Phencyclidine: pharmacology and toxicology

Sections

Introduction
Pharmacology
Metabolism
Side effects
Clinical reports
Toxicity and antidotes
Summary
Acknowledgement
Bibliography

Details

Author: James C. MUNCH
Pages: 9 to 17
Creation Date: 1974/01/01

Phencyclidine: pharmacology and toxicology

Ph.D.F.A.C.C James C. MUNCH
Former member of the Advisory Committee, United States Bureau of Narcotics.

Introduction

Phencyclidine (PCP), (1-(1-phenylcyclohexyl)-piperidine) is a white crystalline powder, molecular weight 243.38. It is legally manufactured under British. Patent No. 836,083, issued in 1960 and United States Patent No. 3,097,136, assigned by Godefroi to Parke, Davis and Co. (Maddox, et al, 1965; Merck Index, 1968).

Solutions of the hydrochloride were licitly used on man as a short-acting analgesic and for general anesthesia under the trade name Sernyl (Chen et al, 1959; McCarthy, 1972). Because of post-operative side effects, however, the regulation was later changed under the New Drug Application to permit the manufacture by Philips Roxane of a solution under the trade name Sernylan (Gouge, 1972), serving as an analgesic for monkeys and other primates. Recent United States legislation (Comprehensive Drug Abuse Prevention, 1970) classified PCP together with barbiturates and lysergide.

PCP was detected by extraction with an organic solvent from an aqueous solution; concentrations of 1:1,000 give colour reactions with gold bromide and with potassium permanganate. It is quantitatively determined by thin layer or by gas chromatography with mass spectrography (Clarke, 1959: Hammar et al, 1969; Finkle et al, 1971; Law et al, 1971; Lindgren et al, 1969; Schnoll et al, 1971). As mentioned before, PCP is licitly produced in the form of a solution which is being sold for veterinary use (Long et al, 1969).

According to seizure reports illicit products containing PCP are sold only in a solid state as tablets or capsules. Apparently the first illicit powder produced by some (unknown) foreign manufacturer was smuggled into the San Francisco area under the nickname "PeaCe Pill" or "THC" about the year 1966. Sprinkled on dried parsley or low-grade marihuana for smoking, it was called "Angel Dust" (Davis et al, 1968; Greene, 1971; Lindgren et al, 1969; Lofholm, 1968; Meyers et al, 1967; Reed et al, 1972). Spreading among the hippies and other users of hallucinogenic drugs along the West Coast, it rapidly crossed the American continent to appear in New York City as "Hog" (Davis et al, 1968; Greene, 1971; Lindgren et al, 1969). Many clandestine laboratories began to produce an impure powder in which the impurities are more toxic than PCP itself (Lampe, 1971), leading to hallucinations, coma and death.

PCP has become the primary constituent of "street drugs", either as the only ingredient of a capsule or in admixture with amphetamine, cocaine, mescaline, THC and LSD, to name a few. Physicians have been warned that in cases necessitating emergency treatment other than the alleged substances may be involved (Anon, 1970; Anon, 1970; Anon, 1971; Anon, 1971; Anon, 1971; Anon, 1971; Medical Letter, 1971). PCP was detected in 184 of 237 samples of "street drugs" submitted for identification to the Department of Chemistry, University of Kansas, between August 1970 and January 1972:(2 of the 57 samples sold as LSD did in fact contain LSD; 17 of the 45 samples sold as mescaline; 2 of the 16 samples sold as psilocybin; one of the samples alleged to be MDA; one of the 5 samples sold as "Hawaian Woodrose"; 2 of the 8 declared to be psychedelics; 10 of the 11 samples sold as THC, and 2 of the 34 samples undesignated (Hart et al, 1972).

Similarly, PCP was detected in 195 samples of "street drugs" during a period of two months: 16 were sold as LSD; 5 of the 10 samples as THC; 5 as psilocybin, and some as mescaline (Pharm. Chem. Labs., 1973). In Philadelphia it was found that PCP was contained in 8 of the 20 samples sold as mescaline, and that other combinations contained cocaine, LSD or amphetamine (Schnoll et al., 1972; Schnoll et al 1971).

