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.

21. History of Ketamine and Control Efforts

"Ketamine is closely related to the internationally controlled drug phencyclidine (also known as PCP or ‘angel dust’) which is listed in Schedule II of the 1971 Convention (see section 2.7.2).

"Phencyclidine was investigated as an intravenous anaesthetic in the 1950s but was later withdrawn due to undesired hallucinogenic and delirium effects.34 Following the withdrawal of phencyclidine, ketamine was synthesized as an anaesthetic in 1962, patented in 1963 in Belgium and three years later in the United States. In the early 1970s, ketamine was marketed as a medical alternative to phencyclidine.

"The use of ketamine as a new psychoactive substance dates back to the 1980s and 1990s. At the international level, ketamine was subject to a series of risk assessments. The Expert Committee on Drug Dependence of the WHO pre-reviewed ketamine in 2003 and conducted a critical review in 2006. After reviewing the information contained before it, the Committee concluded that 'this information was not sufficient to warrant scheduling'.35 It also requested an updated version of the critical review to be presented at the next meeting of the Committee which was held in 2012. At that meeting, the Committee decided that 'bringing ketamine under international control is not appropriate.'36 At the level of European Union, in 2000, growing concern over the use of ketamine as a NPS prompted a risk assessment in the framework of the joint action on new synthetic drugs.37 The European Commission concluded that it was not appropriate to introduce control measures and recommended further monitoring of the use of ketamine."

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. 8.
http://www.unodc.org/documents...

22. Description of Ketamine

"Ketamine and phencyclidine have similar modes of action, affecting a range of central neurotransmitters. Ketamine is frequently sold as ‘ecstasy’ in illicit ATS [Amphetamine-Type Stimulants] markets. Street names for ketamine include ‘K’, ‘special K’, ‘kit kat’, ‘tac’, ‘tic’, ‘cat valium’, ‘cat tranquilizer’, ‘vitamin K’, ‘ket’, ‘super K’.38
"Pharmaceutical preparations of ketamine are usually found in liquid form, but powder and capsules are also available. The powder prepared by evaporation of the original solution is often nasally insufflated (‘bumping’), smoked or swallowed."

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. 8.
http://www.unodc.org/documents...

23. Background on Khat

"The khat shrub (Catha edulis) of the celastraceae family is a plant native to the horn of Africa and the Arabian peninsula. Khat chewing is a social custom in the communities living in these areas. The psychoactive effects resulting from the release of cathinone and cathine alkaloids after chewing of khat are well-documented.78 The khat shrub became known to Europeans in the late 18th century and in the 19th century, and the active constituents of the plant were isolated in the 19th and 20th century. A ‘katin’ alkaloid was identified first in 1887, ‘cathine’ in 1930 and ‘cathinone’ in 1975.79
"In Europe and North America, khat was considered to be traditionally used by migrant communities from Ethiopia, Kenya, Somalia and Yemen, but in recent years its use has spread beyond these communities. Respondents to the UNODC questionnaire on NPS from Bahrain, Canada, Finland, Ireland, Italy, New Zealand, Norway, Oman, United States and Hong Kong (China) reported that khat emerged on their markets in 2009, and was the second most popular plant based substance, after salvia divinorum, reported by Member States from 2009 to 2012.
"Catha edulis is not under international drug control, but cathinone and cathine are listed in Schedules I and III, respectively, of the 1971 Convention. Khat is under national control in several countries."

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. 13.
http://www.unodc.org/documents...

24. Description of Khat

"Street names for khat include ‘qat’, ‘gat’, ‘chat’, ‘miraa’, ‘murungu’ and ‘Arabian or Abyssinian tea’. Due to the degradation of cathinone, khat leaves need to be consumed soon after harvesting and therefore fresh leaves of khat are the preferred form of use, but dried leaves (‘graba’) are also available. Khat is usually consumed by chewing the leaves and shoots of the plant, but infusions are also possible. Recently, alcoholic extracts of khat sold as ‘herbal highs’ have been reported.80"

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. 13.
http://www.unodc.org/documents...

25. Reported Adverse Effects of Khat

"It has been estimated that a typical chewing session of khat results in the absorption of its active constituents with an activity equivalent to that of approximately 5 mg of amphetamine.81 The pharmacological effects of khat resemble those of amphetamine use, and includes increased alertness, euphoria, hyperthermia, anorexia, increased respiration rate, heart rate and blood pressure.82
"Fatalities associated with the sole consumption of khat have not yet been reported. However, prolonged use of khat has been linked to adverse effects that range from psychiatric disturbances (from psychosis to depression) to damage of major organs of the body, as well as to similar neurological disorders to those associated with amphetamine and cocaine use.83"

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. 13-14.
http://www.unodc.org/documents...

26. Description of Kratom

"Mitragyna speciosa Korth (of the Rubiaceae family) is a large tree found in tropical and sub-tropical regions of South-East Asia. In Thailand, the tree known as ‘Kratom’ is found throughout the country but predominantly in the southern region, although the growing and harvesting is prohibited.

"Kratom contains many alkaloids including mitragynine, mitraphylline, and 7-hydroxymitragynine. Traditionally, kratom had been used in Malaysia and Thailand by labourers and farmers to enhance productivity, but also as a substitute to opium and in traditional medicine, allegedly due to its morphine-like pharmacological effects. However, its use as a new psychoactive substance in the global market has been recently reported.

