Introduksjon Rusmidler og Nye Psykoak2ve Stoffer (NPS) Knut Erik Hovda Overlege, PhD Nasjonal behandlingstjeneste for CBRNe- medisin (CBRNe- senteret) Aku>medisinsk avd Oslo universitetssykehus HF Bakgrunn og eksempler De klassiske narko2ske stoffene De nye psykoak2ve stoffene bakgrunn og definisjon Grupper og eksempler Kjemiske formler Navngiving Kliniske utordringer Sammendrag h>p://www.youtube.com/watch?v=bxo- 0iFj8Ys Narko@ka & Motedop De klassiske narko@ske stoffene Cannabis mest brukt Narko2kahandel: 3. største budsje> i verden I Vest- Europa/USA ca 1.5-3.0% av BNP1 Største industri e>er bilindustrien tax- free Nyere drogekultur Internasjonal Mul2medial (Interne>) Ny sosial status ( knarker vs. partydoper ) Peroralt misbruk - ikke IV Trussel mot ungdomshelsen 1 UNDOC/EMCDDA Amphetamines amfetamin vs. metamfetamin Ecstasy UK og Spaina dominerer. Varierende innhold.. Cocaine nest vanligst i Sør- og Vest- Europa. Heroin står for den største sykeligheten og dødeligheten 1
Varia@on in predominant s@mulant drug used across Europe Kokain 25% av alle AMI 18-45 år forbundet med kokainbruk (CA) Aku>e koronarsyndrom som følge av: Coronar vasokonstriksjon Intracoronar trombose Akselerert aterosklerose EF ole 2lnærmet normal, vanligvis åpne coronarkar ved angiografi EMCDDA Kokain overdose - behandling BZD er drugs of choice Bryte den onde sirkelen 2l kokainets toksisitet, ved å s2mulere BZD reseptorene Ekstern kjøling (max 15 min ved >42C) Phentolamine mot persisterende HT & vasospasmer Unngå β- blokkere: Økt α- s2m kan gi hypertensive kriser Hvis Na- kanal blokkade ( QRS): Gi hyperton NaHCO 3 Amfetamin Generell sympa,komime,sk effekt Tachycardier og tachyarrytmier BT, først og fremst systolisk BT Andre komplekse effekter: Generell vasokonstriksjon Ak2vering av trombocy>er Myokard- ischemi og arytmier Intrakranielle blødninger Kan tømme glykogenlagrene hypoglykemi Amfetamin, forts Symptomer: Betydelig økt ak2vitetsnivå, økt smerteterskel, hypertermi, hypertensjon, tachykardi, tallerkenpupiller Motorisk uro; ukri2sk, utagerende aterd OBS! - kroniske misbrukere ole lite symptomer - kontaminanter Behandling: Symptoma2sk BZD og nedkjøling står sentralt Metamfetamin Meget enkelt å synte2sere Gir lengre og mer euforisk effekt enn D- amfetamin Ice : 99-100% rent metamfetamin. Flyk2g når oppvarmet inhalasjon gir 2lsvarende rush som metamfetamin iv. Økende mengde bruk og beslag i Norge Mortalitet i rela2vt antall i Norge: metamfetamin : amfetamin : kokain = 6 : 3 : 1 1 1 SERAF rapporten 2010 2
Amphetamines Ecstasy - MDMA The rela2ve amount of metamphetamine has the recent years been increasing in Norway1, and since 2009 it became the most common; Complex drug with many ac2ons Blokkerer reopptak av dopamin og serotonin i synapser i CNS Hemmer produksjonen av serotonin S2mulerer sympa2kus The three Es: Energi Empa2 Eufori 1Seizures. KRIPOS - Na2onal Criminal Inves2ga2on Service. Knut Erik Hovda. NAACT 2011 Washington DC Ecstasy in Scandinavia Serotoninets funksjon Serotonin: Kropstemperatur Søvn Humør Appetit Smerte Reduced number the recent years, MDMA has had a falling trend un2l 2010, CPP had the opposite trend1 SSRi Skadevirkninger: Lykkepiller Angst SSRi - præparater Depressioner Selective Serotonin Reuptake Inhibitors Tvangsadfærd Serotonin Syndrom MDMA now increasing again? 1Seizures. KRIPOS - Na2onal Criminal Inves2ga2on Service. Report first 6 months 2011 Knut Erik Hovda. NAACT 2011 Washington DC ECSTASY- MEKANISMER Liberg JP et al. Tidsskr Nor Lægeforen 1998; 28: 4384-7. 3
