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AM. J. DRUG ALCOHOL ABUSE, 6(3), pp. 273-281 (1979).
Is phencyclidine (FCP) Abuse Associated with Organic Mental Impairment? ALBERT S. CARLIN,* Ph.D. Deparrment of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle, Washington 98 195
IGOR GRANT, M.D. KENNETH M. ADAMS, Ph.D. Department of Psychiatry University of California San Diego School of Medicine Psychiatry Service Veterans Administration Hospital San Diego, California 92101
ROBERT REED, M.S. Department of Psychiatry Henry Ford Hospital Detroit, Michigan 48233 ABSTRACT The performance of sober (average length of abstinence = 27 months) phencyclidine (PCP) abusers on neuropsychological measures of organicity was compared to that of polydrug users who were not experienced with PCP,and to controls who were not. alcohol or drug abusers. Six of 12 P O users, five of 12 polydrug users, and none of the controls showed neuropsychological impairments. The deficits in PCP users occurred despite negative medical-neurological history, and even though the CTo whom requests for reprints should be sent.
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PCP group abused other drugs previously associated with neuropsychologicalimpairment less than the polydrug group. Deficiencies in abstracting and in perceptualmotor integrative abilities were noted. The results suggest the possibility that PCP abuse might be associated with neuropsychologicaldisturbance which persists for considerable time after PCP use ceases.
INTRODUCTION Phencyclidine (PCP, Sernyl, Sernylan, angel dust, crystal, hog), once considered by the drug-using subculture to be an undesirable substitute for “natural” hallucinogens such as mescaline or tetrahydrocannibinol (THC), has lately become a more accepted, even sought-after drug [l-31.Although the prevalence of untoward effects is unknown, clinical impression suggests that PCP may be responsible for a disproportionate share of toxic reactions to “street drugs” [ 1, 2,4-81. Short-term clinical problems associated with acute intoxication include behavioral disinhibition, depersonalization, sensory disturbance (including anesthesia), delirium, schizophreniform psychoses, paranoid state, stupor, and catatonic excitement [ l , 5, 61. Prolonged disturbances in mood, behavior, and thinking, lasting weeks to months after detoxification, have also been reported [5, 6, 81. In this regard Cohen [5] has observed that some PCP abusers manifested organic brain dysfunction, characterized by memory gaps, some disorientation, visual disturbances, and difficulty with speech, even when they were sober. To follow up this clinical observation, we performed detailed neuropsychological assessments with a group of chronic PCP abusers who were not acutely intoxicated, and compared their performance on measures of organicity to that of groups of non-PCP-using polydrug users and nondrug-abusing controls.
SUBJECTS AND METHODS Subjects Three groups of 12 subjects were examined. In Group 1 were persons who reported use of PCP. Group 2 consisted of multiple drug abusers who used no PCP. In Group 3 were social drinkers who used other drugs minimally or not at all. The average weekly use of various drugs, based on a detailed history for the preceding 10 years, is summarized in Table 1. The mean age for all subjects was 25.9 f 4.6 years and the mean education
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was 12.0 f 2.1 years completed. There were no significant between group differences in age (F = 0.45 for 2/33 d n or in education (F = 0.01 for 2/33 d a . In each group were 9 men and 3 women. Eleven of 12 in each drug group and all in the control group were Caucasian.
