Phencyclidine#Cultural depictions

File:Phencyclidine (PCP).jpg.]]

Phencyclidine is used for its ability to induce a dissociative state.{{cite journal | vauthors = Millan MJ, Brocco M, Gobert A, Joly F, Bervoets K, Rivet J, Newman-Tancredi A, Audinot V, Maurel S | title = 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 | journal = The European Journal of Neuroscience | volume = 11 | issue = 12 | pages = 4419–32 | date = December 1999 | pmid = 10594669 | doi = 10.1046/j.1460-9568.1999.00858.x | s2cid = 43150509 }}

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 produce analgesia and anesthesia. High doses may lead to convulsions.Diaz, Jaime. How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall, 1996. The drug is often illegally produced under poorly controlled conditions; this means that users may be unaware of the actual dose they are taking.{{cite web |url= http://faculty.washington.edu/chudler/pcp.html |title=Neuroscience for Kids – PCP| vauthors = Chudler EM |access-date=2011-01-26 |work=Neuroscience for Kids}}

Psychological effects include severe changes in body image, loss of ego boundaries, paranoia, and depersonalization. Psychosis, agitation and dysphoria, hallucinations, blurred vision, euphoria, and suicidal impulses are also reported, as well as occasional aggressive behavior.{{rp|48–49}} Like many other drugs, PCP has been known to alter mood states unpredictably, causing some individuals to become detached, and others to become animated. PCP may induce feelings of strength, power, and invulnerability as well as a numbing effect on the mind.

Studies by the Drug 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.{{rp|48}} Although uncommon, events of PCP-intoxicated individuals acting in an unpredictable fashion, possibly driven by their delusions or hallucinations, have been publicized.{{cite journal | vauthors = Morgan JP, Kagan D | title = The Dusting of America: The Image of Phencyclidine (PCP) in the Popular Media | journal = Journal of Psychedelic Drugs | volume = 12 | issue = 3–4 | pages = 195–204 | date = July 1980 | pmid = 7431414 | doi = 10.1080/02791072.1980.10471426 }} Other commonly cited types of incidents include inflicting property damage and self-mutilation of various types, such as pulling out one's teeth.{{rp|48}} 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.{{cite journal | vauthors = Brecher M, Wang BW, Wong H, Morgan JP | title = Phencyclidine and violence: clinical and legal issues | journal = Journal of Clinical Psychopharmacology | volume = 8 | issue = 6 | pages = 397–401 | date = December 1988 | pmid = 3069880 | doi = 10.1097/00004714-198812000-00003 | s2cid = 33659160 }}{{cite journal | vauthors = Wish ED | title = PCP and crime: just another illicit drug? | journal = NIDA Research Monograph | volume = 64 | pages = 174–89 | year = 1986 | pmid = 3086733 }}

Recreational doses of the drug also occasionally appear to induce a psychotic state, with emotional and cognitive impairment that resembles a schizophrenic episode.{{cite journal |vauthors=Uchida M, Hida H, Mori K, Yoshimi A, Kitagaki S, Yamada K, Hiraoka Y, Aida T, Tanaka K, Ozaki N, Noda Y |title=Functional roles of the glial glutamate transporter (GLAST) in emotional and cognitive abnormalities of mice after repeated phencyclidine administration |journal=Eur Neuropsychopharmacol |date=August 2019 |volume=29 |issue=8 |pages=918–24 |doi=10.1016/j.euroneuro.2019.06.005 |pmid=31303267 |s2cid=195887087 |doi-access=free}}{{cite journal |vauthors=Luisada PV |title=The phencyclidine psychosis: phenomenology and treatment |journal=NIDA Research Monograph |issue=21 |pages=241–253 |date=August 1978 |pmid=101872 |url=https://archives.drugabuse.gov/sites/default/files/monograph21.pdf |veditors=Petersen RC, Stillman RC |publisher=National Institute on Drug Abuse}} Users generally report feeling detached from reality.{{cite journal |vauthors=Pender JW |title=Dissociative anesthesia |journal=California Medicine |volume=117 |issue=4 |pages=46–47 |date=October 1972 |pmid=18730832 |pmc=1518731}}

