Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances
Abstract
:1. Introduction
2. Results
2.1. Non-Biological Samples
2.2. Biological Samples
2.3. Case Series Reports
Drug Class #Cases | Adulterant #Cases | Analysis | Seizure Yrs Country | Ref. | Drug Class #Cases | Adulterant # Cases | Analysis | Seizure Yrs Country | Ref. | ||
---|---|---|---|---|---|---|---|---|---|---|---|
Cocaine | Opioids | ||||||||||
1 | 7841 | Levamisole; phenacetin; caffeine; lidocaine | GC-MS | 2006–2015 Switzerland | [20] | 33 | Fentanyl 2 | U-47700; lidocaine; heroin; 6-AM; methoxyacetyl fentanyl; phenyl fentanyl; codeine; methacryl fentanyl; caffeine | GEMBE | 2019 USA | [27] |
2 | 728 | Levamisole 433; phenacetin 323; aminopyrine 60; benzocaine 29; lidocaine 22; caffeine 21 | FTIR-MCR-ALSGC-FID | 2009–2015 Brazil | [21] | 34 | Fentanyl 46 | Xylazine 46 | GC-MS LC-HRMS/MS | 2020 Australia | [28] |
3 | 24 | Tetramisole 23; levamisole 1 | LC-MS/MS | 2013–2016 Switzerland | [43] | 35 | Heroin 4 | Ocfentanil 4; caffeine 4; paracetamol 4 | GC-MS LC-MS/ MS | 2015 Spain | [30] |
4 | 351 | Levamisole 214; lignocaine 103; meth 13; MDMA 10; phenacetin 7; benzocaine 6; THC 4; amphetamine 1; heroin 2 | GC-MS | 2015–2016 Canada | [12] | 36 | Heroin 217; cocaine 19; amphetamine 367 | Caffeine 852; nicotine 244; acetaminophen 261; levamisole 8 | GC-MS | 2015–2016 Hungary | [44] |
5 | 292 | Levamisole 292 | SVM-DA GC-FID | 2015 Belgium | [37] | 37 | Heroin 11 | Meth 7; dextromethorphan 3; cocaine 2; diazepam 1 | GC-MS | 2015–2016 Canada | [12] |
6 | 97 | Levamisole 92; phenacetin 22; caffeine 14; hydroxyzine 10; benzocaine 6 | GC-MS GC-TMS UPLC-MS/MS | 2016–2017 USA | [17] | 38 | Heroin 10 | Lead 10; caffeine 8; chloroquine 3; methadone 3; phenobarbital 2; tramadol 2; acetaminophen 1; meth 2 | HPLC-MS GC-MS FAAS | 2016–2017 Iran | [15] |
7 | 17 | Caffeine 11; lidocaine 10; acetaminophen 9; phenacetin 7; diltiazem 4 | HPLC-DAD | 2017 Brazil | [22] | 39 | Heroin 198 | Quinine/quinidine 44; fentanyl 31; lidocaine 24; caffeine 21; levamisole 20; phenacetin 12 | GC-MS LC-Q-ToF | 2017 USA | [13] |
8 | 96 | Levamisole 30; lidocaine 26; phenacetin 13; caffeine 11; quinine/quinidine 12 | GC-MS LC-Q-ToF | 2017 USA | [13] | 40 | Heroin 7 | Acetaminophen 4; caffeine 4; fentanyl 1 | GC-MS | 2018 UK | [29] |
9 | 3 | Caffeine 3 | Colorimetric GC-FID | 2018 Brazil | [21] | 41 | Heroin 30 | Caffeine 30; noscapine 26; papaverine 22; paracetamol 16; lidocaine 2; dextromethorphan 5 | GC-MS GC-FID SWV | 2018 Belgium | [72] |
10 | 50 | Levamisole 17; lidocaine 16 | CE-C4D | 2018 Brazil | [23] | 42 | Heroin 3 | Caffeine 1 | GC-MS GC-VUV | 2019 USA | [38] |
11 | 3 | Levamisole 3 | SWV HPLC-MS GC-MS GC-FID NMR | 2018 Belgium | [36] | 43 | Heroin 59 Meth 26 Oxycodone | Caffeine 7 | GC-MS | 2019 Australia | [39] |
12 | 3 | Levamisole 3 | CV | 2018 Belgium | [14] | 44 | Heroin 659 | Paracetamol 656; caffeine 656 | GC-MS HPLC-UV LC-Q-ToF | 2019–2020 Luxembourg | [16] |
13 | 7 | Levamisole 5; Phenacetin 3; caffeine 2; procaine 1; tetracaine 1 | GC-MS NMR | 2018 France | [24] | 45 | Heroin 1 | 4-AP-t-BOC (tert-butyl-4-anilinopiperidine-1-carboxylate) | GC-MS LC-MS | 2019–2020 Ireland | [40] |
14 | 156 | Levamisole 58; caffeine 39; quinine/quinidine 27; diphenhydramine 20; phenacetin 17; acetaminophen 17; lidocaine 16; procaine 13; diltiazem 10; xylazine 4; atropine 2; aminopyrine 4; hydroxyzine 3; dipyrone 2; guaifenesin 1; gabapentin 1 | GC-MS LC-Q-ToF | 2018 USA | [25] | 46 | Opium 10 | Lead 10; acetaminophen 8; chloroquine 4; tramadol 2 | HPLC-MS GC-MS FAAS | 2016–2017 Iran | [15] |
15 | 47 | Levamisole; phenacetin; lidocaine; caffeine | DART-HRMS | 2019 China | [18] | 47 | Opium 10 | Lead 10 | AAS | 2015–2016 Iran | [31] |
16 | 1078 | Levamisole 584; phenacetin 386; caffeine 113; lidocaine; ketamine; hydroxyzine | GC-MS HPLC-UVLC-Q-ToF | 2019–2020 Luxembourg | [16] | 48 | Morphine 6 | Codeine 4; thebaine 2; papaverine 2; noscapine 2; 6-AM 1; heroin 1; oxycodone 1; acetylcodeine 1; fentanyl 1; alprazolam 1 | GC-MS | 2015–2016 Canada | [12] |