Method The PCP users were recruited by advertisement and personal contact in Seattle and San Diego. At initial contact the research teams performed a brief medical and drug use screening interview to ascertain that subjects were indeed PCP abusers, that they had been abstinent for at least 4 weeks, and that there was no medical history to suggest a neurological disorder unrelated to drug abuse. Subjects satisfying inclusion criteria were scheduled for neuropsychological examination and for a detailed interview regarding medical and drug use history. A urine sample to screen for psychoactive drugs, including PCP, was obtained midway during the examination. On average, these subjects had not taken any PCP in the past 27 months (range 1 month to 7 years). The non-PCP-using polydrug subjects and the nondrug-abusing comparison group were examined as part of the Collaborative Neuropsychological Study of Polydrug Users (CNSP) [ 9 ] . The polydrug users sought treatment at one of several polydrug treatment units across the country. As with the PCP users, these subjects were interviewed concerning their medical and drug abuse histories, and were not entered into the study if there was evidence of preexisting (predrug use) neurological illness. Neuropsychological examinations were performed only after the polydrug users were abstinent for at least 3 weeks. The nondrug-abusing comparison group were medical center and university employees who matched the polydrug and PCP subjects for age, education, sex, and ethnicity. To be included in this group, drug and alcohol use by these subjects had to be below criterion levels. These criteria have been reported previously [ 9 ] . The neuropsychological examination consisted of the Halstead-Reitan Battery and MMPI. The components of this battery and the rationale for its use in assessing brain functions in drug abusing groups are contained in an earlier publication [9]. Beyond comparing the performance of groups on various tests by means of ANOVA and chi square as appropriate, a clinician (IC) blind to group membership also scored the entire set of test results for each subject. Each NP protocol was assigned a score of 1 to 6 on the
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following clinical dimensions: attention, verbal-language skills, abstracting ability, perceptual-motor integrative skills, simple sensory functions, simple motor skills, and an overall global judgment of impairment. For some of the analyses, ratings of 1 to 3 were called “unimpaired” and ratings of 4 to 6, “impaired.”
RESULTS The drug use data presented in Table 1 are based on the 10-year cumulative converted to appropriate standards. All sedative hypnotic use was converted to equivalent dosages of pentobarbital, narcotics, and synthetic opiates to
Table 1. Average Weekly Drug Use of Subjects Based on lO-year History Group 1,
PCP users
Group 2, polydrug
Group3, Ffor conrols 2/33 d p
Post hoc
Ethanol (gf
27 3
188
115
-
CNS depressants (mg pentobarbital)
246
862
0
28
125
0.5
5.17*
1,2> 3
117
149
0
7.97**
1,2> 3
Other opiates (mg morphine) Hallucinogens (occasions of use)
13
39
0
9.75**
2 > 1,3
0
13.61**
Marijuana (occasions of u s )
17
11
1
8.55**
1, 2 > 3
561.88**
1 > 2,3
Central stimulants (mg dextroamphetamines) Heroin (mg morphine)
0.5
0.3
Phencyclidine (occasions of use)
1.1
0
0
Cigarettes (packs of 20)
3.5
6.1
2.8
0.37 22.84**
2>1>3
1>2 >3
1.7
aTo reduce variability, ANOVAS were performed on logarithmically transformed druguse figures - loglo (X+ 1). bNeuman Keuls. 2 > 1 > 3 indicates Group 2 scored significantly @ = .05) higher than Group 1, which in turn scored significantly higher than Group 3. CTengrams of ethanol is roughly equivalent to one 12-02 beer, one 4-02 glass of wine, or 1 shot of 80 proof whiskey. * p < .05. **p < .01.
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Table 2. Clinician’s Neuropsychological Ratings
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PCP Neuropsych assessment
users, N = 12
Unimpaired: Above average Average Borderline
2 3
Impaired: Mildly impaired Moderately impaired Severely impaired
Polydrug users, N = 12
