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Pomeranian J Life Sci 2020;66(2):13-17 doi: 10.21164/pomjlifesci.642

Intoxication with new psychoactive substances in patients diagnosed at the Department of Clinical and Forensic Toxicology, Pomeranian Medical University in Szczecin in 2015–2018 Barbara Potocka-Banaś1, A , Urszula Semeniuk1, B, Sławomir Majdanik2, C, Krzysztof Borowiak1, D, Tomasz Janus1, E

1 Pomeranian Medical University in Szczecin, Department of Clinical and Forensic Toxicology, Powstańców Wlkp. 72, 70-110 Szczecin, Poland 2 Pomeranian Medical University in Szczecin, Department of Forensic Medicine, Powstańców Wlkp. 72, 70-110 Szczecin, Poland

A ORCID: 0000-0003-0259-2006; B ORCID: 0000-0003-0247-4202; C ORCID: 0000-0003-0472-1924; D ORCID: 0000-0002-2526-2686; E ORCID: 0000-0002-2363-2196

[email protected]

ABSTRACT Results: Our research was based on Introduction: Intoxication with new psychoactive substances poisoning with volatile and non-volatile organic compounds car- (NPSs), colloquially known as designer drugs, has become a sig- 5,916 diagnostic tests for-

The aim of the study was to conduct a statistical analysis of ried out in 2015–2018 at Pomeranian Medical University in Szc retrospectivenificant problem data in fromthe last test several records years. for the presence of NPSs zecin. Psychoactive substances used for non-medical purposes weresubstances, detected the in poisonings 1,465 patients. caused In bythe the period intentional under analysisuse NPS 1,328 of these patients were poisoned with classic psychoactive inMaterials patients andhospitalized methods in 2015–2018 in the West Pomeranian Conclusions: A retrospective analysis of the above-mentioned undertakenprovince. at the Department of Clinical and Forensic Toxi- were recorded in 137. gradual increase in the : We analyzed 5,916 results of tests incidence of poisoning with psychoactive substances used for samples had been analyzed by liquid chromatography coupled data for the period 2015–2018 revealed a withcology mass at Pomeranian spectrometry Medical (LC/MS) University and Headspace in Szczecin. gas chroma Blood- Keywords: intoxication; new psychoactive substances; designer non-medical purposes.

tography (GC/Headspace). drugs; data analysis; diagnostic tests.

