'Legal Highs' novel and emerging psychoactive drugs: A chemical overview for the toxicologist

Clinical Toxicology

Volumn 50, Issue 1, 2012, Pages 15-24

  Gibbons, Simon ^a  

^a UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

Amphetamines; Cathinones; Cocaine; Herbal highs; Mephedrone; Neurotransmitters; PCP; Phenylethylamines; Tryptamines

Indexed keywords

1,4 BUTANEDIOL; 3,4 METHYLENEDIOXYMETHAMPHETAMINE; 4' METHYLMETHCATHINONE; CATHINONE; COCAINE DERIVATIVE; EPIBATIDINE; GAMMA BUTYROLACTONE; HORDENINE; IBOTENIC ACID; KETAMINE; LEGAL HIGH; MESCALINE; MESEMBRINE; METHYLENEDIOXY 2 AMINO INDANE; MORPHINE; MUSCIMOL; NEUROTRANSMITTER; OXEDRINE; PHENCYCLIDINE; PHENCYCLIDINE DERIVATIVE; PHENETHYLAMINE DERIVATIVE; PLANT EXTRACT; PSILOCIN; PSILOCYBINE; PSYCHOTROPIC AGENT; SALVIA DIVINORUM EXTRACT; SEROTONIN; TETRAHYDROCANNABINOL; TRYPTAMINE; TRYPTAMINE DERIVATIVE; UNCLASSIFIED DRUG;

BLADDER DYSFUNCTION; DRUG ABUSE; DRUG MARKETING; DRUG STRUCTURE; HALLUCINATION; HEART PALPITATION; HUMAN; HYPERTENSION; INTERNET; NEUROTOXICITY; NONHUMAN; REVIEW; TACHYCARDIA; URINARY DYSFUNCTION;

ALKALOIDS; COCAINE; GREAT BRITAIN; HUMANS; KETAMINE; METHAMPHETAMINE; PHENETHYLAMINES; PLANT EXTRACTS; PSYCHOTROPIC DRUGS; SALVIA; STREET DRUGS; TRYPTAMINES;

EID: 84855935526     PISSN: 15563650     EISSN: 15569519     Source Type: Journal    
DOI: 10.3109/15563650.2011.645952     Document Type: Review

References (62)