Symptoms are summarized by the mnemonic device RED DANES: rage, erythema (redness of skin), dilated pupils, delusions, amnesia, nystagmus (oscillation of the eyeball when moving laterally), excitation, and skin dryness.{{cite book | vauthors = Giannini AJ |title=Drugs of Abuse|edition=Second|publisher=Los Angeles: Practice Management Information Corp|year=1997|page=126|isbn=978-1-57066-053-5}}

PCP is self-administered and induces ΔFosB expression in the D1-type medium spiny neurons of the nucleus accumbens,{{cite book |vauthors=Malenka RC, Nestler EJ, Hyman SE |veditors=Sydor A, Brown RY | title = Molecular Neuropharmacology: A Foundation for Clinical Neuroscience | year = 2009 | publisher = McGraw-Hill Medical | location = New York | isbn = 9780071481274 | pages = 374–375 | edition = 2nd | chapter = Chapter 15: Reinforcement and Addictive Disorders}}{{cite journal| vauthors = Nestler EJ |title=Review. Transcriptional mechanisms of addiction: role of DeltaFosB|journal=Philos. Trans. R. Soc. Lond. B Biol. Sci.|volume=363|issue=1507|pages=3245–3255|date=October 12, 2008|pmid=18640924|doi=10.1098/rstb.2008.0067|pmc=2607320}}{{cite journal|title=Table 1: Drugs of abuse known to induce ΔFosB in nucleus accumbens after chronic administration|pmc=2607320|pmid=18640924|doi=10.1098/rstb.2008.0067|volume=363|issue=1507|date=October 2008|journal=Philos. Trans. R. Soc. Lond. B Biol. Sci.|pages=3245–55|vauthors=Nestler EJ}} and accordingly, excessive PCP use is known to cause addiction. PCP's rewarding and reinforcing effects are at least partly mediated by blocking the NMDA receptors in the glutamatergic inputs to D1-type medium spiny neurons in the nucleus accumbens. PCP has been shown to produce conditioned place aversion and conditioned place preference in animal studies.{{cite journal | vauthors = Noda Y, Nabeshima T | title = Neuronal mechanisms of phencyclidine-induced place aversion and preference in the conditioned place preference task | journal = Methods and Findings in Experimental and Clinical Pharmacology | volume = 20 | issue = 7 | pages = 607–11 | date = September 1998 | pmid = 9819806 | doi = 10.1358/mf.1998.20.7.485726 }}

A 2019 review found that the transition rate from a diagnosis of hallucinogen-induced psychosis (which included PCP) to that of schizophrenia was 26%. This was lower than cannabis-induced psychosis (34%) but higher than amphetamine- (22%), opioid- (12%), alcohol- (10%), and sedative-induced (9%) psychoses. In comparison, the transition rate to schizophrenia for "brief, atypical and not otherwise specified" psychosis was found to be 36%.{{cite journal | vauthors = Murrie B, Lappin J, Large M, Sara G | title = Transition of Substance-Induced, Brief, and Atypical Psychoses to Schizophrenia: A Systematic Review and Meta-analysis | journal = Schizophrenia Bulletin | volume = 46 | issue = 3 | pages = 505–516 | date = April 2020 | pmid = 31618428 | pmc = 7147575 | doi = 10.1093/schbul/sbz102 | doi-access = free }}

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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.{{cite journal | vauthors = Bertron JL, Seto M, Lindsley CW | title = DARK Classics in Chemical Neuroscience: Phencyclidine (PCP) | journal = ACS Chemical Neuroscience | volume = 9 | issue = 10 | pages = 2459–2474 | date = October 2018 | pmid = 29953199 | doi = 10.1021/acschemneuro.8b00266 | s2cid = 49603581 }}

• 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.{{cite web|url=https://www.justice.gov/archive/ndic/pubs11/12208/|title=Fry Fast Facts|publisher=National Drug Intelligence Center|access-date=2017-01-15|archive-date=2021-04-17|archive-url=https://web.archive.org/web/20210417111038/https://www.justice.gov/archive/ndic/pubs11/12208/|url-status=dead}}
• PCP hydrochloride can be insufflated (snorted), depending upon the purity. This is most often referred to as "angel dust".
• An oral pill can also be compressed from the co-compounded powder form of the drug. This is usually referred to as "peace pill".
• The free base is hydrophobic and may be absorbed through skin and mucous membranes (often inadvertently). This form of the drug is commonly called "wack".