17 | 169 | Phenacetin 169 | GC-EA-IRMS | 6 yrs France | [41] | 49 | Fentanyl 100 | Caffeine 96; etizolam 50; carfentanil 8; cocaine 7; heroin 6; acetyl fentanyl 1 | IR SERS PS-MS | 2018–2022 Canada | [73] |
18 | 306 | Phenacetin 231; caffeine 196; aminopyrine 82; levamisole 16; lidocaine 5; benzocaine 1 | GC-MS-QP HPLC-DAD | 2019 Uruguay | [19] | NPS | |||||
19 | 45 | Caffeine 32; phenacetin 30; levamisole 27; lidocaine 15 | GC-MS | 2020 Colombia | [42] | 50 | 3-MEC | 3-MeO-PCP; 4F-α-PVP; DiPT; ketamine | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
Amphetamines stimulants | 51 | 4-Aco-DMT | DPT | LC-Q-ToF NMR | 2010–2014 Sweden | [33] | |||||
20 | Amphetamine 28 | Meth 25; DMA 14; MDMA 2; cocaine 1; methylphenidate 1; lignocaine 1 | GC-MS | 2015–2016 Canada | [12] | 52 | 4-Meo-PCP | 3-MeO-PCP | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
21 | Ecstasy 10 | Lead 10; meth 4; heroin 2 | HPLC-MSGC-MS FAAS | 2016–2017 Iran | [15] | 52 | 4-MeO-PCP 2 | AB-FUBINACA 2; nicotine 2; ketamine 2; amitriptyline 2 | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
22 | MDMA 211 | Unspecified 104; methylone 35; synthetic cathinones 21; methamphetamine 13; benzylpiperazine 8; dextromethorphan 8; mephedrone 5; Amphetamine 4 butylone 4; cocaine 4; ketamine 1; MeO-amphetamine 3; LSD 1 | Colorimetric | 2010–2015 USA | [32] | 53 | 4-OH-MET | Methoxetamine | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
23 | MDMA 122 | Ethylone 189; meth 34; MDA 16; cocaine 10; 5-Meo-DALT 8; phenethylamine 7; 2C-T-2 6; DMA 5; dibutylone 3; DMT 2; amphetamine 2; methylone 2 sildenafil 2; THC 1 methoxetamine 1; 2C-B 1; MDDM 1; | GC-MS | 2015–2016 Canada | [12] | 54 | α-MT | MDPBP; 25B-NBOME | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
24 | MDMA 6 | Caffeine; lidocaine | GC-MS Raman Spectroscopy | 2020 Brazil | [74] | 55 | Butyrylfentanyl 2 | Fentanyl 2; acetylfentanyl 2; 4-ANPP 2 | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
25 | MDMA 302 | Unknown 259; dimethylsulfone 36; dimethylsulfone and Caffeine 2; ketamine 2; MDEA 1; cocaine and ketamine 1; N-Moc-MDMA and T-Boc-MDMA 1 | GC-MS/MS | 2019–2020 Australia | 56 | Ethylphenidate | 5-Meo-DALT; caffeine; phenacetin; lidocaine | LC-Q-ToF NMR | 2010–2014 Sweden | [33] | |
26 | Methamphetamine 181 | N-isopropyl benzylamine 37; DMA 30; amphetamine 24; cocaine 15; α-PHP 1; DMMA 1; N-Me-2AI 1; ethylphenidate 1; phenethylamine 1; praziquantel 1; 25C-NBOME 1; 25I-NBOME 1; ketamine 1; methoxetamine 1; MDMA 36; THC 36; heroin 3; diazepam 3; alprazolam 1; quetiapine 5; lignocaine 7 | GC-MS | 2015–2016 Canada | [12] | 57 | Isopropylphenidate | Methylphenidate | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
27 | Methamphetamine 10 | Lead 10; phenmetrazin e 6; pseudoephedrine 5; caffeine 3; dextromethorphan 3; ketamine 1; MDMA 1 | HPLC-MSGC-MS FAAS | 2016–2017 Iran | [15] | 58 | MDMB-CHMICA | AMB-FUBINACA; 1-(cyclohexylmethyl)-1H-indole-3-carbonyl)valine | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
28 | Methamphetamine 219 | Phenacetin 3; caffeine 2; diltiazem 2 | GC-MS LC-Q-ToF | 2017 USA | [13] | 59 | MET | 3-MeO-PCP/ 4-MeO-PCP; 4-AcO-DMT; 3-MEC; 4F-α-PVP; Ketamine | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
Cannabinoids | 60 | Mitragynine | Caffeine | LC-MS/ MS | 2010–2014 Sweden | [33] | |||||
29 | ∆9-THC 9 | Cocaine 4; 4-F-AMB 3; MDMA 1; methamphetamine 1; 5-UR-144 1; 5F-AKB48 1; desvenlafaxine 1 | GC-MS | 2015–2016 Canada | [12] | 61 | NM2201 and THJ-018 | MDMB-CHMICA | LC-Q-ToF NMR | 2010–2014 Sweden | [33] |
30 | ∆9-THC 1142 | MDMB-4en-PINACA 270 | GC-MS HPLC-MS UPLC-QToF TLC UPLC-MS3 UPLC-DAD FTIR MALDI-HRMS | 2020–2021 Europe | 62 | THJ-018 | MDMB-BB-22 | LC-Q-ToF NMR | 2010–2014 Sweden | [33] | |
Opioids | 63 | 2C-B 46 | 5-MeO-DALT 46; MDMA 1 | GC-MS | 2015–2016 Canada | [12] | |||||
31 | Crack heroin 10 | Lead 10 | AAS | 2015–2016 Iran | [31] | 64 | NEP 10 | Caffeine 10 | GC-MS Raman spectroscopy | 2020 Brazil | [31] |