Pharmacology

Wide species differences were observed in animal studies; mice and rats developed excitation followed by depression, whereas other species showed only depression. Great variations in dosage were required to produce analgesia and anesthesia (Chen et al, 1959). As a local anesthetic PCP was twice as effective as procaine, half as potent as cocaine. Toxic doses produced bradycardia and clonic convulsions, followed by death from respiratory failure. Resistance to electric shock in 200-400 gm trained rats increased as doses were increased from 2 mg/kg to 8 mg/kg subcutaneously. Chlorpromazine blocked the response to PCP (Domino et al, 1960). These observations were confirmed and extended by other investigators (Carr, 1959; Laurence, 1966; Rice, 1972; Usdin et al, 1972), who in their studies on animals and human subjects used it as an analgesic and a general anesthetic. Oral administration to caged wild birds showed LD 50 values ranging from 5.6 mg/kg for bobtail grackles to 75 mg/kg for mallard ducks, 133 mg/kg for sparrows and ring-neck pheasants to 237 mg/kg for starlings and pigeons (Schafer, 1972).

Metabolism

For metabolic studies a lot of tagged PCP was prepared in which C 14 was placed in the phenyl ring, and tritium in the 3.4-positions in the piperidine ring. Monkeys rapidly metabolized the tagged material to both mono- and dihydroxy piperidine derivatives, which were then conjugated and excreted in the urine. Other species of animals varied in metabolic pathways; cats excreted PCP unchanged. Human subjects excreted chiefly the mono-hydroxy-piperidine complex. The metabolites were weaker in action, and not considered to contribute to the pharmacological response evoked by PCP (Ober et al, 1963).

 

Range of hydroxy-derivative excreted:

Species

Dihydroxy-per cent

Mono-hydroxy-per cent

Humans
0
29-68
Mice
25-50
29-68
Rats
75
5-14
Pigeons
75
5-14
Cats
0
5-14
Dogs
0
85-100
Monkeys
25-50
29-68
Sheep
25-50
29-68
Cows
0
85-100
Horses
0
85-100

In another more detailed study on urinary excretion (Hucker, 1970) marked species differences were obtained in urinary excretion of PCP and the hydroxypiperidine derivatives, as shown in the table on p. 10. The unchanged PCP was more active and more toxic than the hydroxypiperidine metabolites.

Side effects

Effects on the skin: Diaphoresis, flushing (Neubauer et al, 1966); numbness and rash (Clarke, 1959).

Gastrointestinal tract: Nausea in 50 of 55 mental patients after intravenous injections of 0.01 to 0.10 mg/kg; occasional nausea and vomiting in half the children receiving PCP (Lister, 1966); and in 12 normal volunteers after injection of 0.075 mg/kg to 0.10 mg/ kg (Davies et al, 1960). Prolonged studies in 15 Nigerian hospitals where PCP was used as a general anesthetic revealed that post-operative nausea and vomiting occurred in 5 out of 500 patients (Gool et al, 1964), and in 1 out of 51 patients after administration of 0.06 mg/kg of PCP intravenously (Greifenstein et al, 1958). Excessive salivation has also been reported (Cutting, 1967).

Nervous system: Following intravenous injections of 0.10 mg/kg or larger doses, and after oral administration of 10 mg or more, PCP has been reported to produce analgesia, anesthesia, delirium, catalepsy, hallucinations and general depression of the central nervous system. Specific comments include: greater disorientation and stronger depersonalization than after LSD, increased schizophrenic-like symptoms (Carr, 1959); centrally mediated schizophreno-mimetic action (Domino, 1964); "introceptive sensory blocking agent" (Gool et al, 1964); excessive verbalization, delirium (Lear, 1968); "acting primarily on the sensory cortex, brain-stem and thalamus" (Marshman et al, 1971); sensory deprivation (Meyer et al, 1959); "dissociative anesthesia" (Ponder, 1971); "akinetic mutism". (Rodin et al, 1959); disturbances of proprioceptive feedback (Rosenbaum et al, 1959); hallucinogenic reactions as to a "psychodysleptic drug" (Stein, 1973; Szara, 1967).