Management of PCP intoxication mostly consists of supportive care – controlling breathing, circulation, and body temperature – and, in the early stages, treating psychiatric symptoms.{{cite journal |url=http://www.emedicine.com/med/TOPIC1813.HTM |title=Phencyclidine Toxicity |vauthors=Helman RS, Habal R |date=October 6, 2008 |journal=eMedicine}} Retrieved on November 3, 2008.{{cite book | vauthors = Olmedo R |chapter=Chapter 69: Phencyclidine and ketamine |title=Goldfrank's Toxicologic Emergencies |veditors=Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS |publisher=McGraw-Hill |location=New York |year=2002 |pages=1034–1041 |isbn=978-0-07-136001-2 |chapter-url=https://books.google.com/books?id=HVYyRsuUEc0C&pg=PA1041}}{{cite journal | vauthors = Milhorn HT | title = Diagnosis and management of phencyclidine intoxication | journal = American Family Physician | volume = 43 | issue = 4 | pages = 1293–302 | date = Apr 1991 | pmid = 2008817 }} Benzodiazepines, such as lorazepam, are the drugs of choice to control agitation and seizures (when present). Typical antipsychotics such as phenothiazines and haloperidol have been used to control psychotic symptoms, but may produce many undesirable side effects – such as dystonia – and their use is therefore no longer preferred; phenothiazines are particularly risky, as they may lower the seizure threshold, worsen hyperthermia, and boost the anticholinergic effects of PCP. If an antipsychotic is given, intramuscular haloperidol has been recommended.{{cite journal | vauthors = Giannini AJ, Price WA | year = 1985 | title = PCP: Management of acute intoxication | journal = Medical Times | volume = 113 | issue = 9| pages = 43–49 }}{{cite journal | vauthors = Giannini AJ, Eighan MS, Loiselle RH, Giannini MC | title = Comparison of haloperidol and chlorpromazine in the treatment of phencyclidine psychosis | journal = Journal of Clinical Pharmacology | volume = 24 | issue = 4 | pages = 202–4 | date = Apr 1984 | pmid = 6725621 | doi = 10.1002/j.1552-4604.1984.tb01831.x | s2cid = 42278510 }}

Forced acid diuresis (with ammonium chloride or, more safely, ascorbic acid) may increase the clearance of PCP from the body, and was somewhat controversially recommended in the past as a decontamination measure. 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, urinary acidification is dangerous, as it may induce acidosis and worsen rhabdomyolysis (muscle breakdown), a not-unusual manifestation of PCP toxicity.

PCP is well known for its primary action on the NMDA receptor, an ionotropic glutamate receptor.{{cite journal | vauthors = Large CH, Bison S, Sartori I, Read KD, Gozzi A, Quarta D, Antolini M, Hollands E, Gill CH, Gunthorpe MJ, Idris N, Neill JC, Alvaro GS | title = The efficacy of sodium channel blockers to prevent phencyclidine-induced cognitive dysfunction in the rat: potential for novel treatments for schizophrenia | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 338 | issue = 1 | pages = 100–113 | date = July 2011 | pmid = 21487071 | doi = 10.1124/jpet.110.178475 | s2cid = 1862326 }} As such, PCP is a non-competitive NMDA receptor antagonist. The role of NMDAR antagonism in the effect of PCP, ketamine, and related dissociative agents was first published in the early 1980s by David Lodge{{Cite journal |vauthors = Anis NA, Berry SC, Burton NR, ((D. Lodge)) | title = The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate | journal = British Journal of Pharmacology | volume = 79 | issue = 2 | pages = 565–575 | year = 1983 | pmc = 2044888 | pmid = 6317114 | doi=10.1111/j.1476-5381.1983.tb11031.x}} and colleagues.{{cite journal|vauthors=Morris H, Wallach J|year=2014|title=From PCP to MXE: a comprehensive review of the non-medical use of dissociative drugs|journal=Drug Testing and Analysis|volume=6|issue=7–8|pages=614–632|doi=10.1002/dta.1620|pmid=24678061}} Other NMDA receptor antagonists include ketamine,{{cite journal | vauthors = Caddy C, Giaroli G, White TP, Shergill SS, Tracy DK | title = Ketamine as the prototype glutamatergic antidepressant: pharmacodynamic actions, and a systematic review and meta-analysis of efficacy | journal = Therapeutic Advances in Psychopharmacology | volume = 4 | issue = 2 | pages = 75–99 | date = April 2014 | pmid = 24688759 | doi = 10.1177/2045125313507739 | pmc=3952483}} tiletamine,{{cite journal | vauthors = Klockgether T, Turski L, Schwarz M, Sontag KH, Lehmann J | title = Paradoxical convulsant action of a novel non-competitive N-methyl-D-aspartate (NMDA) antagonist, tiletamine | journal = Brain Research | volume = 461 | issue = 2 | pages = 343–8 | date = Oct 1988 | pmid = 2846121 | doi = 10.1016/0006-8993(88)90265-X | s2cid = 41671395 }} dextromethorphan,{{cite journal | vauthors = Burns JM, Boyer EW | title = Antitussives and substance abuse | journal = Substance Abuse and Rehabilitation | volume = 4 | pages = 75–82 | year = 2013 | pmid = 24648790 | pmc = 3931656 | doi = 10.2147/SAR.S36761 | doi-access = free }} nitrous oxide, and dizocilpine (MK-801).