INTRODUCTION The most popular and largest group are psychostimulants, which act on the central nervous system (CNS) and often pro- Intoxication with new psychoactive substances (NPSs) has duce effects comparable to those elicited by , ampheta- become a common and serious clinical, social and forensic - ally known as designer drugs, are compounds that have been Psychostimulantsmine and MDMA (3,4-methylenedioxymethamphetamine), cause a i.e. problemchemically in thealtered last severalfrom controlled years. These substances substances, and colloquiare usu- Theseincreased include psychomotor cardiovascular activity, symptoms , suchanorexia, as sinus insomnia. tachy- ally sold online cardia, palpitations, chestbroad pain, spectrumhypertension, of adverse myocarditis, effects. labels that do not precisely describe their contents, and their cardiac arrest; haematological problems such as dissemi- [1, the2]. Theycharacters are distributed of pop culture in packages (Pink Panther), with nated intravascular coagulation, thrombocytopaenia, anae- collectors’ items (driver’s charm), or items of everyday use names refer, e.g. to impairment, reduced mental performance; emotional prob- suggests that these compounds produce only psychoactive lemsmia; cognitivesuch as irritability, dysfunction, aggression, e.g. confusion, panic chronic attacks, cognitive anhedo- (moistureeffects, while absorber). in fact only The someterm “newof them psychoactive do substances” nia, depression, suicidal thoughts; neurological symptoms, chemical structure and mechanisms of action, NPSs are clas- so. Considering the paraesthesia, bruxism, dyskinesia, headache and dizziness; • e.g. insomnia, hyperthermia, mydriasis, visual disturbances, sified into 4 major groups [3]: hallucinations psychostimulants (β- derivatives, perception disorders – paranoid delusions, auditory and visual • derivatives,synthetic 2,5-dimethoxyphenethylamine (indole derivatives, derivatives,cyclohexyl- [4]. phenolcalled 2Cs), derivatives, classic cannabinoids), oftenSynthetic entirely cannabinoidsdifferent from thatare agonistsof natural of cannabinoids, the CB1 and theyCB2 • (derivatives of tryptamine, phenylethyl- receptors.can produce Despite effects the up toaltered chemical structure, which is- and arylcyclohexylamine), • 500 times more potent in the mech anism stimulating the CB1 receptor pathway (central), and synthetic . the CB2 receptor pathway (peripheral), and elicit narcotic, 13 Barbara Potocka-Banaś, Urszula Semeniuk, Sławomir Majdanik, Krzysztof Borowiak, Tomasz Janus empathogenic, intoxicating/psychotropic effects similar MATERIALS AND METHODS to the pharmacological properties The study presents a retrospective analysis of data from toxi- andthose toxicity of Δ-9-THC of synthetic found cannabinomimeticsin products is i.e., very marijuana limited, butand clinicalhashish. data Information imply a broad on spectrum of toxic effects from cology tests carried out analyzed at DoCaFT results PMU inand Szczecin medical in data 2015–2018 from effects include disorders of the cardiovascular system, such as and commissioned by 18 hospitals from the West Pomeranian- hypertension,cannabinol analogues. tachycardia, The mostarrhythmia, frequently chest reported pain, shortness adverse province.tive for the Overall, presence we of psychoactive substances used for non- referrals for 5,916 cases, from which 1,465 patients tested posi are equally frequent: seizures, including tonic-clonic seizures, chromatography coupled with mass spectrometry (LC/MS) and of breath, and myocardial infarction. Neurological symptoms- medicinal purposes. Blood samples were analyzed by liquid stances also leads to psychiatric disorders: panic and anxi- of NPSs detected in the tests was compared to the number of etysleep attacks, disorders, hallucinations, headaches and delusional dizziness. , Abuse of aggressive these sub Headspace gas chromatography (GC/Headspace). The number been reported, including disorientation and disorders of short- all psychoactive substances detected in poisoned patients. behaviour,term memory and depression. Cognitive impairment has also RESULTS receptor, [5]. - Most hallucinogens activate the serotonin 5-HT2 sic and designer drugs used for non-medical purposes, were psychedelicmainly the 5-HT effects2� ofsubtype. hallucinogens Hallucinogens largely depend cause changes on the per in- In the period 2015–2018, psychoactive substances, both clas consciousness,sonality traits andperceptual emotional anomalies, state of andthe hallucinations.user, as well as Thethe (classic substances) included: ethyl , , ,detected in blood samples cocaine, from , 1,465 patients. The 1st MDMA, group after the use of hallucinogens include increased heart rate, increasedexpectations blood and pressure, the circumstances. risk of serotonin Toxic syndrome,effects observed clonic seizures, insomnia, delirium, and rhabdomyolysis Ecstasy, and lysergic acid diethylamide (LSD). The 2nd group New designer opioids act on becauseincluded of NPSs, intoxication also known with as classic designer psychoactive drugs. substances, [6]. - In the analysed period 1,328 patients were hospitalized vation of central receptorsthe produces µ, ð, and anĸ opioid receptors, effect, The study was based on blood samples collected from relievesmainly in anxiety the CNS and and panic less attacks, in the peripheral causes mood tissues. changes, The actiand patientsand 137 patients tested wereat DoCaFT diagnosed PMU with in Szczecin poisoning for caused the presence by NPSs. - - tion, dizziness, reduced blood pressure, seizures, liver damage, lowersand respiratory the seizure depression threshold. leading Toxic toeffects death include constipa of psychoactive substances. The tests for the presence of psy The aim of the study was to conduct a statistical analysis choactive substances were positive in 314 patients (21.4%) in of retrospective data from tests for the presence[7]. of NPSs in 2015, for 371 patients (25.3%) in 2016, for 382 patients (26.1%) in 2017, and for 398 patients (27.2%) in 2018 (Fig. 1). The tests for the presence of NPSs were positive in 8 patients patientsthe Department hospitalized of Clinical in 2015–2018 and Forensic in the Toxicology, West Pomeranian Pomera- (0.54%) in 2015, 19 patients (1.29%) in 2016, 46 patients (3.13%)- province. We analyzed 5,916 results of tests undertaken at in 2017, and 64 patients (4.36%) in 2018 (Fig. 2). Analysis of the data for 2015 showed that synthetic cannabi nian Medical University in Szczecin (DoCaFT PMU in Szczecin). noid (1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl)

