Display options
Cite
Baumeister D, Tojo LM, Tracy DK. Legal highs: staying on top of the flood of novel psychoactive substances. Ther Adv Psychopharmacol. 2015;5(2):97-132doi: 10.1177/2045125314559539.
Baumeister, D., Tojo, L. M., & Tracy, D. K. (2015). Legal highs: staying on top of the flood of novel psychoactive substances. Therapeutic advances in psychopharmacology, 5(2), 97-132. https://doi.org/10.1177/2045125314559539
Baumeister, David, et al. "Legal highs: staying on top of the flood of novel psychoactive substances." Therapeutic advances in psychopharmacology vol. 5,2 (2015): 97-132. doi: https://doi.org/10.1177/2045125314559539
Baumeister D, Tojo LM, Tracy DK. Legal highs: staying on top of the flood of novel psychoactive substances. Ther Adv Psychopharmacol. 2015 Apr;5(2):97-132. doi: 10.1177/2045125314559539. PMID: 26240749; PMCID: PMC4521440.
Copy Download .nbib Format: NLM
Share it on

Ther Adv Psychopharmacol. 2015 Apr;5(2):97-132. doi: 10.1177/2045125314559539.

Legal highs: staying on top of the flood of novel psychoactive substances.

Therapeutic advances in psychopharmacology

David Baumeister, Luis M Tojo, Derek K Tracy

Affiliations

  1. Department of Psychology, Institute of Psychiatry, King's College, London, UK.
  2. Stress, Psychiatry and Immunology Lab, Department of Psychological Medicine, Institute of Psychiatry, King's College, London, UK.
  3. Consultant Psychiatrist and Associate Clinical Director, Oxleas NHS Foundation Trust, Princess Royal University Hospital, and Cognition, Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, Institute of Psychiatry, King's College, London BR6 8NY, UK.

PMID: 26240749 PMCID: PMC4521440 DOI: 10.1177/2045125314559539

Abstract

There has been growing clinical, public, and media awareness and concern about the availability and potential harmfulness of so-called 'legal highs', which are more appropriately called new or novel psychoactive substances (NPS). A cat-and-mouse process has emerged wherein unknown chemists and laboratories are producing new, and as yet nonproscribed, compounds for human consumption; and as soon as they are banned, which they inevitably are, slightly modified analogues are produced to circumvent new laws. This rapidly changing environment, 81 new substances were identified in 2013 alone, has led to confusion for clinicians, psychopharmacologists, and the public at large. Our difficulties in keeping up with the process has had a two-fold negative effect: the danger of ignoring what is confusing; and the problem that some of the newer synthesized compounds appear ever more potent. This review aims to circumscribe a quick moving and growing field, and to categorize NPS into five major groups based upon their 'parent' compounds: stimulants similar to cocaine, amphetamines and ecstasy; cannabinoids; benzodiazepine based drugs; dissociatives similar to ketamine and phencyclidine (PCP); and those modelled after classic hallucinogens such as LSD and psilocybin. Pharmacodynamic actions, subjective and physical effects, harmfulness, risk of dependency and, where appropriate, putative clinical potentials are described for each class. Clinicians might encounter NPS in various ways: anecdotal reportage; acute intoxication; as part of a substance misuse profile; and as a precipitant or perpetuating factor for longer-term physical and psychological ill health. Current data are overall limited, and much of our knowledge and treatment strategies are based upon those of the 'parent' compound. There is a critical need for more research in this field, and for professionals to make themselves more aware of this growing issue and how it might affect those we see clinically and try to help: a brave new world of so-called 'psychonauts' consuming NPS will also need informed 'psychotherapeutonauts'. The paper should serve as a primer for clinicians and interested readers, as well as provide a framework into which to place the new substances that will inevitably be synthesized in the future.