Research also indicates that PCP inhibits nicotinic acetylcholine receptors (nAChRs) among other mechanisms. Analogues of PCP exhibit varying potency at nACh receptors{{cite journal | vauthors = Aguayo LG, Warnick JE, Maayani S, Glick SD, Weinstein H, Albuquerque EX | title = 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 | journal = Molecular Pharmacology | volume = 21 | issue = 3 | pages = 637–647 | date = May 1982 | pmid = 6287200 }} and NMDA receptors.{{cite journal | vauthors = Zarantonello P, Bettini E, Paio A, Simoncelli C, Terreni S, Cardullo F | title = Novel analogues of ketamine and phencyclidine as NMDA receptor antagonists | journal = Bioorganic & Medicinal Chemistry Letters | volume = 21 | issue = 7 | pages = 2059–63 | date = Apr 2011 | pmid = 21334205 | doi = 10.1016/j.bmcl.2011.02.009 }} 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.{{cite journal | vauthors = Lin H, Vicini S, Hsu FC, Doshi S, Takano H, Coulter DA, Lynch DR | title = Axonal α7 nicotinic ACh receptors modulate presynaptic NMDA receptor expression and structural plasticity of glutamatergic presynaptic boutons | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 38 | pages = 16661–6 | date = Sep 2010 | pmid = 20817852 | pmc = 2944730 | doi = 10.1073/pnas.1007397107 | bibcode = 2010PNAS..10716661L | doi-access = free }} These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as the hippocampus{{cite journal | vauthors = Fisher JL, Dani JA | title = Nicotinic receptors on hippocampal cultures can increase synaptic glutamate currents while decreasing the NMDA-receptor component | journal = Neuropharmacology | volume = 39 | issue = 13 | pages = 2756–69 | date = Oct 2000 | pmid = 11044745 | doi = 10.1016/s0028-3908(00)00102-7 | s2cid = 42066117 }} and cerebellum{{cite journal | vauthors = Prestori F, Bonardi C, Mapelli L, Lombardo P, Goselink R, De Stefano ME, Gandolfi D, Mapelli J, Bertrand D, Schonewille M, De Zeeuw C, D'Angelo E | title = Gating of long-term potentiation by nicotinic acetylcholine receptors at the cerebellum input stage | journal = PLOS ONE | volume = 8 | issue = 5 | pages = e64828 | year = 2013 | pmid = 23741401 | pmc = 3669396 | doi = 10.1371/journal.pone.0064828 | bibcode = 2013PLoSO...864828P | doi-access = free }} thus potentially leading to memory loss as one of the effects of prolonged use. Acute effects on the cerebellum manifest as changes in blood pressure, breathing rate, pulse rate, and loss of muscular coordination during intoxication.

PCP, like ketamine, also acts as a potent dopamine D₂^High receptor partial agonist in rat brain homogenate and has affinity for the human cloned D₂^High receptor.{{cite journal | vauthors = Seeman P, Ko F, Tallerico T | title = Dopamine receptor contribution to the action of PCP, LSD and ketamine psychotomimetics | journal = Molecular Psychiatry | volume = 10 | issue = 9 | pages = 877–883 | date = September 2005 | pmid = 15852061 | doi = 10.1038/sj.mp.4001682 | doi-access = free }} 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 as haloperidol) in the treatment of PCP psychosis.{{cite journal | vauthors = Giannini AJ, Nageotte C, Loiselle RH, Malone DA, Price WA | title = Comparison of chlorpromazine, haloperidol and pimozide in the treatment of phencyclidine psychosis: DA-2 receptor specificity | journal = Journal of Toxicology. Clinical Toxicology | volume = 22 | issue = 6 | pages = 573–9 | year = 1984 | pmid = 6535849 | doi = 10.3109/15563658408992586 }}