30

25

20

15

10

psychoactive substances(%) 5 Rates of test positive for non-medical 0 2015 2016 2017 2018 Years

FIGURE 1. Share of positive tests for psychoactive substances used for non-medical purposes annually across the period 2015–2018 in the total sample of positive tests (n = 1465)

14 ojs.pum.edu.pl/pomjlifesci Intoxication with new psychoactive substances in patients diagnosed at the Department of Clinical and Forensic Toxicology, PMU in Szczecin in 2015–2018

5 4.5 4 3.5 3 2.5 2 Ratest of NPS Ratest of 1.5 1 0.5 0 2015 2016 2017 2018 Years

FIGURE 2. Positive tests for the presence of new psychoactive substances in all tests for psychoactive substances in 2015–2018

methanone (UR-144) was the most frequently detected- methyl]indazole-carboxamide (ADB-FUBINACA), were detected NPS, detected in 4 patients (1.27%). Another substance, in single patients (0.26% each) – Table 2. α-pyrrolidinovalerophenone (α-PVP) from the group of psy OtherAnalysis frequently of the datadetected for 2017 substances revealed werethat α-PVP psychostimu was the- chostimulants, was detected in blood samples from psychostimu 2 patients- most frequently detected NPS, identified in 11 patients (2.87%). (0.63%). , also known as 2-(methylamino)- A 1-(4-methylphenyl)propan-1-one (4 MMC), a - lants: 4-CMC (7 patients; 1.83%) and 4-CE (7 patients; 1.83%). lant, was detected in 1 patient (0.31%). Psychostimulant synthetic , MDMB-CHMICA, was detected in- 3-2-(methylamino)-1-(3-methylphenyl)-1-propanone (3-mephe 6 patients (1.57%). Another synthetic cannabinoid, (S)-methyl- TABLEdrone) 1. wasNew psychoactivealso detected substances in 1 patient detected (0.31%) in the blood– Table of patients 1. 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamido)-3-methylb in 2015 utanoate (5F-AMB), was found in 2 patients (0.52%). The syn New psychoactive The incidence rate of thetic opioid, 3,4-dichloro-N-(2-(dimethylamino)cyclohexyl)- Number of cases substance poisoning (%) N-methylbenzamide (U-47700), was detected for the 1st time UR-144 4 1.27 (NEP,in 2 patients N-ethylnorpentedrone), (0.52%). Other substances, a synthetic i.e. N-ethylpentylone, cannabinoid psychostimulating 2-(Ethylamino)-1-phenyl-1-pentanone α-PVP 2 0.63

Mephedrone 1 0.31 N-(1-adamantyl)-1-(5-fluoropentyl)indazole-3-carboxamide (5-F-AKB-48), hallucinogenic 1-[1-(3-methoxyphenyl)cyclohexyl] 3-mephedrone 1 0.31 - (4-MeO-PCP), psychostimulating 1-(3-chlorophenyl) piperazine (m-CPP), psychostimulating 1-(4-fluorophenyl)pro pan-2-amine (4-FA), hallucinogenic 3-[2-[ethyl(methyl)amino]

TABLEethyl]-1H-indol-4-ol 2. New psychoactive (4-HO-Met), substances detected psychostimulating in the blood of patients 4-F-PHP, theAnalysis group of thepsychostimulants data for 2016 showed was that the 1-(4-chlorophenyl)- most frequently in 2016 2-(methylamino)propan-1-one (4-CMC, clephedrone) from New psychoactive The incidence rate of Number of cases - substance poisoning (%) detected NPS (5 patients; 1.34%). The psychostimulant Clephedrone (4-CMC) 5 1.34 α-PVP was detected in 4 patients (1.07%). Psychostimulat α-PVP 4 1.07 Aing 1-(4-chlorophenyl)-2-(ethylamino)propan-1-one (4-CEC, 4-chloroethcathinone) was found in 3 patients (0.80%). 4-CEC 3 0.80 synthetic cannabinoid, methyl (2S)-2-[[1-(cyclohexylmethyl) synthetic indole-3-carbonyl]amino]-3,3-dimethylbutanoate (MDMB- MDMB-CHMICA 2 0.53 -CHMICA), was detected in 2 (0.53%) patients. A FUB-AMB 1 0.26 cannabinoid, methyl (2S)-2-[[1-[(4-fluorophenyl)methyl] 4-methylbuphedrone 1 0.26 indazole-3-carbonyl]amino]-3-methylbutanoate (FUB- -AMB), psychostimulating 2-(methylamino)-1-(4-methylphenyl)-- N-ethylpentylone 1 0.26 1-butanone (4-methylbuphedrone), psychostimulating 4F-MPH 1 0.26 1-(2H-1,3-benzodioxol-5-yl)-2-(ethylamino)pentan-1-one synthetic cannabinoid, (N-eth ylpentylone), psychostimulating methyl (4-fluorophenyl) ADB-FUBINACA 1 0.26 (piperidin-2-yl)acetate (4F-MPH), and a N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-[(4-fluorophenyl)

