Original Author: Paul Perry, Ph.D, BCPP
Latest Reviser: Paul Perry, Ph.D, BCPP
Creation Date: 1996
Peer Review Status: Internally Peer Reviewed
Phencyclidine (PCP) was synthesized by the Parke-Davis pharmaceutical company and initially patented in 1958 as an intravenous general anesthetic (Sernyl). Although the agent was particularly beneficial due to its low potential for depressing respiration in therapeutic doses, its value was seriously questioned because patients emerging from anesthesia appeared agitated, disoriented, and delirious while often experiencing hallucinations. Because of these adverse effects, Parke-Davis discontinued all human testing in 1965. However, in 1967, phencyclidine became commercially available as a veterinary anesthetic (Sernylan). In 1978, Sernylan was withdrawn from the market, leaving illicit laboratories as the sole source of PCP. The first reports of the illicit use of PCP originated from the Haight-Ashbury District of San Francisco in 1967 where the drug was being sold as the "PeaCe Pill." Because of a series of "bad trips," the use of the "Peace Pill" ceased in that area within a year. However, the number of case reports describing acute psychotic reactions and acute organic brain syndromes or delirium implicating PCP as the precipitant increased in other areas (Luisada and Brown 1976). The drug is now widely available on the "street" in the form of capsules, liquids, and various colored tablets or powders, as well as in leaf mixtures for smoking with parsley, tobacco, cloves, mint, or marijuana. Normally, PCP occurs as a white crystalline powder which rapidly dissolves in water or alcohol.
The infamous reputation attributed to PCP by inexperienced users seems to have resulted in the distribution of the drug under a wide variety of "street" names as well as the marketing practice of misrepresenting this agent for other more commonly sought street drugs (Burns and Lerner 1976, Fauman et al 1976). In addition to the pseudonyms, "PCP" and "PeaCe Pill," phencyclidine is sold on the street as "Hog," "Angel Dust," "Angel Mist," "DOA," "Sheets" and numerous other exotic names. When misrepresented, phencyclidine is usually marketed as THC, mescaline, peyote, methamphetamine, and LSD (Lundberg et al 1976).
PRESENTATION
Acute PCP Toxicity
Acute organic brain syndromes resulting from usually smoking, snorting, or ingesting of "low" 5 mg or less doses of PCP may appear within minutes and continue from 1 to 72 hours but more typically from four to six hours (Bakker and Amini 1961, Burns and Lerner 1975, Burns and Lerner 1976, Dorand 1977, Eastman and Cohen 1975, Fauman et al 1976, Johnstone et al 1978, Liden et al 1975, Luby et al 1959, Lundberg et al 1976, Morgenstern et al 1962, Rainey and Crowder 1975, Reynolds 1976). Symptoms often began as a cataleptic state with catatonic rigidity. Mild agitation and excitement may ensue where subjects experience depersonalization, changes in body image, diplopia, feeling of loneliness, paresthesias, tremulousness, analgesia, and other generalized sensory disturbances. Often the individual will appear to be inebriated while demonstrating euphoria, decreased concentration, drowsiness, confusion, ataxia, and slurring of speech. In addition, nausea, vomiting, and, later, a dysphoric mood may accompany the syndrome, thereby enhancing the often encountered, unpleasant sensations associated with PCP use. These undesirable symptoms are usually associated with higher doses taken by mouth, injection, or snorting. The presence of abdominal cramps, hematemesis, and diarrhea may be a result of by-products which were not completely separated during the illicit synthesis of PCP (Cohen 1977).
Physical exam may reveal a diminished or absent response to pin-prick as well as other sensory impairment (taste, visual, and auditory). Systolic and diastolic blood pressure is usually elevated, although it may fluctuate from normal to moderately elevated levels. This is often accompanied by other sympathetic effects such as flushing, diaphoresis, and tachycardia. Ophthalmologic effects include horizontal and vertical nystagmus and pupils of variable size but with normal light reflex. Other signs that might be present include hyperthermia, ptosis, excess salivation, and hyperactive deep tendon reflexes (Burns and Lerner 1975, Burns and Lerner 1976, Cohen 1977, Dorand 1977, Johnstone et al 1959, Liden et al 1975, Luby et al 1959, McMahon et al 1978, Meyer et al 1959, Pollard et al 1960, Rainey and Crowder 1975).
Somatic complaints commonly encountered after ingestion of purportedly large doses of phencyclidine include anesthesia, repetitive motor movement, muscle rigidity, myclonus, and unawareness of temperature changes (Burns and Lerner 1976, Fauman et al 1976, Liden et al 1975, Rainey and Crowder 1975).