Keywords: legal highs; novel psychoactive substances

References

  1. Br J Pharmacol. 2013 Jan;168(2):458-70 - PubMed
  2. Annu Rev Pharmacol Toxicol. 2007;47:681-98 - PubMed
  3. J Psychoactive Drugs. 1986 Oct-Dec;18(4):305-13 - PubMed
  4. Med Hypotheses. 2012 Oct;79(4):504-7 - PubMed
  5. Euro Surveill. 2013 May 30;18(22):null - PubMed
  6. Neuropharmacology. 2014 Apr;79:152-60 - PubMed
  7. Addiction. 2009 Jul;104(7):1085-99 - PubMed
  8. Biochem Pharmacol. 2014 Mar 15;88(2):237-44 - PubMed
  9. Lancet. 2007 Jul 28;370(9584):319-28 - PubMed
  10. Soc Neurosci. 2009;4(4):359-66 - PubMed
  11. PLoS Med. 2006 Nov;3(11):e437 - PubMed
  12. Psychopharmacology (Berl). 2007 Jan;189(4):531-7 - PubMed
  13. West J Emerg Med. 2012 Feb;13(1):58-62 - PubMed
  14. Drug Test Anal. 2014 Jul-Aug;6(7-8):614-32 - PubMed
  15. Neuropsychopharmacology. 2000 Oct;23(4):396-404 - PubMed
  16. Ther Adv Psychopharmacol. 2014 Aug;4(4):156-69 - PubMed
  17. J Anal Toxicol. 2013 Jan-Feb;37(1):43-6 - PubMed
  18. J Psychopharmacol. 2011 Apr;25(4):439-52 - PubMed
  19. Curr Pharm Biotechnol. 2010 Aug;11(5):500-9 - PubMed
  20. Curr Pharm Des. 2014;20(25):4112-8 - PubMed
  21. Dev Psychobiol. 2010 Apr;52(3):263-76 - PubMed
  22. Lancet. 2010 Nov 6;376(9752):1558-65 - PubMed
  23. Am J Med Genet B Neuropsychiatr Genet. 2013 Oct;162B(7):661-70 - PubMed
  24. J Neurosci. 1997 Apr 15;17(8):2921-7 - PubMed
  25. Neuroscience. 2012 Mar 1;204:5-16 - PubMed
  26. Br J Pharmacol. 2011 Dec;164(8):1949-58 - PubMed
  27. Forensic Sci Int. 2011 Mar 20;206(1-3):92-7 - PubMed
  28. Exp Clin Psychopharmacol. 2005 Nov;13(4):311-8 - PubMed
  29. Forensic Sci Int. 2005 Oct 29;153(2-3):196-201 - PubMed
  30. Proc Natl Acad Sci U S A. 2012 Feb 7;109 (6):2138-43 - PubMed
  31. Front Pharmacol. 2012 Jun 29;3:121 - PubMed
  32. Ther Adv Psychopharmacol. 2012 Oct;2(5):179-88 - PubMed
  33. Brain Res. 1997 Jun 13;759(2):205-12 - PubMed
  34. Psychopharmacology (Berl). 1999 Feb;142(1):41-50 - PubMed
  35. BJU Int. 2008 Dec;102(11):1616-22 - PubMed
  36. Drug Alcohol Depend. 2003 Jan 24;69(1):23-8 - PubMed
  37. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Dec 3;39(2):259-62 - PubMed
  38. Addict Biol. 2002 Oct;7(4):357-64 - PubMed
  39. J Anal Toxicol. 2012 Jul;36(6):405-12 - PubMed
  40. Psychopharmacology (Berl). 2007 May;191(4):867-77 - PubMed
  41. J Emerg Med. 2013 Feb;44(2):360-6 - PubMed
  42. Life Sci. 2014 Feb 27;97(1):31-6 - PubMed
  43. Pharmacol Rev. 2010 Sep;62(3):405-96 - PubMed
  44. PLoS One. 2013 Jul 25;8(7):e70378 - PubMed
  45. PLoS One. 2013 Aug 19;8(8):e63972 - PubMed
  46. Addiction. 2004 Nov;99(11):1450-61 - PubMed
  47. Ind Psychiatry J. 2013 Jul;22(2):100-8 - PubMed
  48. Dtsch Arztebl Int. 2009 Jul;106(27):464-7 - PubMed
