Phencyclidine (PCP)-Related Psychiatric Disorders

AUTHOR AND EDITOR INFORMATION

Author: Alan D Schmetzer, MD, Professor and Vice-Chair for Education, Department of Psychiatry, Director of Residency Training, Indiana University School of MedicineAlan D Schmetzer is a member of the following medical societies: American Medical Association and American Psychiatric AssociationCoauthor(s): Roland McGrath, MD, Chairman, Professor, Department of Emergency Medicine, Indiana University School of MedicineEditors: Barry I Liskow, MD, Vice Chairman, Director Psychiatry Residency Program, Professor, Department of Psychiatry, University of Kansas Medical School; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Iqbal Ahmed, MBBS, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii; Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin; Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MAAuthor and Editor Disclosure Synonyms and related keywords: phencyclidine-related psychiatric disorders, PCP, angel dust, crystal, hog, krystal joint, KJ, mintweed, rocket fuel, delta-9-tetrahydrocannabinol, THC, N-methyl-D-aspartate, NMDA, lysergic acid diethylamide, LSD, substance-induced psychosis, 1-(phenylcyclidine) piperidine

INTRODUCTION

Background
Phencyclidine (PCP) was originally developed as an anesthetic agent; however, the agitation that some people developed following such anesthesia quickly led to abandonment of PCP for this indication. Another name for phencyclidine is 1-(phenylcyclidine) piperidine, which probably gave rise to the PCP acronym. PCP was marketed for a time as an animal anesthetic and was studied in animal models of schizophrenia. More recently, PCP-like compounds have been investigated for use in treating brain ischemia. PCP is known to produce a syndrome in humans who are not schizophrenic that is similar to schizophrenia, and it will worsen the psychotic symptoms in people who have a schizophrenic illness. PCP is an N-methyl-D-aspartate (NMDA) antagonist; thus, it blocks the action of glutamate and aspartate, which are amino acids that are excitatory in the CNS. PCP is also highly anticholinergic in nature.
Abuse of PCP seemed to peak in the late 1970s. It has occasional resurgence in abuse. Today, the usual route of administration is smoking, often as an additive to marijuana cigarettes. Because it is inexpensive to produce, PCP is sometimes sold on the streets as delta-9-tetrahydrocannabinol (THC), the active ingredient in marijuana; lysergic acid diethylamide (LSD); or other exotic designer hallucinogens. PCP can be smoked, ingested as a pill, snorted intranasally, or injected intravenously.
PCP first came to the attention of emergency department physicians and psychiatric emergency room physicians in California and New York during the 1960s. At that time, it was ingested in pill form (the "PeaCePill"). During the early 1970s, PCP became available as a white powder, which could also be put into a solution. It could then be insufflated, ingested, or smoked on tobacco or marijuana, or even on mint leaves, parsley, or other leafy materials. The creation of this powdered form led to an increase in use during the 1970s.
Since then, the level of use has waxed and waned. An increase in indicators of use occurred from 1972 to the late 1970s, and then a decline in use occurred until the early 1980s, when use once again increased. Since then, use has declined again. Historically, PCP has gone by many street names, including angel dust, crystal, hog, krystal joint (KJ), mintweed, supergrass, killer weed, embalming fluid, ozone, and rocket fuel. Some of these street names obviously refer to the combination of PCP and marijuana. When PCP is combined with cocaine, the resultant concoction is sometimes called "space base" or "tragic magic."
Pathophysiology
PCP is a sympathomimetic dissociative anesthetic. The term dissociative means that the user feels his or her mind is separated from the body. This can be very upsetting to some people, especially first-time users who are not expecting it. PCP is often classified with the hallucinogens. Chemically, it is an arylcycloalkylamine. At present, at least 20 analogues and metabolites of PCP have been identified within this chemical family. The current understanding is that it acts as a noncompetitive antagonist at the NMDA excitatory amino acid receptor channel complex. PCP binds to a site within this channel system, thereby physically preventing sodium, calcium, and potassium ions from moving across the cell membrane. This prevention of ion movement results in decreased neuronal firing; however, PCP cannot bind within a channel unless the channel initially is opened by glutamate, NMDA, or an NMDA agonist.
