Introduksjon Rusmidler og Nye Psykoak2ve Stoffer (NPS) Knut Erik Hovda Overlege, PhD Nasjonal behandlingstjeneste for CBRNe- medisin 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 uvordringer Sammendrag De klassiske narko?ske stoffene Cannabis mest brukt Amfetaminer amfetamin vs. metamfetamin h>p://www.youtube.com/watch?v=bxo- 0iFj8Ys Ecstasy UK og Spaina dominerer. Varierende innhold.. Kokain nest vanligst i Sør- og Vest- Europa. Heroin står for den største sykeligheten og dødeligheten 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 oie 2lnærmet normal, vanligvis åpne coronarkar ved angiografi EMCDDA 1
Kokain overdose - behandling Amfetamin Generell sympa,komime,sk effekt BZD er drugs of choice Bryte den onde sirkelen 2l kokainets toksisitet, ved å s2mulere BZD/GABA- 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 NaHCO3 Tachycardier og tachyarrytmier BT, først og fremst systolisk BT Andre komplekse effekter: Generell vasokonstriksjon Ak2vering av trombocy>er Myokard- ischemi og arytmier Intrakranielle blødninger U>alt hypoglykemi; Tomme glykogenlagre1? 2 Økt insulinutskillelse? 1Bewsher PD et al. Studies of the hypoglycemic effect of d- amphetamine in aggregated mice. Biochem Pharmacol 1966; 14(3): 197-204. 2McMahon et al. Methamphetamine- induced insulin release. Science 1971; 174: 66-68. Ecstasy - MDMA 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 Ecstasy psykiske senvirkninger Senker serotoninnivået i CNS Personlighetsendringer Schizofrene trekk Kogni2v dysfunksjon Læreproblemer Nedsa> oppmerksomhet Nedsa> hukommelse ECSTASY- MEKANISMER Liberg JP et al. Tidsskr Nor Lægeforen 1998; 28: 4384-7. 2
Pharmacology of s?mulants and empathogens Potency to inhibit NE, DA and 5- HT transport into transporter- transfected cells and their efflux from monoamine- preloaded cells Methamphetamine Dopaminergic S2mulant Highly addic2ve MDMA (ecstasy) Serotonergic Empathogenic Less s2mulant Less addic2ve Simmler & Liech2. BMC Res Notes 2013 NPS - Background and defini?on (I) 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 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 (oien clubbers etc) increasing # of users Informa?on spread especially through internet NPS - Bakgrunn og definisjon (III) Vanligvis uvøres ikke ru2nemessig screening (blod- eller urinprøver) e>ersom det oiest 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), 2012: >70, 2013: >80, 2014: 101 nye stoffer (!) 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 2012-2015 Main groups of new psychoac?ve substances EMCDDA New groups 2015 - > 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 (un2l 2014): 1. Phenetylamines 2. Tryptamines 3. Piperazines 4. Cathinones 5. Synte2c cannabinoids 6. Other substances EWS Update March 2015 1. Piperazines 2. Benzodiazepines 3. Arylamines 4. Tryptamines 5. Opioids 6. Phenethylamines 7. Others Synthe2c 8. Cannabinoids 9. Synthe2c cathinones Update 2015 Technical list 1. Synthe2c cannabinoids 2. Phenethylamines 3. Other substances 4. Arylalkylamines 5. Cathinones 6. Opioids 7. Benzodiazepines 8. Tryptamines 9. Aminoindanes 10. Arylcyclohexylamines 11. Piperazines 12. Piperidines and pyrrolidines 13. Plants and extracts 3
1. Phenetylamines Bromo- dragonfly 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) Synte2sk hallusinogen med amfetaminliknende egenskaper; Sterk effekt på 5HT2A, betydelig s2mulerende og vasokonstringerende effekter Inntas gjerne som blo>ers /papirlapper Typisk dose 0,5-1,5mg Symptomdebut oiest 20-90min Varighet inn2l 1døgn, iblant mer Dødsfall rapportert i Norge, Sverige, Danmark, Finland og USA Thorlacius K, Borna C, Personne M. Lekar2dningen. 200; 16(105): 1199-1200 Bromo- dragonfly Synte2sk hallusinogen med amfetaminliknende egenskaper; Sterk effekt på 5HT2A, betydelig s2mulerende og vasokonstringerende effekter Inntas gjerne som blo>ers /papirlapper Typisk dose 0,5-1,5mg Symptomdebut oiest 20-90min Varighet inn2l 1døgn, iblant mer Dødsfall rapportert i Norge, Sverige, Danmark, Finland og USA 2. Tryptamines Effects: predominantly hallucinogenic effects Examples: α- Methyltryptamine (AMT), dimethyltryptamine (DMT), psilocin, psilocybin, LSD, 4- OH- metyletyltryptamin (4- OH- MET) First- pass- metabolism in the liver through MAO => use of MAO- i Thorlacius K, Borna C, Personne M. Lekar2dningen. 200; 16(105): 1199-1200 3. Piperazines Effects: s2mulants Examples: 1(- 3- chlorophenyl)- piperazine (mcpp), 1- benzylpiperazine (BZP), A2, TFMPP, Beans (Happy Popper) BZP: Effects like amphetamine & MDMA mcpp: Less sympa2co- mime2c, serotonergic overs2mula2on (anxiety, hyperthermia etc.) No known fatali2es 4
4. Cathinones Mephedrone The first cathinone to be formally risk- assessed Effects: s2mulants, oien also hallucinogenic effects The second most common group Bath salts (US) or plant food (Europe) oien refers to this group Examples: mephedrone, flefedron, efedron, methylone, methylene dioxy- pyruvalone (MDPV), methcathinone Mephedrone; Effect on 5HT2A as MDMA and D2 as amphetamine. Toxicity: Cardiovascular + thermoregula2on 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. 5. Synte?c cannabinoids/thc- analogues/ Spice Effects: hallucinogenic, seda2ve and depressant effects (some2mes also s2mulant proper2es) Higher affinity for the CB1 receptor compared to classical cannabinoids, less affinity for CBD 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 6. Other substances 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 GHB/GBL where do we place them? 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 & barbiturates 1Hovda KE et al. Clin Tox 2008: 46; 35-41 2Lund C et al. BMC Public Health. 2012 Oct 9;12:858. The typical clinical features S2mulants uppers Depressants downers Other substances Other substances Piperazines Spices Cathinones Phenetylamines Other substances Tryptamines Hallucinogenic 5
Nomenklatur (I) Ini2alene 2l oppfinneren JWH- 071; John W. Huffman Nomenklatur (II) AKB- 48 & 2NE1 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 Takk 2l Fridtjof Heyerdahl Euro- DEN European Drug Emergencies Network To års EU- finansiert prosjekt Hovedmål: 1. Utvikle et ne>verk av vaktposter sentre i Europa med spesiell interesse for nye psykoak2ve stoffer for å samle informasjon om aku> toksisitet fra et helseperspek2v 2. Bedre den pre- hospitale gjenkjennelsen av det aku>e forgiiningsbildet ved NPS Conclusion Trends in Europe; 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 6