  49. Forensic Sci Rev. 2014 Jan;26(1):53-78 - PubMed
  50. Prostaglandins Leukot Essent Fatty Acids. 2004 Feb;70(2):189-97 - PubMed
  51. Neuropsychopharmacology. 2012 Mar;37(4):1070-1; author reply 1072-3 - PubMed
  52. Forensic Sci Int. 2013 Apr 10;227(1-3):7-14 - PubMed
  53. Pharmacol Biochem Behav. 2014 Sep;124:123-8 - PubMed
  54. Neuropsychopharmacology. 1997 Sep;17(3):141-50 - PubMed
  55. J Forensic Leg Med. 2012 Apr;19(3):122-5 - PubMed
  56. Anesth Analg. 1999 Jan;88(1):174-80 - PubMed
  57. Psychopharmacology (Berl). 2013 Aug;228(4):525-40 - PubMed
  58. Transl Psychiatry. 2012 Mar 20;2:e94 - PubMed
  59. Prog Neuropsychopharmacol Biol Psychiatry. 2008 Jan 1;32(1):140-4 - PubMed
  60. Addiction. 2006 Aug;101(8):1212-3 - PubMed
  61. Psychol Med. 2008 Sep;38(9):1331-40 - PubMed
  62. J Mass Spectrom. 2013 Nov;48(11):1150-9 - PubMed
  63. Hum Psychopharmacol. 2013 Jul;28(4):379-89 - PubMed
  64. Eur Neuropsychopharmacol. 2000 Jul;10(4):289-95 - PubMed
  65. Ann Emerg Med. 2012 Jul;60(1):97-9 - PubMed
  66. J Psychopharmacol. 2013 Sep;27(9):823-36 - PubMed
  67. Neuropsychopharmacology. 2010 Feb;35(3):764-74 - PubMed
  68. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Jun;30(4):640-6 - PubMed
  69. J Clin Psychopharmacol. 2012 Dec;32(6):839-40 - PubMed
  70. PLoS One. 2013;8(3):e59334 - PubMed
  71. Addiction. 2010 Jan;105(1):121-33 - PubMed
  72. Ther Adv Psychopharmacol. 2014 Apr;4(2):75-99 - PubMed
  73. PLoS One. 2010 Aug 31;5(8):e12412 - PubMed
  74. Anesth Analg. 1995 Jul;81(1):57-62 - PubMed
  75. Life Sci. 2014 Feb 27;97(1):45-54 - PubMed
  76. Expert Opin Investig Drugs. 2012 Sep;21(9):1309-22 - PubMed
  77. Eur J Clin Pharmacol. 2013 Mar;69(3):361-3 - PubMed
  78. Hum Psychopharmacol. 2014 Mar;29(2):105-8 - PubMed
  79. Addiction. 2009 Jan;104(1):77-87 - PubMed
  80. Curr Pharm Des. 2012;18(32):5045-54 - PubMed
  81. Neuropsychol Rev. 2007 Sep;17(3):275-97 - PubMed
  82. Psychopharmacology (Berl). 2012 Jul;222(2):293-302 - PubMed
  83. Drug Alcohol Depend. 2003 Mar 1;69(2):109-19 - PubMed
  84. Hong Kong Med J. 2009 Feb;15(1):53-6 - PubMed
  85. Prog Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):687-700 - PubMed
  86. Pharmacol Biochem Behav. 2013 Jan;103(3):501-9 - PubMed
  87. Addict Biol. 2014 Mar;19(2):237-9 - PubMed
  88. J Affect Disord. 2015 Mar 15;174:467-78 - PubMed
  89. Neuropsychopharmacology. 2000 Oct;23 (4):388-95 - PubMed
  90. J Comput Neurosci. 2012 Feb;32(1):25-53 - PubMed
  91. Anal Bioanal Chem. 2013 Jul;405(19):6307-21 - PubMed
  92. Arch Gen Psychiatry. 1994 Mar;51(3):199-214 - PubMed
  93. Neurosci Biobehav Rev. 1984 Winter;8(4):493-501 - PubMed
  94. J Forensic Sci. 2009 Nov;54(6):1485-7 - PubMed
  95. Eur Psychiatry. 2013 Jan;28(1):7-20 - PubMed
