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Ketamine & Phencyclidine-type substances

 

 

Ketamine

 

Background

 

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Phencyclidine was investigated as an intravenous anaesthetic in the 1950s but was later withdrawn due to undesired hallucinogenic and delirium effects.[1] Following the withdrawal of phencyclidine, ketamine was synthesized as an anaesthetic in 1962,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”.[2] 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.”[3] 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.[4] The European Commission concluded that it was not appropriate to introduce control measures and recommended further monitoring of the use of ketamine.

 

Description

 

Ketamine and phencyclidine have similar modes of action, affecting a range of central neurotransmitters. Ketamine is frequently sold as ‘ecstasy’ in illicit ATS markets. Street names for ketamine include ‘K’, ‘special K’, ‘kit kat’, ‘tac’, ‘tic’, ‘cat valium’, ‘cat tranquilizer’, ‘vitamin K’, ‘ket’, ‘super K’.[5]

 

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.

 

Reported adverse effects

 

Ketamine appears to stimulate the cardiovascular system, producing changes in the heart rate and blood pressure. As such, tachycardia is one of the most common symptoms identified in recreational users. Findings of neurotoxicity in animal studies have raised concerns on the consumption of ketamine by recreational users, for a number of reasons: unlike when it is clinically administered, substance users will not take ketamine in combination with protective agents. Moreover, substances which may increase the neurotoxic potency of ketamine might be co-administered (including PCP, tiletamine as well as alcohol). Furthermore, recreational use usually implies repeated exposure, whereas clinical use is mostly incidental.[6]

 

Side effects related to the use of ketamine in conjunction with other drugs include hypertension and pulmonary oedema. Psychological dependence in some users has also been identified. Adverse effects in long-term users of ketamine have been reported albeit scarce. These included persistent impairment of attention and recall, and a subtle visual anomaly. Other reported effects include anxiety, changes of perception, an impairment of motor function and rhabdomyolysis.

 

Between 1987 and 2000, 12 fatal cases in which ketamine was identified were reported, but only three of them involved ketamine alone. Chronic ketamine use has been reported to result in potential lasting memory and cognitive dysfunction.[7]

 

  

Phencyclidine-type substances

 

Background

 

Another group of NPS that has recently appeared in the market include phencyclidine-type substances. Phencyclidine (PCP) and ketamine (see section 2.3) show structural similarity and are classified as arylcycloalkylamines.[8]

 

PCP was first synthesized in the 1950s and sold until 1967 as an injectable anaesthetic in the United States under the trade names Sernyl and Sernylan. It was withdrawn from the market due to intensely negative psychological effects, such as dysphoria, confusion, delirium, and psychosis.[9]Its use as a recreational drug started in the mid-1960s, but its unpredictable dysphoric reactions made the drug infamous.

 

PCP-type substances appeared for the first time in Europe as ‘research chemicals’ in 2010, when the United Kingdom reported 3-methoxyeticyclidine (3-MeOPCE) to the European Early Warning System.[10]In 2011, 4-methoxyphencyclidine (4-MeO-PCP) was identified in Norway, Russian Federation and the United Kingdom.[11]UN Member States reported 4-MeO-PCP as the most common PCP-type substance.

 

PCP and phenylcyclohexyl analogues, including eticyclidine (PCE), rolicyclidine (PHP, PCPY), tenocyclidine (TCP) are controlled in Schedule I of the 1971 Convention but derivatives such as 3-MeO-PCE and 4-MeO-PCP are not under international control.

 

Description

 

3-MeO-PCE and 4-MeO-PCP are frequently sold as research chemicals and usually in powder form.

 

Phencyclidine-type substances act predominantly either as central nervous system stimulants, or dissociativesStimulants mediate the actions of dopamine, norepinephrine and/or serotonin, mimicking the effects of traditional drugs such as cocaine, amphetamine, methamphetamine, and ecstasy.  Dissociatives form a class of hallucinogens which modulate effects at the N-methyl-D-aspartate (NMDA) receptor in the brain and produce feelings of detachment and dissociation from self and the environment.



