PCP is most commonly used in the United States. While usage peaked in the US in the 1970s, between 2005 and 2011 an increase in visits to emergency departments as a result of the drug occurred. As of 2017 in the United States, about 1% of people in Twelfth grade reported using PCP in the prior year while 2.9% of those over the age of 25 reported using it at some point in their lives.
Behavioral effects can vary by dosage. Low doses produce a 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. The drug is often illegally produced under poorly controlled conditions; this means that users may be unaware of the actual dose they are taking.
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.: 48–49  Like many other drugs, PCP has been known to alter mood states in an unpredictable fashion, 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.: 48 Although uncommon, events of PCP-intoxicated individuals acting in an unpredictable fashion, possibly driven by their delusions or hallucinations, have been publicized. Other commonly cited types of incidents include inflicting property damage and self-mutilation of various types, such as pulling one's own teeth.: 48  These effects were not noted in its medicinal use in the 1950s and 1960s, however, and reports of physical violence on PCP have often been shown to be unfounded.
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.
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 (9%) induced psychoses. In comparison, the transition rate to schizophrenia for "brief, atypical and not otherwise specified" psychosis was found to be 36%.
Methods of administration
"Sherm stick" redirects here. For the song by Jayo Felony, see Take a Ride.
Research also indicates that PCP inhibits nicotinic acetylcholine receptors (nAChRs) among other mechanisms. Analogues of PCP exhibit varying potency at nACh receptors and NMDA receptors. Findings demonstrate that presynaptic nAChRs and NMDA receptor interactions influence postsynaptic maturation of glutamatergic synapses and consequently impact synaptic development and plasticity in the brain. These effects can lead to inhibition of excitatory glutamate activity in certain brain regions such as the hippocampus and cerebellum 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 dopamineD2High receptorpartial agonist in rat brain homogenate and has affinity for the human cloned D2High receptor. 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.
Phencyclidine is an NMDA receptor antagonist that blocks the activity of the NMDA receptor to cause anaesthesia and analgesia without causing cardiorespiratory depression. 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 enters the ion channel and binds, reversibly and non-competitively, inside the channel pore to block the entry of positive ions to the cell, thereby inhibiting cell depolarisation.
Some studies found that, like other NMDA receptor antagonists, PCP can cause a kind of brain damage called Olney's lesions in rats. 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 NDMA antagonist ketamine, a structurally similar drug, far beyond recreational doses, 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. It also induces symptoms in humans that mimic schizophrenia. 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. PCP-induced augmentation of dopamine release may link the NMDA and dopamine hypotheses of schizophrenia.
When smoked, some of the compound is broken down by heat into 1-phenylcyclohexene (PC) and piperidine.
Conversion of PCP into PC and piperidine by heat.
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.
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 some countries such as the United States, Australia, and New Zealand, 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.
PCP was initially made in 1956 and brought to market as an anesthetic medication.  Its use in humans was disallowed in the United States in 1965 due to the high rates of side effects, while its use in animals was disallowed in 1978. Moreover, ketamine was discovered and was better tolerated as an anesthetic. PCP is classified as a schedule II drug in the United States. A number of derivatives of PCP have been sold for recreational and non-medical use.
Society and culture
PCP is a Schedule II substance in the United States and its ACSCN is 7471. Its manufacturing quota for 2014 was 19 grams.
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 United Kingdom.
Frequency of use
PCP began to emerge as a recreational drug in major cities in the United States in 1960s. In 1978, People magazine and Mike Wallace of 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.: 46–49
^ 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. ISBN9780071481274.
^ abcdeBush DM (2013). "Emergency Department Visits Involving Phencyclidine (PCP)". The CBHSQ Report. Rockville (MD): Substance Abuse and Mental Health Services Administration (US). PMID27656747. PCP can lead to hostile behavior that may result in episodes of extreme violence
^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.
^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.19188.8.131.525726. PMID9819806.
^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. Retrieved 14 August 2017.
^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 (Jul 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): 100–13. 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): 614–32. 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): 637–47. 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.
^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 (Dec 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): 887–96. PMID2557536.
^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.