Phencyclidine Information & Phencyclidine Links at HealthHaven.com

Phencyclidine
Systematic (IUPAC) name
	1-(1-phenylcyclohexyl)piperidine
Identifiers
CAS number	77-10-1
ATC code	none
PubChem	6468
ChemSpider	6224
Chemical data
Formula	C17H25N
Mol. mass	243.387 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	7-46 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status	Schedule I(CA) Class A(UK) Schedule II(US)
Routes	Smoked, Insufflated, Oral
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Phencyclidine (a complex clip of the chemical name phenylcyclohexylpiperidine, commonly initialised as PCP), also known as angel dust and other street names, is a recreational, dissociative drug formerly used as an anaesthetic agent, exhibiting hallucinogenic and neurotoxic effects.^[1] Developed in 1926,^[2] it was first patented in 1952 by the Parke-Davis pharmaceutical company and marketed under the brand name Sernyl. In chemical structure, PCP is an arylcyclohexylamine derivative, and, in pharmacology, it is a member of the family of dissociative anesthetics. PCP works primarily as an NMDA receptor antagonist, which blocks the activity of the NMDA receptor.^[3] Other NMDA receptor antagonists include ketamine, tiletamine, and dextromethorphan. Although the primary psychoactive effects of the drug lasts for a few hours, the total elimination rate from the body typically extends 8 days or longer.

[edit] Biochemistry and pharmacology

[edit] Biochemical action

The N-methyl-D-Aspartate (NMDA) receptor, a type of ionotropic receptor, is found on the dendrites of neurons and receives signals in the form of neurotransmitters. It is a major excitatory receptor in the brain. Normal physiological function requires that the activated receptor fluxes positive through the channel part of the receptor. PCP enters the ion channel from the outside of the neuron and binds, reversibly, to a site in the channel pore, blocking the flux of positive ions into the cell. PCP therefore inhibits depolarization of neurons and interferes with cognitive and other functions of the nervous system.

In a similar manner, PCP and analogues also inhibit nicotinic acetylcholine receptor channels (nAChR). Some analogues have greater potency at nAChR than at NMDAR. In some brain regions, these effects act synergistically to inhibit excitatory activity.^{[citation needed]}

PCP is retained in fatty tissue and is broken down by the human metabolism into PCHP, PPC and PCAA.

The most troubling clinical effects are likely produced by the indirect action of phencyclidine on the presynaptic dopamine receptor (DA-2). This has been suggested to account for most of the psychotic features.^[4] The relative immunity to pain is likely produced by indirect interaction with the endogenous endorphin and enkephalin system in rats.^[5]^{[clarification needed]}

[edit] Structural analogs

Possible Analogues of PCP

More than 30 different analogues of PCP were reported as being used on the street during the 1970s and 1980s, mainly in the USA. The best known of these are PCPy (rolicyclidine, 1-(1-phenylcyclohexyl)pyrrolidine); PCE (eticyclidine, N-ethyl-1-phenylcyclohexylamine); and TCP (tenocyclidine, 1-(1-(2-Thienyl)cyclohexyl)piperidine). These compounds were never widely-used and did not seem to be as well-accepted by users as PCP itself, however they were all added onto Schedule I of the Controlled Substance Act because of their putative similar effects.^[6]^{[citation needed]}

The generalized structural motif required for PCP-like activity is derived from structure-activity relationship studies of PCP analogues, and summarized below. All of these analogues would have somewhat similar effects to PCP itself, although, with a range of potencies and varying mixtures of anesthetic, dissociative and stimulant effects depending on the particular substituents used. In some countries such as the USA, Australia, and New Zealand, all of these compounds would be considered controlled substance analogues of PCP, and are hence illegal drugs, even though many of them have never been made or tested.^[7]^[8]^{[clarification needed]}

[edit] Brain effects

Like other NMDA receptor antagonists, it is postulated that phencyclidine can cause a certain kind of brain damage called Olney's lesions.^[9]^[10] Studies conducted on rats showed that high doses of the NMDA receptor antagonist MK-801 caused irreversible vacuoles to form in certain regions of the rats' brains, and experts say that it is possible that similar brain damage can occur in humans.^{[citation needed]} All studies of Olney's Lesions have only been performed on animals and may not apply to humans. The research into the relationship between rat brain metabolism and the creation of Olney's Lesions has been discredited and may not apply to humans, as has been shown with ketamine.^[11]^[12]