Controls N = 12
I
1
0 3 4
6 0 0
2 3 0
0 0 0
3 2
morphine and stimulants to dextroamphetamine. Analysis of variance (ANOVA) and Neuman-Keuls procedures carried out on these converted data revealed that except for hallucinogen and PCP use, the PCP group consumed equivalent or lesser amounts of drugs than did the polydrug group. The clinician’s global neuropsychological ratings are displayed in Table 2. Six PCP users, five polydrug users, and no controls received ratings in the impaired range. Because of small cell size, Categories 1, 2, and 3 were collapsed into an unimpaired category and 4, 5 , and 6 into an impaired category. The resulting 2 X 3 comparison reveals that the two drug groups and controls are significantly different (x2 = 8.12, p < .02, df = 2). The commonest specific deficiencies which contributed to a judgment of “impaired” were disturbances in abstracting ability and in handling of tasks requiring higher order perceptualmotor integrative skills. Selected results from the Halstead-Reitan Battery are presented in Table 3. For the sake of space, only WAIS summary scores are shown, and data from the aphasia screening and sensory-perceptual exams, on which there were no between-group differences, are omitted. Because the sample sizes were small and variability in many test scores was large, few significant differences emerged. In general, polydrug users scored worst, controls did best, and PCP users were intermediate in performance. Those test results which did separate groups tended to be supportive of the clinician’s judgment that the two drugusing groups were deficient in abstracting (e.g., categories test) and perceptualmotor IQ abilities. . The medical interview conducted with each subject inquired about 20 medical events and symptoms which, if they occurred, might raise the possibility that a person experienced neurological insult unrelated to drug abuse. The
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278 Table 3. Performance of Subjectson Selected Neuropsychologicaltests
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PCP users
Polydrug
SD
Mean
SD
Controls Mean SD
Ffor
Mean
108.3 107.3 108.3
13.9 13.4 12.3
104.8 101.0 103.3
17.8 12.7 14.9
116.2 113.8 116.2
2.01 3.31* 3.28*
2/33df
WAIS:
Verbal IQ Perf. IQ
Full IQ
10.0 10.3 9.3
Halstead tests: Impairment index Category (errors) TPT total time TPT memory TIT location Speech (errors) Rhythm R Tapping L Tapping
34 46.0 10.3 7.6 4.3 5.1 25.4 48.2 44.2
.27 22.5 5.1 0.9 2.4 2.4 2.6 5.6 7.1
.32 .27 50.8 28.8 13.9 7.0 8.0 1.3 4.4 2.4 7.5 4.8 26.4 3.6 54.6 5.4 49.8 6.7
-13 .13 27.5 14.4 2.7 9.7 1.2 8.3 2.5 5.7 2.3 4.8 1.2 28.7 4.3 52.8 3.9 47.4
2.98 3.545 2.24 0.99 1.16 2.38 4.72** 4.9 ** 2.56+
Other tests: Trails A (sec) Trails B (sec) R name Writing (sec) L name writing (sec) R Grip @g) L Grip (kg)
25.3 59.7 7.7 12.1 43.8 42.9
11.1 19.9 6.6 3.6 16.2 14.9
30.8 78.3 6.3 13.7 45.6 42.9
12.8 42.2 2.3 4.6 17.8 17.5
21.3 54.8 5.9 9.8 48.3 44.8
5.0 18.4 2.7 2.4 16.1 16.3
2.56 2.26 0.56 3.41* 0.23 0.05
2.9
1.2
3.4
1.2
1.9
0.7
Clinician rating
6.29**
* p = .1. **p = .01. t p = .l.
groups differed on endorsement of only one event (hospitalization for overdose) and one symptom (complaints of frequent muscular weakness), more polydrug users reporting these in each instance. The entire subject pool was then divided into “at risk” (the subject said yes to at least one of nine medical items which could be directly related to neuropsychological risk, e.g., head injury with unconsciousness, prematurity) and “not at risk” groups. There was no relationship between medical risk status and neuropsychological impairment (Fisher’s Exact Test p = .288). Despite the request to abstain from drug use for 72 hours prior to testing five subjects produced urines contaminated by drugs. However, no statistically significant relationship was found between contaminated urine and impariment among the drugusing groups (Fisher’s Exact Test p > .lo). In addition, the
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examiners who were experienced in the observation of toxic states did not believe any of the subjects to be toxic during the testing.