Ecstasy psykiske senvirkninger NPS - Background and defini@on (I) Senker serotoninnivået i CNS Personlighetsendringer Schizofrene trekk Kogni2v dysfunksjon Læreproblemer Nedsa> oppmerksomhet Nedsa> hukommelse Either synte2c, semi- synte2c or naturally occuring substances intended to illicit a psychoac@ve response, being either s@mulant, hallucinogenic, seda@ve or a combina@on of these There are many chemical similari2es between legal highs and endogenous neurotransmi>ers, specifically serotonin, norepinephrine and dopamine 1 Several classes of legal highs have been modeled on exis@ng and controlled drugs of abuse because of ease in synthesizing (esp. phenylethylamine (amphetamine), cocaine, phencyclidine and tryptamine classes). 1 1 Gibbons S. Clinical Toxicology (2012), 50, 15 24 Knut Erik Hovda, European Society of Emergency Medicine, Turkey- 2012 NPS - Background and defini@on (II) Marketed as not for human consump2on, plant food, bath salts or even pond cleaner Significant variability in the contents of novel psychoac2ve substances 1,2,3 Typically appearing in smaller groups first (olen clubbers etc) increasing # of users Informa@on spread especially through internet NPS - Bakgrunn og definisjon (III) Vanligvis utøres ikke ru2nemessig screening (blod- eller urinprøver) e>ersom det olest ikke vil påvirke den aku>e behandlingen Drama2sk økning i 2lgjengelighet og bruk de siste årene: 2005-2011: 164 nye psykoak2ve stoffer ble formelt meldt inn gjennom systemet for 2dlig varsling (EWS) 1. 1 Ramsey J et al (2010). Q J Med 103:777 783 2 Davies S et al (2010) Q J Med 103:489 493 3 Spiller HA et al (2011) Clin Toxicol (Phila) 49:499 505 De nye trendene øker vik2gheten av å kjenne toksisiteten 2l forbindelsene og deres raskt endrede panorama: What is really out there?. 1 EMCDDA 2012 Knut Erik Hovda, European Society of Emergency Medicine, Turkey- 2012 Main groups of new psychoac@ve substances Grouping can be done different ways; usually according to their chemical structure or their clinical effect (hallucinogenic, s2mulant etc). Below is the grouping used by EMCDDA: 1. Phenetylamines 2. Tryptamines 3. Piperazines 4. Cathinones 5. Synte2c cannabinoids 6. Other substances 1. Phenetylamines Effects: s2mulant, entactogenic or hallucinogenic effects The most common group un2l 2010 Examples: amphetamine, methamphetamine, PMA, PMMA, MDMA, MBDB, MDEA, mescaline, 2C- E, Benzofurans and benzodifuranes (e.g. BromoDragonfly, benzo fury) Knut Erik Hovda, European Society of Emergency Medicine, Turkey- 2012 Knut Erik Hovda, European Society of Emergency Medicine, Turkey- 2012 4
PMMA (I) PMMA (II) PMMA; Para- methoxy- methyl- amphetamine Sudden outbreak in Norway in 2010, classified as a narco2c in November 2010 20 reported mortali2es1 + found in 10-20 persons driving under the influence during 14 months Why PMMA? Possibly because of one of the precursors in the produc2on of amphetamine & metamphetamine became illegal in Russia1 Why this high mortality with PMMA? Olen sold as ecstasy or amphetamine, but with a slower onset of symptoms. Users olen think it is weak drugs and use more to gain effect. Norway; locally produced??? 1Vevelstad M et al. The PMMA epidemic in Norway. Comparison of fatal and non- fatal intoxica2ons. Forensic Sci Int. 2012. 10;219(1-3):151-7. 2Bones T, KRIPOS - Na2onal Criminal Inves2ga2on Service. Personal communica2on 1Bønes T, KRIPOS - Na2onal Criminal Inves2ga2on Service. Personal communica2on Knut Erik Hovda. NAACT 2011 Washington DC Knut Erik Hovda. NAACT 2011 Washington DC Alfa-Methyl-Tryptamin 2. Tryptamines Effects: predominantly hallucinogenic effects Examples: α- Methyltryptamine (AMT), dimethyltryptamine (DMT), psilocin, psilocybin, LSD, 4- OH- metyletyltryptamin (4- OH- MET) Psilocybin AMT 3. Piperazines Effects: s2mulants Examples: 1- (3- chlorophenyl)piperazine (mcpp), 1- benzylpiperazine (BZP), A2, TFMPP, Beans (Happy Popper) Serotonin 4. Cathinones Effects: s2mulants, olen also hallucinogenic effects The second most common group Bath salts (US) or plant food (Europe) olen refers to this group Examples: mephedrone, flefedron, efedron, methylone, methylene dioxy- pyruvalone (MDPV), methcathinone 5
