PCP is most commonly used in the US.[11] While usage peaked in the US in the 1970s,[12] between 2005 and 2011, an increase in visits to emergency departments as a result of the drug occurred.[7] As of 2022, in the US, about 0.7% of12th-grade students reported using PCP in the prior year, while 1.7% of people in the US over age 25 reported using it at some point in their lives.[13]
Behavioral effects can vary by dosage. Low doses produce numbness in the extremities and intoxication, characterized by staggering, unsteady gait, slurred speech, bloodshot eyes, and loss of balance. Moderate doses (5–10 mg intranasal, or 0.01–0.02 mg/kg intramuscular or intravenous) will produceanalgesia and anesthesia. High doses may lead toconvulsions.[15] The drug is often illegally produced under poorly controlled conditions; this means that users may be unaware of the actual dose they are taking.[16]
Psychological effects include severe changes inbody image,loss of ego boundaries,paranoia, anddepersonalization. Psychosis, agitation and dysphoria, hallucinations, blurred vision,euphoria, andsuicidal impulses are also reported, as well as occasional aggressive behavior.[17][18]: 48–49 [15] PCP may induce feelings of strength, power, and invulnerability as well as a numbing effect on the mind.[5]
Studies by theDrug Abuse Warning Network in the 1970s show that media reports of PCP-induced violence are greatly exaggerated and that incidents of violence are unusual and often limited to individuals with reputations for aggression regardless of drug use.[18]: 48 Although uncommon, events of PCP-intoxicated individuals acting in an unpredictable fashion, possibly driven by their delusions or hallucinations, have been publicized.[19] Other commonly cited types of incidents include inflicting property damage and self-mutilation of various types, such as pulling out one's teeth.[18]: 48 [19] These effects were not noted in its medicinal use in the 1950s and 1960s, however, reports of physical violence on PCP have often been shown to be unfounded.[20][21]
Recreational doses of the drug also occasionally appear toinduce a psychotic state, with emotional and cognitive impairment that resembles aschizophrenic episode.[22][23] Users generally report feeling detached from reality.[24]
Symptoms are summarized by themnemonic device RED DANES: rage,erythema (redness of skin), dilated pupils, delusions,amnesia,nystagmus (oscillation of the eyeball when moving laterally), excitation, and skin dryness.[25]
A 2019 review found that the transition rate from a diagnosis ofhallucinogen-induced psychosis (which included PCP) to that of schizophrenia was 26%. This was lower thancannabis-induced psychosis (34%) but higher thanamphetamine- (22%),opioid- (12%),alcohol- (10%), andsedative-induced (9%) psychoses. In comparison, the transition rate to schizophrenia for "brief, atypical and not otherwise specified" psychosis was found to be 36%.[28]
"Sherm stick" redirects here. For the song by Jayo Felony, seeTake a Ride.
PCP has multiple routes of administration. Most commonly, the powder form of the drug is snorted. PCP can also be orally ingested, injected subcutaneously or intravenously, or smoked laced with marijuana or cigarettes.[29]
PCP can be ingested through smoking. "Fry" and "sherm" are street terms for marijuana or tobacco cigarettes that are dipped in PCP and then dried.[30]
PCP hydrochloride can be insufflated (snorted), depending upon the purity. This is most often referred to as "angel dust".[29]
An oral pill can also be compressed from the co-compounded powder form of the drug. This is usually referred to as "peace pill".[29]
Thefree base is hydrophobic and may be absorbed through skin and mucous membranes (often inadvertently). This form of the drug is commonly called "wack".[29]
Management of PCP intoxication mostly consists of supportive care – controlling breathing, circulation, and body temperature – and, in the early stages, treating psychiatric symptoms.[31][32][33]Benzodiazepines, such aslorazepam, are thedrugs of choice to control agitation and seizures (when present).Typical antipsychotics such asphenothiazines andhaloperidol have been used to control psychotic symptoms, but may produce many undesirable side effects – such asdystonia – and their use is therefore no longer preferred; phenothiazines are particularly risky, as they may lower theseizure threshold, worsenhyperthermia, and boost theanticholinergic effects of PCP.[31][32] If an antipsychotic is given,intramuscular haloperidol has been recommended.[33][34][35]
Forced acid diuresis (withammonium chloride or, more safely,ascorbic acid) may increase the clearance of PCP from the body, and was somewhat controversially recommended in the past as adecontamination measure.[31][32][33] However, it is now known that only around 10% of a dose of PCP is removed by the kidneys, which would make increased urinary clearance of little consequence; furthermore, urinaryacidification is dangerous, as it may induceacidosis and worsenrhabdomyolysis (muscle breakdown), a not-unusual manifestation of PCP toxicity.[31][32]
Research also indicates that PCP inhibitsnicotinic acetylcholine receptors (nAChRs) among other mechanisms. Analogues of PCP exhibit varying potency at nACh receptors[52] and NMDA receptors.[53] Findings demonstrate that presynaptic nAChRs and NMDA receptor interactions influence the postsynaptic maturation of glutamatergic synapses and consequently impact synaptic development and plasticity in the brain.[54] These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as thehippocampus[55] andcerebellum[56] thus potentially leading to memory loss as one of the effects of prolonged use. Acute effects on thecerebellum manifest as changes in blood pressure, breathing rate, pulse rate, and loss of muscular coordination during intoxication.[8]