Circulation: Wide differences are noted in animals and in patients, partly but not entirely dose-related. Hypotension and bradycardia developed in some species of animals (Chen et al, 1959). No effects were claimed in 735 patients after PCP administration (Gool et al, 1964). Increases in systolic and diastolic pressures, associated with tachycardia and increased pulse rate have been reported in other studies on man (Gershon et al, 1960; Greifenstein et al, 1958; Helrich et al, 1964; Lister, 1966; Marshman et al, 1971; Neubauer et al, 1966).

Respiration: After injection of toxic doses to animals, death followed from respiratory failure (Chen et al, 1959). In patients minimal changes were observed in the rate and depth of respiration (Bakker et al, 1961; Ban et al, 1961; Cutting, 1967; Davies et al, 1963; Domino, 1964; Gershon et al, 1960; Gool et al, 1964; Greifenstein et al, 1958; Marshman et al, 1971). Intravenous injections of 0.06 mg/kg to 2 volunteers produced decreases in volume of 100 ml and 700 ml; however, in 5 other volunteers the same dose produced increases of 200 ml to 700 ml; after administration of 0.25 mg/kg all 7 volunteers showed increases ranging from 100 ml to 1,900 ml, averaging 1,140 ml (Greifenstein, et al, 1958).

Muscular system: Clonic convulsions were observed in animals (Chen et al, 1959). Poor or no muscular relaxation was stressed (Cutting, 1967; Domino, 1964; Greifenstein et al, 1958). Other effects reported in man (as well as some species of animals) included: convulsions (Domino, 1964; Lampe, 1971); catatonia or catalepsy (Chen et al, 1959; Clarke, 1959; Lindgren et al, 1969; Ponder, 1971; Rodin et al, 1959); vertigo (Luby et al, 1959); "slapping gait" after 0.01 mg/kg to 0.10 mg/kg; staggering, ataxia, changed tension reflexes (Bodi et al, 1959; Luby et al, 1959; Meyer et al, 1959); purposeless rolling of the head, restlessness, limb movements in 32 of 735 postoperative patients (Gool et al, 1960); altered tapping speed (Ban et al, 1961; Davies et al, 1960).

Vision: Diplopia (Davies et al, 1960; Gershon et al, 1960; Greifenstein et al, 1958; Luby et al, 1959); ptosis (Meyer et al, 1959); vertical and lateral nystagmus (Ban et al, 1961; Davies et al, 1960; Domino, 1964; Gershon et al, 1960; Greifenstein et al, 1958; Luby et al, 1959; Meyer et al, 1959; Pollard et al, 1960); decreased reaction to light (Meyer et al, 1959; Morganstern et al, 1962; Neubauer et al, 1966).

Clinical reports

Normal volunteers: After intravenous injections of 5 to 12 mg of PCP to 7 volunteers, apathy and interference with proprioceptive functions were noted, relating to both subjective and objective performances (Bakker et al, 1961). Injections of 0.075 mg/kg to 0.10 mg/kg to 12 subjects changed their body image, impaired learning and recall of words; apathy, drowsiness and hostility developed (Davies et al, 1960). A dose of 0.10 mg/kg administered to 18 subjects produced reactions within 3 minutes, lasting for 1 hour: apathy, depression, disturbed body image, hostility; toxic symptoms followed doses over 20 mg., corresponding to 0.25 mg/kg (Luby et al, 1959).

Oral administration of 7.5 mg of PCP to 18 subjects led to increased visual acuity, touch threshold, position and sensory thresholds for 2 hours, which then returned to the pre-administration values (Morganstern et al, 1962). In another study oral doses of 10 mg produced mental confusion, delirium, hallucinations, apathy and a feeling of isolation in a group under observation (Domino, 1964). An oral dose of 10 mg of PCP given 8 healthy college graduates over 21 years of age produced only slight changes while in a test chamber; however, on emerging, distorted perception and prolonged reaction time were noted; proprioceptive senses were especially depressed, by comparison no effect developed in a double-blind study after administration of a placebo (Pollard et al, 1960).