In addition to its well-explored interactions with NMDA receptors, PCP has also been shown to inhibit dopamine reuptake, and thereby leads to increased extracellular levels of dopamine and hence increased dopaminergic neurotransmission.{{cite journal | vauthors = Rothman RB, Reid AA, Monn JA, Jacobson AE, Rice KC | title = 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 | journal = Molecular Pharmacology | volume = 36 | issue = 6 | pages = 887–896 | date = December 1989 | pmid = 2557536 }} However, PCP has little affinity for the human monoamine transporters, including the dopamine transporter (DAT). Instead, its inhibition of monoamine reuptake may be mediated by interactions with allosteric sites on the monoamine transporters. PCP is notably a high-affinity ligand of the PCP site 2 (K_i = 154 nM), a not-well-characterized site associated with monoamine reuptake inhibition.

Studies on rats indicate that PCP interacts indirectly with opioid receptors (endorphin and enkephalin) to produce analgesia.{{cite journal | vauthors = Castellani S, Giannini AJ, Adams PM | title = Effects of naloxone, metenkephalin, and morphine on phencyclidine-induced behavior in the rat | journal = Psychopharmacology | volume = 78 | issue = 1 | pages = 76–80 | year = 1982 | pmid = 6815700 | doi = 10.1007/BF00470593 | s2cid = 21996319 }}

A binding study assessed PCP at 56 sites including neurotransmitter receptors and transporters and found that PCP had K_i values of >10,000 nM at all sites except the dizocilpine (MK-801) site of the NMDA receptor (K_i = 59 nM), the σ₂ receptor (PC12) (K_i = 136 nM), and the serotonin transporter (K_i = 2,234 nM). The study notably found K_i values of >10,000 nM for the D₂ receptor, the opioid receptors, the σ₁ receptor, and the dopamine and norepinephrine transporters. These results suggest that PCP is a highly selective ligand of the NMDAR and σ₂ receptor. However, PCP may also interact with allosteric sites on the monoamine transporters to produce inhibition of monoamine reuptake.

Phencyclidine is a noncompetitive NMDA receptor antagonist that blocks the activity of the NMDA receptor to cause anaesthesia and analgesia without causing cardiorespiratory depression.{{cite web |title=Phencyclidine |url=https://www.drugbank.ca/drugs/DB03575 |website=www.drugbank.ca |access-date=28 January 2019}}{{cite journal | vauthors = Bey T, Patel A | title = Phencyclidine intoxication and adverse effects: a clinical and pharmacological review of an illicit drug | journal = The California Journal of Emergency Medicine | volume = 8 | issue = 1 | pages = 9–14 | date = February 2007 | pmid = 20440387 | pmc = 2859735 }} 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.{{cite journal | vauthors = Martin D, Lodge D | title = Phencyclidine receptors and N-methyl-D-aspartate antagonism: electrophysiologic data correlates with known behaviours | journal = Pharmacology, Biochemistry, and Behavior | volume = 31 | issue = 2 | pages = 279–286 | date = October 1988 | pmid = 2854262 | doi = 10.1016/0091-3057(88)90346-2 | s2cid = 12247783 }} The PCP binding site is within close proximity to the magnesium blocking site, which may explain the similar inhibitory effects.{{cite journal | vauthors = Kohrs R, Durieux ME | title = Ketamine: teaching an old drug new tricks | journal = Anesthesia and Analgesia | volume = 87 | issue = 5 | pages = 1186–1193 | date = November 1998 | pmid = 9806706 | doi = 10.1097/00000539-199811000-00039 | doi-access = free }} Binding at the PCP site is mediated by two non-covalent interactions within the receptor: hydrogen bonding and hydrophobic interaction.{{cite journal | vauthors = Kroemer RT, Koutsilieri E, Hecht P, Liedl KR, Riederer P, Kornhuber J | title = Quantitative analysis of the structural requirements for blockade of the N-methyl-D-aspartate receptor at the phencyclidine binding site | journal = Journal of Medicinal Chemistry | volume = 41 | issue = 3 | pages = 393–400 | date = January 1998 | pmid = 9464369 | doi = 10.1021/jm9704412 }} 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.{{cite journal | vauthors = Nadler V, Kloog Y, Sokolovsky M | title = Distinctive structural requirement for the binding of uncompetitive blockers (phencyclidine-like drugs) to the NMDA receptor | journal = European Journal of Pharmacology | volume = 188 | issue = 2–3 | pages = 97–104 | date = March 1990 | pmid = 2156715 | doi = 10.1016/0922-4106(90)90044-X }}

