Khat
Background
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. [1] 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.[2]
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. 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 it 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.
Description
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.[3]
Reported adverse effects
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.[4] The pharmacological effects of increased alertness, euphoria, hyperthermia, anorexia, increased respiration rate, heart rate and blood pressure.[5] 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.[6]
Kratom
Background
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’.[7] 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.
Internet surveys conducted by the EMCDDA in 2008 and 2011 revealed that kratom is one of the most widely offered NPS.[8] Respondents to the UNODC questionnaire on NPS reported kratom among the top three plant-based substances, along with khat and salvia divinorum.[9] As kratom is often not monitored in national drug abuse surveys, there is little information on prevalence of its use.
Neither kratom nor any of its active alkaloids are listed under the 1961 and 1971 Conventions, but several countries have adopted control measures on kratom, mitragynine and 7-hydroxymitragynine.
Description
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.
Reported adverse effects
In spite of the increasing use of this substance, scientific literature about the effects and toxicity of kratom alone remains very scarce. Kratom is a central nervous system stimulant, from which over 40 alkaloids have been isolated. In low doses it is reported to have stimulant effects (used to combat fatigue during long hours of work), while at high doses, it can have sedative-narcotic effects.[10] In 1921, the major alkaloid found in this plant, ‘Mitragynine’, was first isolated. Mitragynine has an opioid agonistic activity and its derivative 7-hydroxymitragynine (7-OH-mitragynine) is reported to be more potent than mitragynine or morphine.[11]
Nine fatal cases of intoxication associated with the use of ‘krypton’, a mixture of mitragynine and O-desmethyltramadol, have been described in scientific literature. However, these fatalities have been attributed to the addition of O-desmethyltramadol to the dried kratom leaves.[12]
Salvia divinorum
Background
Salvia divinorum (of the mint family Lamiaceae), is a psychoactive plant indigenous to forest areas in Oxaca, Mexico. It was traditionally used by the Mazatec Indians for religious practices and medical purposes, although there is no approved medicinal use for salvia divinorum or its active ingredient salvinorin A. The use of salvia divinorum as a new psychoactive substance dates back to the 1990s but UN Member Sates identified this plant as the most common plant-based substance in 2009, and the third, after khat and kratom, in 2012. Neoclerodane diterpene (i.e. salvinorin A) is the active component responsible for the psychoactive effects of the plant in the 1980s. The concentration of salvinorin A in salvia divinorum leaves varies and depends on the stage of development of the plant and the type of preparation.
Neither salvia divinorum nor salvinorin A are under international control. However, due to the increasing use of this plant as a new psychoactive substance, the plant and its active constituent salvinorin A are increasingly controlled in several countries under different regulatory frameworks.
Description
Street names for salvia divinorum include ‘Maria Pastora’, ‘Sage of the Seers’, ‘Diviner’s Sage’, ‘Salvia’, ‘Sally-D’, ‘Magic Mint’, ‘Purple Sticky’, ‘Shepherdess’s Herb’.[13] Salvia divinorum is usually sold as seeds or leaves, but a liquid extract purported to contain salvinorin A and a combination of dried leaves and extracts of salvinorin A (known as ‘the fresh-man selection’ or the ‘starter pack’) are also available on the market.[14] Recent studies of products containing salvia divinorum have shown a mismatch between the label and the actual constituent of the products. Vitamin E and caffeine have also been reported as adulterants.