Phencyclidine has also been shown to cause schizophrenia-like changes in the rat brain, which are detectable both in living rats and upon necropsy examination of brain tissue.^[13] It also induces symptoms in humans that are virtually indistinguishable from schizophrenia.^[14]

[edit] History and medicinal use

PCP was first synthesized in 1926, and later tested after World War II as a surgical anesthetic. Because of its adverse side effects, such as hallucinations, mania, delirium, and disorientation, it was shelved until the 1950s. In 1953, it was patented by Parke-Davis and named Sernyl (referring to serenity), but was withdrawn from the market two years later because of side-effects. It was renamed Sernylan in 1967, and marketed as a veterinary anesthetic, but again discontinued. Its side effects and long half-life in the human body made it unsuitable for medical applications.

When smoked, some of it is broken down by heat into 1-phenyl-1-cyclohexene (PC) and piperidine.

Conversion of PCP into PC and piperidine by heat. (Image in the PD)

[edit] Recreational use

Illicit PCP seized by the DEA in several forms.

PCP comes in both powder and liquid forms (PCP base is dissolved most often in ether), but typically it is sprayed onto leafy material such as cannabis, mint, oregano, parsley, or ginger leaves, then smoked.

PCP is a Schedule II substance in the United States, a List II drug of the Opium Law in the Netherlands and a Class A substance in the United Kingdom.

[edit] Method of absorption

The term "embalming fluid" is often used to refer to the liquid PCP in which a cigarette is dipped, to be ingested through smoking, commonly known as "boat" or "water." The name most likely originated from PCP's somatic "numbing" effect and the feeling of physical dissociation from the body, and has led to the widespread (mistaken) belief that the liquid is made up of or contains real embalming fluid. Smoking actual formaldehyde will cause intoxication, but may cause serious adverse health consequences above and beyond those of consuming PCP, due to the toxicity of formaldehyde and other embalming chemicals. Smoking PCP is known as "getting wet", and a tobacco or cannabis cigarette dipped in PCP may be referred to on the street as a "sherm stick," "sherm," "fry stick," "amp," "toe tag", "dippa", "happy stick," or "wet stick." "Getting wet" is an increasingly popular method of using PCP, especially in the western United States where its is sold for about $10 to $25 per cigarette.

In its pure (base) form, PCP is a yellow oil (usually dissolved in petroleum or diethyl ether or tetrahydrofuran). Upon treatment with hydrogen chloride gas, or isopropyl alcohol saturated with HCl, this oil precipitates into white - tan crystals or powder (PCP hydrochloride) In this form, PCP can be insufflated, depending upon the purity. However, most PCP on the illicit market contains a number of contaminants as a result of makeshift manufacturing, causing the color to range from tan to brown, and the consistency to range from powder to a gummy mass. These contaminants can range from unreacted piperidine and other precursors, to carcinogens like benzene and cyanide-like compounds such as PCC (piperidinocyclohexyl carbonitrile).

[edit] Effects

Behavioural effects can vary by dosage. Small 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.^[15]

Psychological effects include severe changes in body image, loss of ego boundaries, and depersonalization. Hallucinations and euphoria are reported infrequently.^[15]

The drug has been known to alter mood states in an unpredictable fashion, causing some individuals to become detached, and others to become animated. Intoxicated individuals may act in an unpredictable fashion, driven by their delusions and hallucinations.

Included in the portfolio of behavioral disturbances are acts of self-injury including suicide, and attacks on others or destruction of property. The analgesic properties of the drug can cause users to feel less pain, and persist in violent or injurious acts as a result. Recreational doses of the drug can also induce a psychotic state that resembles schizophrenic episodes which can last for months at a time with toxic doses. Users generally report an "out-of-body" experience where they feel detached from reality, or one's consciousness seems somewhat disconnected from consensus reality.