Mephedrone 5. Synte@c cannabinoids/thc- analogues/ Spice The first cathinone to be formally risk- assessed Effects: hallucinogenic, seda2ve and depressant effects (some2mes also s2mulant proper2es) Higher affinity for the CB1 receptor compared to classical cannabinoids Increasing fastest along with the cathinones now most common Examples: JWH- 011, JWH- 018, JWH- 019, JWH- 122, JWH- 133, JWH- 250, JWH- 251, Remix, Space Sta2on, Rainbow in Heaven, Black Widow, Double Dutch, Jamaican Spirit, Jamaican Potpurri, DJ, Bonzai Citrus, XXXL, Package 69, Aroma2c Potpurri The first report on Mephedrone (female 18yrs) died in Stockholm December 20081. Since that appearantly among the most frequently used novel psychoac2ve drug in various recrea2onal se ngs; A night- club study showing 53% last month use and 41% use on the night of the survey2 Internet surveys from UK clubbers: approx 40% life2me- use in 20103, and 61% in 20114. Possible decrease with change in legisla2on; possible change towards similar products ( research chemicals / legal alterna2ves to mephedrone ) 1Gustavsson D, Escher C. Lakar2dningen. 2009 Oct 21-27;106(43):2769-71. 2Wood DM et al. QJM. 2012: Oct;105(10):959-64. Epub 2012 Jun 19. 3Dick D, Torrance C. 2010. Mixmag drugs survey, Mixmag 225:44 53. 4Winstock A. 2011. The 2011 Mixmag drugs survey, Mixmag, March, pp. 49 59. 6. Other substances GHB/GBL where do we place them? Effects: Large varia2ons; depending on the substance Examples: plant derived and synte2c psycoac2ve substances (indanes (e.g. MDAI), narco2c analge2cs, synthe2c cocaine deriva2ves, ketamine- and phencyclidine deriva2ves), and medicinal products Originally developed as an anesthe2c in the 60 s Used as a recrea2onal drug for at least three decades Very easy to make from easily available ingredients Stable, high- frequency use in many countries; Example - Norway; number of seizures (rela2vely & total), but small part of the total number of seizures Oslo; 5th most common main agent for all tox. hospitaliza2ons in 20031 and 20082 Withdrawals can be severe BZD drug of choice. Baclofen, propofol & barbiturates3,4 1Hovda KE et al. Clin Tox 2008: 46; 35-41 2Lund C et al. BMC Public Health. 2012 Oct 9;12:858. Hovedgrupper NPS registrert via EWS 2005-2011 3McDonough M. Drug Alc Depend 2004 4Wood D et al. Drug Test. Analysis 2011 The typical clinical features S2mulants uppers Depressants downers Other substances Other substances Piperazines Spices Cathinones Phenetylamines Other substances Tryptamines EMCDDA Annual Report 2012 Hallucinogenic 6
Nomenklatur (I) Nomenklatur (II) AKB- 48 & 2NE1 Ini2alene 2l oppfinneren JWH- 071; John W. Huffman Stedet de ble synte2sert: HU- 210; Hebrew University, Jerusalem Kodenavn: APICA: N- (1- adamantyl)- 1- pentyl- 1H- indole- 3- carboxamide APINACA: N- (1- adamantyl)- 1- pentyl- 1H- indole- 3- carboxamide Navn for å hjelpe markedsføringen APICA = 2NE1 = jenteband fra Sør- Korea APINACA = AKB- 48 = Populært japansk jenteband Data collec@on. Solu@on? Mul@- layer approach Novel drug of abuse User reports Subpopula2on level studies PCC data Case reports/ series Human volunteer studies Takk 2l Fridtjof Heyerdahl Poten2al acute toxicity Wood DM, Dargan PI. Ther Drug Monit. 2012; 34(4): 363-7. 7
Data om akuie forgijninger med NPS Conclusion Trends in Europe; (Nye) rusmidler er vanlige Systema2ske data er 2lgjengelige for: Prevalensen av bruk Beslagstall Bruken av rusklinikker for problem drug use Rusrelaterte dødsfall Det finnes ingen systema5ske data om aku> toksisitet for disse rusmidlene Conclusion (II) Increasing number of substances; difficult to keep up Increasing # of reports on severe toxicity and mortali2es Difficult to be ahead of 2me ; how do we collate data regarding Clinical toxicology? Effects and side- effects are highly varying and unpredictable Na2onal varia2ons, but the new recrea2onal drugs respect no borders Fast- track varia2ons in panorama depending on legisla2on, availability of substances/precursors etc. Impuri2es might compose big user- and diagnos2c problems Anbefalt liieratur May encompass various unthinkable problems.. The Huffington Post, September 27, 2012 and so; ask your pa2ents and kids to think twice!!! 8