial compounds, fungicides, and impurities in the manufacturing process. All can be found within a single street purchase of heroin or cocaine. Routine clinical or workplace drug testing will not detect all these toxic adulterants. Only specialty forensic tests, specifically ordered, will detect them. The synergistic effect on the human body of such an unprecedented combination of pharmacologically active compounds is unknown and potentially deadly. This is especially seen in daily substance users who are exposed to these combinations multiple times a day over an extended period of time. Individuals with substance use disorders (SUDs) have several co-occurring health problems that make them more susceptible to COVID-19, including compromised immune, pulmonary, cardiovascular, and respiratory systems. These problems are high-risk factors for the acquisition of COVID-19 infection and more serious complications from the virus, including hospitalization and death.

Objective: The study aims to bring to the attention of public health officials, addiction medicine specialists, treatment officials, therapists, and the general public the alarming increase of dangerous toxic adulterants being added to street drugs and their potentially lethal synergistic effects. Also, it aims to provide insights into how these new formulations can have serious pathophysiological effects on individuals with Substance Abuse Disorders (SUDs) during the COVID-19 pandemic.

Methods: The literature on street drug cutting agents, toxic adulterants, NPS, manufacturing byproducts, and other industrial compounds will be reviewed. Also, a review of the literature of pathophysiological effects, especially on SUD patients, in light of the COVID-19 pandemic will be presented. This is combined with international and USA studies that were carried out by the Colombo Plan that identified these new combinations of toxic adulterants in street drugs, using state-of-the-art field and forensic laboratory detection technologies.

Results: The majority of street drugs, in some cases more than ninety-five percent, now have multiple toxic adulterants. It is rare that a street purchase of cocaine or heroin does not contain multiple toxic adulterants, cutting agents, NPS, manufacturing byproducts, or industrial chemicals.

Conclusion: This dangerous new composition in world street drug supply is unprecedented and may be the undetected cause of many psychostimulant and opioid overdose deaths, as many toxic adulterants are not routinely tested in post-mortem or street drug seizure cases. In addition, several of these toxic adulterants create a catastrophic drop in white blood cells, causing neutropenia and making the substance users susceptible to a wide range of opportunistic infections, including COVID-19. This profound change in the world street drug supply has catastrophic implications for individuals with SUDs and our health care system, especially in the era of the COVID-19 pandemic.

Keywords: Street drugs, cocaine, heroin, toxic adulterants, COVID-19, synergism, health care, overdose, NPS, Colombo Plan Secretariat.

[1]
Solimini R, Rotolo MC, Pellegrini M, et al. Adulteration practices of psychoactive illicit drugs: an updated review. Curr Pharm Biotechnol 2017; 18(7): 524-30.
[http://dx.doi.org/10.2174/1389201018666170710184531 ] [PMID: 28699480]
[2]
Broséus J, Gentile N, Esseiva P. The cutting of cocaine and heroin: A critical review. Forensic Sci Int 2016; 262: 73-83.
[http://dx.doi.org/10.1016/j.forsciint.2016.02.033 ] [PMID: 26974713]
[3]
Gold MS. Deadly adulterants: new dangers of illicit drugs The Sober World Magazine. 2017; Available at:. https://www.thesoberworld.com/2017/07/01/deadly-adulterants-new-dangers-of-illicit-drugs/
[4]
Broséus J, Gentile N, Bonadio Pont F, Garcia Gongora JM, Gasté L, Esseiva P. Qualitative, quantitative and temporal study of cutting agents for cocaine and heroin over 9 years. Forensic Sci Int 2015; 257: 307-13.
[http://dx.doi.org/10.1016/j.forsciint.2015.09.014 ] [PMID: 26448535]
[5]
Singh VM, Browne T, Montgomery J. The emerging role of toxic adulterants in street drugs in the US illicit opioid crisis. Public Health Rep 2020; 135(1): 6-10.
[http://dx.doi.org/10.1177/0033354919887741 ] [PMID: 31738861]
[6]
Fiorentin TR, Fogarty M, Limberger RP, Logan BK. Determination of cutting agents in seized cocaine samples using GC-MS, GC-TMS and LC-MS/MS. Forensic Sci Int 2019; 295: 199-206.
[http://dx.doi.org/10.1016/j.forsciint.2018.12.016 ] [PMID: 30634141]
[7]
US Department of State, Bureau for International Narcotics and Law Enforcement Affairs 2018. International narcotics control strategy report. Volume I: drug and chemical control. 2018; Available at: . https://www.state.gov/2018-international-narcotics-control-strategy-report/
[8]
United Nations office on drugs and crime. Global synthetic drugs assessment. 2017; Available at:. https://www.unodc.org/documents/scientific/Global_Drugs_Assessment_2017.pdf
[9]
Wang P. Review and recent progress of handheld spectrometry at Thermo Fisher Scientific Proc SPIE 9482, next-generation spectroscopic technologies VIII 2015; 9485204. Available at:. http://proceedings.spiedigitallibrary.org/proceeding.aspx?doi=10.1117/12.2178140
[10]
Gold MS, Browne T, Martin DM. America’s hidden drug epidemic: it is more than opioidsNational Rx and drug abuse summit 2018.Available at:. https://ncric.ca.gov/files/D2DF00000/069.pdf
[11]
Thiruchelvam M, Richfield EK, Goodman BM, Baggs RB, Cory-Slechta DA. Developmental exposure to the pesticides paraquat and maneb and the Parkinson’s disease phenotype. Neurotoxicology 2002; 23(4-5): 621-33.
