New Psychoactive Substances (including kratom, synthetic cannabinoids, synthetic opioids, synthetic cathinones, and more).

Related Chapters:
Fentanyl
Entheogens and Psychedelics

Chapter Sections:
Overview
Ketamine
Khat
Kratom
Krokodil
Synthetic Opioids (e.g. Fentanyl)
Synthetic Cathinones (Mephedrone, Methylone)
Phenethylamines
Salvia Divinorum
Synthetic Cannabinoids
Others - New psychoactive substances are being developed at a rapid rate

Page last updated June 10, 2020 by Doug McVay, Editor/Senior Policy Analyst.

41. Mephedrone and Synthetic Cathinones

"Cathinone and its derivatives are closely related to the phenethylamine family (which includes amphetamine and methamphetamine), but with a lower potency than the latter.13 They are characterised by the presence of a ?-keto group on the side chain of the phenethylamines. Cathinone, the principal active ingredient in the leaves of the khat plant (catha edulis), can be considered as the prototype from which a range of synthetic cathinones have been developed.
"Synthetic cathinones appeared in drug markets in the mid 2000s. In 2005, methylone, an analogue of MDMA, was the first synthetic cathinone reported to the European Monitoring Centre on Drugs and Drug Addiction (EMCDDA). In 2007, reports of 4-methyl-methcathinone (mephedrone) use emerged, first in Israel and then in other countries and regions, including Australia, Scandinavia, Ireland and the United Kingdom.14 Mephedrone was reportedly first synthesized in 1929.15"

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 5.
http://www.unodc.org/documents...

42. Description of Synthetic Cathinones

"Synthetic cathinones are frequently found in products sold as ‘research chemicals’, ‘plant food’, ‘bath salts’ or ‘glass cleaner’ and are usually sold in powder, pill or capsule form. Mephedrone (‘m-cat’, ‘meph’, ‘drone’ or ‘miaow’) and methylone (‘explosion’ or ‘top cat’) are usually available as white or brown powders or in the form of pills that are often sold as ‘ecstasy’. Most synthetic derivatives are ingested but may be injected. Mephedrone is commonly nasally insufflated, injected, ingested by swallowing a powder wrapped in paper (‘bombing’), or mixed in a drink."

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 7.
http://www.unodc.org/documents...

43. Reported Adverse Effects and Toxicity of Synthetic Cathinones

"Few reports on the toxicity of synthetic cathinones exist to date. Much of the current knowledge on health-related effects comes from user reports and clinical observations. Further research is needed to provide evidence of short and long-term health risks and the addiction potential associated with the use of these substances.
"Whereas cardiac, psychiatric, and neurological signs are some of the adverse effects reported by synthetic cathinone users, agitation, ranging from mild agitation to severe psychosis, is the most common symptom identified from medical observations.25 Studies of patients under the apparent influence of mephedrone have also shown that synthetic cathinones present similar sympathomimetic effects (including tachycardia and hypertension as well as psychoactive effects) to similar amphetamine derivatives.26 In a student survey, more than half of those who had taken mephedrone reported adverse effects associated with the central nervous system, nasal/respiratory system and cardiovascular system.27 The first fatality related to the sole use of mephedrone, confirmed by toxicological analysis, was reported in Sweden in 2008.28 Most fatalities associated with the use of mephedrone involved the use of other substances.29 Deaths associated with the use of other synthetic cathinones include two deaths related to methedrone30 and two other deaths related to butylone.31
"The Finnish Poisons Information Centre reported 33 calls regarding exposures to MDPV during the period of January 2008 to October 2009. Post mortem toxicological analysis confirmed 6 deaths related to MDPV between 2009 and 2010, although in most of the cases the presence of other drugs was also detected.32 A report from the United States provided details on the case of 35 patients who visited an Emergency Department over a 3-month-period after ingesting, inhaling or injecting substances sold as ‘bath salts’ and asserted that these products could contain stimulant compounds such as MDPV or mephedrone. One person was dead upon arrival at the emergency department. The toxicological analysis revealed a high level of MDPV, along with cannabis and prescription drugs, but the autopsy results revealed MDPV toxicity to be the primary factor contributing to death.33"

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 7.
http://www.unodc.org/documents...