Some studies found that, like other NMDA receptor antagonists, PCP can cause a kind of brain damage called Olney's lesions in rats.{{cite journal |vauthors=Olney JW, Labruyere J, Price MT |title=Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs |journal=Science |volume=244 |issue=4910 |pages=1360–1362 |date=June 1989 |pmid=2660263 |doi=10.1126/science.2660263 |bibcode=1989Sci...244.1360O}}{{cite book |vauthors=Hargreaves RJ, Hill RG, Iversen LL |chapter=Neuroprotective NMDA Antagonists: The Controversy over Their Potential for Adverse Effects on Cortical Neuronal Morphology |title=Brain Edema IX |series=Acta Neurochirurgica. Supplementum |volume=60 |pages=15–19 |year=1994 |pmid=7976530 |isbn=978-3-7091-9336-5 |doi=10.1007/978-3-7091-9334-1_4}} Studies conducted on rats showed that high doses of the NMDA receptor antagonist dizocilpine caused reversible vacuoles 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,Jansen, Karl. Ketamine: Dreams and Realities. MAPS, 2004. {{ISBN|0-9660019-7-4}} but due to the study never having been published, its validity is controversial.

PCP has also been shown to cause schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate levels in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue.{{cite journal |vauthors=Reynolds LM, Cochran SM, Morris BJ, Pratt JA, Reynolds GP |title=Chronic phencyclidine administration induces schizophrenia-like changes in N-acetylaspartate and N-acetylaspartylglutamate in rat brain |journal=Schizophrenia Research |volume=73 |issue=2–3 |pages=147–152 |date=March 2005 |pmid=15653257 |doi=10.1016/j.schres.2004.02.003 |s2cid=1651693}} It also induces symptoms in humans that mimic schizophrenia.{{cite journal |vauthors=Murray JB |title=Phencyclidine (PCP): a dangerous drug, but useful in schizophrenia research |journal=The Journal of Psychology |volume=136 |issue=3 |pages=319–327 |date=May 2002 |pmid=12206280 |doi=10.1080/00223980209604159 |s2cid=20334137}} PCP not only produced symptoms similar to schizophrenia, it also yielded electroencephalogram changes in the thalamocortical pathway (increased delta decreased alpha) and in the hippocampus (increase theta bursts) that were similar to those in schizophrenia.{{cite journal |vauthors=Lodge D, Mercier MS |title=Ketamine and phencyclidine: the good, the bad and the unexpected |journal=British Journal of Pharmacology |volume=172 |issue=17 |pages=4254–4276 |date=September 2015 |pmid=26075331 |pmc=4556466 |doi=10.1111/bph.13222}} PCP-induced augmentation of dopamine release may link the NMDA and dopamine hypotheses of schizophrenia.{{cite journal |vauthors=Javitt DC, Zukin SR, Heresco-Levy U, Umbricht D |title=Has an angel shown the way? Etiological and therapeutic implications of the PCP/NMDA model of schizophrenia |journal=Schizophrenia Bulletin |volume=38 |issue=5 |pages=958–966 |date=September 2012 |pmid=22987851 |pmc=3446214 |doi=10.1093/schbul/sbs069}}

File:PCP2PCandPOPERIDINE.png

PCP is both water- and lipid-soluble and is therefore distributed throughout the body quickly. PCP is metabolized into PCHP, PPC and PCAA. The drug is metabolized 90% by oxidative hydroxylation in the liver during the first pass. Metabolites are glucuronidated and excreted in the urine. Nine percent of ingested PCP is excreted in its unchanged form.

When smoked, some of the compound is broken down by heat into 1-phenylcyclohexene (PC) and piperidine.

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.

PCP is an arylcyclohexylamine.

