Update U d t on N Novell P Psychoactive h ti Substances Fabrizio Schifano, MD, FRCPsych, Dip Clin Pharmacology gy Chair Clinical Pharmacology and Therapeutics Consultant Psychiatrist (Addictions) University of Hertfordshire (UK) ....SOME 700 DIFFERENT PSYCHOACTIVE SUBSTANCES POSSIBLY AVAILABLE....... AVAILABLE                179 PIA/phenethylamines/MDMA-like drugs; amphet-type substances (fluoroamphetamine, PMA, 2C-T, 2C-B etc); 14 PIA derivatives: ‘fly’; NBOMe; indanes; benzofurans (5; 6-APB/APDB); ‘BenzoFury’ 220 synthetic cannabimimetics; incl: AM-2201; AM-2233; AKB-48F 30 synthetic cathinones; incl: mephedrone; methedrone; methylone; etc Novel stimulants; aminorex derivatives; 4,4-DMAR A few synthetic opiate/opioids opiate/opioids, such as 4-fluorbutyrfentanyl; 4 fluorbutyrfentanyl; AH AH-7921; 7921; IC IC-26; 26; MT MT-45; 45; nortilidine; W15; W18 3 synthetic cocaine substitutes: RTI 111; RTI 121; RTI 126 64 tryptamine classical derivatives and 5 tryptamine derivatives such as 5-Meo-DALT; AMT; 5-Meo-AMT etc 126 psychedelic phenethylamines/stimulants from the Shulgin Index (2011); about 1,300 molecules being covered; including DMAA; related deaths reported in the UK 3 GHB-like drugs: GHB; GBL; 1,4-BD 7 PCP-like drugs: PCP; ketamine; methoxetamine; PCE; 3-MeO-PCP; ethylketamine; 3-HO-PCP etc 2 piperazines: BZP; TFMPP 12 Herbs/plants/fungi/animals: Salvia divinorum; Mytragina speciosa/kratom; Tabernanthe iboga/ibogaine; Kava Kava; Psychotria viridis/Ayahuasca; hydrangea; Rhodiola rosea; Datura stramonium; psychedelic mushrooms; bufo; sponges; flies; etc 11 medicinal products: tramadol, oxycodone, and remaining opiates/opiods; anticonvulsants (gabapentin and pregabalin); antiseptics (benzydamine); DXM; benzodiazepines/sedatives (phenazepam ‘Zinnie’; methaqualone); stimulants (ethylphenidate; camfetamine); antiparkinsonian /anticholinergics: selegiline; tropicamide); chloroquine; anitretrovirals/’whoonga’; xylazine 6 PIEDs: minikikke/super strength caffeine tablets; DNP; testosterone booster concoctions such as Tribulus terrestriscontaining products; cognitive enhancers (aniracetam; piracetam) FROM: DEBORALABS.COM DEBORALABS COM Cannabinoids  5F-AB-PINACA 5F-AKB-48 5F-AMB 5F-MN-18  5F-PB22                  5F-SDB-005 5F-SDB-006 AB-CHMINACA AB-FUBINACA AB-PINACA AB PINACA Sale BB-22 New EG-018 New FAB-144 New FDU-PB22 FUB-PB22 Sale NM-2201 New PB-22 Sale THJ 018 New THJ-018 THJ-2201 New (ACCESSED ON JUNE 4TH, 2014) Stimulants                               3-MeOMC New 3-MMC (crystals) New 4-BMC (crystals) New 4 MEC 4-MEC 4-MeO-a-PVP 4-MeO-PBP 4-MeO-PV9 4-MPD 4F-PV8 4F PV9 4F-PV9 4F-PVP 5-APB 5-APDB New 5-EAPB 5-MAPB a-PBT a-PHP New a-PVT Dibutylone (crystals) New Diclofensine DL-4662 New Ethylone (crystals) New Ethylphenidate (crystals) New MDPPP New Methiopropamine MOPPP New N-Methyl-2-AI y NEB Pentedrone (crystals) New PV-8 (crystals) New FROM: DEBORALABS.COM DEBORALABS COM (2) Dissociatives  3-MeO-PCP  4-MeO-PCP New    New Diphenidine p Methoxetamine Methoxphenidine et o p e d e New Opioids  MT-45 Benzodiazepine derivatives  Diclazepam New  Etizolam  Flubromazepam New Sigmaergics  PRE084 Overall summary of misusing drugs’ ph. dynamics OPIATES’ BINDING TO OPIATE RECEPTORS IN THE NUCLEUS ACCUMBENS: INCREASED DOPAMINE RELEASE DA NEURONS IN THE VTA AND OPIOIDS Schematic illustration of the way in which DA-containing g area ((VTA)) are excited neurons in the ventral tegmental by opioids. GABA-containing interneurons are hyperpolarized by opioids acting at p-receptors. This results in decreased (-) GABA release and increased (+) firing and DA release of DA-containing neurons in the VTA towards the nucleus accumbens (NAc). THC BINDING TO THC RECEPTORS IN THE NUCLEUS ACCUMBENS: INCREASED DOPAMINE RELEASE; THE ROLE OF ANANDAMIDE AND 2-AG IN MODULATING DA RELEASE /PROTECTING FROM THE EMERGENCE OF PSYCHOTIC DISTURBANCES THC INDUCES DOPAMINE RELEASE IN THE SHELL OF NUCLEUS ACCUMBENS ACTING ON CB1 RECEPTOR. THIS EFFECT MAY BE INDIRECT AND MEDIATED IN PART BY CANNABINOID REGULATION OF ENDOGENOUS OPIOID SYSTEMS IN THE VTA CB1 RECEPTOR SYNTHETIC CANNABIMIMETICS  Most SC are CANNABIMIMETIC INDOLES  SEROTONIN SYNDROME SYNTHETIC CANNABIMIMETICS; IS IT A POLYSUBSTANCE MISUSE PER SE? STS-35 NMDA antagonist CB-rs ligand Indole 5HT-rs ligand Fluorination THE 5-HT2A 5 HT2A RECEPTOR THE VANILLOID RECEPTOR Mechanism of action of cocaine/most synth cathinones/1 Mechanism of action of cocaine/most synth cathinones/2 Mechanism of action of amphetamines/PIAs/other stimulants PCP-LIKE DRUGS; NMDA RECEPTORS’ NON COMPETITIVE ANTAGONISTS PCP-LIKE DRUGS; MGLU2/3 RECEPTOR ANTAGONISTS GABAA RECEPTOR GHB RECEPTOR [3H]GHB ] NCS382 antagonist g G0/i Kd1=30-580 nM High affinity GHB binding site Kd2=2,3-16 µM Low affinity GHB binding site