44. Background on Phenethylamines (including 2-C-C-N-BOME "N-Bomb")

"Phenethylamines refer to a class of substances with documented psychoactive and stimulant effects and include amphetamine, methamphetamine and MDMA, all of which are controlled under the 1971 Convention.41 The phenethylamines also include ring-substituted substances such as the ‘2C series’, ring-substituted amphetamines such as the ‘D series’ (e.g. DOI, DOC), benzodifurans (e.g. Bromo-Dragonfly, 2C-B-Fly) and others (e.g. p-methoxymethamphetamine (PMMA)).
"Seizures of phenethylamines were first reported from the United States and European countries and since 2009 substances such as 2C-E, 2C-I, 4-FA and PMMA have been commonly reported by several countries in different regions. Other phenethylamines increasingly reported in the UNODC questionnaire on NPS since 2011 include 4-FMA, 5-APB, 6-APB and 2C-C-NBOMe.
"A number of studies have reported the synthesis of some phenethylamines and amphetamine substitutes. In the 1980s and 1990s, Alexander Shulgin, a biochemist and pharmacologist, reported the synthesis of numerous new psychoactive compounds.42 This included the ‘D series’ (e.g. DOC, DOI) and the ‘2C series’ (e.g. 2C-T-7, 2C-T-2) of phenethylamines."

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 9.
http://www.unodc.org/documents...

45. Description of Phenethylamines

"Street names for some phenethylamines include ‘Europa’ for 2C-E; ‘4-FMP’, ‘para-fluoroamphetamine’, ‘RDJ’ for 4-FA; and ‘4-MMA’, ‘Methyl-MA’ for PMMA. Phenethylamines are usually available in form of pills, but FLY compounds are commonly sold in powder form, while oral doses (on a slip of blotter paper) are usually available for ‘D substances’. Ingestion is the most common route of administration of phenethylamines."

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 10.
http://www.unodc.org/documents...

46. Reported Adverse Effects of Phenethylamines

"Phenethylamines included in the ‘D series’ are described to be longer lasting, more potent and reportedly more liable to induce vasoconstriction than other members of the phenethylamine family.49 Reported adverse effects associated with the use of the ‘D series’ derivatives include agitation, tachycardia, mydriasis, hallucinations, severe limb ischemia, seizures, liver and renal failure.50 Bromo-Dragonfly has also been associated with a number of deaths in Scandinavia.51 A case of acute psychosis after ingestion of 2C-T-4 was reported in Japan.52 Three fatal cases associated with the use of 2C-T-7 have been identified, two of which involved poly-drug use.53
"PMA, PMMA and 4-methylthioamfetamine have been more often associated with incidental deaths than other phenethylamines. PMA and PMMA are known to have a particularly high toxicity but there is no data available on fatalities associated with their use. Clinical observations have reported severe hyperthermia following the use of these substances.54 Studies in animals have suggested that some metabolites may be exposed to increased toxicity from 4-MTA."

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), pp. 10-11.
http://www.unodc.org/documents...

47. Background on Piperazines

Piperazines

"Piperazines have been described as ‘failed pharmaceuticals’, as some had been evaluated as potential therapeutic agents by pharmaceutical companies but never brought to the market.55 While the best known piperazine that has been used as a new psychoactive substance is 1-benzylpiperazine (BZP), during the last decade other compounds such as 1-(3-chlorophenyl) piperazine (mCPP), 1-(3-trifluoromethylphenyl) piperazine (TFMPP) and, to a lesser extent, 1-Benzyl-4-methyl-piperazine (MBZP) and 1-(4-Fluorophenyl)piperazine (pFPP) have been identified on the market.56
"BZP was initially developed as a potential antidepressant drug, but was found to have similar properties to amphetamine and therefore liable to abuse. In the 1980s, it was used in Hungary to manufacture piberaline, a substance marketed as an antidepressant, but later withdrawn.57 In the late 1990s, BZP emerged in New Zealand as a ‘legal alternative’ for MDMA and methamphetamine.58 In Europe, its use was first reported in Sweden in 1999, but it only became widespread as a NPS from 2004 onwards until controls over the substance were introduced in 2008, in the European Union.59
"MCPP, reportedly more widespread than BZP in some regions of the world,60 was developed during the late 1970s and is used as an intermediate in the manufacture of several antidepressants, e.g. trazodone and nefazodone.61 TFMPP is almost always seen in combination with BZP to produce the entactogenic62 effects of MDMA.63
"Neither BZP nor any other piperazines are under international control, although several (BZP, TFMPP, mCPP, MDBP) were pre-reviewed by the WHO Expert Committee on Drug Dependence in 2012. Several countries have introduced national control measures over piperazines."