32 | Fentanyl and analogs 26 Heroin 5 | Caffeine 33; AMB-FUBINACA 29; heroin 17; phencetin 10; etizolam 6 AB-FUBINACA 5; fentanyl analogs 6 benzocaine 3; 5F-MDMB-PINACA 3 metformin 2; meth 3 lidocaine 1; acetaminophen 3; dextromethorphan 2; 4Cl-α-PVP 1; UF-17 1; furanyl 5F-MDMB-PICA 1; hydromorphone 1; flubromazolam 1 | FTIR Fentanyl immunoassay GC-MS LC-HRMS/MS LC-MS | 2018–2019 Canada | [42] |
Clinical Description | Adulterant | Adulterant Analysis | Matrix | Drug Analysis ng/mL | Ref. |
---|---|---|---|---|---|
Cocaine | |||||
Hx: 52 y F chronic cocaine user admitted with ulcers on extremities; pustule, rash on arms/axilla/temple; longstanding perforation hard palate Lab: c-ANCA+; LA+ Skin biopsy: superficial neutrophil-rich dermal infiltrate, papillary derma edema Dx: pyoderma gangrenosum associated with LAC Tx: prednisone, topical betamethasone | Levamisole * | NA | U | Cocaine + | [54] |
Hx: 31 y F cocaine user admitted with facial pain, chronic fronto-maxillary sinus pain, yellow/green discharge, rhinorrhea, crusting, rash legs Lab: ESR 2 mm/h; CRP 24 mg/L; WCC 7.7; p-ANCA+; c-ANCA-; anti-PR3+; anti-MPO Nasal biopsy: ulceration, necrosis surrounded macrophages and fibrotic stroma; chronic inflammatory infiltrate, no vasculitis Dx: CIMDLs, systemic levamisole vasculitis Tx: abstinence, mycophenolate, azathioprine, rituximab, surgical debridement | Levamisole * | NA | U | Cocaine + | [44] |
Hx: 30 y F cocaine user, chronic sinusitis, left deviated septum, rhinitis, purulent rhinorrhea, macular rash on hands; Lab: ESR 5 mm/h; CPR 30 mg/L; WCC 11.1; p-ANCA+; c-ANCA-; anti-MPO-; anti-PR3- Nasal biopsy: ulceration, acute/chronic inflammation, fibrotic stroma, vessels permeated by inflammatory cells, no fibrinoid necrosis Dx: CIMDLs and systemic levamisole vasculitis Tx: abstinence, drug rehabilitation, surgical debridement | Levamisole * | NA | U | Cocaine + | [44] |
Hx: 36 y M cocaine user, severe facial pain, epistaxis, crusting, rhinorrhoea, rash/livedo in thighs; hematuria, proteinuria Lab: ESR 36 mm/h; CPR 44 mg/L; WCC 8.0; p-ANCA+; c-ANCA-; anti-MPO-; anti-PR3-; IgG4 increase Nasal biopsy (n = 3): extensive ulceration, fibrin, proliferative fibrosis; acute/chronic inflammatory cells; no vasculitis (1st); geographic necrosis, fibrinoid necrosis foci (2nd); ulcerated mucosa and granulation; no vasculitis (3rd); Dx: CIMDLs and systemic levamisole vasculitis Tx: abstinence, steroids; methotrexate; mycophenolate; rituximab, surgical debridement | Levamisole | NA | U | Cocaine +; levamisole + | [44] |
Hx: 48 y F, severe facial pain, epistaxis, septal perforation with fistula from skin to intra-nasal cavity, soft palate ulceration; hematuria Lab: ESR 80 mm/h; CPR 48 mg/L; WCC 7,6; p-ANCA+; c-ANCA-; anti-MPO-; anti-PR3 + Dx: CIMDLs and systemic levamisole vasculitis Tx: abstinence, steroids, methotrexate, surgical debridement | Levamisole | NA | U | Cocaine +; levamisole + | [44] |
Hx: 48 y M, previous Chron’s disease and pneumonia, admitted with purpuric rash worsening in four limbsLab: c-ANCA+; ANA+; anti-MPO- Skin biopsy: leukocytoclastic vasculitis and multiple fibrin thrombi; Dx: levamisole adulterated cocaine-associated vasculitis Tx: supportive therapy | Levamisole * | NA | U | Cocaine + | [60] |
Hx: 53 y F cannabis/cocaine user, admitted with extensive, painful retiform symmetric purpura patches in limbs, buttocks/abdomen with necrosis evolution Lab: neutropenia, thrombocytopenia, CPR 13 mg/L; LA-; anticardiolipin antibody-; cryoglobulins-; c-ANCA+ Skin biopsy: thrombotic vasculopathy Dx: levamisole-induced vasculitis Tx: corticosteroids, surgical debridement of necrotic tissue | Levamisole * | NA | U | Cocaine +; THC + | [61] |