[http://dx.doi.org/10.1016/S0161-813X(02)00092-X ] [PMID: 12428734]
[12]
O’Donnell JK, Halpin J, Mattson CL, Goldberger BA, Gladden RM. Deaths involving fentanyl, fentanyl analogs, and U-47700-10 States, July-December. 2016. MMWR Morb Mortal Wkly Rep 2017; 66(43): 1197-202.
[http://dx.doi.org/10.15585/mmwr.mm6643e1 ] [PMID: 29095804]
[13]
Overdose Death Rates National institute on drug abuse 2020.Available at:. https://www.drugabuse.gov/drug-topics/trends-statistics/overdose-death-rates
[14]
Ahmad F, Rossen L, Sutton P. Provisional drug overdose death counts National Center For Health Statistics 2020. Available at:. https://www.cdc.gov/nchs/nvss/vsrr/drug-overdose-data.htm
[15]
Phillips KA, Hirsch GA, Epstein DH, Preston KL. Cardiac complications of unwitting co-injection of quinine/quinidine with heroin in an intravenous drug user. J Gen Intern Med 2012; 27(12): 1722-5.
[http://dx.doi.org/10.1007/s11606-012-2089-2 ] [PMID: 22592353]
[16]
Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis M. Adulterants in illicit drugs: a review of empirical evidence. Drug Test Anal 2011; 3(2): 89-96.
[http://dx.doi.org/10.1002/dta.220 ] [PMID: 21322119]
[17]
Gilman AG, Rall TW, Nies AS, Taylor P. Goodman and Gilman’s The pharmacological basis of therapeutics. 8th ed. New York: Pergamon Press 1990.
[18]
Maldaner AO, Botelho ÉD, Zacca JJ, et al. Chemical profiling of street cocaine from different Brazilian regions. J Braz Chem Soc 2016; 27(4): 719-26.
[http://dx.doi.org/10.5935/0103-5053.20150321]
[19]
National Institute of Criminalistics. Evaluation by the PeQui Methodology of Cocaine Samples from SR/DPF/PR. Brasilia, DF, Brazil: Brazilian Federal Police 2014.
[20]
Maldaner AO, Botelho ÉD, Zacca JJ, Camargo MA, Braga JW, Grobério TS. Brazilian federal district cocaine chemical profiling - Mass balance approach and new adulterant routinely quantified (Aminopyrine). J Braz Chem Soc 2015; 26(6): 1227-31.
[http://dx.doi.org/10.5935/0103-5053.20150088]
[21]
Duffau B, Rojas S, Ayala S. A decade of analysis of illicit street cocaine in Chile. J Pharm Pharmacogn Res 2020; 8(2): 146-54.
[22]
Mthembi PM, Mwenesongole EM, Cole MD. Chemical profiling of the street cocktail drug ‘nyaope’ in South Africa using GC-MS I: Stability studies of components of ‘nyaope’ in organic solvents. Forensic Sci Int 2018; 292: 115-24.
[http://dx.doi.org/10.1016/j.forsciint.2018.08.001 ] [PMID: 30296627]
[23]
Pichini S, Busardò FP, Gregori A, Berretta P, Gentili S, Pacifici R. Purity and adulterant analysis of some recent drug seizures in Italy. Drug Test Anal 2017; 9(3): 485-90.
[http://dx.doi.org/10.1002/dta.2134 ] [PMID: 27860443]
[24]
Fiorentin TR, Krotulski AJ, Martin DM, et al. Detection of cutting agents in drug-positive seized exhibits within the United States. J Forensic Sci 2019; 64(3): 888-96.
[http://dx.doi.org/10.1111/1556-4029.13968 ] [PMID: 30485426]
[25]
Janssen PAJ. The Levamisole Story Progress in Drug Research/Fortschritte der Arzneimittelforschung/Progrés des recherches pharmaceutiques. Basel: Birkhäuser Basel 1976; pp. 347-83.http://link.springer.com/10.1007/978-3-0348-7094-8_11
[http://dx.doi.org/10.1007/978-3-0348-7094-8_11]
[26]
Auffenberg C, Rosenthal LJ, Dresner N. Levamisole: a common cocaine adulterant with life-threatening side effects. Psychosomatics 2013; 54(6): 590-3.
[http://dx.doi.org/10.1016/j.psym.2013.02.012 ] [PMID: 23756121]
[27]
Espinoza LR, Perez Alamino R. Cocaine-induced vasculitis: clinical and immunological spectrum. Curr Rheumatol Rep 2012; 14(6): 532-8.
[http://dx.doi.org/10.1007/s11926-012-0283-1 ] [PMID: 22875288]
[28]
Knowles L, Buxton JA, Skuridina N, et al. Levamisole tainted cocaine causing severe neutropenia in Alberta and British Columbia. Harm Reduct J 2009; 6(1): 30.