PCP, like ketamine, also acts as a potentdopamineD2High receptorpartial agonist in rat brain homogenate[43] and has affinity for the human cloned D2High receptor.[57] This activity may be associated with some of the other more psychotic features of PCP intoxication, which is evidenced by the successful use of D2 receptor antagonists (such ashaloperidol) in the treatment of PCP psychosis.[58]
Phencyclidine is a noncompetitive NMDA receptor antagonist that blocks the activity of the NMDA receptor to cause anaesthesia and analgesia without causing cardiorespiratory depression.[61][17] NMDA is an excitatory receptor in the brain, when activated normally the receptor acts as an ion channel and there is an influx of positive ions through the channel to cause nerve cell depolarisation. Phencyclidine inhibits the NMDA receptor by binding to the specific PCP binding site located within the ion channel.[62] The PCP binding site is near the magnesium blocking site, which may explain the similar inhibitory effects.[63] Binding at the PCP site is mediated by two non-covalent interactions within the receptor: hydrogen bonding and hydrophobic interaction.[64] Binding is also controlled by the gating mechanism of the ion channel. Because the PCP site is located within the ion channel, a coagonist such as glycine must bind and open the channel for PCP to enter, bind to the PCP site, and block the channel.[65]
Some studies found that, like other NMDA receptor antagonists, PCP can cause a kind ofbrain damage calledOlney's lesions in rats.[66][67] Studies conducted on rats showed that high doses of the NMDA receptor antagonistdizocilpine caused reversiblevacuoles to form in certain regions of the rats' brains. All studies of Olney's lesions have only been performed on non-human animals and may not apply to humans. One unpublished study by Frank Sharp reportedly showed no damage by the NMDA antagonist ketamine, a structurally similar drug, far beyond recreational doses,[68] but due to the study never having been published, its validity is controversial.
PCP has also been shown to cause schizophrenia-like changes inN-acetylaspartate andN-acetylaspartylglutamate levels in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue.[69] It also induces symptoms in humans that mimic schizophrenia.[70] PCP not only produced symptoms similar to schizophrenia, it also yieldedelectroencephalogram changes in the thalamocortical pathway (increased delta decreased alpha) and in the hippocampus (increase theta bursts) that were similar to those in schizophrenia.[71] PCP-induced augmentation of dopamine release may link the NMDA anddopamine hypotheses of schizophrenia.[72]
The time taken before the effects of PCP manifest is dependent on the route of administration. The onset of action for inhalation occurs in 2–5 minutes, whereas the effects may take 15 to 60 minutes when ingested orally.[17]
The generalized structural motif required for PCP-like activity is derived from structure-activity relationship studies of PCP derivatives. All of these derivatives are likely to share some of their psychoactive effects with PCP itself, although a range of potencies and varying mixtures of anesthetic, dissociative, and stimulant effects are known, depending on the particular drug and its substituents. In the United States, all of these compounds would be considered controlled substance analogs of PCP under theFederal Analog Act and are hence illegal drugs if sold for human consumption.[73][74]
Phencyclidine was initially discovered in 1926 byArthur Kötz [de] and his student Paul Merkel as a product of aGrignard reaction of 1-piperidinocyclohexancarbonitrile.[75]
It was again synthesized in 1956 by chemist H Victor Maddox and brought to market as ananesthetic medication by pharmaceutical company Parke-Davis, now a subsidiary ofPfizer.[71][10][76][75][77] Its use in humans was disallowed in the US in 1965 due to the high rates ofside effects, while its use in animals was disallowed in 1978.[1][10][78] Moreover,ketamine was discovered and was better tolerated as an anesthetic.[78]
PCP is classified as aschedule II drug in the US.[1] Derivatives of PCP have been sold for recreational and non-medical use.[48]
PCP began to emerge as arecreational drug in major cities in the US in the 1960s.[7] In 1978,People magazine andMike Wallace of the TV news program60 Minutes called PCP the country's "number one drug problem". Although recreational use of the drug had always been relatively low, it began declining significantly in the 1980s. In surveys, the number ofhigh school students admitting to trying PCP at least once fell from 13% in 1979 to less than 3% in 1990.[18]: 46–49
Tsukasa Hojo's 1985mangaCity Hunter features a drug, Angel Dust, presumably a reference to PCP'sstreet name. The related 2023 animated film,City Hunter: Angel Dust, more directly moved the franchise's angel dust into the realm of fantasy, as it is portrayed as a science fictionnanomachine serum developed by abiotech company to create super-soldiers with a tendency to drive them berserk, side-stepping the real-life PCP.[83]
InVivienne Medrano's adult animated musical comedy television seriesHazbin Hotel, Angel Dust is an adult film star in Hell and one of the main protagonists,[84] who in Hell took on the name "Angel Dust" as his chosen all-encompassing persona name, and one he uses exclusively in place of his actual name. It is intended as multipurpose for both his drag queen persona and his sex-work persona.[85]
^abcdMalenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.).Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 374–375.ISBN978-0-07-148127-4.