  96. Ann Emerg Med. 1999 Oct;34(4 Pt 1):492-7 - PubMed
  97. J Psychopharmacol. 2014 Sep;28(9):857-65 - PubMed
  98. Cochrane Database Syst Rev. 2009 Jan 21;(1):CD003026 - PubMed
  99. Drug Alcohol Depend. 2013 Sep 1;132(1-2):1-12 - PubMed
  100. Psychopharmacology (Berl). 2007 Jan;189(4):557-63 - PubMed
  101. Brain Sci. 2013 Apr 26;3(2):642-69 - PubMed
  102. J Psychopharmacol. 2014 Jan;28(1):62-6 - PubMed
  103. Behav Brain Res. 1996;73(1-2):121-4 - PubMed
  104. Br J Pharmacol. 2002 Jun;136(4):510-9 - PubMed
  105. Drug Alcohol Depend. 2008 Jun 1;95(3):219-29 - PubMed
  106. Behav Brain Res. 1996 Jan;74(1-2):45-55 - PubMed
  107. Forensic Sci Int. 2014 Oct;243:55-60 - PubMed
  108. Expert Opin Ther Targets. 2011 May;15(5):557-77 - PubMed
  109. Pharmacol Toxicol. 1995 Dec;77(6):355-9 - PubMed
  110. J Forensic Sci. 2014 May;59(3):844-6 - PubMed
  111. J Psychopharmacol. 2014 Aug;28(8):780-8 - PubMed
  112. Eur J Pharmacol. 2004 Sep 24;499(3):291-5 - PubMed
  113. Addiction. 2011 Nov;106(11):1991-6 - PubMed
  114. PLoS One. 2014 Apr 09;9(4):e93955 - PubMed
  115. QJM. 2010 Nov;103(11):875-9 - PubMed
  116. J Spec Pediatr Nurs. 2014 Apr;19(2):119-26 - PubMed
  117. Brain Res Mol Brain Res. 2001 Aug 15;92(1-2):138-48 - PubMed
  118. Eur J Pharmacol. 2007 Jan 26;555(2-3):156-63 - PubMed
  119. Nat Rev Neurosci. 2008 Jan;9(1):46-56 - PubMed
  120. Exp Clin Psychopharmacol. 2007 Dec;15(6):599-609 - PubMed
  121. Science. 2010 Aug 20;329(5994):959-64 - PubMed
  122. Eur Neuropsychopharmacol. 2012 Apr;22(4):308-17 - PubMed
  123. J Anal Toxicol. 2010 Apr;34(3):162-8 - PubMed
  124. Clin Pharmacol Ther. 1965 May-Jun;6:279-91 - PubMed
  125. Neuropsychopharmacology. 2010 Jan;35(1):217-38 - PubMed
  126. BJU Int. 2012 Dec;110(11):1762-6 - PubMed
  127. J Leukoc Biol. 2014 Oct;96(4):523-34 - PubMed
  128. Curr Pharm Des. 2012;18(32):4966-79 - PubMed
  129. Science. 2003 Jun 6;300(5625):1504-5; author reply 1504-5 - PubMed
  130. Eur J Pharmacol. 2013 Jan 30;700(1-3):147-51 - PubMed
  131. J Med Chem. 1979 Nov;22(11):1390-8 - PubMed
  132. Clin Toxicol (Phila). 2014 Mar;52(3):176-80 - PubMed
  133. Neuropsychopharmacology. 2004 Sep;29(9):1715-22 - PubMed
  134. N Z Med J. 2005 Dec 16;118(1227):U1784 - PubMed
  135. Psychopharmacology (Berl). 2009 Nov;207(1):73-83 - PubMed
  136. Hum Psychopharmacol. 2013 Jul;28(4):390-3 - PubMed
  137. Br J Pharmacol. 2012 Jul;166(5):1518-20; discussion 1521-2 - PubMed
  138. Neuroreport. 1998 Dec 1;9(17 ):3897-902 - PubMed
  139. J Psychoactive Drugs. 2000 Oct-Dec;32(4):419-33 - PubMed
  140. Birth Defects Res B Dev Reprod Toxicol. 2012 Apr;95(2):137-50 - PubMed
  141. Biol Psychiatry. 2015 Oct 15;78(8):554-62 - PubMed