[http://dx.doi.org/10.1186/1477-7517-6-30 ] [PMID: 19919709]
[29]
Czuchlewski DR, Brackney M, Ewers C, et al. Clinicopathologic features of agranulocytosis in the setting of levamisole-tainted cocaine. Am J Clin Pathol 2010; 133(3): 466-72.
[http://dx.doi.org/10.1309/AJCPOPQNBP5THKP1 ] [PMID: 20154286]
[30]
Graf J, Lynch K, Yeh C-L, et al. Purpura, cutaneous necrosis, and antineutrophil cytoplasmic antibodies associated with levamisole-adulterated cocaine. Arthritis Rheum 2011; 63(12): 3998-4001.
[http://dx.doi.org/10.1002/art.30590 ] [PMID: 22127712]
[31]
Muirhead TT, Eide MJ. Images in clinical medicine. Toxic effects of levamisole in a cocaine user. N Engl J Med 2011; 364(24)e52
[http://dx.doi.org/10.1056/NEJMicm1008722 ] [PMID: 21675882]
[32]
Brunt TM, Rigter S, Hoek J, Vogels N, van Dijk P, Niesink RJM. An analysis of cocaine powder in the Netherlands: content and health hazards due to adulterants. Addiction 2009; 104(5): 798-805.
[http://dx.doi.org/10.1111/j.1360-0443.2009.02532.x ] [PMID: 19413792]
[33]
Brunt TM, van den Berg J, Pennings E, Venhuis B. Adverse effects of levamisole in cocaine users: a review and risk assessment. Arch Toxicol 2017; 91(6): 2303-13.
[http://dx.doi.org/10.1007/s00204-017-1947-4 ] [PMID: 28314885]
[34]
Lee KC, Ladizinski B, Federman DG. Complications associated with use of levamisole-contaminated cocaine: an emerging public health challenge. Mayo Clin Proc 2012; 87(6): 581-6.
[http://dx.doi.org/10.1016/j.mayocp.2012.03.010 ] [PMID: 22677078]
[35]
World drug report. United Nations office on drugs and crime. 2015; Available at: . https://www.unodc.org/wdr2015/
[36]
Casale JF, Colley VL, Legatt DF. Determination of phenyltetrahydroimidazothiazole enantiomers (Levamisole/Dexamisole) in illicit cocaine seizures and in the urine of cocaine abusers via chiral capillary gas chromatography-flame-ionization detection: clinical and forensic perspectives. J Anal Toxicol 2012; 36(2): 130-5.
[http://dx.doi.org/10.1093/jat/bkr025 ] [PMID: 22337783]
[37]
Laar M, Cruts G, Ooyen M, et al. The Netherlands Drug Situation 2014 Report to the EMCDDA by the Reitox National Focal Point. Lisbon, Portugal: European Monitoring Centre for Drugs and Drug Addiction 2015.
[38]
Karch SB, Busardò FP, Vaiano F, Portelli F, Zaami S, Bertol E. Levamisole adulterated cocaine and pulmonary vasculitis: Presentation of two lethal cases and brief literature review. Forensic Sci Int 2016; 265: 96-102.
[http://dx.doi.org/10.1016/j.forsciint.2016.01.015 ] [PMID: 26855022]
[39]
Indorato F, Romano G, Barbera N. Levamisole-adulterated cocaine: Two fatal case reports and evaluation of possible cocaine toxicity potentiation. Forensic Sci Int 2016; 265: 103-6.
[http://dx.doi.org/10.1016/j.forsciint.2016.01.005 ] [PMID: 26866560]
[40]
Hantson P. Adultération de la cocaïne par le lévamisole: quels risques? Toxicol Anal Clin 2015; 27(4): 216-25.
[http://dx.doi.org/10.1016/j.toxac.2015.08.002]
[41]
SAMHSA. Nationwide public health alert issued concerning lifethreatening risk posed by cocaine laced with veterinary Antiparasite drug. US Department of Health and Human Services. 2009; Available at:. http://www.samhsa.gov/newsroom/advisories/090921vet 5101.aspx
[42]
Tallarida CS, Egan E, Alejo GD, Raffa R, Tallarida RJ, Rawls SM. Levamisole and cocaine synergism: a prevalent adulterant enhances cocaine’s action in vivo. Neuropharmacology 2014; 79: 590-5.
[http://dx.doi.org/10.1016/j.neuropharm.2014.01.002 ] [PMID: 24440755]
[43]
Tallarida CS, Tallarida RJ, Rawls SM. Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats. Drug Alcohol Depend 2015; 149: 145-50.
[http://dx.doi.org/10.1016/j.drugalcdep.2015.01.035 ] [PMID: 25683823]
[44]
Larocque A, Hoffman RS. Levamisole in cocaine: unexpected news from an old acquaintance. Clin Toxicol (Phila) 2012; 50(4): 231-41.
[http://dx.doi.org/10.3109/15563650.2012.665455 ] [PMID: 22455354]
[45]
Pawlik E, Mahler H, Hartung B, Plässer G, Daldrup T. Drug-related death: adulterants from cocaine preparations in lung tissue and blood. Forensic Sci Int 2015; 249: 294-303.