That PCP may cause neurotoxicity is a matter of some concern, but little scientific evidence for CNS damage presently exists, even in chronic users. Evidence for behavioral toxicity exists, however, and numerous deaths from suicide, homicide, and accidents related to bizarre behavior have been reported in those intoxicated with PCP.
PCP is absorbed rapidly whether it is smoked, ingested orally, inhaled intranasally, or injected into the veins. PCP hydroxylated metabolites are excreted mainly in the urine. Primary intoxication lasts from 4-6 hours, but the behavioral toxicities noted above may last for as long as several weeks. The lasting presence of behavioral toxicities is thought to be due to storage of PCP within fatty tissues of the body because PCP is highly lipophilic.
The effects depend on dose, with lower blood levels in the range of 20-30 ng/mL usually causing sedation, irritability, hyperactivity, impaired attention, and mood elevation. As serum levels rise above 30 ng/mL, ataxia, psychosis, analgesia, paresthesia, and mood lability may occur. The range in which paranoia and aggressive behaviors are most likely to occur is 30-100 ng/mL. When serum levels are higher than 100 ng/mL, patients become stuporous, hyperreflexive, and hypertensive, and, ultimately, this may lead to seizures, coma, and death. Note that serum levels with PCP are relatively unreliable, so judgment always should be based on the specific patient's clinical status.
In terms of metabolism, PCP has a large volume of distribution due to its lipid solubility. This is the reason for the relative lack of correlation between serum or urine values and clinical manifestations. It is metabolized primarily in the liver, with renal secretion primarily of the hydroxylase metabolites; hence, the failure of urinary acidification to have much effect in speeding detoxification. In addition, alkalinization is the recommended treatment for the myoglobinuria that can accompany PCP intoxication, so acidification is both irrational and in conflict with current treatment recommendations.
Frequency
United States
Abuse of PCP began in the 1960s and peaked in the late 1970s. In 1978, the National Annual High School Senior and Young Adult Survey found that 12.8% of high school seniors had used PCP. Actually, more may have used PCP without realizing it because a 1975 survey showed that 91% of the street substances sold as THC and hallucinogens, such as mescaline and LSD, actually contained PCP. Overall, abuse of this substance has decreased in the United States, and a 1988 survey found that only 2.9% of high school seniors had ever knowingly used PCP. In the United States, quite a lot of regional variability in the abuse of PCP exists.
International
International use of this substance also is regional. The use of all drugs, including PCP, in Canada is similar to use in the United States, except that the relative percentages usually are smaller in Canada. Mexico has an unusually large number of available indigenous hallucinogens, such as peyote cacti, Psilocybe mushrooms, and psychedelic morning glory seeds (ololiuqui); therefore, artificial hallucinogens are not as much in demand. In the rest of the world, various preferred substances of abuse are regionally determined. PCP use has never been as much of a problem globally as it was in the United States in the 1960s and 1970s.
Mortality/Morbidity
Death from PCP usually is caused by overdose (serum levels >100 ng/mL), suicide while under the influence of the drug, or accidental death due to bizarre behavior during intoxication or withdrawal. Those intoxicated with PCP also have been reported to be more likely to be violent, and they have committed homicides. Nonlethal physical injuries also are a possibility when a person is intoxicated on PCP because it does have anesthetic properties. Intoxicated individuals may not realize how badly injured they are.
Race
PCP seems to have been abused more often by members of inner-city minority groups than by members of the middle class. The reasons for this are not clear.
Sex
In terms of sexual distribution, PCP is more likely to be knowingly abused by males, but this is true of many substances that are abused.
Age
PCP is a drug primarily abused by children, adolescents, and young adults. Older users tend to have started using when they were young.