DISCUSSION Prior to commenting on these results, it may be necessary to discuss whether the drug use differences between the study groups are meaningful. Can drug users’ self-reports be trusted? The answer must be a qualified yes. Although drug users may not be able or willing to reliably report their drug usage, there is no reason to believe that distortions would be systematic. Polydrug patients had no reason to underreport PCP or hallucinogen use, and PCP abusers had no reason to underreport depressant or opiate use. Another question which arises is the extent to which illicit phencyclidine is phencyclidine versus phencyclidine and impurities. This question is moot and perhaps irrelevant since the issue is the risks involved in substances consumed as PCP. These questions are potentially troublesome, and although they should not be cavalierly swept aside, they also should not preclude engaging in clinical research with substance abusers. Half of the PCPusers we studied showed neuropsychological deficits sug gestive of mild organic mental disorder. This high rate of impairment is noteworthy, particularly because the PCP users generally consumed other illicit drugs, except for hallucinogens, less heavily than did the comparison group of PCP-naive polydrug users. In particular, the PCP group reported significantly less experience with depressant drugs and opiates, the two classes of agents whose abuse previous studies have linked to neuropsychological impairment [9-111. The one substance aside from PCP which the PCP group consumed in significantly greater amounts was hallucinogens (primarily LSD). A number of investigators have examined LSDs impact on neuropsychological functioning [12-161 with inconsistent results. in the light of the minimal differences found by the more carefully designed of the studies cited above, it would appear it is PCP use which is associated with the significant proportion of impairment observed in the PCP group. Additionally, there is no evidence from the medical-developmental history to suggest that the PCP group suffered from neuropsychological difficulties prior to or independent of their drug use. The absence of such obvious causes of impairment leaves open the possibility that neuropsychological deficit in the PCP users may be related to their experience with PCP. Such an influence would be consistent with clinical
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observation that delirium is common during acute toxicity, and that some patients manifest behavioral disturbances for considerable periods even when sober [S, 6, 81. Basic research conducted in the early 1960s documented a number of cognitive changes in relation to PCP intoxication. Psychotic (schizophreniclike) cognitive disorders were observed; in particular, defects in abstracting ability, attention, perception, and motor performance were noted [ 17-22]. The most common disturbance in our PCP group was in abstracting ability; the next most common was disturbance in complex perceptual-motor skills. Attention, language ability, sensory, and simple motor abilities were generally unaffected. To the extent that performance on neuropsychological tests can be construed to reflect underlying brain function, the present results do not support Domino’s [23] speculation that the primary cortical effect of PCP is on the sensory cortex. Another possibility is that the clinical manifestation of such a sensory effect may have vanished by the time our subjects were examined. Although the findings presented here are provocative, they should be regarded tentatively. Our sample size was small and we cannot be assured that these PCP users might not somehow have been atypical. Drug use and medical histories must be regarded with caution. Although our subjects reported no medical events which might explain their high rate of neuropsychological deficit, we must be mindful of the possibility of distorted memory or motivation. Forgetting may be a particular hazard in PCP users had deficits before they ever took the drug, and selected it to correct perceived cognitive disturbances. Finally, although the Halstead-Reitan method has proven validity in assessing organicity, external criteria of neurological functioning (EEG, CAT scan, neurological exam) would have been helpful in establishing a more certain diagnosis. Despite these limitations, the results of this pilot study suggest the possibility that PCP abuse might carry with it longer term neurological risk. Larger, more comprehensive neurological and neuropsychological investigations seem to be warranted to confirm these preliminary findings, and to define more precisely the nature and time course of possible PCP-related deficit. ACKNOWLEDGMENT