  142. Clin Toxicol (Phila). 2013 Jul;51(6):487-92 - PubMed
  143. Psychopharmacology (Berl). 2001 Mar 1;154(2):161-8 - PubMed
  144. Neurosci Biobehav Rev. 2004 Jan;27(8):821-6 - PubMed
  145. Expert Rev Neurother. 2010 Aug;10(8):1347-59 - PubMed
  146. Life Sci. 2014 Feb 27;97(1):27-30 - PubMed
  147. Drug Test Anal. 2014 Jun;6(6):506-15 - PubMed
  148. Forensic Sci Rev. 2013 Mar;25(1-2):27-46 - PubMed
  149. World J Biol Psychiatry. 2013 Aug;14(6):412-31 - PubMed
  150. Neuropharmacology. 2014 Feb;77:200-7 - PubMed
  151. Singapore Med J. 2003 Jan;44(1):31-4 - PubMed
  152. Am J Psychiatry. 2011 Oct;168(10):1119 - PubMed
  153. Br J Pharmacol. 2010 Jun;160(3):585-93 - PubMed
  154. JAMA Psychiatry. 2014 Mar;71(3):281-91 - PubMed
  155. J Psychopharmacol. 2015 Mar;29(3):280-8 - PubMed
  156. J Psychopharmacol. 2013 Jan;27(1):40-52 - PubMed
  157. Biochem Pharmacol. 2009 Nov 1;78(9):1095-104 - PubMed
  158. Brain Behav Immun. 2014 Aug;40:269-82 - PubMed
  159. J Psychopharmacol. 2008 Aug;22(6):603-20 - PubMed
  160. Soc Psychiatry Psychiatr Epidemiol. 2014 Jun;49(6):841-9 - PubMed
  161. Emerg Med Australas. 2008 Oct;20(5):391-402 - PubMed
  162. CNS Drugs. 2005;19(2):105-23 - PubMed
  163. Clin Pharmacol Ther. 2011 Aug;90(2):246-55 - PubMed
  164. Drug Alcohol Depend. 2011 Oct 1;118(1):19-22 - PubMed
  165. ACS Chem Neurosci. 2012 May 16;3(5):349-55 - PubMed
  166. Front Psychiatry. 2013 Oct 14;4:129 - PubMed
  167. Forensic Sci Int. 2009 Oct 30;191(1-3):58-63 - PubMed
  168. Schizophr Bull. 2013 Nov;39(6):1343-51 - PubMed
  169. Soc Cogn Affect Neurosci. 2014 Nov;9(11):1645-52 - PubMed
  170. J Med Chem. 1969 May;12(3):473-7 - PubMed
  171. Neuropsychol Rev. 2010 Mar;20(1):21-32 - PubMed
  172. Neuropsychobiology. 2009;60(3-4):130-6 - PubMed
  173. Am J Emerg Med. 2013 Feb;31(2):445.e3-5 - PubMed
  174. J Clin Invest. 2005 Nov;115(11):3104-16 - PubMed
  175. Psychopharmacology (Berl). 2004 Mar;172(2):145-56 - PubMed
  176. J Neurochem. 2011 Jan;116(2):164-76 - PubMed
  177. Int J Neuropsychopharmacol. 2013 Nov;16(10):2165-80 - PubMed
  178. Pharmacol Ther. 2004 Feb;101(2):131-81 - PubMed
  179. Psychopharmacology (Berl). 2006 Nov;188(4):408-24 - PubMed
  180. J Forensic Sci. 1978 Jul;23(3):503-7 - PubMed
  181. J Psychiatr Res. 2000 Jan-Feb;34(1):35-43 - PubMed
  182. Psychopharmacology (Berl). 2006 Aug;187(3):268-83; discussion 284-92 - PubMed
  183. Science. 2013 May 3;340(6132):615-9 - PubMed
  184. Regul Toxicol Pharmacol. 2011 Apr;59(3):423-9 - PubMed
  185. Gen Hosp Psychiatry. 2013 Sep-Oct;35(5):571-3 - PubMed
  186. Drug Alcohol Depend. 2004 Oct 5;76(1):55-62 - PubMed
  187. Br J Pharmacol. 2008 Jan;153(2):199-215 - PubMed
  188. N Engl J Med. 2005 Mar 17;352(11):1112-20 - PubMed