Salvia divinorum is traditionally consumed by sucking and chewing the fresh leaves from a cigar-like roll or alternatively the fresh leaves are crashed to make a drinkable infusion. Many users reportedly inhale vaporized salvinorin A extract, or smoke the dried leaves of the plant. Smoking of the dry leaves is reported to produce short but intense hallucinations, and the effects of salvinorin A have been compared to those of LSD or DOB.[15]
Reported adverse effects
Animal studies have shown low toxicity and low addictive potential for salvia divinorum.[16] Like other plant-based substances, there are limited scientific studies in humans that report acute or chronic toxicity associated with its use, but clinical observations have indicated lasting psychosis in vulnerable individuals. Thus far, there are no reports on fatalities from use of salvia divinorum. However, toxicological analyses have proved difficult as salvinorin A and other diterpenoids of the plant are not detected by conventional drug screening methods.[17]
References
[1]Sawair, F.A., Al-Mutwakel, A., Al-Eryani, K., Al-Surhy, A., Maruyama, S., Cheng, J., Al-Sharabi, A. and Saku, T., ‘High relative frequency of oral squamous cell carcinoma in Yemen: qat and tobacco chewing asits aetiological background’, International Journal of Environmental Health Research, 2007, 17, 185-95
[2]See Szendrei, K., ‘The chemistry of khat’, Bulletin on Narcotics, 1980, 32, 3, 5-35 for further information.
[3]European Monitoring Centre for Drugs and Drug Addiction, ‘khat’, Drug Profiles (www.emcdda.europa.eu)
[4]Dhaifalah I. and Santavy J., ‘Khat habit and its health effect. A natural amphetamine’, Biomedical Papers, 2004, 148, 11-5
[5]Kelly, J.P., ‘Cathinone derivatives: a review of their chemistry, pharmacology and toxicology’, Drug Testing and Analysis, 2011, 3, 439-53
[6]Hoffman, R. and Al’absi, M., ‘Khat use and neurobehavioural functions: suggestions for future studies’, Journal of Ethnopharmacology, 2010, 132, 554; Morrish, P.K., Nicolaou, N., Brakkenberg, P. and Smith, P.E., ‘Leukoencephalopathy associated with khat misuse’, Journal of Neurology, Neurosurgery, and Psychiatry, 1999, 67, 556; Odenwald, M., ‘Chronic khat use and psychotic disorders: a review of the literature and future prospects’, Sucht, 2007, 53, 9-22
[7] European Monitoring Centre for Drugs and Drug Addiction, ‘kratom’, Drug Profiles (www.emcdda.europa.eu)
[8]European Monitoring Centre for Drugs and Drug Addiction, ‘kratom’, Drug Profiles (www.emcdda.europa.eu)
[9]United Nations Office on Drugs and Crime, ‘UNODC questionnaire on new psychoactive substances’, submitted by Member States and a network of drug analysis laboratories in 2012.
[10] European Monitoring Centre for Drugs and Drug Addiction, ‘kratom’, Drug Profiles (www.emcdda.europa.eu)
[11]Kikura-Hanajiri, R., Kawamura, M., Maruyama, T., Kitajima, M., Takayama, H. and Goda, Y., ‘Simultaneous analysis of mitragynine, 7-hydroxymitragynine, and other alkaloids in the psychotropic plant “kratom” (Mitragynaspeciosa) by LC-ESI-MS’, Forensic Toxicology, 2009, 27 (2), 67-74
[12]Kronstrand, R., Roman, M., Thelander, G. and Eriksson, A., ‘Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend krypton’, Journal of Analytical Toxicology, 2011, 35 (4), 242-7
[13]United States, Drug Enforcement Administration, ‘Salvia divinorum and salvinorin A’, 2012 (http://www.deadiversion.usdoj.gov/drugs_concern/salvia_d.pdf); European Monitoring Centre for Drugs and Drug Addiction, ‘Salvia divinorum’, Drug Profiles (www.emcdda.europa.eu)
[14]Babu, K.M., McCurdy, C.R. and Boyer, E.W., ‘Opioid receptors and legal highs: Salvia divinorum and Kratom’, Clinical Toxicology (Philadelphia), 2008, 46 (2), 146-52
[15]European Monitoring Centre for Drugs and Drug Addiction, ‘Salvia divinorum’, Drug Profiles (www.emcdda.europa.eu)
[16]Mowry, M., Mosher, M., and Briner, W., ‘Acute physiologic and chronic histologic changes in rats and mice exposed to the unique hallucinogen salvinorin A’, Journal of Psychoactive Drugs, 2003, 35, 379-82
[17]European Monitoring Centre for Drugs and Drug Addiction, ‘Salviadivinorum’, Drug Profiles (www.emcdda.europa.eu)