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), pp. 11-12.
http://www.unodc.org/documents...

48. Description of Piperazines

"Piperazines are frequently sold as ‘ecstasy’. Some of the generic names for these substances include, ‘pep pills’, ‘social tonics’ or simply ‘party pills’. The latter term was used to commercialize BZP in New Zealand.64 Other street names include Jax, A2, Benny Bear, Flying Angel, Legal E or Legal X, and Pep X, Pep Love or Nemesis.65 MCPP is known as 3CPP, 3C1-PP or CPP.
"Piperazines are usually available in the form of pills (regularly pressed with logos similar to ecstasy pills), capsules or loose powders, and are mainly consumed by ingestion. Liquid forms are rarely seen, but injection, smoking and snorting is also possible."

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 12.
http://www.unodc.org/documents...

49. Reported Adverse Effects of Piperazines

"Information on the toxicological aspects of many piperazines listed in this group remain limited. Further research is required to provide evidence on short and long term health-effects associated with the use of these substances. Current knowledge comes from user reports, studies in animals, limited human studies, and clinical observations.
"Piperazines have been found to act as stimulants as a result of dopaminergic, noradrenergic, and predominantly serotoninergic effects produced in the brain. BZP produces toxic effects similar to amphetamine and other sympathomimetics, although, according to animal studies, its effects are less potent than amphetamine, methamphetamine and MDMA.66 TFMPP, used in conjunction with BZP, has been reported to produce some of the effects of MDMA, but with a lower potency,67 while mCPP has been indicated to produce similar stimulant and hallucinogenic effects as MDMA.68
"In New Zealand, toxic seizures and respiratory acidosis after the use of BZP alone or in conjunction with other drugs were reported from three patients.69 Another study of 61 patients reported toxic effects of BZP, with two cases presenting life-threatening toxicity.70 Hyperthermia, rhabdomyolysis and renal failure associated with BZP ingestion have also been reported.71 In the United Kingdom, self-terminating grand mal seizures72 after the use of BZP have also been reported.73
"Between 2004 and 2008, six fatal cases involving piperazines use were reported in Europe. Two of the cases involved the use of BZP in conjunction with TFMPP and none referred to the use of piperazines alone.74 BZP and TFMPP were also associated with 19 fatalities between 2007 and 2010.75 While reported effects of mCPP include the serotonin syndrome, no fatal poisonings from mCPP have been reported so far.76 Similarly, toxic effects from the use of TFMPP alone have not been documented.77"

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), pp. 12-13.
http://www.unodc.org/documents...

50. Description of Salvia Divinorum

"Salvia divinorum is a perennial herb in the mint family native to certain areas of the Sierra Mazateca region of Oaxaca, Mexico. The plant, which can grow to over three feet in height, has large green leaves, hollow square stems and white flowers with purple calyces, can also be grown successfully outside of this region. Salvia divinorum has been used by the Mazatec Indians for its ritual divination and healing. The active constituent of Salvia divinorum has been identified as salvinorin A. Currently, neither Salvia divinorum nor any of its constituents, including salvinorin A, are controlled under the federal Controlled Substances Act (CSA)."

Drug Enforcement Administration, Office of Diversion Control, "Salvia Divinorum and Salvinorin A," (Washington, DC: U.S. Department of Justice, October 2013).
https://www.deadiversion.usdoj...

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