"In the early 2000s, products labelled as ‘kratom acetate’ or ‘mitragynine acetate’ became available in Europe, although it was found that neither of them contained mitragynine. Caffeine and synthetic O-desmethyltramadol (an active metabolite of tramadol) were found in products under the name ‘krypton’.84 More recently, products containing kratom have been sold as ‘incense’ for their psychoactive effects, but concentrations of the active components mitragynine and 7-hydroxymitragynine in these products differ depending on the variety of the plant used, the environment and the time of harvesting."

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. 14.
http://www.unodc.org/documents...

27. Current Use of Kratom in the US

"Evidence suggests that kratom is being used extensively for both medical and nonmedical purposes. Recent studies have shown that kratom contains a variety of active compounds that produce major pharmacologic effects at opioid and other receptors. Kratom and kratom-derived drugs may potentially be used for the management of pain, opioid withdrawal symptoms, and other clinical problems. At the same time, serious questions remain regarding the potential toxic effects and the abuse and addiction potential of kratom. This issue is further confounded by the lack of quality control and standardization in the production and sale of kratom products. The possibilities of kratom products being adulterated or interacting with other drugs are also serious concerns. Until these issues are resolved, it would not be appropriate for physicians to recommend kratom for the treatment of patients. Nevertheless, physicians need to be aware that patients may use kratom or kratom-based products on their own. Further studies to clarify the efficacy, safety, and addiction potential of kratom are needed."

Prozialeck, WC, Jivan, JK, and Andurkar, SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. Journal of the American Osteopathic Association. December 2012;112(12):792-9.
https://www.ncbi.nlm.nih.gov/p...
http://jaoa.org/article.aspx?a...

28. Description of Kratom

"Street names for kratom include ‘thang’, ‘kakuam’, ‘thom’, ‘ketum’ and ‘biak’. Kratom leaves are usually consumed fresh, although dried leaves in powder form are also available. The fresh leaves are chewed while the powder form is often either swallowed or brewed into tea. Dried leaves are rarely smoked."

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. 14.
http://www.unodc.org/documents...

29. Mentions of Kratom in Overdose Deaths in the US

"Data on 27,338 overdose deaths that occurred during July 2016–December 2017 were entered into SUDORS, and 152 (0.56%) of these decedents tested positive for kratom on postmortem toxicology (kratom-positive). Postmortem toxicology testing protocols were not documented and varied among and within states. Kratom was determined to be a cause of death (i.e., kratom-involved) by a medical examiner or coroner for 91 (59.9%) of the 152 kratom-positive decedents, including seven for whom kratom was the only substance to test positive on postmortem toxicology, although the presence of additional substances cannot be ruled out (4).

"In approximately 80% of kratom-positive and kratom-involved deaths in this analysis, the decedents had a history of substance misuse, and approximately 90% had no evidence that they were currently receiving medically supervised treatment for pain. Postmortem toxicology testing detected multiple substances for almost all decedents (Table). Fentanyl and fentanyl analogs were the most frequently identified co-occurring substances; any fentanyl was listed as a cause of death for 65.1% of kratom-positive decedents and 56.0% of kratom-involved decedents. Heroin was the second most frequent substance listed as a cause of death (32.9% of kratom-positive decedents), followed by benzodiazepines (22.4%), prescription opioids (19.7%),** and cocaine (18.4%)."

Olsen EO, O’Donnell J, Mattson CL, Schier JG, Wilson N. Notes from the Field: Unintentional Drug Overdose Deaths with Kratom Detected — 27 States, July 2016–December 2017. MMWR Morb Mortal Wkly Rep 2019;68:326–327. DOI: http://dx.doi.org/10.15585/mmw...
https://www.cdc.gov/mmwr/volum...

30. Current Legal Status of Kratom in the US

"Although the findings of our literature and Internet searches strongly suggest a marked increase in kratom use in the United States and Europe, kratom still appears to be somewhat of an 'underground phenomenon.' During our searches of the literature and the internet, we found no evidence that kratom is currently marketed by any of the large nutritional supplement chain stores in the United States. However, a wide variety of kratom products—including raw leaves, capsules, tablets, and concentrated extracts—are readily available from Internet-based suppliers.20,21 In addition, these products are often sold in specialty stores commonly known as 'head shops' or 'smoke shops.' In February 2012, our own informal in-person and telephone survey of 5 smoke shops in the metropolitan Chicago area revealed that purported kratom products were available in all of them. Figure 2 and Figure 3 show images of several kratom products (ie, chopped leaves, capsules, and pressed tablets) that were legally purchased at a smoke shop in suburban Chicago.
"From a legal standpoint, kratom is regulated as an herbal product under US law and US Food and Drug Administration and US Drug Enforcement Administration (DEA) policies. As of this writing, Mitragyna speciosa (kratom) is not prohibited by the Controlled Substances Act28 and is considered a legal substance in the United States. However, the DEA's December 2010 version of the Drugs and Chemicals of Concern list states that 'there is no legitimate medical use for kratom in the U.S.'29 Therefore, it cannot legally be advertised as a remedy for any medical condition."

Prozialeck, WC, Jivan, JK, and Andurkar, SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. Journal of the American Osteopathic Association. December 2012;112(12):792-9.
https://www.ncbi.nlm.nih.gov/p...
http://jaoa.org/article.aspx?a...

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