Background
Phencyclidine-type substances show structural similarity to phencyclidine (PCP) and ketamine and are classified as arylcycloalkylamines.[1]
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 It was withdrawn from the market due to intensely negative psychological effects, such as dysphoria, confusion, delirium, and psychosis.[2] Its use as a recreational drug started in the mid-1960s, but its unpredictable dysphoric reactions made the drug infamous. PCP and phenylcyclohexyl analogues, including eticyclidine (PCE), rolicyclidine (PHP, PCPY), tenocyclidine (TCP) are controlled in Schedule I of the 1971 Convention, and methoxetamine (MXE) is controlled in Schedule II of the 1971 Convention, but derivatives such as 3-MeO-PCE and 4-MeO-PCP are not under international control.
Phencyclidine-type substances appeared for the first time in Europe as ‘research chemicals’ in 2010, when the United Kingdom reported 3-methoxyeticyclidine (3-MeO-PCE) to the European Early Warning System.[3] In 2011, 4-methoxyphencyclidine (4-MeO-PCP) was identified in Norway, the Russian Federation and the United Kingdom.[4] UN Member States reported 4-MeO-PCP as the most common PCP-type substance.
Description
Phencyclidine-type substances act predominantly either as central nervous system stimulants, or dissociatives. Stimulants 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.
Ketamine has been widely used in human and veterinary medicine and is listed as an essential medicine by the World Health Organization (WHO).[5] However, the non-medical use of ketamine is a long-standing issue that dates back to the 1980s and is related to a number of severe adverse health effects. In a 2015 WHO survey, the use of ketamine for non-medical purposes was reported by 32 countries.[6]
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.[7] Severe adverse effects, such as hypertension and lung edema, have been reported in relation to ketamine use. However, these effects may be related to the combined use of ketamine and other substances.[8]
References
[1] 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
[2] 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
[3] 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
[4] 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
[5] World Health Organization, Model List of Essential Medicines: 19th List (April 2015) amended November 2015
[6] World Drug Report 2017 (United Nations publication, Sales No. E.17.XI.6)
[7] 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
[8] World Health Organization, Ketamine (INN) Update Review Report, Agenda Item 6.1. Expert Committee on Drug Dependence. Thirty-seventh Meeting. Geneva, 16 to 20 November 2015