Hx 46 y M, increased cocaine use last 3 months, admitted with weakness/fatigue, blood-tinged sputum, cough Lab (n = 2) creatinine 9.61; GFR 7 mL/min; K+ 7 meq/L (1st); AST 196; ALT 235; total bilirubin 13; A-phosphatase 520 (2nd); ANA+; p-ANCA+; c-ANCA+; anti-α-SME+; anti-HCV+; HCV-RNA- CT chest: cavitary lesions Renal biopsy: fibrous glomerular crescents, few cellular crescents (severe kidney damage) Liver biopsy: isolated intrahepatic bile duct with onion skinning and foci injury, canalicular cholestasis, periportal ductal reaction Dx: intrahepatic duct injury associated with LAC-induced glomerulonephritis Tx: dialysis for AKI; ursodeoxycholic/cholestyramine for duct damage | Levamisole * | NA | U | Cocaine + | [62] |
Hx: 29 y M, 3 months cocaine abuse, admitted with severe head-pain, incomprehensible vocalization, amnesia, aggressiveness, agitation, sleep inversion, space/time disoriented; MRI brain (n = 2): ubiquitous white matter small lesions (1–14 d after adm); additional punctate lesions in corpus callosum, abn meningeal enhancement, contrast agent in CSF (15–31 d after adm); CSF: protein 224 mg/dL; albumin 37.9; RFA: multiple segmental occlusion in central retinal artery Audiogram: bilateral sensorineural hearing loss; Dx: acute SS associated to LAC; Tx: methylprenisolone, mycophenolate (at brain damage relapse) | Levamisole | UPLC-ESI+-MS/MS | H segments (n = 6) | Cocaine >5; BE > 5; EME 0.07–0.11; norcocaine 0.58–1; levamisole 0.07–1.14; tramadol 1.38–2.16 | [45] |
Hx: 33 y M cocaine abuse history, admitted with 4 weeks of nasal obstruction, dysphagia, otalgia, nasal bridge deformity; Endoscopy: nasal corridor necrosis; CT head/chest: nasal cavity extensive bone destruction, multiple small pulmonary nodules; Lab: leukocytosis, high CRP, high ESR; c-ANCA+; Nasal biopsy: no vasculitis signs; Dx: CIMDL; Tx: counseling on cocaine cessation | Levamisole * | NA | U | Cocaine +; metabolites + | [57] |
Hx: 59 y M active cocaine use, anamnestic febrile syndrome with neutropenia/agranulocytosis treated and recovered; new ED admission with 4 days abdominal pain/bloody diarrhea probably due to rectal cocaine administration CT abdomen: rectum/sigmoid/descending colon/caecum/appendix with increased bowel wall thickness Flexible sigmoidoscopy: sigmoid colon/rectum edema, severe ulceration; bowel ischemia/necrosis Lab: normal ENA and ANCA+ Dx: neutropenia agranulocytosis induced by levamisole complicated by bowel necrosis Tx: surgery sigmoid colectomy, ileocecectomy with end ileostomy and descending mucus fistula | Levamisole * | NA | U | Cocaine + | [46] |
Hx: 53 y M crack cocaine user, anamnestic hypertension/dyslipidemia/chronic pain syndrome, developed 2 wks limb rash/hematuria/creatinine increase (150 µmol/L); ED admission with abdomen/thighs/legs purpura and ear necrosis Lab: urea 24.8 mmol/L; cr 449; PCR 186.8 mg/mmol; Na = 137 mmol/L; K+ = 4.9 mmol/L; ANA -; ENA -; c-ANCA -; p-ANCA +; HCV/HBV/HIV neg; Renal biopsy: active focal crescentic and necrotizing GN, glomerular capillary wall thickening; tubular epithelial injury; no active vasculitis Dx: concurrent AAV secondary to LAC and associated MN Tx: corticosteroids, ACE inhibitor | Levamisole * | CEDIA | U | Cocaine metabolites (s) + | [58] |
Hx: 35 y M tobacco/cannabis smoker, intranasal cocaine use, inhaled crack use; admitted to ED with hemoptysis, iron deficiency anemia CT chest: bilateral ground glass opacities; Lab: urea 7.1 mmol/L; Cr 150 µmol/L; Na 136 mmol/L; K+ 4 mmol/L; ANA -; c-ANCA -; p-ANCA +; cryoglobulinus -; HBV/HCV/HIV neg; Renal biopsy: active segmental fibrinoid necrosis, no arteries vasculitis, diffuse epithelial cell foot process effacement and deposit of immune complex; Dx: concurrent AAV secondary to LAC and associated MN; Tx: prednisone, cyclophosphamide | Levamisole | CEDIA and LC-MS | U | Cocaine metabolite (s) +; cannabinoids, opiates, benzodiazepines, levamisole (c) + | [58] |
Hx: 34 y M cocaine user; anamnestic obesity, hyperpigmented lesions, leukocitoclastic vasculitis due to levamisole; recently admitted to ED with proteinuria associated with fatigue/arthralgias Lab: urea 4.6 mmol/L; Cr 71 µmol/L; PCR 449.9mg/mmol; Na+ 140 mmol/L; K+ 4.4 mmol/L; ANA-; ENA-; c-ANCA-; p-ANCA+; HBV/HCV/HIV neg Renal biopsy: no glomerular crescentic or necrotizing injury, glomerular artery wall normal, no artery vasculitis Dx: development of MN after AAV secondary to LAC | Levamisole | CEDIA and LC-MS | U | Cocaine metabolites (s) +;opiates +; benzodiazepines +; levamisole (c) + | [58] |