1. McNabb CB, Russell BR, Caprioli D, Nutt DJ, Gibbons S, Dalley JW. Single chemical entity legal highs: assessing the risk for long term harm. Curr Drug Abuse Rev 2011; (Submitted).
2. Winstock AR, Ramsey JD. Legal highs and the challenges for policy makers. Addiction 2010; 105:1685-1687.
3. Gibbons S, Zloh M. An analysis of the legal high mephedrone. Bioorg Med Chem Lett 2010; 20:4135-4139.
4. http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/ acmd1/acmd-cathinodes-report-2010.
5. Langston JW, Ballard P, Tetrud JW, Irwin I. Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis. Science 1983; 219:979-980. (Pubitemid 13189531)
6. Langston JW, Irwin I, Langston EB, Forno LS. 1-Methyl-4- phenylpyridinium ion (MPP- ): identifi cation of a metabolite of MPTP, a toxin selective to the substantia nigra. Neurosci Lett 1984; 48:87-92.
7. Benyhe S. Morphine: new aspects in the study of an ancient compound. Life Sci 1994; 55:969-979. (Pubitemid 24269390)
8. Appendino G, Chianese G, Taglialatela-Scafati O. Cannabinoids: occurrence and medicinal chemistry. Curr Med Chem 2011; 18: 1085-1099.
9. Harvey AL, Young LC, Viljoen AM, Gericke NP. Pharmacological actions of the South African medicinal and functional food plant Sceletium tortuosum and its principal alkaloids. J Ethnopharmacol 2011; 137:1124-1129.
10. Michelot D, Melendez-Howell LM. A manita muscaria : chemistry, biology, toxicology, and ethnomycology. Mycol Res 2003; 107: 131-146.
11. Brown SD, Melton TC. Trends in bioanalytical methods for the determination and quantifi cation of club drugs: 2000-2010. Biomed Chromatogr 2011; 25:300-321.
12. Palmer RB. Gamma-butyrolactone and 1,4-butanediol: abused analogues of gamma-hydroxybutyrate. Toxicol Rev 2004; 23:21-31. (Pubitemid 40484569)
13. Wood DM, Brailsford AD, Dargan PI. Acute toxicity and withdrawal syndromes related to gamma-hydroxybutyrate (GHB) and its analogues gamma-butyrolactone (GBL) and 1,4-butanediol (1,4-BD). Drug Test Anal 2011; 3:417-425.
14. Halpern JH. Hallucinogens and dissociative agents naturally growing in the United States. Pharmacol Ther 2004; 102:131-138. (Pubitemid 38681012)
15. Daly JW, Spande TF, Garraffo HM. Alkaloids from amphibian skin: a tabulation of over eight-hundred compounds. J Nat Prod 2005; 68:1556-1575. (Pubitemid 41658912)
16. Daly JW. Nicotinic agonists, antagonists, and modulators from natural sources. Cell Mol Neurobiol 2005; 25:513-552. (Pubitemid 41199710)
17. McLaughlin JL. Peyote: an introduction. Lloydia 1973; 36:1-8.
18. Kalix P. The pharmacology of psychoactive alkaloids from E phedra and Catha . J Ethnopharmacol 1991; 32:201-208.
19. Klein A, Metaal P. A good chew or good riddance-how to move forward in the regulation of khat consumption. J Ethnopharmacol 2010; 132:584-589.
20. Pemberton IJ, Smith GR, Forbes TD, Hensarling CM. Technical note: an improved method for extraction and quantifi cation of toxic phenethylamines from Acacia berlandieri . J Anim Sci 1993; 71:467-470.
21. Gjessing L, Armstrong MD. Occurrence of (-)-sympatol in oranges. Proc Soc Exp Biol Med 1963; 114:226-229.
22. Rossato LG, Costa VM, Limberger RP, Bastos Mde L, Remiã o F. Synephrine: from trace concentrations to massive consumption in weight-loss. Food Chem Toxicol 2011; 49:8-16.
23. Brunt TM, Poortman A, Niesink RJ, van den Brink W. Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol 2011; 25:1543-1547.
24. Cozzi NV, Sievert MK, Shulgin AT, Jacob P 3rd, Ruoho AE. Inhibition of plasma membrane monoamine transporters by betaketoamphetamines. Eur J Pharmacol 1999; 381:63-69. (Pubitemid 29488590)
25. Schifano F, Albanese A, Fergus S, Stair JL, Deluca P, Corazza O, et al. Psychonaut Web Mapping; ReDNet Research Groups. Mephedrone (4- methylmethcathinone; meow meow): chemical, pharmacological and clinical issues. Psychopharmacology (Berl). 2011; 214:593-602.
26. Kehr J, Ichinose F, Yoshitake S, Goiny M, Sievertsson T, Nyberg F, Yoshitake T. Mephedrone, compared to MDMA (ecstasy) and amphetamine, rapidly increases both dopamine and serotonin levels in nucleus accumbens of awake rats. Br J Pharmacol 2011; 164:1949-1958.
27. http://www.homeoffice.gov.uk/publications/alcohol-drugs/drugs/ acmd1/acmd-cathinodes-report-2010.
28. Gorceix A, Jacquemin C. Value of pyrovalerone in the ambulatory treatment of fatigue states. Ann Med Psychol (Paris) 1970; 2:624-632.
29. Meltzer PC, Butler D, Deschamps JR, Madras BK. 1-(4- Methylphenyl)-2- pyrrolidin-1-yl-pentan-1-one (Pyrovalerone) analogues: a promising class of monoamine uptake inhibitors. J Med Chem 2006; 49:1420-1432. (Pubitemid 43271895)
30. http://www.homeoffi ce.gov.uk/drugs/drug-law/naphyrone/
31. Nichols DE, Brewster WK, Johnson MP, Oberlender R, Riggs RM. Nonneurotoxic tetralin and indan analogues of 3,4-(methylenedioxy) amphetamine (MDA). J Med Chem 1990; 33:703-710. (Pubitemid 20047595)
32. Monte AP, Marona-Lewicka D, Cozzi NV, Nichols DE. Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine. J Med Chem 1993; 36:3700-3706. (Pubitemid 24004369)
33. Marona-Lewicka D, Nichols DE. Behavioral effects of the highly selective serotonin releasing agent 5-methoxy-6-methyl-2-amino indan. Eur J Pharmacol 1994; 258:1-13. (Pubitemid 24174979)