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.^[16]

[edit] Controversy

The American rapper Big Lurch was accused of murdering an acquaintance and eating her lungs while on PCP.^[17]

In April 2009, 34-year-old Angel Vidal Mendoza Sr. bit out his 4-year-old son's eye, and severely damaged the other, while on PCP, before attempting to chop off his own legs with an axe.^[18]

[edit] Management of intoxication

Management of phencyclidine intoxication mostly consists of supportive care — controlling breathing, circulation, and body temperature — and, in the early stages, treating psychiatric symptoms.^[19]^[20]^[21] 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.^[19]^[20] If an antipsychotic is given, intramuscular haloperidol has been recommended.^[21]^[22]^[23]

Forced acid diuresis (with ammonium chloride or, more safely, ascorbic acid) may increase clearance of PCP from the body, and was somewhat controversially recommended in the past as a decontamination measure.^[19]^[20]^[21] 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), which is not an unusual manifestation of PCP toxicity.^[19]^[20]

[edit] See also

Arylcyclohexylamine

[edit] References

^ Maisto, Stephen A.; Mark Galizio, Gerard Joseph Connors (2004). Drug Use and Abuse. Thompson Wadsworth. ISBN 0155085174.
^ [www.cesar.umd.edu/cesar/drugs/pcp.pdf Development of PCP]
^ Kapur, S. and P. Seeman. "NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2receptors¾implications for models of schizophrenia" Molecular Psychiatry. 7(8): 837–844 (2002)
^ 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. PMID 6535849.
^ 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. PMID 6815700.
^ PCP synthesis and effects: table of contents
^ Itzhak Y, Kalir A, Weissman BA, Cohen S. New analgesic drugs derived from phencyclidine. Journal of Medicinal Chemistry. 1981; 24(5):496–499
^ Chaudieu I, Vignon J, Chicheportiche M, Kamenka JM, Trouiller G, Chicheportiche R. Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs. Pharmacology Biochemistry and Behaviour. 1989 Mar;32(3):699–705.
^ Olney J, Labruyere J, Price M (1989). "Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs". Science 244 (4910): 1360–2. doi:10.1126/science.2660263. PMID 2660263.
^ Hargreaves R, Hill R, Iversen L (1994). "Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology". Acta Neurochir Suppl (Wien) 60: 15–9. PMID 7976530.
^ Jansen, Karl. Ketamine: Dreams and Realities. MAPS, 2004. ISBN 0966001974
^ Erowid DXM Vault : Response to "The Bad News Isn't In": Please Pass The Crow, by William E. White
^ Reynolds, Lindsay M.; Susan M. Cochran, Brian J. Morris, Judith A. Pratt and Gavin P. Reynolds (March 1, 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. PMID 15653257.
^ Murray JB (May 2002). "Phencyclidine (PCP): a dangerous drug, but useful in schizophrenia research". J Psychol 136 (3): 319–27. PMID 12206280.
^ ^a ^b Diaz, Jaime. How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall, 1996.
^ AJ Giannini. Drugs of Abuse--Second Edition. Los Angeles, Practice Management Information Corp.,1997,pg. 126. ISBN 1-57066-053-0.
^ "Big Lurch Ate His Girlfriend" (video). Liveleak. 18 Feb 2008. http://www.liveleak.com/view?i=b08_1203391329. Retrieved 16 Sept 2009.
^ "Bakersfield dad accused of biting out son's eye". May 15, 2009. http://www.bakersfield.com/news/local/x339729128/Bakersfield-dad-accused-of-biting-out-sons-eye.
^ ^a ^b ^c ^d Helman RS, Habal R (October 6, 2008). "Phencyclidine Toxicity". eMedicine. http://www.emedicine.com/med/TOPIC1813.HTM. Retrieved on November 3, 2008.
^ ^a ^b ^c ^d Olmedo R (2002). "Chapter 69: Phencyclidine and ketamine". in Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS (eds.). Goldfrank's Toxicologic Emergencies. New York: McGraw-Hill. pp. 1034–41. ISBN 0-07-136001-8. http://books.google.com/books?id=HVYyRsuUEc0C&pg=PA1041. Retrieved on November 3, 2008 through Google Book Search.
^ ^a ^b ^c Milhorn HT (April 1991). "Diagnosis and management of phencyclidine intoxication". American Family Physician 43 (4): 1293–302. PMID 2008817.
^ Giannini AJ. Price WA. PCP: Management of acute intoxication. Medical Times. 1985;113(9):43-49
^ Giannini AJ, Eighan MS, Loiselle RH, Giannini MC (April 1984). "Comparison of haloperidol and chlorpromazine in the treatment of phencyclidine psychosis". Journal of Clinical Pharmacology 24 (4): 202–4. PMID 6725621. http://jcp.sagepub.com/cgi/pmidlookup?view=long&pmid=6725621.