Hx: 68 y M cocaine user, recent haemorrhagic lesions on forearms/face, anamnestic analogous vasculitis 6 months prior Lab: pancytopenia/neutropenia; ANA+; p-ANCA+; anti-PR3+; anti-MPO+ Skin biopsy: leukocytoclastic vasculitis with subepidermal bullae Dx: levamisole-induced vasculitis Tx: 6 months cocaine abstinence | Levamisole * | NA | U | Cocaine + | [47] |
Hx: 58 y M polysubstance user presented 4 d after last cocaine use with painful pruritic rash/polyarthralgyas Lab: high CRP, leukopenia; p-ANCA-; c-ANCA-; ANA-; RA-; HCV/HIV neg Skin biopsy:acute/chronic inflammation of superficial derma, acute perivascular inflammation in deeper derma; acute leukocytoclastic vasculitis; eosinophilic infiltrate Dx: cutaneous levamisole induced vasculitis Tx: steroids | Levamisole | LC-MS/MS | U | Cocaine +; levamisole (c)+ | [33] |
Hx: 40 y F tobacco and cocaine smoker, methadone and hydroxyzine user; anamnestic HCV+, previous septic shock; admitted with extensive retiform purpura/ bullous necrotic lesion legs/nose/ear/cheeks Lab: lactate elevated; PCR 180 mg/L; p-ANCA+; ANA+; LA+; cryoglubulinaemia+; RF+; HBV/HIV neg; HCV pos Skin biopsy: vasculitis, microthrombi/fibrinoid degeneration of vascular walls Dx: transient renal failure, extensive levamisole induced vasculitis | Levamisole | LC-MS/MS | U | Opiates; cocaine; methadone + | [59] |
H segments (n = 2) | Levamisole 1–1.78 ng/mg | ||||
Hx: 39 y F intravenous cocaine user dead in bathroom with recent needle marks Autopsy: pulmonary edema, brain/heart/coronary vessels/aorta/kidneys moderately congested COD: cardiorespiratory arrest due to intravenous cocaine and foreign body pulmonary granuloma Histology: foreign bodies (asbestos fibers) in pulmonary parenchyma associated with non-necrotising granulomas in lung Dx: pulmonary granulomatosis due to asbestos fibers related to intravenous cocaine | Asbestos fibers in lung | Histology | VH | Cocaine 40 | [53] |
B | BE 300 | ||||
Hx: about 20 y M after white drug insufflation (sold as cocaine); presented at ED with hypertension; combative/delirious behaviour; decreased level of consciousness; Clinical: GCS = 7/15–13/15; pin-pupils; systolic pressure = 123 mmHg; HR = 85; Dx: poisonings with LSD after nasal insufflation of a white powder sold as cocaine; Tx: intravenous droperidol; midazolam; intubation (for 12 h). | LSD | UHPLC-Q-ToF | U | Cannabis; benzodiazepine +; ketamine +; | [48] |
UHPLC-MS/MS | B | LSD 60; THC-COOH 38 | |||
Hx: about 20 y M history of cocaine and THC as recreational use; after white drug insufflation (as cocaine); his thoughts were “foggy”; sedation; Clinical: GCS = 13/15; pin-pupils; BP = 130/70 mmHg; HR = 64; vomiting develops hypokalaemia (K 2.9 mmol/L). Dx: poisonings with LSD after nasal insufflation of a white powder sold as cocaine; Tx: anti-emetics; anticonvulsant | LSD | UHPLC-Q-ToF | U | Cannabis +; amphetamines +; | [48] |
UHPLC-MS/MS | S | LSD 60; MDMA 20 | |||
Hx: about 20 y M past recreational use of cocaine/LSD; before white drug insufflation (sold as cocaine); smoked THC; drunk alcohol; reported thoughts-clouding; sensation of dying; vivid hallucinations; sedation; Clinical: HR = 97; BP = 227/145 mmHg; pin-pupils; GCS = 14/15; vomiting developing hypokalaemia (K 2.8 mmol/L); Dx: poisonings with LSD after nasal insufflation of a white powder sold as cocaine; Tx: diazepam; droperidol | LSD | UHPLC-Q-ToF | U | THC +; amphetamines + | [48] |
UHPLC-MS/MS | B | LSD 40; MDMA 10; THC-COOH 22; | |||
Hx: about 20 y M 10–15 min after white drug insufflation (sold as cocaine) developed hypersalivation; palpitations; nausea; dissociative state; Clinical: pin-pupils; Dx: poisonings with LSD after nasal insufflation of a white powder sold as cocaine Tx: diazepam | LSD | UHPLC-MS/MS | B | LSD < 5; MDMA < 30; THC-COOH < 3 | [48] |
Heroin | |||||