Patients: Following intravenous injections of 0.01 to 0.10 mg/kg schizophrenic-like symptoms increased as did the reaction time; it was concluded that "side effects preclude clinical use in humans" (Ban et al, 1961). In 735 patients observed in 15 Nigerian hospitals intravenously administered doses from 0.275 mg/kg to 0.44 mg/kg produced anesthesia of short duration, averaging 25 minutes; the principal disadvantage reported was postoperative confusion and hallucinations. Even though 77 per cent of the entire group showed no complications, the authors concluded that "routine use for adults is unacceptable" (Gool et al, 1964). In another study on 51 patients 0.25 mg/kg caused mild excitement in 12 of them; severe excitement in 3, and disorientation in 13 patients for 3 to 18 hours. After trials on 64 patients, 10 developed unmanageable severe maniac behaviour, 3 became violent, and 1 patient was semiconscious for 10 days. In 6 surgical patients, EEG showed slow t waves after administration of 2 to 3 mg intravenously, and after administration of 7 to 10 mg, slowed temporal and parietal region responses. The authors concluded that PCP was "worth further study" (Greifenstein et al, 1958). Doses of 10 mg administered postoperatively produced excellent relief from pain and muscle disturbances; 20 mg prolonged hallucinations and psychoses, especially in young adults, and excitement lasting up to 12 hours; so the authors concluded: "inadvisable as sole agent for anesthesia" (Johnstone et al, 1959). After doses of 2.0 to 2.5 mg/kg severe reactions developed, such as loss of speech for 15 minutes, followed by excessive talking: irritability lasting for 1 to 2 hours, acting as an "interoceptive sensory blocking agent" (Lambert, 1964).

Oral doses of 0.25 mg administered three times daily for several weeks, then increased to 0.5 mg three times daily, improved the state of health of 25 of 32 psychoneurotics, but only 3 became asymptomatic; 29 were maintained at the larger dose level without adverse side effects: the authors conclude that PCP was "only moderately effective" (Bodi et al, 1959). Patients became calm, with a feeling of "utter nothingness" during treatment (Cohen et al, 1960; 1962).

Successful anesthesia developed in 93 of the 100 patients, but 11 showed postoperative disturbances, so PCP was considered as "clinically unacceptable" (Helrich et al, 1964). Another investigator (Lister, 1966) listed a high incidence of toxic effects; overstimulation of the central nervous system, marked irritation, unpleasant nausea, and salivation in half of the patients, so that PCP was "withdrawn from clinical use". Analgesia produced by PCP was adequate in 78 per cent of children treated for burns, but half developed severe crying spells and hallucinations (Muir et al, 1961). In other studies apathy and feelings of isolation, especially characteristic reaction of schizophrenic patients, were reported (Freedman et al, 1967; Kaufman et al, 1969).

At a conference on environmental mutagens it was reported that PCP has been found to be teratogenic; "Users of phencyclidine had increased rates of fetal loss, decreased fertility, extensive chromosome breakage, and increased presence of a small chromosome that resembled the Philadelphia chromosome. Their offspring had an abnormally large incidence of spinal defects, limb reduction anomalies, triploidy, and trisomy" (Walker, 1974).

Toxicity and antidotes

The range from the effective to the toxic dose is narrow (Clarke, 1959). PCP is relatively more toxic to the aged (Cooper, 1968; Medical Letter, 1970). Missynthesis of PCP produces byproducts that are very toxic, causing abdominal cramps, bloody emesis, coma and respiratory death (Lampe, 1971). Two women "procured" and ate a chicken which had been treated experimentally with PCP; both developed marked mental symptoms but survived (Poison Information Service, 1967). No deaths from ingestion of PCP were reported until 1971 (Marshman et al, 1969; 1971); a fatal case appeared in the literature the next year (Reed et al, 1972). A 19-year old man was found dead in his room: his clothing contained 10 packets of PCP, each assaying between 2.0 and 3.5 mg of PCP. Visceral congestion and posterior lobe pneumonia were found at autopsy. Analyses confirmed the presence of 70 mg of PCP in the gastric contents; the urine contained 3.8 mg, the liver 0.09 mg, the lungs 0.04 mg, the blood 0.03 mg, the brain and the kidney 0.01 mg per cent. No other drug was detected in the stomach contents, urine or liver. In another poison case, another 19-year old male was hospitalized after taking 50 tablets, each 110 mg containing 97 per cent pure PCP. The blood and urine values on admission were within normal limits; blood pressure 200/80. Treated with "benign neglect" for several days, the blood pressure fell to 120/80. Then treatment with 100 mg of chlorpromazine four times daily, and hydrocortisone sodium succinate daily over the next 10 days led to recovery. The patient showed aggressive hostility during treatment (Stein, 1973). Similar reports have been published on two children by Liden et al, 1973, and by Rainey et al, 1974.