  189. Urology. 2007 May;69(5):810-2 - PubMed
  190. Arch Gen Psychiatry. 2006 Aug;63(8):856-64 - PubMed
  191. Curr Top Behav Neurosci. 2014;18:13-24 - PubMed
  192. Drug Test Anal. 2014 May;6(5):492-9 - PubMed
  193. Am J Addict. 2012 Jul-Aug;21(4):320-6 - PubMed
  194. Eur J Pharmacol. 2000 Oct 6;406(1):1-13 - PubMed
  195. Psychiatry Res. 1998 Sep 28;83(3):149-62 - PubMed
  196. J Med Toxicol. 2012 Mar;8(1):69-75 - PubMed
  197. Int J Drug Policy. 2011 Jul;22(4):274-7 - PubMed
  198. Hum Psychopharmacol. 2013 Jul;28(4):356-64 - PubMed
  199. Clin Toxicol (Phila). 2014 Jun;52(5):561-5 - PubMed
  200. Emerg Med Serv. 2001 Nov;30(11):30, 32, 34 passim - PubMed
  201. Pharmacol Rev. 2006 Sep;58(3):389-462 - PubMed
  202. Hong Kong Med J. 2010 Feb;16(1):6-11 - PubMed
  203. J Psychopharmacol. 2013 Jan;27(1):28-39 - PubMed
  204. Lancet. 2014 Mar 15;383(9921):952 - PubMed
  205. Neurosci Biobehav Rev. 2013 Sep;37(8):1466-84 - PubMed
  206. Psychopharmacology (Berl). 2002 Aug;162(4):396-405 - PubMed
  207. Eur J Pharmacol. 2007 Mar 22;559(2-3):132-7 - PubMed
  208. Psychopharmacology (Berl). 2014 Dec;231(24):4723-33 - PubMed
  209. Forensic Sci Int. 2013 Dec 10;233(1-3):416-22 - PubMed
  210. J Pharmacol Exp Ther. 2008 Mar;324(3):948-56 - PubMed
  211. Hum Psychopharmacol. 2012 May;27(3):254-61 - PubMed
  212. J Med Toxicol. 2013 Jun;9(2):196-8 - PubMed
  213. Addict Biol. 2013 Sep;18(5):786-99 - PubMed
  214. Drug Chem Toxicol. 2015 Jan;38(1):113-9 - PubMed
  215. Ann N Y Acad Sci. 2006 Aug;1074:245-60 - PubMed
  216. Acta Anaesthesiol Belg. 2011;62(1):47-58 - PubMed
  217. PLoS One. 2012;7(8):e42421 - PubMed
  218. Pharm Acta Helv. 1997 Jun;72 (3):175-84 - PubMed
  219. Expert Opin Investig Drugs. 2014 Sep;23(9):1181-92 - PubMed
  220. J Clin Psychopharmacol. 2008 Feb;28(1):114-6 - PubMed
  221. J Neurochem. 2012 Mar;120(6):1097-107 - PubMed
  222. J Psychopharmacol. 2012 Jul;26(7):994-1002 - PubMed
  223. Neuropsychopharmacology. 2006 May;31(5):1064-74 - PubMed
  224. Curr Pharm Des. 2009;15(22):2603-14 - PubMed
  225. Hum Psychopharmacol. 2001 Dec;16(8):589-598 - PubMed
  226. Am J Psychiatry. 1960 Mar;116:843-4 - PubMed
  227. Mol Psychiatry. 2009 Feb;14(2):123-42 - PubMed
  228. Brain Res Brain Res Rev. 1993 Sep-Dec;18(3):247-91 - PubMed
  229. CNS Drugs. 2014 Jun;28(6):491-6 - PubMed
  230. Addiction. 2011 Jan;106(1):154-61 - PubMed
  231. Neuropsychopharmacology. 2012 May;37(6):1526-33 - PubMed
  232. Pharmacol Biochem Behav. 2005 Jun;81(2):263-84 - PubMed
  233. J Psychoactive Drugs. 1998 Oct-Dec;30(4):371-9 - PubMed
  234. Forensic Sci Int. 2011 Jul 15;210(1-3):195-200 - PubMed
  235. Ann Ist Super Sanita. 2013;49(4):402-5 - PubMed
  236. J Anal Toxicol. 2011 Apr;35(3):188-91 - PubMed

Publication Types