^abcdeBush DM (2013). "Emergency Department Visits Involving Phencyclidine (PCP)".The CBHSQ Report. Rockville, MD: Substance Abuse and Mental Health Services Administration.PMID27656747.PCP can lead to hostile behavior that may result in episodes of extreme violence
^"PCP".ginad.org. Archived fromthe original on 2018-09-10. Retrieved2018-02-20.
^"PCP".cesar.umd.edu. Archived fromthe original on 12 March 2010. Retrieved20 February 2018.
^"Hallucinogens".drugabuse.gov. National Institute on Drug Abuse. Archived fromthe original on 3 June 2020. Retrieved20 February 2018.
^Millan MJ, Brocco M, Gobert A, Joly F, Bervoets K, Rivet J, et al. (December 1999). "Contrasting mechanisms of action and sensitivity to antipsychotics of phencyclidine versus amphetamine: importance of nucleus accumbens 5-HT2A sites for PCP-induced locomotion in the rat".The European Journal of Neuroscience.11 (12):4419–32.doi:10.1046/j.1460-9568.1999.00858.x.PMID10594669.S2CID43150509.
^abMorgan JP, Kagan D (July 1980). "The Dusting of America: The Image of Phencyclidine (PCP) in the Popular Media".Journal of Psychedelic Drugs.12 (3–4):195–204.doi:10.1080/02791072.1980.10471426.PMID7431414.
^Giannini AJ (1997).Drugs of Abuse (Second ed.). Los Angeles: Practice Management Information Corp. p. 126.ISBN978-1-57066-053-5.{{cite book}}: CS1 maint: publisher location (link)
^Noda Y, Nabeshima T (September 1998). "Neuronal mechanisms of phencyclidine-induced place aversion and preference in the conditioned place preference task".Methods and Findings in Experimental and Clinical Pharmacology.20 (7):607–11.doi:10.1358/mf.1998.20.7.485726.PMID9819806.
^abcMilhorn HT (Apr 1991). "Diagnosis and management of phencyclidine intoxication".American Family Physician.43 (4):1293–302.PMID2008817.
^Giannini AJ, Price WA (1985). "PCP: Management of acute intoxication".Medical Times.113 (9):43–49.
^Giannini AJ, Eighan MS, Loiselle RH, Giannini MC (Apr 1984). "Comparison of haloperidol and chlorpromazine in the treatment of phencyclidine psychosis".Journal of Clinical Pharmacology.24 (4):202–4.doi:10.1002/j.1552-4604.1984.tb01831.x.PMID6725621.S2CID42278510.
^Roth BL, Driscol J."PDSP Ki Database".Psychoactive Drug Screening Program (PDSP). University of North Carolina at Chapel Hill and the United States National Institute of Mental Health. Retrieved14 August 2017.
^Large CH, Bison S, Sartori I, Read KD, Gozzi A, Quarta D, et al. (July 2011). "The efficacy of sodium channel blockers to prevent phencyclidine-induced cognitive dysfunction in the rat: potential for novel treatments for schizophrenia".The Journal of Pharmacology and Experimental Therapeutics.338 (1):100–113.doi:10.1124/jpet.110.178475.PMID21487071.S2CID1862326.
^abcdMorris H, Wallach J (2014). "From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs".Drug Testing and Analysis.6 (7–8):614–632.doi:10.1002/dta.1620.PMID24678061.
^Aguayo LG, Warnick JE, Maayani S, Glick SD, Weinstein H, Albuquerque EX (May 1982). "Site of action of phencyclidine. IV. Interaction of phencyclidine and its analogues on ionic channels of the electrically excitable membrane and nicotinic receptor: implications for behavioral effects".Molecular Pharmacology.21 (3):637–647.PMID6287200.