Hx: 28 y M 7 yrs cannabis/tobacco use disorders; 2 yrs inhaled heroin use; Due to reduced heroin supply and high cost used “CUT” heroin to save money and discover new drug; ED admission with time/space disorientation, confused; outburst at minimal provocation; pupils constricted/symmetrical; slurring speech, saliva drooling; wide-based gait, staggering/stumbling; unable to perform a tandem walk; Brain MRI: no detectable lesions Lab: ALT 271 U/L; ASL 148 U/L; urea 34 mg/dL; Cr 0.86 mg/dL; anti-HCV-; HCV-RNA 7.27000/mm3; HIV/HBV neg Dx: cognitive–behavioural and neurological symptoms due to CUT agent; Tx: sublingual buprenorphine–naloxone for 7 months | Methaqualone, caffeine, oxazepam, Ketazolam, nordazepa, pinazepam, alprazolam, acetaminophen | GC-MS | U | Morphine; benzodiazepines | [55] |
CD | acetaminophen; caffeine; methaqualone; Oxazepam; ketazolam; nordiazepam; pinazepam, alprazolam | ||||
Hx: 28 y M anamnestic with treated bipolar disorder, polysubstance abuse including intravenous heroin, found unresponsive at home with packets of “Santa Muerte”; on arrival typical initial opioid toxidrome Clinical: SpO2 78%; tachycardia, flushing, dry mucous membranes, mydriasis Chest X-ray chest: pneumonia and ARDS CT brain: negative Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA, pneumonia/ARDS Tx: after 2 doses of naloxone, became agitated and combative; OI for 12 d | 5F-MDMB-PINACA | LC-MSMS | S | Cocaine +; 6-MAM +; heroin +; fentanyl +; THC +; alprazolam + | [52] |
Immunoassay | U | Cocaine; opiates; fentanyl; THC; benzodiazepines | |||
GC-MS and LC-Q-ToF | CD | 5F-MDMB-PINACA; Heroin; Fentanyl | |||
Hx: 25 y M intravenous heroin abuse; admitted at ED for typical opioid toxidrome after intravenous ‘heroin’ injection; Clinical: HR = 102 b/m; BP = 146/89 mm Hg, RR = 24 breaths/min; SpO2 = 98%, flushing, tachycardia, agitation; Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA; Tx: 2 doses of naloxone, became anxious and tachycardic so EV lorazepam was added; intravenous fluids, supportive care. He confirmed Santa Muerte use. | 5F-MDMB-PINACA | Immunoassay | U | Opiates+; amphetamine+; barbiturates +; cocaine+ | [52] |
GC-MS/LC-Q-ToF-MS | CD | 5F-MDMB-PINACA; Heroin; fentanyl | |||
Hx: 31 y M history of intravenous heroine abuse; admitted at ED after intravenous “heroin” injection associated to typical opioids overdose symptoms; Clinical: HR = 163 b/m; BP = 131/81 mmHg, RR = 29 breaths/minute, SpO2 99%; tachycardic, flushed, dilated pupils; full bladder; Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA, and ARDS; Tx: after naloxone, became combative, anxious, agitated, so intravenous lorazepam was added; intubated for airway protection | 5F-MDMB- PINACA | Immunoassay | U | Opiates | [52] |
LC-MS-MS | S | Heroin; 6-MAM, fentanyl | |||
GC-MS/LC-Q-ToF-MS | CD | 5F-MDMB-PINACA; heroin; fentanyl | |||
Hx: 25 y M admitted at ED after intravenous heroin (found a drug packet labeled “Santa Muerte”); Clinical: HR = 158 b/m; BP = 215/158 mm Hg; RR = 26 breaths/minute; SpO2 = 99%; urinary retention; anhidrosis; Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA; Tx: naloxone; afterwards tachycardia/agitation; so lorazepam and physostigmine to calm him down; | 5F-MDMB- PINACA | Immunoassay | U | Cocaine; opiates; THC | [52] |
LC-MS/MS | S | 5F-MDMB-PICA (5F-ADB); heroin; 6-MAM; fentanyl; | |||
GC-MS LC-Q-ToF/MS | CD | 5F-MDMB-PINACA; heroin; fentanyl | |||
Hx: 45 y M presented at ED with tachycardia; pinpoint pupils; flushing of skin; drug packet “50 CAL” found in his pocket; Clinical: HR = 124 b/m; BP = 140/82 mmHg; RR = 22 breaths/minute; SpO2 = 99%; pinpoint pupils; flushing of skin; Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA; Tx: midazolam/olanzepine to calm; afterward intravenous diazepam; dexmedetomidine infusion in case of agitation returning; 24 hrs in hospital | 5F-MDMB-PINACA | Immunoassay | U | Opiates; fentanyl | [52] |
GC-MS LC-Q-ToF/MS | CD | 5F-MDMB-PINACA; heroin; fentanyl | |||