CLINICAL

History
If a patient, or any family or friends who are present, can tell the physician reliably what the patient has used, it is obviously of help. Asking specifically about PCP can produce better information some of the time. However, since PCP is sold under other names, the history may be inaccurate.
Physical
The Mental Status Examination is the most important area of abnormality in PCP intoxication. A great deal of variability frequently occurs in the mental status findings with these patients, and, at times, their results may appear normal or nearly so, while a few (20 or so) minutes later, obvious psychosis and possible evidence of dangerousness to self and/or others will appear. Therefore, one must document the hallucinations, delusions, and mood-related issues (such as suicidal and homicidal thinking) carefully and with reference to the time of the examination because changes may occur. Orientation and mentation are also important to document because PCP produces a drug-induced delirium, which is the cause of the psychosis. Look for typical anticholinergic findings because PCP is a highly anticholinergic substance. Elevations in vital signs often are present for this reason, with tests of blood pressure and pulse, as well as temperature, likely to present abnormal findings.
The physical examination may be difficult because these patients usually are not very cooperative, but, if possible, look for decreased deep tendon reflexes and nystagmus or other evidence of coordination loss. Keep in mind that PCP is related to anesthetics, and the findings will be similar to those observed as people descend into anesthesia, which again is dose dependent.
Physical examination findings of PCP-intoxicated individuals vary in accord with the serum level of the drug.
Lower blood levels (20-30 ng/mL) cause a picture of sedation, irritability, hyperactivity, impaired attention, and mood elevation.
As the level rises above 30 ng/mL, physical examination will show progressive levels of ataxia, paresthesias, and psychosis.
At 100 ng/mL, stimulant effects are noted most, with hypertension and hyperreflexia becoming more pronounced.
Above 100 ng/mL, stupor and seizures can occur. In this range, death is possible.

Causes
Risk factors for use of PCP include the following:
Male sex (72%)
African American (54%) or Hispanic ethnicity
Young adult age range (62% of people treated for PCP overdose are in the second decade of life)
Obviously, to ingest PCP, one must have access to this illicit substance, but it is fairly inexpensive and simple to synthesize and is thus relatively easy to obtain.
Sometimes, people who are intoxicated on PCP do not know that PCP is the drug they have received. Rather, the buyer of the drug is often told that PCP is something more exotic, such as THC or a designer drug.

DIFFERENTIALS

Amphetamine-Related Psychiatric DisordersBipolar Affective DisorderCocaine-Related Psychiatric DisordersDeliriumDelirium TremensDepressionHypertensionHypertension, MalignantHyperthyroidismNeuroleptic Malignant SyndromeSchizophreniaStimulants
Other Problems to be Considered
Abuse of multiple drugs

WORKUP

Lab Studies
Always order a urine drug screen for a person with agitation or psychosis, unless the patient is well known to the treating physician and staff. Even then, if the clinical picture seems at all different from the usual presentation, a drug screen may be useful. Serum levels of specific drugs also may be available in some emergency departments. However, be aware that specific urine or serum levels may have little correlation with clinical manifestations.
Phencyclidine is excreted in the urine, both in unchanged form and as conjugated metabolites. The usual laboratory test for PCP is an enzyme immunoassay technique that detects both PCP and the analog, 1-[1-(2-thienyl)-cyclohexyl]-piperidine (TCP). This is a qualitative test; that is, it tells whether the drug is present or absent. Gas chromatography/mass spectometry (GC/MS), as with other drugs, is the confirmatory test providing the highest confidence level for PCP.
Because rhabdomyolysis is a potential complication, serum enzyme levels may be useful, particularly skeletal muscle creatine phosphokinase (CPK).

Imaging Studies
Imaging studies have not proved helpful in PCP-induced psychosis. Eventually, however, it is hoped that diagnostic clues to PCP psychosis may be found from more complex imaging techniques.