[http://dx.doi.org/10.1016/j.forsciint.2015.02.006 ] [PMID: 25747329]
[46]
Hofmaier T, Luf A, Seddik A, et al. Aminorex, a metabolite of the cocaine adulterant levamisole, exerts amphetamine like actions at monoamine transporters. Neurochem Int 2014; 73(100): 32-41.
[http://dx.doi.org/10.1016/j.neuint.2013.11.010 ] [PMID: 24296074]
[47]
Hess C, Ritke N, Broecker S, Madea B, Musshoff F. Metabolism of levamisole and kinetics of levamisole and aminorex in urine by means of LC-QTOF-HRMS and LC-QqQ-MS. Anal Bioanal Chem 2013; 405(12): 4077-88.
[http://dx.doi.org/10.1007/s00216-013-6829-x ] [PMID: 23436169]
[48]
Chang A, Osterloh J, Thomas J. Levamisole: a dangerous new cocaine adulterant. Clin Pharmacol Ther 2010; 88(3): 408-11.
[http://dx.doi.org/10.1038/clpt.2010.156 ] [PMID: 20668440]
[49]
Karch SB, Defraia B, Messerini L, Mari F, Vaiano F, Bertol E. Aminorex associated with possible idiopathic pulmonary hypertension in a cocaine user. Forensic Sci Int 2014; 240: e7-e10.
[http://dx.doi.org/10.1016/j.forsciint.2014.03.028 ] [PMID: 24794740]
[50]
Gurtner HP. Aminorex and pulmonary hypertension. A review. Cor Vasa 1985; 27(2-3): 160-71.
[PMID: 3928246]
[51]
Karch SB, Mari F, Bartolini V, Bertol E. Aminorex poisoning in cocaine abusers. Int J Cardiol 2012; 158(3): 344-6.
[http://dx.doi.org/10.1016/j.ijcard.2011.06.105 ] [PMID: 21764154]
[52]
Ruiz-Quiñone AK, Browne TJ, Espinosa-Riquer Z, González-Espinosa C, Cruz SL. Levamisole as opioid adulterant in mice: lethal, analgesic and hematological effects 2020; Available at: National Institute on Drug Abuse 2020.https://www.drugabuse.gov/nternational/abstracts/ levamisole-opioid-adulterant-in-mice-lethalanalgesic-hematolo- gical-effects
[53]
Goromaru T, Noda A, Matzuyama K, Iguchi S. Metabolism and excretion of aminopyrine in man. Chem Pharm Bull (Tokyo) 1976; 24(6): 1376-83.
[http://dx.doi.org/10.1248/cpb.24.1376 ] [PMID: 1021292]
[54]
Zhu NY, Legatt DF, Turner AR. Agranulocytosis after consumption of cocaine adulterated with levamisole. Ann Intern Med 2009; 150(4): 287-9.
[http://dx.doi.org/10.7326/0003-4819-150-4-200902170-00102 ] [PMID: 19153405]
[55]
Millar J, Péloquin R, De Leeuw NKM. Phenacetin-induced hemolytic anemia. Can Med Assoc J 1972; 106(7): 770-5.
[PMID: 5016923]
[56]
Hunter L, Gordge L, Dargan PI, Wood DM. Methaemoglobinaemia associated with the use of cocaine and volatile nitrites as recreational drugs: a review. Br J Clin Pharmacol 2011; 72(1): 18-26.
[http://dx.doi.org/10.1111/j.1365-2125.2011.03950.x ] [PMID: 21352269]
[57]
Cole C, Jones L, McVeigh J, Kicman A, Syed Q, Bellis MA. CUT: a guide to adulterants, bulking agents and other contaminants found in illicit drugs. Liverpool John Moores University, Centre for Public Health 2010.
[58]
Andreasen MF, Lindholst C, Kaa E. Adulterants and diluents in heroin, amphetamine, and cocaine found on the illicit drug market in Aarhus, Denmark. Open Forensic Sci J 2009; 2(1): 16-20.
[http://dx.doi.org/10.2174/1874402800902010016]
[59]
Brunt TM. Monitoring illicit psychostimulants and related health issues 2012.Available at:. https://hdl.handle.net/11245/1.385857
[60]
Maxwell JC, Coleman JJ, Feng S-Y, Goto CS, Tirado CF. Cheese: an old drug in a new wrapper. Drug Alcohol Depend 2012; 126(1-2): 161-7.
[http://dx.doi.org/10.1016/j.drugalcdep.2012.05.015 ] [PMID: 22765999]
[61]
Husain Z, Hussain K, Nair R, Steinman R. Diphenhydramine induced QT prolongation and torsade de pointes: an uncommon effect of a common drug. Cardiol J 2010; 17(5): 509-11.
[PMID: 20865683]
[62]
Wang Z, Woolverton WL. Self-administration of cocaine-antihistamine combinations: super-additive reinforcing effects. Eur J Pharmacol 2007; 557(2-3): 159-60.