The support of the Services Research Branch of the National Institute on Drug Abuse is gratefully acknowledged.
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Burns, R. S., and Lerner, S. E., Perspectives: Acute phencyclidine intoxication, Clin. Toxicol. 9:477-501(1976). Showalter, C. V., and Thornton, W. E., The increasing abuse of phencyclidine, Ill. Med. J. 151:387-389(1977). Balster, R. L., and hoss, R. S., Phencyclidine: A bibliography of biomedical and behavioral research, J. Psychedelic Drugs 1O:l-15 (1978). Fauman, B., Aldinger, G., Faumen, M.,and Rosen, P., Psychiatric sequelae of phencyclidine abuse, Clin. Toxicol. 9529-538(1976). Cohen, S., Angel dust, J. Am. Med. Assoc. 283515416 (1977). Showalter, C. V.,and Thornton, W. E., Clinical pharmacology of phencyclidine toxicity, Am. J. Psychiatry 134:1234-1238(1977). Dorand, R. D., Phencyclidine ingestion: Therapy review, South. Med. J. 70:117-
119 (1977). Rainey, J. M., and Crowder, M. K., Prolonged psychosis attributed to phencyclidine: Report of three cases, Am. J. Aychiutry 132:1076-1078(1975). Grant, I., Adams, K. M., Carlin, A. S., Rennick, P. M.,Judd, L. L., and Schooff, K., The collaborative neuropsychological study of polydrug users, Arch. Gen. Psychiatry
35:1063-1074(1978). Adams, K., Rennick, P., Schooff, K., and Keegan, J., Neuropsychological measurement of drug effects: Polydrug research, J. Psychedelic Drugs 7:151-160(1975). Grant, I., and Judd, L. L.,Neuropsychological and EEG disturbances in polydrug users, Am. J. Psychhtry 133:1039-1042(1976). Accord, L. D., Hallucinogenic drugs and brain damage, Mil. Med. 137:18-19(1972). Accord, L. D., and Barker, D. D.. Hallucinogogenic drugs and cerebrial deficit, J. Nerv. Ment. Dis. 156:281-283(1973). Cohen, S., and Edwards, A. C., LSD and organic brain impairment, Drug Dependence
2:14 (1969). McClothlin, W. H., Arnold, D. O., and Freedman, D. X., Organicity measures following repeated LSD ingestion, Arch. Gen. Psychiatry 21:704-709(1969). Wright, M.,and Hogan, T. P., Repeated LSD ingestion and performance on neurophyschological tests, J. Nerv. Ment. Dis. 154532438 (1972). Luby, E. D., Cohen, B. D., Rosenbaum, G., Gotlieb, J. S., and Kelley, R.,Study of a new schizophrenomimetic drug-Sernyl, Arch. Neurol. Psychiatry 81 :363-369
(1959). Bakker, C. B., and Amini, F. B., Observations on the psychotometic effects of Sernyl, Compre. Psychium 2:269-280(1961). Beech, H. R., Davies, B. M.,and Morgenstem, F. S., Preliminary investigation of the effects of Sernyl upon cognitive and sensory processes, J. Ment. Sci. 107:509-513
(1961). Morgenstern, F. S., Beech, H. R., and Davies, B. M., An investigation of drug induced sensory disturbances, Psychophurmucologiu 3:193-201 (1962). Luby, E. D., Gottlieb, J. S., Cohen, B. D., Rosenbaum, G., and Domino, E. F., Model psychosis and schizophrenia, Am. J. Psychiutty 119:61-67 (1962). Cohen, B. D., Luby, E. D., Rosenbaum, G., and Gottlieb, J. S., Comparison of phencyclidine hydrochloride (Sernyl) with other drugs, Arch. Gen. Psychhtry
6:395401 (1962). Domino, E. F., Neurobilogy of phencyclidine (Sernyl), a drug with an unusual spectrum of pharmacologicalactivity, Neurobiology 6:303-347(1964).
AM. J. DRUG ALCOHOL ABUSE, 6(3), pp. 273-281 (1979).
Is phencyclidine (FCP) Abuse Associated with Organic Mental Impairment? ALBERT S. CARLIN,* Ph.D. Deparrment of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle, Washington 98 195
IGOR GRANT, M.D. KENNETH M. ADAMS, Ph.D. Department of Psychiatry University of California San Diego School of Medicine Psychiatry Service Veterans Administration Hospital San Diego, California 92101
ROBERT REED, M.S. Department of Psychiatry Henry Ford Hospital Detroit, Michigan 48233 ABSTRACT The performance of sober (average length of abstinence = 27 months) phencyclidine (PCP) abusers on neuropsychological measures of organicity was compared to that of polydrug users who were not experienced with PCP,and to controls who were not. alcohol or drug abusers. Six of 12 P O users, five of 12 polydrug users, and none of the controls showed neuropsychological impairments. The deficits in PCP users occurred despite negative medical-neurological history, and even though the CTo whom requests for reprints should be sent.
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PCP group abused other drugs previously associated with neuropsychologicalimpairment less than the polydrug group. Deficiencies in abstracting and in perceptualmotor integrative abilities were noted. The results suggest the possibility that PCP abuse might be associated with neuropsychologicaldisturbance which persists for considerable time after PCP use ceases.