Haloperidol has been suggested to modify PCP actions and effects (Gool et al, 1964; Helrich, 1964). The administration of succinates has been advocated as antidotes for both the central and peripheral effects of PCP; one patient rapidly developed mental clearing following oral administration (Gershon et al, 1960). However another study (Neubauer et al, 1966) failed to confirm the value of the succinates. A warning has been issued against the use of atropine or the belladonna alkaloids as definitely contraindicated (Taylor et al, 1970). No other reports of antidotal therapy have been found in a search of the literature.

Summary

Phencyclidine (PCP) was introduced in 1960 as an analgesic and general anesthetic for man, but too many severe adverse effects developed, including hallucinations, manic depressive and schizophrinic-like symptoms. A solution of the hydrochloride has been approved for anesthesia of monkeys and other primates. PCP powder from clandestine sources has become a primary constituent of the "street drugs" illegally used by narcotic addicts, displacing heroin to a large extent. It may be found in dilute powder form alone, or admixed with LSD, amphetamine, cocaine, tetrahydrocannabinol (THC), mescaline or other drugs. Users of "street drugs" have experienced violent mental disturbances. Antidotes are still to be developed; one death has been reported to date. PCP is properly classed as a "dangerous drug".

Acknowledgement

The author wishes to thank Mrs. Jane Zack, Librarian, Drug Enforcement Administration. Washington, D.C.; Dr. D. A. McCarthy, Director Pharmacological Research, Parke Davis and Co., Ann Arbor, Mich, and Dr. Hardin Gouge, Director Pharmaceutical Research, Philips Roxane, St. Joseph, Mo. for their great help in bibliographic exploration of PCP.

(Originally presented at Eighth Inter-American Conference on Toxicology, and Occupational Medicine, Miami, Florida, 8-11 July, 1973.)

Bibliography

Anonymous. Illicit drugs found to be "mislabeled" as well as to vary widely in potency. Hospital Tribune, 4, 1,18, 20 April 1970.

____________On Brand "X" Acid, STASH Capsules, 2, 1-2, Oct. 1970.

____________Acid Rescue Test Results. Acid Rescue, lnc., July, 1971.

____________Many 'Street Drugs' are Phony American Druggist, 164, 53-54, 1971.

____________Buyers of Street Drugs get Animal Tranquilizers. HSMHA Health Reports, 86, 790, 1971.

____________Street Groups Analyze Drugs as Police Close One Eye. Mescaline Everything But... Drugs and Drug Education Letter, 2, 1,7, 1971.

____________Drug I. D. Program to Take the Guess Work out of "Street Psychedelicts". Milwaukee Med. Soc. Times, 44, 9, 1971.

Bakker, C. B. and F.B. Amini. Observations on the Psychotomimetic Effects of Sernyl. Comp. Psychiatr., 2, 269-280, 1961.

Ban, T. A., J. J. Lehrens, and H. E. Lehmann. Observations on the Action of Sernyl - A New Psychiatric Drug. Can. Psychiatr. Assoc. J., 6, 150-157, 1961.

Bodi, T., I. Share, H. Levy, and J. H. Moyer. Clinical Trial of Phencyclidine (Sernyl) in Patients with Psychoneurosis. Antibiotic Med., 6, 79-84, 1959.