[http://dx.doi.org/10.1016/j.ejphar.2006.11.056 ] [PMID: 17196194]
[63]
Banks ML, Andersen ML, Murnane KS, Meyer RC, Howell LL. Behavioral and neurochemical effects of cocaine and diphenhydramine combinations in rhesus monkeys. Psychopharmacology (Berl) 2009; 205(3): 467-74.
[http://dx.doi.org/10.1007/s00213-009-1555-y ] [PMID: 19430765]
[64]
Mehta MC, Jain AC, Billie M. Effects of cocaine and caffeine alone and in combination on cardiovascular performance: an experimental hemodynamic and coronary flow reserve study in a canine model. Int J Cardiol 2004; 97(2): 225-32.
[http://dx.doi.org/10.1016/j.ijcard.2003.08.022 ] [PMID: 15458688]
[65]
Grewal RS. The role of quinine in haemolysis. Br J Pharmacol Chemother 1958; 13(2): 175-7.
[http://dx.doi.org/10.1111/j.1476-5381.1958.tb00213.x ] [PMID: 13536282]
[66]
Bodenhamer JE, Smilkstein MJ. Delayed cardiotoxicity following quinine overdose: a case report. J Emerg Med 1993; 11(3): 279-85.
[http://dx.doi.org/10.1016/0736-4679(93)90047-B ] [PMID: 8340583]
[67]
Greene SA, Thurmon JC. Xylazine-a review of its pharmacology and use in veterinary medicine. J Vet Pharmacol Ther 1988; 11(4): 295-313.
[http://dx.doi.org/10.1111/j.1365-2885.1988.tb00189.x ] [PMID: 3062194]
[68]
Reyes JC, Negrón JL, Colón HM, et al. The emerging of xylazine as a new drug of abuse and its health consequences among drug users in Puerto Rico. J Urban Health 2012; 89(3): 519-26.
[http://dx.doi.org/10.1007/s11524-011-9662-6 ] [PMID: 22391983]
[69]
Ruiz-Colón K, Chavez-Arias C, Díaz-Alcalá JE, Martínez MA. Xylazine intoxication in humans and its importance as an emerging adulterant in abused drugs: a comprehensive review of the literature. Forensic Sci Int 2014; 240: 1-8.
[http://dx.doi.org/10.1016/j.forsciint.2014.03.015 ] [PMID: 24769343]
[70]
Torruella RA. Xylazine (veterinary sedative) use in Puerto Rico. Subst Abuse Treat Prev Policy 2011; 6(1): 7.
[http://dx.doi.org/10.1186/1747-597X-6-7 ] [PMID: 21481268]
[71]
Silva-Torres L, Veléz C, Álvarez L, Zayas B. Xylazine as a drug of abuse and its effects on the generation of reactive species and DNA damage on human umbilical vein endothelial cells. J Toxicol 2014; 2014492609
[http://dx.doi.org/10.1155/2014/492609 ] [PMID: 25435874]
[72]
Wong SC, Curtis JA, Wingert WE. Concurrent detection of heroin, fentanyl, and xylazine in seven drug-related deaths reported from the Philadelphia Medical Examiner’s Office. J Forensic Sci 2008; 53(2): 495-8.
[http://dx.doi.org/10.1111/j.1556-4029.2007.00648.x ] [PMID: 18284526]
[73]
Hoffmann U, Meister CM, Golle K, Zschiesche M. Severe intoxication with the veterinary tranquilizer xylazine in humans. J Anal Toxicol 2001; 25(4): 245-9.
[http://dx.doi.org/10.1093/jat/25.4.245 ] [PMID: 11386637]
[74]
Lu D-Z, Fan H-G, Kun M, et al. Antagonistic effect of atipamezole, flumazenil and naloxone following anaesthesia with xylazine, tramadol and tiletamine/zolazepam combinations in pigs. Vet Anaesth Analg 2011; 38(4): 301-9.
[http://dx.doi.org/10.1111/j.1467-2995.2011.00625.x ] [PMID: 21672125]
[75]
Jage J, Laufenberg-Feldmann R, Heid F. Medikamente zur postoperativen Schmerztherapie: Bewährtes und Neues. Teil 1: Nichtopioide. Anaesthesist 2008; 57(4): 382-90.
[http://dx.doi.org/10.1007/s00101-008-1326-x ] [PMID: 18351305]
[76]
Brack A, Rittner HL, Schäfer M. Nichtopioidanalgetika zur perioperativen SchmerztherapieRisiken und rationale Grundlagen für den Einsatz bei Erwachsenen. Anaesthesist 2004; 53(3): 263-80.
[http://dx.doi.org/10.1007/s00101-003-0641-5 ] [PMID: 15021958]
[77]
Brayfield A. Dipyrone Martindale: the complete drug reference. 38th ed. London: Pharmaceutical Press 2014.
[78]
Taylor J, Mellström B, Fernaud I, Naranjo JR. Metamizol potentiates morphine effects on visceral pain and evoked c-Fos immunoreactivity in spinal cord. Eur J Pharmacol 1998; 351(1): 39-47.