Reported adverse effects

 

There is very limited information on the PCP analogues. Acute PCP intoxication results in a wide range of behavioural/psychological effects, from mild neurologic and physiologic abnormalities, stupor or light coma to deep coma. Manifestations of behavioural toxicity resemble psychiatric syndromes. PCP has also been claimed to cause violent behaviour.[12]

 

 

References

[1]European Monitoring Center for Drugs and Drug Addiction, ‘Report on the risk assessment of ketamine in the framework of the joint action on new synthetic drugs’, Belgium, 2002

[2]World Health Organization, ‘WHO Expert Committee on Drug Dependence. Thirty-fourth Report’, Geneva, 2006

[3]World Health Organization, ‘WHO Expert Committee on Drug Dependence. Thirty-fifth Report’, Geneva, 2012

[4]European Monitoring Center for Drugs and Drug Addiction, ‘Report on the risk assessment of ketamine in the framework of the joint action on new synthetic drugs’, Belgium, 2002

[5]European Monitoring Center for Drugs and Drug Addiction, ‘Report on the risk assessment of ketamine in the framework of the joint action on new synthetic drugs’, Belgium, 2002

[6]Jansen, K.L., ‘Ketamine - Can chronic use impair memory?’, International Journal of the Addictions, 1990, 25, 133-139, in World Health Organization, ‘WHO Expert Committee on Drug Dependence. Thirty- fifth Meeting’, 2012

[7]Okon, T., a case based review ‘Ketamine: an introduction for the pain and palliative medicine physician’, Pain Physician, 2007, 10, 493-500

[8]Baldridge, E.B., Bessen, H.A., ‘Phencyclidine’, Emergency Medicine Clinics of North America, 1990, 8 (3), 541-50; Balster, R.L., ‘The behavioral pharmacology of phencyclidine’, in H.Y. Meltzer (Eds.), Psychopharmacology: The third generation of progress, New York, 1987, 1573–9; The structure-activity relationships among arylcycloalkylamines can be further consulted in Manallack, D.T., Davies, J.W., Beart, P.M., Saunders, M.R. and Livingstone, D.J., ‘Analysis of the biological and molecular properties of phencyclidine-like compounds by chemometrics’, Arzneimittelforschung, 1993, 43 (10), 1029-32

[9]Pearlson, G.D., ‘Psychiatric and medical syndromes associated with phencyclidine (PCP) abuse’, Johns Hopkins medical journal, 1981, 148, 25-33; Smith, J.B., ‘Situational specificity of tolerance to effects of phencyclidine on responding of rats under fixed-ratio and spacedresponding schedules’, Psychopharmacology, 1991, 103, 121-8

[10]European Monitoring Centre for Drugs and Drug Addiction and European Police Office, ‘EMCDDA–Europol 2010 Annual report on the implementation of Council Decision 2005/387/JHA. Annex 2 — New psychoactive substances reported to the EMCDDA and Europol for the first time in 2010 under the terms of Council Decision 2005/387/JHA’, Lisbon, 2011

[11]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

[12]Gorelick, D.A. and Balster, R.L., ‘Phencyclidine (PCP)’, in F.E. Bloom & R.L. Kupfer (Eds.), Psychopharmacology: The fourth generation of progress, New York, 1995, 1767-76; Brecher, M., Wang B.W., Wong, H. and Morgan, J.P., ‘Phencyclidine and violence: clinical and legal issues’, Journal of Clinical Psychopharmacology, 1988, 8 (6), 397-401; Daghestani, A.N. and Schnoll, S.H., ‘Phencyclidine abuse and dependence’, Treatments of Psychiatric Disorders: A task force report of the American Psychiatric Association, American Psychiatric Association, Washington D.C., 1989, 1209-18

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