Carr, C. J. The Pharmacology of the Psychomimetic Agents. Internat. Record Med., 172, 702-716, 1959.

Cheek, F. E., S. Newell and M. Joffe. Deceptions in the Illicit Drug Market. Science, 167, 1276, 1970.

Chen, G., C. R. Ensor, D. Russell and B. Bohner. The Pharmacology of 1-(1-phenylcyclohexyl)-piperidine Hydrochloride. J. Pharmacol Exp. Therap., 127, 241-250, 1959.

Clarke, E. C. G. Isolation and Identification of Drugs, Pharmaceuticals, Body Fluids and Post-Mortem Material. p. 481, Pharmaceutical Press, London, 1959.

Cohen, B. D., E. D. Luby, G. Rosenbaum and J. S. Gottlieb. Combined Sernyl and Sensory Deprivation. Comp. Psychiatr., 1, 345-348, 1960.

Cohen, B. D., G. Rosenbaum, E. D. Luby and J. S. Gottlieb. Comparison of Phencyclidine Hydrochloride (Sernyl) with Other Drugs. Arch. Gen. Psychiatr., 6, 395-401, 1962.

Comprehensive Drug Abuse, Prevention and Control Act of 1970: Public Law 91-513, H.R. 18 583, 27 Oct., 1970. Section 202 (c), Schedule III (b) (7) Phencyclidine.

Cooper, P. Current aspects of toxicology. Pharm. J., 200, 595-598, 1968.

Cutting, W. C. Handbook of Pharmacology, 3rd Ed., 491-492, Appleton-Century-Crofts, New York, 1967.

Davies, B. M. Phencyclidine: Its Use in Psychiatry; in R. A. Crocket, A.W. Sanadison and E. D. S. Walk. Proc. Quart. Meeting Royal Medico-Psychological Assoc., 42-47, Lewis, Ltd., London, 1963.

Davies, B. M. and H. R. Beech. The Effect of 1-Arylcyclohexylamine (Sernyl) on Twelve Normal Volunteers. J. Mental Science, 106, 912-924, 1960.

Davis, F., and L. Munoz. Heads and Freaks: Patterns and Meanings of Drug Use Among Hippies. J. Health Soc. Behaviour, 9, 156-164, 1968.

Domino, E. G. Neurobiology of Phencyclidine (Sernyl), A Drug with an Unusual Spectrum of Pharmacological Activity. Internat. Rev. Neurobiology, 6, 303-347, 1964.

Domino, E.G., S. Gershon and J. Olarin. Phencyclidine. J. Neuropsychiatr., 2, 311-317, 1960.

Finkle, B. S., D. M. Taylor and E. J. Bonelli. A GC-MS Reference Data System for the Identification of Drugs of Abuse. J. Chromatogr. Science, 9, 393, 1971; ibid, 10, 312333, 1972.

Freedman, A.M. and H. 1. Kaplan. Comprehensive Textbook of Psychiatry. Williams and Wilkins, Baltimore, 1967.

Gershon, S. and J. Olarin. JB 329 - A New Psychomimetic: Its Antagonism to Tetrahydroaminoacridin and Its Comparison with LSD, Mescaline and Sernyl. J. Neuropsychiatr., 1, 283-293, 1960.

Gool, R. Y. and H. L. Clarke. Anesthesia for Under-doctor Areas. Anesthesia, 18, 265-270, 1964.

Gouge, H. E., Director of Pharmaceutical Research, Philips Roxane, Inc., St. Joseph, Mo. Personal Communication, 1 Dec. 1972.

Greene, D. S. A. Charlie's Awful "Trip". National Observer, 10, 1, 16, 1971.

Greifenstein, F. E., M. DeVault, J. Yoshitake and J. E. Gajewski. 1-Arylcyclohexylamine for Anesthesia, Current Res. Anesthesia, Analgesia. 37, 283-294, 1958.

Hammar, C. G., B. Holmstedt and J. E. Lindgren. The Combination of Gas Chromatography and Mass Spectrometry in the Identification of Drugs and Metabolites. Advances Pharmacol. Chemother., 7, 53-89, 1969.