McCarron et al (1981) evaluated 1000 PCP intoxications at the time of the first examination in the ER. Of these cases 403 were multiple drug intoxications with alcohol (223) and marijuana (151) being the most commonly involved agents. Table 1 lists the incidence of the adverse effects observed in these patients.
PCP - Psychotic Episodes
Psychiatric symptoms associated with the larger doses include social withdrawal, hostility, ideas of reference, auditory and visual hallucinations, and delusions characterized by grandiosity, paranoia, religiosity, or other content (Bakker and Amini 1961, Burns and Lerner 1975, Burns and Lerner 1976, Cohen 1977, Dorand 1977, Fauman et al 1976, Johnstone et al 1959, Liden et al 1975, Luby et al 1959, Meyer et al 1959, Pollard et al 1960, Rainey and Crowder 1975). An absence of hallucinations has been claimed to differentiate PCP intoxications from those caused by LSD, mescaline, and other "hallucinogens." To the contrary, however, hallucinations are frequently experienced following large doses of phencyclidine (McCarron et al 1981).
Individuals often present with deficits in the conceptual disorganization, neologisms, thought blocking, word salad, echolalia, proverb interpretation, disruption of sequential thinking, stuporous or excited catatonia, unpredictability, aimless running, and insomnia followed by irritability and depression. The syndrome may require from one day to several weeks for resolution.
Physical exam obtained after extremely high doses of phencyclidine may indicate the presence of tachy or brady arrhythmias, high or low extremes of blood pressure, muscle rigidity, decerebrate or opisthotonic posturing, depressed deep tendon reflexes, rhabdomyolysis, generalized seizures, prolonged coma, and death (Burns and Lerner 1975, Burns and Lerner 1976, Cogen et al 1978, Showalter and Thornton 1977).
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TABLE 1: Incidence of Adverse Effect in 1000 PCP Acute Intoxications (McCarron et al 1981) |
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Finding |
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Hallmarks |
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Nystagmus |
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Hypertension |
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Sensorium |
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Alert and oriented |
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Acute brain syndrome |
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Unconscious |
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Lethargy/stupor |
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Behavior |
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Violent |
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Agitated |
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Bizarre |
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Hallucinating delusional |
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Mute and staring |
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Nudism |
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No behavioral effects |
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Motor Signs |
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Generalized rigidity |
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Grand mal seizures |
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Localized dystonias |
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Facial grimacing |
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Athetosis |
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Cholinergic Signs |
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Profuse diaphoresis |
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Bronchospasm |
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Pupils < 1 mm |
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Hypersalivation |
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Bronchorrhea |
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Anticholinergic Signs |
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Pupils > 4 mm |
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Urinary retention |
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Abnormal Vital Signs |
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Tachycardia |
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Hypothermia |
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Apnea respiratory arrest |
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Hyperthermia |
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Cardiac arrest |
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Chronologically, severe toxicities often initially present as a comatose state which can persist for a period of several days. An organic state usually follows which may last as long as 15 days and, in a small fraction of users, be followed by a psychosis persisting for several weeks (Rainey and Crowder 1975). This is usually followed by a three- to five-day period during which the patient's mental status normalizes (Luisada and Brown 1976).
Occasionally, intoxicated patients may be neither comatose nor organic but have initial symptoms compatible with a psychosis. Luisada (1977) describes three phases in the recovery process from acute psychotic reactions. The initial phase is characterized by misperceptions, paranoia, confusion, and a tendency towards violence which makes them a danger to others. After about five days patients enter a second phase in which they are restless but not hyperactive or hostile and are now cooperative. The last phase occurring after about 10 days is marked by rapid reintegration of the personality and is often accompanied by amnesia for the early events of the psychosis. Although recovery is usually complete, like LSD, patients may experience recurrences that are not drug-induced. Patients often do not present for admission until several days after ingestion, giving a history of confusion, paranoid ideation, insomnia, and restlessness while exhibiting hyperactivity, tension, and aggression (Luisada and Brown 1976).
Chronic schizophrenic patients administered phencyclidine under controlled conditions experience stimulation of affect and an intensified thought disorder (Luby et al 1959). The symptomatology of these patients resembled an acute exacerbation of their illness which was still evident one month after the initial ingestion.