File:ACHA SAR.png

Fewer than 30 different analogs of PCP were reported as being used as a street drug during the 1970s and 1980s, mainly in the United States. Only a few of these compounds were widely used, including rolicyclidine (PCPy), eticyclidine (PCE), and tenocyclidine (TCP). Less common analogs include 3-HO-PCP, 3-MeO-PCMo, and 3-MeO-PCP.

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 the Federal Analog Act and are hence illegal drugs if sold for human consumption.{{cite journal | vauthors = Itzhak Y, Kalir A, Weissman BA, Cohen S | title = New analgesic drugs derived from phencyclidine | journal = Journal of Medicinal Chemistry | volume = 24 | issue = 5 | pages = 496–9 | date = May 1981 | pmid = 7241506 | doi = 10.1021/jm00137a004 }}{{cite journal | vauthors = Chaudieu I, Vignon J, Chicheportiche M, Kamenka JM, Trouiller G, Chicheportiche R | title = Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs | journal = Pharmacology Biochemistry and Behavior | volume = 32 | issue = 3 | pages = 699–705 | date = Mar 1989 | pmid = 2544905 | doi = 10.1016/0091-3057(89)90020-8 | s2cid = 7672918 }}

Phencyclidine was initially discovered in 1926 by {{ill|Arthur Kötz|de}} and his student Paul Merkel as a product of a Grignard reaction of 1-piperidinocyclohexancarbonitrile.{{cite journal | vauthors=Kötz A, Merkel P |date=May 1926 |title=Zur Kenntnis hydroaromatischer Alkamine |journal=Journal für Praktische Chemie |language=de |volume=113 |issue=1 |pages=49–76 |doi=10.1002/prac.19261130107 |issn=0021-8383}}

It was again synthesized in 1956 by chemist H Victor Maddox and brought to market as an anesthetic medication by pharmaceutical company Parke-Davis, now a subsidiary of Pfizer.{{cite book |url=https://books.google.com/books?id=tX7nCAAAQBAJ&pg=PA717|title=Neuropsychopharmacology: Proceedings of the XVIth C.I.N.P. Congress, Munich, August, 15-19, 1988|vauthors=Bunney Jr WE, Hippius H, Laakmann G, Schmauß M|date=2012|publisher=Springer Science & Business Media |isbn=978-3-642-74034-3 |page=717 |via=Google Books}}{{cite book|vauthors=Lindgren JE, Holmstedt B|title=Toxicology in the Use, Misuse, and Abuse of Food, Drugs, and Chemicals |series= Archives of Toxicology | publisher=Springer Berlin Heidelberg| year= 1983 |isbn= 978-3-540-12392-7|volume=6|location=Berlin, Heidelberg|pages=61–73| chapter= Guide to the Analysis of Phencyclidine and its Metabolites in Biological Material| doi= 10.1007/978-3-642-69083-9_10|issn=0171-9750|pmid=6578750}} Its use in humans was disallowed in the US in 1965 due to the high rates of side effects, while its use in animals was disallowed in 1978.{{cite book| url= https://books.google.com/books?id=l2KRBgAAQBAJ&pg=PT4843 |title= Psychiatry, 2 Volume Set|vauthors=Tasman A, Kay J, Lieberman JA, First MB, Riba M |year= 2015| publisher= John Wiley & Sons|isbn=978-1-118-75336-1 |page=4943 | via= Google Books}} Moreover, ketamine was discovered and was better tolerated as an anesthetic.

PCP is classified as a schedule II drug in the US. Derivatives of PCP have been sold for recreational and non-medical use.

PCP is a Schedule II substance in the US. The Administrative Controlled Substances Code Number (ACSCN) for PCP is 7471.{{cite web | publisher= Drug Enforcement Administration | location= US| website= deadiversion.usdoj.gov |date=March 12, 2014 |url= http://www.deadiversion.usdoj.gov/schedules/orangebook/d_cs_drugcode.pdf |title= Controlled Substances |access-date=June 15, 2014 |archive-date=2014-04-17 |archive-url=https://web.archive.org/web/20140417100237/http://www.deadiversion.usdoj.gov/schedules/orangebook/d_cs_drugcode.pdf |url-status=live}} Its manufacturing quota for 2014 was {{convert|19|g}}.{{cite web | website= deadiversion.usdoj.gov| publisher= Drug Enforcement Administration |date=August 30, 2013 | location= US |url= http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0909.htm |title= Established Aggregate Production Quotas for Schedule I and II Controlled Substances and Established Assessment of Annual Needs for the List I Chemicals Ephedrine, Pseudoephedrine, and Phenylpropanolamine for 2014 |access-date=June 15, 2014 |url-status=dead |archive-date=2014-04-17 |archive-url= https://web.archive.org/web/20140417130426/http://www.deadiversion.usdoj.gov/fed_regs/quotas/2013/fr0909.htm}} It is a Schedule I drug by the Controlled Drugs and Substances act in Canada, a List I drug of the Opium Law in the Netherlands, and a Class A substance in the UK.{{cite web| title= The Misuse of Drugs Act 1971 (Modification) Order 1979 |website= legislation.gov.uk |url= http://www.legislation.gov.uk/uksi/1979/299/article/2/made#text%253DPhencyclidine |access-date=2016-01-31}}