INTRODUCTION Phencyclidine (PCP, Sernyl, Sernylan, angel dust, crystal, hog), once considered by the drug-using subculture to be an undesirable substitute for “natural” hallucinogens such as mescaline or tetrahydrocannibinol (THC), has lately become a more accepted, even sought-after drug [l-31.Although the prevalence of untoward effects is unknown, clinical impression suggests that PCP may be responsible for a disproportionate share of toxic reactions to “street drugs” [ 1, 2,4-81. Short-term clinical problems associated with acute intoxication include behavioral disinhibition, depersonalization, sensory disturbance (including anesthesia), delirium, schizophreniform psychoses, paranoid state, stupor, and catatonic excitement [ l , 5, 61. Prolonged disturbances in mood, behavior, and thinking, lasting weeks to months after detoxification, have also been reported [5, 6, 81. In this regard Cohen [5] has observed that some PCP abusers manifested organic brain dysfunction, characterized by memory gaps, some disorientation, visual disturbances, and difficulty with speech, even when they were sober. To follow up this clinical observation, we performed detailed neuropsychological assessments with a group of chronic PCP abusers who were not acutely intoxicated, and compared their performance on measures of organicity to that of groups of non-PCP-using polydrug users and nondrug-abusing controls.
SUBJECTS AND METHODS Subjects Three groups of 12 subjects were examined. In Group 1 were persons who reported use of PCP. Group 2 consisted of multiple drug abusers who used no PCP. In Group 3 were social drinkers who used other drugs minimally or not at all. The average weekly use of various drugs, based on a detailed history for the preceding 10 years, is summarized in Table 1. The mean age for all subjects was 25.9 f 4.6 years and the mean education
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was 12.0 f 2.1 years completed. There were no significant between group differences in age (F = 0.45 for 2/33 d n or in education (F = 0.01 for 2/33 d a . In each group were 9 men and 3 women. Eleven of 12 in each drug group and all in the control group were Caucasian.
Method The PCP users were recruited by advertisement and personal contact in Seattle and San Diego. At initial contact the research teams performed a brief medical and drug use screening interview to ascertain that subjects were indeed PCP abusers, that they had been abstinent for at least 4 weeks, and that there was no medical history to suggest a neurological disorder unrelated to drug abuse. Subjects satisfying inclusion criteria were scheduled for neuropsychological examination and for a detailed interview regarding medical and drug use history. A urine sample to screen for psychoactive drugs, including PCP, was obtained midway during the examination. On average, these subjects had not taken any PCP in the past 27 months (range 1 month to 7 years). The non-PCP-using polydrug subjects and the nondrug-abusing comparison group were examined as part of the Collaborative Neuropsychological Study of Polydrug Users (CNSP) [ 9 ] . The polydrug users sought treatment at one of several polydrug treatment units across the country. As with the PCP users, these subjects were interviewed concerning their medical and drug abuse histories, and were not entered into the study if there was evidence of preexisting (predrug use) neurological illness. Neuropsychological examinations were performed only after the polydrug users were abstinent for at least 3 weeks. The nondrug-abusing comparison group were medical center and university employees who matched the polydrug and PCP subjects for age, education, sex, and ethnicity. To be included in this group, drug and alcohol use by these subjects had to be below criterion levels. These criteria have been reported previously [ 9 ] . The neuropsychological examination consisted of the Halstead-Reitan Battery and MMPI. The components of this battery and the rationale for its use in assessing brain functions in drug abusing groups are contained in an earlier publication [9]. Beyond comparing the performance of groups on various tests by means of ANOVA and chi square as appropriate, a clinician (IC) blind to group membership also scored the entire set of test results for each subject. Each NP protocol was assigned a score of 1 to 6 on the
CARLIN ET AL.
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27 6
following clinical dimensions: attention, verbal-language skills, abstracting ability, perceptual-motor integrative skills, simple sensory functions, simple motor skills, and an overall global judgment of impairment. For some of the analyses, ratings of 1 to 3 were called “unimpaired” and ratings of 4 to 6, “impaired.”