Hx: 36 y M found unresponsive in the street; after naloxone; agitation; benzo/physostigmine with improvement in agitation behaviour. Clinical: HR = 130 b/M; BP = 160/100 mm Hg; RR = 24 breaths/minute; oxygen saturation 95%; Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA; Tx: naloxone; benzo/physostigmine; intubated to avoid to risk of aspiration from vomiting; found blue packet (“50 CAL”). | 5F-MDMB- PINACA | Immunoassay | U | Opiates; fentanyl | [52] |
GC-MS and LC-Q-ToF | CD | Fentanyl; heroin; 5F-MDMB-PINACA | |||
Hx: 23 y F admitted at ED for severe agitation/combative behavior; Clinical: HR = 156 b/m; BP = 147/64 mm Hg; RR = 20 breaths/minute; Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA; Tx: lorazepam/physostigmine. The patient reported consuming a substance named “50 CAL.” | 5F-MDMB- PINACA * | Immunoassay | U | Opiates; fentanyl | [52] |
Hx: 27 y M presented at ED after intravenous heroin use; he was admitted with respiratory and CNS depression; Clinical: HR = 130 b/M; BP = 130–94 mm Hg; RR = 22 breaths/minute; sPO2 = 95%; dilated pupils; dry oral mucous membrane Tx: lorazepam; physostigmine. Dx: anticholinergic toxicity after heroin containing 5F-MDMB-PINACA | 5F-MDMB- PINACA * | Immunoassay | U | Opiates; fentanyl | [52] |
Hx: 36 y F 3 yrs oral opium abuse (dose = 0.3 gr/day); presented at ED with nausea; acute/severe abdominal pain; vomiting; pleuritic chest pain; Clinical: severe hypochromic-microcytic anemia; CT abdomen: multiple radiopaque flakes in intestinal lumen and in its wall due to metal deposition; Dx: lead poisoning in oral opium user; Tx: intravenous chelators (Ca Na2 EDTA) | lead | NA | B | Lead 780; lead (7 day after) 460 | [49] |
Γ-hydroxybutyrate (GHB) | |||||
Hx: 29 y M and 34 y M bought two GHB doses that were dissolved in 200 mL of alcohol each; 1st case drunk the whole drink in 10 min; 2nd case drunk 2/3 of his drink; Clinical: after 20 min 29 y began to accuse chest pain; tachycardia; short of breath; 34 y accused just headache. Dx: acute intoxication GHB and SLD | SDF | B | GHB 55–100 (case 1); 37–800 ng/mL (case 2); SDF 340 (case 1), SDF< LOQ; desMe-SDF < LOQ; desMe-SDF < LOQ | [50] | |
U | GHB: 35;700 and 15;500; SDF = 1;270 and SDF 1;220 desMe-SDF = 810 and 1;210 | ||||
Drink | GHB 7460;7 μg/mL; SDF 521;2 μg/mL | ||||
Alprazolam | |||||
Hx: 49 y M past substance abuse; found dead in his bed; nearby the corpse; a glass with dried; white; crystalline substance; on a shelf/living room; 2 plastic-bags containing white tablets (imprint XANAX); Autopsy: heart; lungs; liver; kidney: sign of decomposition; COD: acute intoxication of caffeine and etizolam. | Etizolam and caffeine | GC-MS and HPLC-DAD | FB | Etizolam = 770; caffeine = 190 Etoh 24 mg/mL | [51] |
CB | Caffeine 426 mg/mL | ||||
U | THC-COOH 192 | ||||
H segments (n = 4) | Etizolam 0.05–0.11; THC 0.06–0.19; amphetamine 0.42–2;568; cocaine 0.03–0.22. BEG 0.04–0.07 | ||||
Stomach content | Etizolam + | ||||
Drug | Caffeine; etizolam | ||||
Kratom | |||||
Hx: 54 y M past history of HCV treated; alcohol use disorder; OUD; admitted at ED with altered mental status after 1 spoon of “Kratom crazy®®” taken for an entire year; in morning he added a table spoon of “Vivazen Botanical De Kratom®®”; headache; vomit; fall asleep; when he woke up; he had incomprehensible speech. Clinical: BP = 120/70 mmHg; HR = 70; RR 18; sPo2 = 98%; Lab: glucose = 124 mg/dL; leukocytosis; troponin T = 91 ng/L; CT brain: large right frontal intraparenchymal haemorrhage with extension to ventricles (40 cm3) and mass effect; MRI brain: intraparenchymal hemmorrhage with 7 mm midline shift. Dx: PEA-adulterated kratom intoxicationTx: surgical craniotomy | PEA | LC-MS/MS | S | Mitragynine 340 | [56] |
LC-HRMS/MS | CD | PEA |
Number of Cases | Adulterant | Analytical Technique | Matrices | LOD (ng/mL) | LOQ (ng/mL) | Quantification (ng/mL) | Reference |
---|---|---|---|---|---|---|---|
DUID (n = 724) | Levamisole; PTHIT | LC-MS/MS | H | 2.5 pg/mg | 10 pg/mg | Cocaine 500–800.000 pg/mg (n = 627); PTHIT 3.5–61,000 pg/mg; levamisole/dexamisole 0.71–1.34 | [43] |