Hart, J. B., J. G. McChesney, M. Greif and G. Schulz. Composition of Illicit Drugs and the Use of Drug Analysis in Abuse Abatement. J. Psychedelic Drugs, 5, 83-88, Fall 1972.

Helrich, M. and J. M. Atwood. Modification of Sernyl Anesthesia with Haloperidol. Anesthesia, Analg. Current Res., 43, 471-474, 1964.

Hucker, H. B. Species Differences in Drug Metabolism. Annual Rev. Pharmacol., 10, 99-118, 1970.

Johnstone, M. E., V. Evans and S. Baigel. Sernyl (CI-395) in Clinical Anesthesia. British J. Anesthesia, 31, 433-439, 1959.

Kaufman, J., J. F. Allen and L. J. West. Runaways, Hippies and Marijuana. American J. Psychiatr., 126, 717-720, 1969.

Lambert, C. The Use of Intravenous Phencyclidine (Sernyl) in the Treatment of Neuroses. Neuropsychopharmacol., 3, 365-369, 1964.

Lampe, M. Drugs: Information for Crisis Treatment. STASH, Beloit, 5, 1971.

Laurence, D. R. Clinical Pharmacology, 3rd Ed., 318, Little, Brown Co., Boston, 1966.

Law, N. C., V. Anndahl and H. M. Fales. Identification of Dangerous Drugs by Mass Spectrometry. Clin. Chim. Acta, 32, 221-228, 1971.

Lear, E. Intravenous Anesthesia: A Survey of Newer Agents. Anesthesia, Analg., 47, 154-159, 1968.

Liden, C. B., F. H. Lovejoy and C. Costello. Phencyclidine (Sernylan) Poisoning. J. Pediatrics, 83, 844-845, 1973.

Lindgren, J. E., C. G. Hammar, R. Heasley and B. Holmstedt. The Chemical Identity of "HOG"; A "New" Hallucinogen. American J. Pharmacy, 141, 86-90, 1969.

Lister, R. E. The Toxicity of Some of our Newer Narcotic Analgesics. J. Pharmacy Pharmacol., 18, 364-382, 1966.

Lofholm, P. "Turning On". J. American Pharm. Assoc., 8, 106, 1968.

Long, R. E. and R. P. Penna. Drugs of Abuse, in Drug Abuse Education, 2nd Ed, American Pharm. Assoc., 6-15, 1969.

Luby, E. D., B. Cohen, G. Rosenbaum, J. Gottlieb and R. Kelley. Study of a new Schizophrenomimetic Drug - Sernyl. Arch. Neurol. Psychiatr., 81, 363-369, 1959.

Maddox, V. H., E. F. Godefroi and R. F. Parcell. The Synthesis of Phencyclidine and other Aryl Cyclohexylamines. J. Med. Chem., 8, 230-235, 1965.

Marshman, J. A. and R. J. Gibbins. The Credibility Gap in the Illicit Drug Market. Addiction, 16, 22-25, 1969.

Marshman, V. H. and L. Adair. Phencyclidine (PCP): A Street Drug in the Laboratory. Addiction, 18, 30-35, 1971.

McCarthy, D. A., Director, Pharmacological Research, Parke, Davis and Co., Ann Arbor, Mich. Personal Communication, 8 Nov. 1972.

Medical Letter Drugs and Therapy. Diagnosis and Management of Reactions to Drug Abuse. 12, 65-68, 7 Aug., 1970.

Merck Index, 8th Ed., Phencyclidine, 806, Merck, Rayway, N.J., 1968.

Meyer, J. S., F. Greifenstein and M. DeVault. Pharmacological Effects of Sernyl: A New Drug showing Symptoms of Sensory Deprivation: Neurological, Electroencephalographic and Pharmacological Effects. J. Nervous Dis., 129, 54-61, 1959.

Meyers, F. H., A. J. Rose and D. E. Smith. Incidents involving the Haight-Ashbury Population and some Uncommonly Used Drugs. J. Psychiatr., Drugs, 1, 139-146, 1967.