RESULTS The drug use data presented in Table 1 are based on the 10-year cumulative converted to appropriate standards. All sedative hypnotic use was converted to equivalent dosages of pentobarbital, narcotics, and synthetic opiates to
Table 1. Average Weekly Drug Use of Subjects Based on lO-year History Group 1,
PCP users
Group 2, polydrug
Group3, Ffor conrols 2/33 d p
Post hoc
Ethanol (gf
27 3
188
115
-
CNS depressants (mg pentobarbital)
246
862
0
28
125
0.5
5.17*
1,2> 3
117
149
0
7.97**
1,2> 3
Other opiates (mg morphine) Hallucinogens (occasions of use)
13
39
0
9.75**
2 > 1,3
0
13.61**
Marijuana (occasions of u s )
17
11
1
8.55**
1, 2 > 3
561.88**
1 > 2,3
Central stimulants (mg dextroamphetamines) Heroin (mg morphine)
0.5
0.3
Phencyclidine (occasions of use)
1.1
0
0
Cigarettes (packs of 20)
3.5
6.1
2.8
0.37 22.84**
2>1>3
1>2 >3
1.7
aTo reduce variability, ANOVAS were performed on logarithmically transformed druguse figures - loglo (X+ 1). bNeuman Keuls. 2 > 1 > 3 indicates Group 2 scored significantly @ = .05) higher than Group 1, which in turn scored significantly higher than Group 3. CTengrams of ethanol is roughly equivalent to one 12-02 beer, one 4-02 glass of wine, or 1 shot of 80 proof whiskey. * p < .05. **p < .01.
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Table 2. Clinician’s Neuropsychological Ratings
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PCP Neuropsych assessment
users, N = 12
Unimpaired: Above average Average Borderline
2 3
Impaired: Mildly impaired Moderately impaired Severely impaired
Polydrug users, N = 12
Controls N = 12
I
1
0 3 4
6 0 0
2 3 0
0 0 0
3 2
morphine and stimulants to dextroamphetamine. Analysis of variance (ANOVA) and Neuman-Keuls procedures carried out on these converted data revealed that except for hallucinogen and PCP use, the PCP group consumed equivalent or lesser amounts of drugs than did the polydrug group. The clinician’s global neuropsychological ratings are displayed in Table 2. Six PCP users, five polydrug users, and no controls received ratings in the impaired range. Because of small cell size, Categories 1, 2, and 3 were collapsed into an unimpaired category and 4, 5 , and 6 into an impaired category. The resulting 2 X 3 comparison reveals that the two drug groups and controls are significantly different (x2 = 8.12, p < .02, df = 2). The commonest specific deficiencies which contributed to a judgment of “impaired” were disturbances in abstracting ability and in handling of tasks requiring higher order perceptualmotor integrative skills. Selected results from the Halstead-Reitan Battery are presented in Table 3. For the sake of space, only WAIS summary scores are shown, and data from the aphasia screening and sensory-perceptual exams, on which there were no between-group differences, are omitted. Because the sample sizes were small and variability in many test scores was large, few significant differences emerged. In general, polydrug users scored worst, controls did best, and PCP users were intermediate in performance. Those test results which did separate groups tended to be supportive of the clinician’s judgment that the two drugusing groups were deficient in abstracting (e.g., categories test) and perceptualmotor IQ abilities. . The medical interview conducted with each subject inquired about 20 medical events and symptoms which, if they occurred, might raise the possibility that a person experienced neurological insult unrelated to drug abuse. The
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278 Table 3. Performance of Subjectson Selected Neuropsychologicaltests
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PCP users
Polydrug
SD
Mean
SD
Controls Mean SD
Ffor
Mean
108.3 107.3 108.3
13.9 13.4 12.3
104.8 101.0 103.3
17.8 12.7 14.9
116.2 113.8 116.2
2.01 3.31* 3.28*
2/33df
WAIS:
Verbal IQ Perf. IQ
Full IQ
10.0 10.3 9.3
Halstead tests: Impairment index Category (errors) TPT total time TPT memory TIT location Speech (errors) Rhythm R Tapping L Tapping
34 46.0 10.3 7.6 4.3 5.1 25.4 48.2 44.2
.27 22.5 5.1 0.9 2.4 2.4 2.6 5.6 7.1
.32 .27 50.8 28.8 13.9 7.0 8.0 1.3 4.4 2.4 7.5 4.8 26.4 3.6 54.6 5.4 49.8 6.7
-13 .13 27.5 14.4 2.7 9.7 1.2 8.3 2.5 5.7 2.3 4.8 1.2 28.7 4.3 52.8 3.9 47.4
2.98 3.545 2.24 0.99 1.16 2.38 4.72** 4.9 ** 2.56+
Other tests: Trails A (sec) Trails B (sec) R name Writing (sec) L name writing (sec) R Grip @g) L Grip (kg)
25.3 59.7 7.7 12.1 43.8 42.9
11.1 19.9 6.6 3.6 16.2 14.9
30.8 78.3 6.3 13.7 45.6 42.9
12.8 42.2 2.3 4.6 17.8 17.5
21.3 54.8 5.9 9.8 48.3 44.8
5.0 18.4 2.7 2.4 16.1 16.3
2.56 2.26 0.56 3.41* 0.23 0.05
2.9
1.2
3.4
1.2
1.9
0.7
Clinician rating
6.29**
* p = .1. **p = .01. t p = .l.