Other Tests
No other tests help identify PCP intoxication.

TREATMENT

Medical Care
Medical care of these patients must consider both the variability of their presentations and the high risk of violence to self and/or others during the time of drug-induced psychosis. These patients often must be admitted for safety for this reason. In the intensive care area, where these patients may be admitted in the occasion of large overdoses, treatment is aimed primarily at decreased absorption by induced emesis and/or gastric lavage and charcoal. In medical or psychiatric settings, restraints may be necessary to protect these patients from harming themselves or other patients and staff members. Use of a benzodiazepine or an antipsychotic medicine, particularly those that are not highly anticholinergic, often will help to reduce risk, but remember that risk will not be eliminated.
Once the diagnosis has been established, the treatment of choice generally is considered benzodiazepine tranquilization. Typically, diazepam is used first, unless liver damage is present. In case of liver damage, other benzodiazepines that do not undergo oxidative metabolism by the liver, such as lorazepam, can be administered. Starting at 10 mg, titrate diazepam until the patient is sufficiently sedated. Monitor respiratory status. Treatment with diazepam often treats aggressiveness, psychotic symptoms, hypertension, and tachycardia.
If psychosis remains problematic, consider the addition of an antipsychotic. In the past, this would often have been haloperidol, but now that injectable ziprasidone and quick-dissolving olanzapine and risperidone are available, these will undoubtedly be used more frequently. If antipsychotics are necessary, use one that is low in anticholinergic activity because of the anticholinergic properties of PCP itself.
In the past, acidification of the urine was performed using ammonium chloride, but this generally is not recommended currently because of the possibility of renal toxicity, metabolic acidosis, and increased risk of rhabdomyolysis.
Keep the possibility of seizures, coma, and death in mind with higher (>100 ng/mL) levels of PCP and be prepared to support respiration if needed.
Following acute medical stabilization, psychiatric care is indicated. The patient may require transfer to a psychiatric unit if psychosis is not under adequate control.
Evaluate for chemical dependence once the patient is no longer psychotic, and refer him or her for treatment if appropriate. This is a serious and potentially fatal drug of abuse. Regard PCP intoxication and abuse with the same seriousness as any other potentially life-threatening condition.

Consultations
Obtain psychiatric consultation if the patient is in the emergency department or a general medical unit. If a separate consultation team for addictive disorders is available, ask that group to evaluate the patient. Likewise, if the patient is in a psychiatric unit or in the psychiatry emergency department, consultation with internal medicine and/or addiction subspecialists may be indicated.
Activity
Patients may require seclusion and/or restraint while acutely intoxicated with PCP. Patients who require seclusion or restraint can be highly violent and confused, and they often complain of very disturbing thoughts about harming themselves or others. Current regulations require frequent monitoring of all persons in seclusion or restraint, including a face-to-face assessment by an independent, licensed practitioner within 1 hour of initiation. Suicide and assault precautions are usually necessary. When ataxia is present, do not allow ambulation without assistance.

FOLLOW-UP

Further Inpatient Care
PCP-induced psychosis may be very difficult to treat, and, sometimes, psychotic symptoms may persist for 6 weeks or more. In such cases, transfer to a long-term psychiatric hospital may be required in some areas because of a shortage of acute psychiatric beds or managed care restrictions. Usually, managed care companies do not approve inpatient substance dependence rehabilitation at present, but an intensive outpatient program certainly may be justified for a person who uses PCP.
Rhabdomyolysis may require more prolonged medical hospitalization in the rare instances when this complication occurs.

Further Outpatient Care
Psychiatric follow-up care and follow-up care (if the patient is dependent) in addiction treatment usually is needed.
The goal of psychiatric treatment is to assess when the person can safely be weaned from an antipsychotic, if it has been needed. Generally, most patients can be weaned from antipsychotics necessitated by PCP-induced psychosis within a 6-month period.
Extend addiction treatment until all goals have been met and the person is working with a personal program for continued abstinence.
Occasionally, additional booster addiction treatment may be needed because all people with addictions have some tendency to relapse.