DUID (n = 55) | Caffeine DZ; hydroxyzine; levamisole; lidocaine; benzocaine; diphenhydramine; phenazone; procaine | SWATH LC-HRMS | U | __ | __ | THC + (n = 19) THC, cocaine + (n = 19); cocaine + (n = 17) | [65] |
U (n = 100) PL (n = 8) | Levamisole Aminorex | LC-HRMS | U PL | ___ | 1 0.1 | U: levamisole (n = 72) average conc.= 565 (4–72,970 µg/L); BE (n = 100) averange conc. = 13,510 (174–251,000 µg/mL); Aminorex not detected U: metabolites: 4-OH-LEV; LEV sulfoxide; LEV glucuronide; OH-LEV glucuronide; PL (n = 8): LEV average conc. = 10.6 (0.9–64.1 µg/L); U (n = 8) average conc. =144.50 (50–10,050); aminorex not detected | [66] |
H (n= 100) CRATOD admission | THC; lidocaine; phenacetin; levamisole; benzocaine; procaine hydroxyzine | LC-MS/MS | H | ___ | ___ | Cocaine (n = 100), BE + (n = 100); CE + (n = 94) THC + (n = 23); lidocaine (n = 92) +; phenacetin + (n = 69); levamisole + (n = 31) benzocaine + (n = 19); procaine + (n = 5); hydroxyzine (n = 2) | [67] |
Brain tissue (n = 10) Blood (n = 5) U (n = 1) | DZ; hydroxyzine; levamisole; lidocaine; phenacetin; procaine; cetirizine | GC-MS | Brain tissue; U; BL | Cocaine 3.6 BE 27 EME 67 CET 71 DZ 26 HYD 9 LEV 14 LID 38 PHE 21 PRO 16 | Cocaine 30 BE 93 EME 105 CET 363 DZ 101 HYD 152 LEV 66 LID 81 PHE 132 PRO 121 | Cocaine 530.8 ng/g; benzodiazepine 423.1 ng/g; EME 548.7 ng/g; LEV 128.1 ng/mg; LID 73.5 ng/mg; HYD 170.5 ng/g; ALC (BL) 0.86‰; ALC (brain) 0;54‰; ALC (U) 4;97‰ | [65] |
U (n = 3665) | Levamisole | Immunoassay LC-Q-ToF | U | ___ | ___ | Cocaine + (n = 51); levamisole + (n = 27); methamphetamine/MDMA + (n = 23); cannabis metabolites + (n = 12); heroin or metabolite + (n = 2). | [69] |
H (n = 55) | Levamisole | LC-MS/MS | H | ___ | Levamisole 0.002 pg/mg; Cocaine 0.005 pg/mg | H [cocaine + samples > 500 pg/mg]: 4265.4 pg/mg (levamisole); 322.9 pg/mg (MDMA); 253.9 g/week (alcohol); H [cocaine—samples]: 0 (levamisole); 0.99 pg/mg (MDMA); 56.5 g/week (alcohol) | [68] |
Heroin | |||||||
H (n = 40) | Fentanyl; acetylfentanyl; furanylfentanyl; U-47700 | UHPLC-MS/MS | H | 0.1–0.3 pg/mg | 0.3–0.9 pg/mg | Fentanyl 2.3–8600 pg/mg (mean = 860 pg/mg; median = 440 pg/mg); acetylfentanyl = 2.1–3200 pg/mg (mean = 160 pg/mg; median = 26 pg/mg); furanylfentanyl = 0.7–42 pg/mg (mean = 8.0 pg/mg; median = 1.6 pg/mg); U-47700 (n = 3/40): 1.4–4.5 pg/mg | [70] |
OF (n = 30) U (n = 30) | Fentanyl; norfentanyl; acetylfentanyl; U-47700 | LC-Q-ToF-MS | OF U | Fentanyl 1; norfentanyl 2; acetylfentanyl 1; carfentanil 1; U-47700 1 | ___ | U (n = 29 fentanyl +); OF (n = 27 fentanyl +); norfentanyl; acetylfentanyl; U-47700 | [71] |
3. Discussion
4. Method
- (1)
- Articles not written in English
- (2)
- Commentary; editorial letters; and surveys
- (3)
- Duplicates were removed
- (4)
- Irrelevant studies
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
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Di Trana, A.; Berardinelli, D.; Montanari, E.; Berretta, P.; Basile, G.; Huestis, M.A.; Busardò, F.P. Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances. Int. J. Mol. Sci. 2022, 23, 14619. https://doi.org/10.3390/ijms232314619
Di Trana A, Berardinelli D, Montanari E, Berretta P, Basile G, Huestis MA, Busardò FP. Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances. International Journal of Molecular Sciences. 2022; 23(23):14619. https://doi.org/10.3390/ijms232314619
Chicago/Turabian StyleDi Trana, Annagiulia, Diletta Berardinelli, Eva Montanari, Paolo Berretta, Giuseppe Basile, Marilyn A. Huestis, and Francesco Paolo Busardò. 2022. "Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances" International Journal of Molecular Sciences 23, no. 23: 14619. https://doi.org/10.3390/ijms232314619
APA StyleDi Trana, A., Berardinelli, D., Montanari, E., Berretta, P., Basile, G., Huestis, M. A., & Busardò, F. P. (2022). Molecular Insights and Clinical Outcomes of Drugs of Abuse Adulteration: New Trends and New Psychoactive Substances. International Journal of Molecular Sciences, 23(23), 14619. https://doi.org/10.3390/ijms232314619