[http://dx.doi.org/10.1016/S0014-2999(98)00298-2 ] [PMID: 9698203]
[79]
López‐Muñoz FJ. Surface of synergistic interaction between dipyrone and morphine in the PIFIR model. Drug Dev Res 1994; 33(1): 26-32.
[http://dx.doi.org/10.1002/ddr.430330105]
[80]
Zelcer S, Kolesnikov Y, Kovalyshyn I, Pasternak DA, Pasternak GW. Selective potentiation of opioid analgesia by nonsteroidal anti-inflammatory drugs. Brain Res 2005; 1040(1-2): 151-6.
[http://dx.doi.org/10.1016/j.brainres.2005.01.070 ] [PMID: 15804436]
[81]
Kudlacek O, Hofmaier T, Luf A, et al. Cocaine Adulterants and Effects on Monoamine Transporters.In: Preedy VR, ed.The Neuroscience of Cocaine. San Diego, California: Academic Press 2017; pp. 59-68.
[http://dx.doi.org/10.1016/B978-0-12-803750-8.00007-5]
[82]
Knuth M, Temme O, Daldrup T, Pawlik E. Analysis of cocaine adulterants in human brain in cases of drug-related death. Forensic Sci Int 2018; 285: 86-92.
[http://dx.doi.org/10.1016/j.forsciint.2018.02.001 ] [PMID: 29454838]
[83]
Rossi S. Australian Medicines Handbook 2013. Adelaide: Australian Medicines Handbook Unit Trust 2013.
[84]
Bureau of Justice Assistance; Law Enforcement Naloxone Toolkit BJA National Training and Technical Assistance Center. Available at:. https://bjatta.bja.ojp.gov/tools/naloxone
[85]
Hernández-Delgadillo GP, Cruz SL. Endogenous opioids are involved in morphine and dipyrone analgesic potentiation in the tail flick test in rats. Eur J Pharmacol 2006; 546(1-3): 54-9.
[http://dx.doi.org/10.1016/j.ejphar.2006.07.027 ] [PMID: 16914138]
[86]
Mohr ALA, Browne T, Martin DM, Logan BK. Xylazine: a toxic adulterant found in illicit street drugs 2020.Available at: . https://www.npsdiscovery.org/wp-content/uploads/2020/11/Public-Alert_ Xylazine-Final.pdf
[87]
Spoerke DG, Hall AH, Grimes MJ, Honea BN III, Rumack BH. Human overdose with the veterinary tranquilizer xylazine. Am J Emerg Med 1986; 4(3): 222-4.
[http://dx.doi.org/10.1016/0735-6757(86)90070-7 ] [PMID: 3964361]
[88]
Maryland Poison Center. Xylazine. ToxTidbits. 2019; Available at: . https://www.mdpoison.com/media/SOP/mdpoisoncom/ToxTidbits/2019/Jan%202019%20ToxTidbits.pdf
[89]
Michigan Regional Poison Control Center. Xylazine. Michigan Regional Poison Control Center, Children’s Hospital of Michigan The Rapidly Changing Composition of the Global Street Drug Supply and its Effects Current Psychopharmacology, 2021, Vol. 10, No. 2 153 2020; Available at: . https://www.michigan.gov/documents/mdhhs/Xylazine03042019_648483_7.pdf
[90]
Johnston A, King LA. Heroin profiling: Predicting the country of origin of seized heroin. Forensic Sci Int 1998; 95(1): 47-55.
[http://dx.doi.org/10.1016/S0379-0738(98)00081-4]
[91]
Akhgari M, Etemadi-Aleagha A, Jokar F. Street level heroin, an overview on its components and adulterants.In: Preedy VR, edNeuropathology of drug addictions and substance misuse. San Diego, California: Academic Press 2016; pp. 867-77.http://www.sciencedirect.com/science/article/pii/B978012800213100081X
[http://dx.doi.org/10.1016/B978-0-12-800213-1.00081-X]
[92]
Akhgari M, Jokar F, Bahmanabadi L, Aleagha AE. Street-level heroin seizures in Iran: a survey of components. J Subst Use 2012; 17(4): 348-55.
[http://dx.doi.org/10.3109/14659891.2011.592898]
[93]
Cunha-Oliveira T, Rego AC, Garrido J, Borges F, Macedo T, Oliveira CR. Street heroin induces mitochondrial dysfunction and apoptosis in rat cortical neurons. J Neurochem 2007; 101(2): 543-54.
[http://dx.doi.org/10.1111/j.1471-4159.2006.04406.x ] [PMID: 17250679]
[94]
Drug Enforcement Administration. DEA, El Paso Intelligence Center Bulletin. Suspected heroin seizures turn out to be Noscapine. 2017.
[95]
Kloner RA, Rezkalla SH. Cocaine and the heart. N Engl J Med 2003; 348(6): 487-8.
[http://dx.doi.org/10.1056/NEJMp020174 ] [PMID: 12571254]
[96]
Michaud K, Grabherr S, Shiferaw K, Doenz F, Augsburger M, Mangin P. Acute coronary syndrome after levamisole-adultered cocaine abuse. J Forensic Leg Med 2014; 21: 48-52.