In/Out Patient Meds
Unlike the opiates and their antagonists, no phencyclidine antagonist currently is available.

Transfer
Transfer to a psychiatric unit after acute medical stabilization often is necessary. The need for this can be assessed by a psychiatric consultant.
Transfer to a long-term psychiatric hospital from an acute psychiatric unit may be necessary, depending on the local interactions of state hospitals and acute units.
Once the acute medical and psychiatric symptoms have been adequately treated, always provide patients with the opportunity to transfer to some type of chemical dependency treatment program, because the tendency of PCP users to return to the drug has been noted often in the literature.

Deterrence/Prevention
In all disorders of drug abuse and dependence, the earlier the intervention, the better the outcome.
No solid proof exists that treatment of PCP dependence in a chemical dependency program will succeed, perhaps because people tend to decrease use with age. However, encouraging a patient to begin (or resume) a substance dependence treatment program is worthwhile.

Complications
A number of patients who abuse hallucinogenic drugs eventually are diagnosed with another psychiatric disorder, such as depression, anxiety disorder, or schizophrenia. Whether these drugs cause these other disorders is not clear, and, in any case, multiple factors contribute to the major psychiatric syndromes. Additionally, sound evidence indicates that people who have a psychiatric disorder have a higher likelihood of abusing drugs, so this may simply be an issue of which condition is diagnosed first.
PCP can cause a prolonged psychosis, and users are subject to so-called flashbacks, and either or both of these may be misdiagnosed as a comorbid psychiatric condition.
Other longer-term complications that can arise from acute PCP intoxication include rhabdomyolysis with resulting renal disease, as well as complications of acute hypertension. Some evidence indicates that prolonged use of PCP may cause prolonged symptoms of confusion, but this is not yet clear.
Weak evidence supports the existence of a withdrawal syndrome. Animal studies show a withdrawal syndrome, and reports exist in the literature of prolonged users of PCP showing a dysphoria and intense craving for the drug, which have been described as a withdrawal syndrome. Abuse of PCP is not known to cause liver disease, and no evidence suggests that PCP causes a Parkinson-like syndrome such as that observed with designer drugs such as 1-methyl1-4-phenyl-1,2,3,6-tetrahydropyridine (MTPT).

Prognosis
Because 62% of people abusing PCP are aged 20-29 years, most people clearly stop using PCP once they have passed young adulthood. Thus, for most people, the long-term prognosis probably is good.

Patient Education
PCP is a drug that has a significant likelihood of adverse effects. Point out these effects during drug education opportunities.
For excellent patient education resources, visit eMedicine's Substance Abuse Center. Also, see eMedicine's patient education article Drug Dependence and Abuse.

MISCELLANEOUS

Medical/Legal Pitfalls
A physician may have to consider involuntary hospitalization and treatment in patients using PCP, because these patients sometimes do not have the capacity to make their own treatment decisions. Always document whether the patient appears medically competent to make such decisions.
These patients, as with anyone with a delirium, can wax and wane in the severity of their symptoms and confusion. It takes time to decide if improvement will continue enough to justify release of such patients.

Special Concerns
Some physicians suggest warning the patient and family about the possibility of later psychiatric disorders so that they can catch symptoms early. On the other hand, others suggest against warning the patient and family about possible future psychiatric disorders because most people have no such complications. Until a better understanding of the reason(s) for any higher likelihood of a comorbid psychiatric diagnosis is developed, the decision about whether to discuss this issue or not is best left to the discretion of the individual clinician.
Consider abuse of other drugs as possible in causing the signs and symptoms observed in a person with a chemical abuse or dependence history. This especially is true with PCP, which sometimes is sprinkled or sprayed on other intoxicants, such as marijuana.

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