Cohen (1977) reports that repeated use of PCP may result in organic brain damage probably as a result of intracerebral hemorrhages and that during other intervals, long-term chronic users may demonstrate memory gaps, some disorientation, visual disturbances, and difficulty with speech probably as a result of hypertensive encephalopathies.
PCP - Induced Depression
PCP-induced depression is a very frequent condition that many clinicians miss, particularly when it comes after a PCP-precipitated psychotic reaction. The clinician discharges the patients without any follow-up plan not that severe dysphoria may occur in which the patient is predisposed to developing suicidal ideation and may use drugs such as cocaine or amphetamines to relieve the depression. A paradox of PCP is that it does produce a energizing, numbing, consciousness-altering effect which the patient perceives as antidepressant. Clinically, it appears that many of these patients have prolonged cerebral dysfunction as well as depression. The complaints of memory impairment subside as the depression clears. Patients note that they feel less depressed as they think their "brain damage" is clearing. It is difficult to determine whether the dysphoria clears as the cerebral dysfunction itself clears or as their concern over the cerebral dysfunction wanes because they are no longer dysphoric and can now concentrate. PCP-induced depression can last from one day to several months and can follow any of the preceding stages. The patient can be in PCP acute toxicity and clear with no problem, or go into PCP toxic psychosis, or into a PCP-precipitated psychotic episode, and then have prolonged PCP-induced depression. Or, the patient can wake up from a PCP acute toxic reaction and go right into a prolonged depression. Laboratory results will show blood and urine both negative for PCP (Smith and Wesson 1980).
PCP - Effects of Long-Term Use
Chronic PCP users often engage in two to three day "runs" or "sprees" analogous to those observed in the amphetamine or cocaine abusers. The action phase characterized by insomnia and anorexia is followed by a reaction phase marked by prolonged sleep from which the abuser often awakens feeling disoriented and dysphoric. The "runs" may be repeated as often as two to four times per month (Cox et al 1983).
Chronic users often have complaints of impairment of thinking and memory, especially recent memory that can last for several months following discontinuation of the abuse pattern. Persistent speech difficulties (e.g., stuttering, inability to articulate, and inability to speak at all) have been reported. Additional chronic problems include severe anxiety and depression with suicidal ideation. Psychosocial problems include social withdrawal, social isolation, divorce, unemployment, and disrupted education (Cox et al 1983).
TOXICOLOGY
Fatalities have occurred from doses in the range of 150-200 mg. The clinical presentation includes coma, status epilepticus, acute hypertensive crisis, cerebrovascular hemorrhages and renal failure. The concomitant presence of CNS depressant (e.g., hypnotics and/or opiates) increases the risk of respiratory arrest (Cox et al 1983).
MANAGEMENT
Important phencyclidine-related medical problems that have ultimately resulted in fatal complications include respiratory depression, tonic-clonic seizures, renal failure, and elevated blood pressure. Prompt institution of appropriate supportive treatment of these problems along with periodic monitoring of vital functions is essential.
Generally, the behavioral effects of PCP are the most commonly encountered severe complication and appear to be responsible for the majority of deaths, i.e., drownings (Burns and Lerner 1978, Reynolds 1976), automobile accidents (Reynolds 1976), and suicides (Burns and Lerner 1976, Burns and Lerner 1978), associated with PCP ingestion. Therefore, individuals displaying dramatic psychotomimetic effects resulting from phencyclidine ingestion should be treated as a psychiatric emergency. Although most cases usually do not present in this manner, those that do should be hospitalized Also, due to the high percentage of AMA discharges, institution or commitment proceedings is advised (Luisada and Brown 1976). Goals of this approach are to prevent injury to the patient and others, decrease environmental stimuli and agitation, and ameliorate the psychotic reaction.
There is no clinically tested antidote available to antagonize the psychotomimetic symptomatology induced by PCP. Phenothiazine and butyrophenone antipsychotics, sedative/hypnotics such as diazepam, physostigmine, verapamil and ECT have been recommended for use in PCP intoxications.
Antipsychotics. Giannini et al (1984) treated 20 males admitted for treatment of PCP psychosis confirmed by urine screen. Patients were randomly assigned to receive haloperidol 5 mg IM q 20 minutes or chlorpromazine IM q 20 minutes for a total of three doses. According to BPRS scores, both antipsychotics were found effective in treating PCP psychosis. However, haloperidol produced significantly more improvement than chlorpromazine in ratings of anxiety, conceptual disorganization, mannerisms/posturing, unusual thought content, and visual hallucinations. Both drugs were equally efficacious in improving auditory hallucinations and suspiciousness. Chlorpromazine was rated more effective than haloperidol in reducing tension. Overall, haloperidol was more effective than chlorpromazine in treating the patients.