PCP began to emerge as a recreational drug in major cities in the US in the 1960s. In 1978, People magazine and Mike Wallace of the TV news program 60 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 of high school students admitting to trying PCP at least once fell from 13% in 1979 to less than 3% in 1990.{{cite book | vauthors = Inciardi JA |title = The War on Drugs II|publisher = Mayfield Publishing Company |year = 1992 |isbn = 978-1-55934-016-8}}{{rp|46–49}}

Jean-Michel Basquiat depicted two angel dust users in his 1982 painting Dustheads.{{cite news | vauthors = Nag A |date=April 11, 2013 |title= Christie's Evening Auction to present a major painting by Jean-Michel Basquiat |work= The Economic Times |url=https://economictimes.indiatimes.com/christies-evening-auction-to-present-a-major-painting-by-jean-michel-basquiat/articleshow/19496301.cms?from=mdr |access-date=2020-09-26}}

Tsukasa Hojo's 1985 manga City Hunter features a drug, Angel Dust, presumably a reference to PCP's street 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 fiction nanomachine serum developed by a biotech company to create super-soldiers with a tendency to drive them berserk, side-stepping the real-life PCP.{{cite web |date=2024-06-28 |title=New City Hunter Anime Film's Trailer Unveils More Cast, Theme Songs, September 8 Debut |url=https://www.animenewsnetwork.com/news/2023-06-13/new-city-hunter-anime-film-trailer-unveils-more-cast-theme-songs-september-8-debut/.199110 |access-date=2024-06-28 |website=Anime News Network}}

In Vivienne Medrano's adult animated musical comedy television series Hazbin Hotel, Angel Dust is an adult film star in Hell and one of the main protagonists,{{cite press release |title=Prime Video Debuts Teaser of an Original Song and Announces Main Cast for Hazbin Hotel at New York Comic Con |url=http://press.amazonstudios.com/us/en/press-release/prime-video-debuts-teaser-of-an-original-song-and- |access-date=2024-02-22 |website=press.amazonstudios.com |publisher=Amazon Studios |language=en-US}} 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.[https://www.youtube.com/watch?v=qtIJvv70hoo&t=9088s HAZBIN HOTEL Animation Cleanup Pt. 7 Ft. Michael Kovach and Vivziepop] (2:31:28) – via YouTube.

{{reflist}}

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{{Commons category|Phencyclidine}}

• [http://www.erowid.org/chemicals/pcp/pcp.shtml Erowid.org – PCP Information]
• [http://www.drugabuse.gov/DrugPages/PCP.html National Institute of Drug Abuse InfoFacts: PCP (Phencyclidine)] {{Webarchive|url=https://web.archive.org/web/20120106220052/http://www.drugabuse.gov/drugpages/pcp.html |date=2012-01-06 }}
• [https://web.archive.org/web/20080514004144/http://www.nhtsa.dot.gov/PEOPLE/INJURY/research/job185drugs/phencyclidine.htm Drugs and Human Performance Fact Sheets on Phencyclidine]
• [http://www.timothywyllie.com/PCP.htm Phencyclidine and Ketamine: A View From the Street-1981 article on the use and effects of PCP] {{Webarchive|url=https://web.archive.org/web/20190121194233/http://www.timothywyllie.com/PCP.htm |date=2019-01-21 }}
• {{cite web | url = https://druginfo.nlm.nih.gov/drugportal/name/phencyclidine | publisher = U.S. National Library of Medicine | work = Drug Information Portal | title = Phencyclidine }}

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