Pomeranian J Life Sci 2020;66(2) 15 Barbara Potocka-Banaś, Urszula Semeniuk, Sławomir Majdanik, Krzysztof Borowiak, Tomasz Janus

- synthetic cannabinoid MDMB-CHMICA, psychostimulating- amino]-3,3-dimethyl-butanoate (5F-MDMB-PICA), psycho mephedrone, hallucinogenic 3-[2-[methyl(propan-2-yl)amino] stimulating (RS)-1-(4-Fluorophenyl)-N-methylpropan-2-amine- ethyl]-1H-indol-4-ol (4-HO-MiPT), were each detected in indi (4-FMA), psychostimulating (RS)-2-ethylamino-1-phenyl-propan- vidual patients (0.26% each) – Table 3. 1-one (), psychostimulating N-ethylpentylone, synthetic psy mostAnalysis frequently of data detected for 2018 revealedNPS was another psychostimulating significant increase clephe- chostimulating propan-2-yl 2-phenyl-2-(piperidin-2-yl) acetate in the number of cases of acute intoxication with NPSs. The- (), hallucinogenic 4-HO-Met, and a cannabinoid, 5F-AMB (each accounted for 0.26% of all positive drone, detected in 29 (7.28%) patients. The 1st case of psy TABLEtests) 4. – NewTable psychoactive 4. substances detected in the blood of patients chostimulating 2-(ethylamino)-1-phenylhexan-1-one (HEX-EN,- in 2018 N-ethylhexedrone) was detected in 12 patients (3.01%). Another - New psychoactive The incidence rate of Number of cases psychostimulant, 1-(4-Methylphenyl)-2-methylamino-pen substance poisoning (%) tan-1-one (4-MDP), was detected in 4 patients (1.0%). Psycho stimulating 1-(1,3-benzodioxol-5-yl)-2-pyrrolidin-1-ylhexan- Clephedrone (4-CMC) 26 7.28 N-ethylhexedrone 1-one (MDPHP) was detected in 3 patients (0.75 %). Synthetic 12 3.01 (HEX-EN) cannabinoid, methylN-{[1-(cyclohexylmethyl)-1H-indol-3-yl]- carbonyl}-L-valinate (MMB-CHMICA), was detected in blood 4-MDP 4 1.00 samples from 2 patients (0.50%). Another synthetic cannabi MDPHP 3 0.75 noid, (RS)-1-(4-Methylphenyl)-2-(1-pyrrolidinyl)-1-hexanone (MPHP), was found in blood from 2 patients (0.50%). Other 4-CMC 3 0.75 werepsychostimulants also single cases were of also poisoning detected: with 4F-MPH psychostimulating in 2 patients MMB-CHMICA 2 0.50 (0.50%), and N-ethylpentylone in 2 patients (0.50%). synthetic There LSD 2 0.50

2-(methylamino)-1-phenylpentan-1-one (), a MPHP 2 0.50 cannabinoid, methyl 2-[[1-(5-fluoropentyl)indole-3-carbonyl] 4F-MPH 2 0.50 TABLE 3. New psychoactive substances detected in the blood of patients in 2017 N-ethylpentylone 2 0.50 New psychoactive The incidence rate of Number of cases Pentedrone 1 0.25 substance poisoning (%) 5F-MDMB-PICA 1 0.25 α-PVP 11 2.87 4-FMA 1 0.25 Clephedrone (4-CMC) 7 1.83 ethcathinone 1 0.25 4-CEC 7 1.83 N-ethylnorpentedrone 1 0.25 AMB-CHMICA 6 1.57 isopropylphenidate 1 0.25 5F-AMB 2 0.52 4-HO-Met 1 0.25 U-47700 2 0.52 5F-AMB 1 0.25 N-ethylpentylone 1 0.26