Morganstern, F. S., H. R. Beech and B.M. Davies. An Investigation of Drug-induced Sensory Disturbances. Psychopharmacology, 3, 195-201, 1962.

Muir, B. J., V. Evans and J. J. Mulcahy. Phencyclidine. British J. Anesthesia, 33, 51, 1961.

Neubauer, H., D. M. Sundland and S. Gershon. Sernyl, Ditran and Their Antagonists: Succinates and THA. Internat. J. Neuropsychiatr., 2, 218-222, 1966.

Ober, R. E., G. W. Gwynn, T. Chang, D. A. McCarthy and Glazko A. J. Metabolism of l-(1-phenylcyclohexyl)-piperidine (Sernyl). Fed. Proc., 22, 539, 1963.

Pharm. Chem. Laboratories, Palo Alto, Calif. Analysis Anonymous. The Attack, 4, FallWinter 1973.

Poisons Information Service: Phencyclidine et al. Fourth Ann. Report for the Year Ending Dec. 31, 1967., British Med. J., 4, 248, 1968.

Pollard, J. C., C. Bakker, L. Uhr and D. F. Feuerfile. Controlled Sensory Input: A Note on the Technic of Drug Evaluation, with a Preliminary Report on a Comparative Study of Sernyl, Psilocybin and LSD-25. Comprehensive Psychiatry, 1, 377-380, 1960.

Phencyclidine: pharmacology and toxicology 17

Ponder, J. W. Dissociative Anesthesia. J. American Med. Assoc., 215, 1126-1130, 1971,

Rainey, J. M. and M. K. Crowder. Phencyclidine. New England J. Med., 290, 466-467, 1974.

Reed, A., and A.W. Kane. Phencyclidine (PCP): Another Illicit Psychedelic Drug. J. Psychedelic Drugs, 5, 8-12, Fall 1972.

Reed, D., R. H. Gravey and P. R. Sedgwick. A Fatal Case Involving Phencyclidine. Bull. Internat. Assoc. Forensic Toxicologists, 7, June 1972.

Rice, J. UPS and DOWNS Drugging and Doping. 214, Macmillan Co., New York, 1972.

Rodin, E. A., E. D. Luby and J. S. Meyer. Electroencephalographic Findings Associated with Sernyl Infusions. Electroenceph. Neuropsychiatr., 11, 796-798, 1959.

Rosenbaum, G., B. D. Cohen, E. D. Luby, J. S. Gottlieb and D. Yelen. Comparison of Sernyl with other Drugs. Simulation of Schizophrenic Performance with Sernyl, LSD-25, and Amobarbital (Amytal) Sodium. I. Attention, motor function and proprioception. Arch. Gen. Psychiatr., 1, 651-656, 1959.

Schafer, E. W. The Acute Oral Toxicity of 369 Pesticidal, Pharmaceutical and other Chemicals to Wild Birds. Toxicology and Appli. Pharmacology, 21, 315-330, 1972.

Schnoll, S. H., R. D. Cohn and W. H. Vogel. A Rapid Thin Layer Chromatographic Screening Procedure for Various Abused Psychotropic Agents. J. Psychedelic Drugs, 5, 75-78, Fall 1972.

Schnoll, S. H. and W. H. Vogel. Analysis of 'Street Drugs'. New England J. Med., 284, 791-795, 1971.

Stein, J. I. Phencyclidine Induced Psychosis. The Need to Avoid Unnecessary Sensory Influx. Military Med., 138, 590-591, 1973.

Szara, S. The Hallucinogenic Drugs - Curse or Blessing? American J. Psychiatr., 123, 1513-1518, 1967.

Taylor, R., J. I. Maurer and J. R. Tinklenberg. Management of Bad 'Trips' in an Evolving Drug Scene. J. American Med. Assoc., 231, 422-425, 1970.

Usdin, E. and D. Effron. Psychiatric Drugs and Related Compounds. 2nd Ed., 72-9074, DHEW (HSM) NIMH, Washington, D.C., 1972.

Walker, F. Phencyclidine. First Internat. Conference Environmental Mutagens, Ashomar, Calif., Sept. 1973: Science, 1974, 184, 189.