[http://dx.doi.org/10.1016/j.jflm.2013.10.015 ] [PMID: 24365689]
[97]
Marsden J, Darke S, Hall W, et al. Mitigating and learning from the impact of COVID-19 infection on addictive disorders. Addiction 2020; 115(6): 1007-10.
[http://dx.doi.org/10.1111/add.15080 ] [PMID: 32250482]
[98]
Schwartz BG, Rezkalla S, Kloner RA. Cardiovascular effects of cocaine. Circulation 2010; 122(24): 2558-69.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.940569 ] [PMID: 21156654]
[99]
Havakuk O, Rezkalla SH, Kloner RA. The cardiovascular effects of cocaine. J Am Coll Cardiol 2017; 70(1): 101-13.
[http://dx.doi.org/10.1016/j.jacc.2017.05.014 ] [PMID: 28662796]
[100]
Riezzo I, Fiore C, De Carlo D, et al. Side effects of cocaine abuse: multiorgan toxicity and pathological consequences. Curr Med Chem 2012; 19(33): 5624-46.
[http://dx.doi.org/10.2174/092986712803988893 ] [PMID: 22934772]
[101]
Gold M. Fentanyl-adulterated Cocaine: Strategies to Address the New Normal. Addiction Policy Forum. 2019; Available at:. https://www.addictionpolicy.org/post/fentanyl-adulterated-cocaine-strategies-to-address-the-new-normal
[102]
Haim DY, Lippmann ML, Goldberg SK, Walkenstein MD. The pulmonary complications of crack cocaine. A comprehensive review. Chest 1995; 107(1): 233-40.
[http://dx.doi.org/10.1378/chest.107.1.233 ] [PMID: 7813284]
[103]
Tashkin DP, Khalsa ME, Gorelick D, et al. Pulmonary status of habitual cocaine smokers. Am Rev Respir Dis 1992; 145(1): 92-100.
[http://dx.doi.org/10.1164/ajrccm/145.1.92 ] [PMID: 1731605]
[104]
Restrepo CS, Carrillo JA, Martínez S, Ojeda P, Rivera AL, Hatta A. Pulmonary complications from cocaine and cocaine-based substances: imaging manifestations. Radiographics 2007; 27(4): 941-56.
[http://dx.doi.org/10.1148/rg.274065144 ] [PMID: 17620460]
[105]
Hind CR. Pulmonary complications of intravenous drug misuse. 1. Epidemiology and non-infective complications. Thorax 1990; 45(11): 891-8.
[http://dx.doi.org/10.1136/thx.45.11.891 ] [PMID: 2256022]
[106]
Wilson LE, Torbenson M, Astemborski J, et al. Progression of liver fibrosis among injection drug users with chronic hepatitis C. Hepatology 2006; 43(4): 788-95.
[http://dx.doi.org/10.1002/hep.21091 ] [PMID: 16557548]
[107]
Radke JB, Owen KP, Sutter ME, Ford JB, Albertson TE. The effects of opioids on the lung. Clin Rev Allergy Immunol 2014; 46(1): 54-64.
[http://dx.doi.org/10.1007/s12016-013-8373-z ] [PMID: 23636734]
[108]
Drug Enforcement Administration. The Heroin Signature Program and Heroin Domestic Monitor Program 2014. DEA; 2016 Sep (DEA Intelligence Report) Report No: DEA-DCW-DIR-051-16 2014..
[109]
Drug Enforcement Administration. The 2015 Heroin Signature Program Report. DEA; 2017 Aug (DEA Intelligence Report) Report No: DEA-DCW-DIR-032-17. 2017.
[110]
Drug Enforcement Administration. The 2015 Heroin Domestic Monitor Program. DEA; 2017 Oct (DEA Intelligence Report) Report No: DEA-DCW-DIR-035-17. 2017.
[111]
Drug Enforcement Administration. The 2016 Heroin Signature Program Report. DEA; 2018 Oct (DEA Intelligence Report) Report No: DEA-DCW-DIR-035-18. 2018.
[112]
Drug Enforcement Administration. The 2017 Heroin Domestic Monitor Program. DEA; 2019 Jul (Joint Intelligence Report) Report No: DEA-DCW-DIR-028-19. 2019.
[113]
DuPont RL. The opioid epidemic is an historic opportunity to improve both prevention and treatment. Brain Res Bull 2018; 138: 112-4.
[http://dx.doi.org/10.1016/j.brainresbull.2017.06.008 ] [PMID: 28627395]
[114]
Wang Y, Goldberg B, Delcher C. Florida Drug-Related Outcomes Surveillance and Tracking System 2020.Available at:. https://frost.med.ufl.edu/
[115]
Coomber R. Vim in the veins-fantasy or fact: the adulteration of illicit drugs. Addict Res 1997; 5(3): 195-212.
[http://dx.doi.org/10.3109/16066359709005261]
[116]
Zibbell J. Non-fatal opioid overdose and associated health outcomes: final summary report. US Department of Health and Human Services. 2019; Available at: . https://aspe.hhs.gov/basic-report/non-fatal-opioid-overdose
[117]
Zhao SX, Kwong C, Swaminathan A, Gohil A, Crawford MH. Clinical characteristics and outcome of methamphetamine-associated pulmonary arterial hypertension and dilated cardiomyopathy. JACC Heart Fail 2018; 6(3): 209-18.