^Zarantonello P, Bettini E, Paio A, Simoncelli C, Terreni S, Cardullo F (Apr 2011). "Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists".Bioorganic & Medicinal Chemistry Letters.21 (7):2059–63.doi:10.1016/j.bmcl.2011.02.009.PMID21334205.
^Fisher JL, Dani JA (Oct 2000). "Nicotinic receptors on hippocampal cultures can increase synaptic glutamate currents while decreasing the NMDA-receptor component".Neuropharmacology.39 (13):2756–69.doi:10.1016/s0028-3908(00)00102-7.PMID11044745.S2CID42066117.
^Giannini AJ, Nageotte C, Loiselle RH, Malone DA, Price WA (1984). "Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis: DA-2 receptor specificity".Journal of Toxicology. Clinical Toxicology.22 (6):573–9.doi:10.3109/15563658408992586.PMID6535849.
^Rothman RB, Reid AA, Monn JA, Jacobson AE, Rice KC (December 1989). "The psychotomimetic drug phencyclidine labels two high affinity binding sites in guinea pig brain: evidence for N-methyl-D-aspartate-coupled and dopamine reuptake carrier-associated phencyclidine binding sites".Molecular Pharmacology.36 (6):887–896.PMID2557536.
^Castellani S, Giannini AJ, Adams PM (1982). "Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat".Psychopharmacology.78 (1):76–80.doi:10.1007/BF00470593.PMID6815700.S2CID21996319.
^Martin D, Lodge D (October 1988). "Phencyclidine receptors and N-methyl-D-aspartate antagonism: electrophysiologic data correlates with known behaviours".Pharmacology, Biochemistry, and Behavior.31 (2):279–286.doi:10.1016/0091-3057(88)90346-2.PMID2854262.S2CID12247783.
^Kroemer RT, Koutsilieri E, Hecht P, Liedl KR, Riederer P, Kornhuber J (January 1998). "Quantitative analysis of the structural requirements for blockade of the N-methyl-D-aspartate receptor at the phencyclidine binding site".Journal of Medicinal Chemistry.41 (3):393–400.doi:10.1021/jm9704412.PMID9464369.
^Nadler V, Kloog Y, Sokolovsky M (March 1990). "Distinctive structural requirement for the binding of uncompetitive blockers (phencyclidine-like drugs) to the NMDA receptor".European Journal of Pharmacology.188 (2–3):97–104.doi:10.1016/0922-4106(90)90044-X.PMID2156715.
^Hargreaves RJ, Hill RG, Iversen LL (1994). "Neuroprotective NMDA Antagonists: The Controversy over Their Potential for Adverse Effects on Cortical Neuronal Morphology".Brain Edema IX. Acta Neurochirurgica. Supplementum. Vol. 60. pp. 15–19.doi:10.1007/978-3-7091-9334-1_4.ISBN978-3-7091-9336-5.PMID7976530.
^Jansen, Karl.Ketamine: Dreams and Realities. MAPS, 2004.ISBN0-9660019-7-4
^Reynolds LM, Cochran SM, Morris BJ, Pratt JA, Reynolds GP (March 2005). "Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain".Schizophrenia Research.73 (2–3):147–152.doi:10.1016/j.schres.2004.02.003.PMID15653257.S2CID1651693.
^Itzhak Y, Kalir A, Weissman BA, Cohen S (May 1981). "New analgesic drugs derived from phencyclidine".Journal of Medicinal Chemistry.24 (5):496–9.doi:10.1021/jm00137a004.PMID7241506.
^Chaudieu I, Vignon J, Chicheportiche M, Kamenka JM, Trouiller G, Chicheportiche R (Mar 1989). "Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs".Pharmacology Biochemistry and Behavior.32 (3):699–705.doi:10.1016/0091-3057(89)90020-8.PMID2544905.S2CID7672918.
^abKötz A, Merkel P (May 1926). "Zur Kenntnis hydroaromatischer Alkamine".Journal für Praktische Chemie (in German).113 (1):49–76.doi:10.1002/prac.19261130107.ISSN0021-8383.
^Lindgren JE, Holmstedt B (1983). "Guide to the Analysis of Phencyclidine and its Metabolites in Biological Material".Toxicology in the Use, Misuse, and Abuse of Food, Drugs, and Chemicals. Archives of Toxicology. Vol. 6. Berlin, Heidelberg: Springer Berlin Heidelberg. pp. 61–73.doi:10.1007/978-3-642-69083-9_10.ISBN978-3-540-12392-7.ISSN0171-9750.PMID6578750.
^"Controlled Substances"(PDF).deadiversion.usdoj.gov. US: Drug Enforcement Administration. March 12, 2014.Archived(PDF) from the original on 2014-04-17. RetrievedJune 15, 2014.
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