Physostigmine. PCP is known to possess anticholinergic properties, which might explain some of the features of the intoxication. Physostigmine, an acetylcholinesterase inhibitor has been suggested as a possible partial antidote for PCP. Castellani et al (1982) studied seven patients with clinical evidence of acute PCP intoxication confirmed by urine analysis. The patients were disoriented, obtunded, delusional, disorganized in their thinking and manifested nystagmus. Physostigmine 2 mg IM repeated in 15 minutes prn was administered. One patient demonstrated remarkable improvement after one dose while the remaining six patients showed "overall clinical improvement" following the second dose that persisted for approximately two hours. Despite, these preliminary findings clinicians are advised to be cautious when utilizing physostigmine in acute PCP intoxicated patients.
Verapamil. Price et al (1986) described a 29 year old male who had ingested PCP 3 hours prior to admission. The patient's mental status was marked by confusion, hostility, paranoia, agitation, and depersonalization. The physical examination noted a blood pressure of 160/90 mm Hg, a pulse of 120 beats/min, horizontal nystagmus, and clonic jerks of the upper extremities. The patient was treated with verapamil 5 mg IV every 20 min for three doses. The signs and symptoms of intoxication cleared within 20 minutes of the last injection. The authors proposed a mechanism of action whereby the calcium channel blocker inhibited the presynaptic release of neurotransmitters. Additionally, the cerebral artery vasospasm purported to cause PCP-induced hallucinations was reversed by the verapamil.
ECT. Two case reports described ECT as being of benefit in antipsychotic resistant PCP intoxications. Rosen et al (1984) described four cases of PCP intoxications. All four patients had little or no response to antipsychotics that included haloperidol to a 100 mg/d, chlorpromazine 1500 mg/d, trifluoperazine to 8 mg/d, thioridazine 200 mg/d, and thiothixene 25 mg/d. The first patient responded to six bilateral ECTs and then five ECTs in a subsequent PCP intoxication. The second and third patients responded to four and nine ECTs respectively while the last patient refused ECT and was discharged from the hospital in a psychotic state. Grover et al (1986) reported a case of a 21 year old male who ingested PCP two weeks prior to admission. The patient was described as aggressive and assaultive with auditory and visual hallucinations, paranoid delusions, and feelings of depersonalization. The patient failed to respond to haloperidol up to 200 mg/d, fluphenazine decanoate 37.5 mg every 4-7 days and diazepam 40 mg/d. The patient finally responded to a course of ten ECTs that was supplemented by fluphenazine decanoate 25 mg every 10 to 14 days.
Ion Trapping. The half-life of the drug in the body is ordinarily approximately three days, but it can be significantly reduced by acidifying the urine and employing continuous gastric suction, because the drug is first a weak base and secondly because large amounts of PCP are secreted in the gastric juices and can be reabsorbed in the small intestine (Peterson and Stillman 1978). Successful utilization of the method "Ion Trapping" to hasten the excretion of phencyclidine has been reported (Aronow and Done 1978). The goals of lowering the urine pH are to shorten the duration of psychosis and hospitalization as well as to alleviate any concomitant medical problems that might be present. This method appears to offer an important supplement to the gross therapeutic approach for PCP intoxications once emergency supportive measures have been initiated for the medical and behavioral complications. The effect of acidifying the urine on PCP clearance has been demonstrated by Done et al (1980). With the urine pH above 6.5 the clearance rate was 7.0 ml/min; at a pH between 5 to 6.5 the pH was 57 ml/min; at a pH of < 5,135 ml/min; and at a pH of < 5 and furosemide being administered 299 ml/min.
Many clinicians recommend sensory isolation to treat the behavioral effects while reserving medications for medical complications. Diminished psychotic activity has been demonstrated after a patient is placed in a secluded, quiet, dimly-lit room (Burns et al 1975, Rainey and Crowder 1975).
SUMMARY
Phencyclidine is an easily manufactured drug with an increasing illicit distribution and use in the United States. Due to its frequent misrepresentation, PCP should be suspected in patients with psychosis who report recent illicit drug use regardless of which drug is claimed to have been taken. Given these problems, it is important that the physician and pharmacist alike should be able to recognize the medical and behavioral manifestations associated with this drug so that prompt hospitalization and appropriate supportive therapy may be accomplished.
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