[http://dx.doi.org/10.1016/j.jchf.2017.10.006 ] [PMID: 29496022]
[118]
Möbius C, Kustermann A, Struffert T, Kornhuber J, Müller HH. c-MRI findings after crystal meth abuse. J Addict Med 2014; 8(5): 384-5.
[http://dx.doi.org/10.1097/ADM.0000000000000051 ] [PMID: 25026102]
[119]
Gold MS, Kobeissy FH, Wang KKW, et al. Methamphetamine- and trauma-induced brain injuries: comparative cellular and molecular neurobiological substrates. Biol Psychiatry 2009; 66(2): 118-27.
[http://dx.doi.org/10.1016/j.biopsych.2009.02.021 ] [PMID: 19345341]
[120]
Hegde VL, Nagarkatti M, Nagarkatti PS. Cannabinoid receptor activation leads to massive mobilization of myeloid-derived suppressor cells with potent immunosuppressive properties. Eur J Immunol 2010; 40(12): 3358-71.
[http://dx.doi.org/10.1002/eji.201040667 ] [PMID: 21110319]
[121]
Huang Y-HJ, Zhang Z-F, Tashkin DP, Feng B, Straif K, Hashibe M. An epidemiologic review of marijuana and cancer: an update. Cancer Epidemiol Biomarkers Prev 2015; 24(1): 15-31.
[http://dx.doi.org/10.1158/1055-9965.EPI-14-1026 ] [PMID: 25587109]
[122]
Bell GL, Lau K. Perinatal and neonatal issues of substance abuse. Pediatr Clin North Am 1995; 42(2): 261-81.
[http://dx.doi.org/10.1016/S0031-3955(16)38946-5 ] [PMID: 7536914]
[123]
Wagner CL, Katikaneni LD, Cox TH, Ryan RM. The impact of prenatal drug exposure on the neonate. Obstet Gynecol Clin North Am 1998; 25(1): 169-94.
[http://dx.doi.org/10.1016/S0889-8545(05)70364-8 ] [PMID: 9547766]
[124]
COVID-19 and the drug supply chain: from production and trafficking to use. United Nations Office on Drugs and Crime 2020.. https://www.unodc.org/documents/data-andanalysis/covid/COVID-19-and-drug-supply-chain-Mai2020.pdf
[125]
Ribeiro M, Trevizol AP, Frajzinger R, et al. Adulterants in crack cocaine in Brazil. Trends Psychiatry Psychother 2019; 41(2): 186-90.
[http://dx.doi.org/10.1590/2237-6089-2017-0143 ] [PMID: 31314858]
[126]
Report on pain management best practices: updates, gaps, inconsistencies, and recommendations US Department of Health andHuman Services. 2019; Available at: . https://www.hhs.gov/ash/advisory-committees/pain/reports/index.html
[127]
Grinspoon P. A tale of two epidemics: When COVID-19 and opioid addiction collide. Harvard Health Blog. 2020; Available at:. https://www.health.harvard.edu/blog/a-tale-of-two-epidemics-when-COVID-19-and-opioid-addiction-collide-2020042019569
[128]
Volkow N. COVID-19: Potential Implications for Individuals with Substance Use Disorders. National Institute on Drug Abuse. 2020; Available at: . https://www.drugabuse.gov/about-nida/noras- blog/2020/04/COVID-19-potential-implications-individuals-substance-use-disorders
[129]
Volkow ND. Collision of the COVID-19 and addiction epidemics. Ann Intern Med 2020; 173(1): 61-2.
[http://dx.doi.org/10.7326/M20-1212 ] [PMID: 32240293]
[130]
Gold M. The fentanyl crisis is only getting worseAddiction Policy Forum 2019.Available at:. https://www.addictionpolicy.org/post/the-fenta-nyl-crisis-is-only-getting-worse
[131]
Luthra S. Opioid Addiction Accelerate Coronavirus Risks, Says NIDA Director. Kaiser Health News. 2020; Available at:. https://khn.org/news/vaping-opioid-addiction-accelerate-coronavirus-risks-says-nida-director/
[132]
Coronaviruses National Institute of Allergy and Infectious Diseases.; 2020.Available at:. http://www.niaid.nih.gov/diseases-conditions/coronaviruses
[133]
National Institute on Drug Abuse. Substance use disorders linked to COVID-19 susceptibility. National Institutes of Health (NIH). 2020; Available at: . https://www.nih.gov/news-events/news-releases/substance-use-disorders-linked-COVID-19-susceptibility
[134]
Wang QQ, Kaelber DC, Xu R, Volkow ND. COVID-19 risk and outcomes in patients with substance use disorders: analyses from electronic health records in the United States. Mol Psychiatry 2020; 26(1): 30-9.
[http://dx.doi.org/10.1038/s41380-020-00880-7 ] [PMID: 32929211]


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VOLUME: 10
ISSUE: 2
Year: 2021
Published on: 25 January, 2021
Page: [138 - 154]
Pages: 17
DOI: 10.2174/2211556010666210125124645

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