34. Wood DM, Button J, Lidder S, Ovaska H, Ramsey J, Holt DW, Dargan PI. Detection of the novel recreational drug Diphenyl-2- pyrrolidinemethanol (D2PM) sold legally in combination with 1-Benzylpiperzaine (BZP). Clin Toxicol 2008; 46:393.
35. Corey EJ, Bakshi RK, Shibata S. Highly enantioselective borane reduction of ketones catalyzed by chiral oxazaborolidines Mechanism and synthetic implications. J Am Chem Soc 1987; 109:5551-5553.
36. Perlstein IB. The use of pipradrol in the problems of obesity. Int Rec Med Gen Pract Clin 1957; 170:55-58.
37. Ross SB, Kelder D. Inhibition of 3 H-dopamine accumulation in reserpinized and normal rat striatum. Acta Pharmacol Toxicol (Copenh) 1979; 44:329-335. (Pubitemid 9197115)
38. Ursillo RC, Jacobsen JJ. Potentiation of norepinephrine in the isolated vas deferens of the rat by some CNS stimulants and antidepressants. J Pharmacol Exp Ther 1965; 148:247-251.
39. Tripod J, Sury E, Hoffmann K. Analeptic effect of a new piperidine derivative. Experientia 1954; 10:261-262.
40. Ferris, RM, Tang FL. Comparison of the effects of the isomers of amphetamine, methylphenidate and deoxypipradrol on the uptake of l- 3 H-norepinephrine and 3 H-dopamine by synaptic vesicles from rat whole brain, striatum and hypothalamus. J Pharmacol Exp Ther 1979; 210:422-428. (Pubitemid 10226347)
41. James DA, Potts S, Thomas SHL, Chincholkar VM, Clarke S, Dear J, Ramsey J. Clinical features associated with recreational use of Ivory Wave preparations containing desoxypipradrol. Clin Toxicol 2011; 49:201.
42. http://www.homeoffi ce.gov.uk/media-centre/news/drug-import-ban.
43. Iversen SD, Iversen LL. Dopamine: 50 years in perspective. Trends Neurosci 2007; 30:188-193. (Pubitemid 46654233)
44. Markowitz JS, Devane CL, Boulton DW, Nahas Z, Risch SC, Diamond F, et al. Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol. Drug Metab Dispos 2000; 28:620-624. (Pubitemid 30390399)
45. Patrick KS, Williard RL, VanWert AL, Dowd JJ, Oatis JE Jr, Middaugh LD. Synthesis and pharmacology of ethylphenidate enantiomers: the human transesterifi cation metabolite of methylphenidate and ethanol. J Med Chem 2005; 48:2876-2881. (Pubitemid 40548102)
46. Woolverton WL, Balster RL. Effects of local anesthetics on fi xedinterval responding in rhesus monkeys. Pharmacol Biochem Behav 1983; 18:383-387. (Pubitemid 13146896)
47. Graham JH, Balster RL. Cocaine-like discriminative stimulus effects of procaine, dimethocaine and lidocaine in rats. Psychopharmacology 1993; 110:287-294. (Pubitemid 23051129)
48. Wilcox KM, Kimmel HL, Lindsey KP, Votaw JR, Goodman MM, Howell LL. In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys. Synapse 2005; 58:220-228. (Pubitemid 41690805)
49. Morgan CJ, Curran HV; the Independent Scientifi c Committee on Drugs (ISCD). Ketamine use: a review. Addiction 2011; 107:27-38.
50. McCarron MM, Schulze BW, Thompson GA, Conder MC, Goetz WA. Acute phencyclidine intoxication: incidence of clinical fi ndings in 1,000 cases. Ann Emerg Med 1981; 10:237-242. (Pubitemid 12123785)
51. Wood D, Cottrell A, Baker SC, Southgate J, Harris M, Fulford S, et al. Recreational ketamine: from pleasure to pain. Brit J Urol 2011; 107:1881-1884.
52. Lyttle T, Goldstein D, Gartz J. Bufo toads and bufotenine: fact and fi ction surrounding an alleged psychedelic. J Psychoactive Drugs 1996; 28:267-290. (Pubitemid 26337625)
53. Nonaka R, Nagai F, Ogata A, Satoh K. In vitro screening of psychoactive drugs by [(35)S]GTPgammaS binding in rat brain membranes. Biol Pharm Bull 2007; 30:2328-2333. (Pubitemid 350223736)
54. Nagai F, Nonaka R, Satoh Hisashi Kamimura K. The effects of nonmedically used psychoactive drugs on monoamine neurotransmission in rat brain. Eur J Pharmacol 2007; 559:132-137. (Pubitemid 46295399)
55. Beckett AH, Shellard EJ, Phillipson JD, Lee CM. Alkaloids from Mitragyna speciosa (Korth.). J Pharm Pharmacol 1965; 17:753-755.
56. Lee CM, Trager WF, Beckett AH. Corynantheidine-type alkaloids. II. Absolute confi guration of mitragynine, speciociliatine, mitraciliatine and speciogynine. Tetrahedron 1967; 23:375-385.
57. Thongpradichote S, Matsumoto K, Tohda M, Takayama H, Aimi N, Sakai S, Watanabe H. Identifi cation of opioid receptor subtypes in antinociceptive actions of supraspinally-administered mitragynine in mice. Life Sci 1998; 62:1371-1378. (Pubitemid 28143979)
58. Hylin JW, Watson DP. Ergoline alkaloids in tropical wood roses. Science 1965; 148:499-500.
59. Van Hout MC, Brennan R. H eads held high : an exploratory study of legal highs in pre-legislation Ireland. J Ethn Subst Abuse 2011; 10:256-72.
60. Klinke HB, Müller IB, Steffenrud S, Dahl-Sørensen R. Two cases of lysergamide intoxication by ingestion of seeds from Hawaiian Baby Woodrose. Forensic Sci Int 2010; 197:e1-e5.
61. Siebert DJ. S alvia divinorum and salvinorin A: new pharmacologic fi ndings. J Ethnopharmacol 1994; 43:53-56. (Pubitemid 24186510)
62. Roth BL, Baner K, Westkaemper R, Siebert D, Rice KC, Steinberg S, Ernsberger P, Rothman RB. Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proc Natl Acad Sci U S A 2002; 99:11934-11939. (Pubitemid 34994502)