[edit] External links

[0] Maisto, Stephen A.; Mark Galizio, Gerard Joseph Connors (2004). Drug Use and Abuse. Thompson Wadsworth. ISBN 0155085174.

[1] [www.cesar.umd.edu/cesar/drugs/pcp.pdf Development of PCP]

[2] Kapur, S. and P. Seeman. "NMDA receptor antagonists ketamine and PCP have direct effects on the dopamine D2 and serotonin 5-HT2receptors¾implications for models of schizophrenia" Molecular Psychiatry. 7(8): 837–844 (2002)

[3] 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. PMID 6535849.

[4] 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. PMID 6815700.

[5] PCP synthesis and effects: table of contents

[6] Itzhak Y, Kalir A, Weissman BA, Cohen S. New analgesic drugs derived from phencyclidine. Journal of Medicinal Chemistry. 1981; 24(5):496–499

[7] Chaudieu I, Vignon J, Chicheportiche M, Kamenka JM, Trouiller G, Chicheportiche R. Role of the aromatic group in the inhibition of phencyclidine binding and dopamine uptake by PCP analogs. Pharmacology Biochemistry and Behaviour. 1989 Mar;32(3):699–705.

[8] Olney J, Labruyere J, Price M (1989). "Pathological changes induced in cerebrocortical neurons by phencyclidine and related drugs". Science 244 (4910): 1360–2. doi:10.1126/science.2660263. PMID 2660263.

[9] Hargreaves R, Hill R, Iversen L (1994). "Neuroprotective NMDA antagonists: the controversy over their potential for adverse effects on cortical neuronal morphology". Acta Neurochir Suppl (Wien) 60: 15–9. PMID 7976530.

[10] Jansen, Karl. Ketamine: Dreams and Realities. MAPS, 2004. ISBN 0966001974

[11] Erowid DXM Vault : Response to "The Bad News Isn't In": Please Pass The Crow, by William E. White

[psychotic_PCP_rats-12] Reynolds, Lindsay M.; Susan M. Cochran, Brian J. Morris, Judith A. Pratt and Gavin P. Reynolds (March 1, 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. PMID 15653257.

[13] Murray JB (May 2002). "Phencyclidine (PCP): a dangerous drug, but useful in schizophrenia research". J Psychol 136 (3): 319–27. PMID 12206280.

[Diaz-14] Diaz, Jaime. How Drugs Influence Behavior. Englewood Cliffs: Prentice Hall, 1996.

[15] AJ Giannini. Drugs of Abuse--Second Edition. Los Angeles, Practice Management Information Corp.,1997,pg. 126. ISBN 1-57066-053-0.

[16] "Big Lurch Ate His Girlfriend" (video). Liveleak. 18 Feb 2008. http://www.liveleak.com/view?i=b08_1203391329. Retrieved 16 Sept 2009.

[Bakersfield-17] "Bakersfield dad accused of biting out son's eye". May 15, 2009. http://www.bakersfield.com/news/local/x339729128/Bakersfield-dad-accused-of-biting-out-sons-eye.

[eMedicine-18] Helman RS, Habal R (October 6, 2008). "Phencyclidine Toxicity". eMedicine. http://www.emedicine.com/med/TOPIC1813.HTM. Retrieved on November 3, 2008.

[Goldfrank-19] Olmedo R (2002). "Chapter 69: Phencyclidine and ketamine". in Goldfrank LR, Flomenbaum NE, Lewin NA, Howland MA, Hoffman RS, Nelson LS (eds.). Goldfrank's Toxicologic Emergencies. New York: McGraw-Hill. pp. 1034–41. ISBN 0-07-136001-8. http://books.google.com/books?id=HVYyRsuUEc0C&pg=PA1041. Retrieved on November 3, 2008 through Google Book Search.

[Milhorn-20] Milhorn HT (April 1991). "Diagnosis and management of phencyclidine intoxication". American Family Physician 43 (4): 1293–302. PMID 2008817.

[21] Giannini AJ. Price WA. PCP: Management of acute intoxication. Medical Times. 1985;113(9):43-49

[22] Giannini AJ, Eighan MS, Loiselle RH, Giannini MC (April 1984). "Comparison of haloperidol and chlorpromazine in the treatment of phencyclidine psychosis". Journal of Clinical Pharmacology 24 (4): 202–4. PMID 6725621. http://jcp.sagepub.com/cgi/pmidlookup?view=long&pmid=6725621.

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