N-ethylpentedrone 1 0.26

5F-AKB48 1 0.26 DISCUSSION AND CONCLUSION 4-MeO-PCP 1 0.26

mCPP 1 0.26 - Between 2015–2018 the DoCaFT PMU in Szczecin carried out 4FA 1 0.26 5,916 diagnostic tests for poisoning with volatile and non-vol 4-HO-met 1 0.26 atile organic compounds. Psychoactive substances used for non-medical purposes were detected in 1,465 patients. In the 4F-PHP 1 0.26 - analyzed period 1,328 of these patients were poisoned with MDMB-CHMICA 1 0.26 classic psychoactive substances, and in 137 of these tests, poi

Mephedrone 1 0.26 soning was caused by the gradual intentional increase use ofin NPSs. the incidence of poisoningsRetrospective with psychoactiveanalysis of the substances data for the used period for 2015–2018non-med- 4HO-MiPT 1 0.26 (Fig. 1 and 2) revealed similar a increase was found in the number of

ical purposes. A

16 ojs.pum.edu.pl/pomjlifesci Intoxication with new psychoactive substances in patients diagnosed at the Department of Clinical and Forensic Toxicology, PMU in Szczecin in 2015–2018

growing popularity of poisonings with NPSs. This implies a were detected in 17.5% of positive these drugs among patients. Importantly, tests carried out in tests for NPSs and were the 2nd most frequently used designer- reasonsubsequent for the years emergence detected of NPSs NPSs in is patients’ changes blood: in Polish 4 drugs legisla in- oidsdrug weredetected the at least DoCaFT popular PMU groupin Szczecin. of NPSs Only among 2.2% of the patients diag- 2015,tion and 9 in faster 2016, 17inclusion in 2017, ofand NPSs 18 in in 2018. regularly Apparently, updated the annexes major tested positive for hallucinogens. Analysis revealed that opi to results, among other things, in criminal sanctions for the pos- nosed patients, with only 1 patient (1.5%) testing positive for sessionthe Act of of substances 29 July 2005 listed on counteracting in the Act on drug Counteracting . These Drug EMCDDAthe opioid report, substance which (U-477). shows that opioid derivatives represent avoid criminal responsibility, man- a smallThis percentagetrend is also of NPSsconfirmed on the Europeanby data presented market, yet in they the ufacturers modify the chemical structure of the listed designer cause serious harm due to their very high potency Addiction.drugs in order To to put on the market derivatives that are not yet statistics indicating that synthetic opioids accounted only for the alarmingly[8]. Despite high emerging substances may produce dramatically different and rate at which this group of substances reaches the market, and unpredictablemonitored. Due effects, to these both modifications, short-term (acute) even minor and long-term ones, the 2%this of particularly all seized drugs, concerns researchers synthetic point to derivatives in fentanyl analogs is associated and toxic and fatal doses of NPSs is very limited because of the with a high risk of , risk of acute intoxications (chronic).dynamic changes Knowledge in NPSs of the appearing clinical symptomson of poisoning, theand last fatalities 3 years. Easier access to The European Monitoring Centre for Drugs and Drug Addic- the market. a steady year-on-year[11, 12]. increase in the incidence of poisonings withStatistical NPSs, as analysis well as of an data increase for the in period the range 2015–2018 of detected showed tion (EMCDDA) reported that over 670 NPSs were monitored in Europe by the end of 2017, and 51 of them were identified for the 1st time [8]. - designer drugs. The rapid emergence of modified NPSs creates diagnostic REFERENCES problemsthe substances and also contained clinical indifficulties the powders in the (salts, treatment herbs) and because medi thesecal care products of poisoned have multiple patients. ingredients Most drug andusers lack are label unaware informa of- - common problem, par- 1. Michael FW, Hopper JA, Gunderson EW. Designer drugs 2015: assess ticularly concerning the production of synthetic cannabinoids, ment and management. Addict Sci Clin Pract 2015;10(1):8. doi: 10.1186/ tion about the chemical composition. A - s13722-015-0024-7. comparison of methods in 2. Korfa cross-national D, Benschop survey A, Werse among B, Kamphausen three groups ofG, currentFelvinczi users K, Dąbrowska of new psy- K, et al. 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