groups differed on endorsement of only one event (hospitalization for overdose) and one symptom (complaints of frequent muscular weakness), more polydrug users reporting these in each instance. The entire subject pool was then divided into “at risk” (the subject said yes to at least one of nine medical items which could be directly related to neuropsychological risk, e.g., head injury with unconsciousness, prematurity) and “not at risk” groups. There was no relationship between medical risk status and neuropsychological impairment (Fisher’s Exact Test p = .288). Despite the request to abstain from drug use for 72 hours prior to testing five subjects produced urines contaminated by drugs. However, no statistically significant relationship was found between contaminated urine and impariment among the drugusing groups (Fisher’s Exact Test p > .lo). In addition, the
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examiners who were experienced in the observation of toxic states did not believe any of the subjects to be toxic during the testing.
DISCUSSION Prior to commenting on these results, it may be necessary to discuss whether the drug use differences between the study groups are meaningful. Can drug users’ self-reports be trusted? The answer must be a qualified yes. Although drug users may not be able or willing to reliably report their drug usage, there is no reason to believe that distortions would be systematic. Polydrug patients had no reason to underreport PCP or hallucinogen use, and PCP abusers had no reason to underreport depressant or opiate use. Another question which arises is the extent to which illicit phencyclidine is phencyclidine versus phencyclidine and impurities. This question is moot and perhaps irrelevant since the issue is the risks involved in substances consumed as PCP. These questions are potentially troublesome, and although they should not be cavalierly swept aside, they also should not preclude engaging in clinical research with substance abusers. Half of the PCPusers we studied showed neuropsychological deficits sug gestive of mild organic mental disorder. This high rate of impairment is noteworthy, particularly because the PCP users generally consumed other illicit drugs, except for hallucinogens, less heavily than did the comparison group of PCP-naive polydrug users. In particular, the PCP group reported significantly less experience with depressant drugs and opiates, the two classes of agents whose abuse previous studies have linked to neuropsychological impairment [9-111. The one substance aside from PCP which the PCP group consumed in significantly greater amounts was hallucinogens (primarily LSD). A number of investigators have examined LSDs impact on neuropsychological functioning [12-161 with inconsistent results. in the light of the minimal differences found by the more carefully designed of the studies cited above, it would appear it is PCP use which is associated with the significant proportion of impairment observed in the PCP group. Additionally, there is no evidence from the medical-developmental history to suggest that the PCP group suffered from neuropsychological difficulties prior to or independent of their drug use. The absence of such obvious causes of impairment leaves open the possibility that neuropsychological deficit in the PCP users may be related to their experience with PCP. Such an influence would be consistent with clinical
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observation that delirium is common during acute toxicity, and that some patients manifest behavioral disturbances for considerable periods even when sober [S, 6, 81. Basic research conducted in the early 1960s documented a number of cognitive changes in relation to PCP intoxication. Psychotic (schizophreniclike) cognitive disorders were observed; in particular, defects in abstracting ability, attention, perception, and motor performance were noted [ 17-22]. The most common disturbance in our PCP group was in abstracting ability; the next most common was disturbance in complex perceptual-motor skills. Attention, language ability, sensory, and simple motor abilities were generally unaffected. To the extent that performance on neuropsychological tests can be construed to reflect underlying brain function, the present results do not support Domino’s [23] speculation that the primary cortical effect of PCP is on the sensory cortex. Another possibility is that the clinical manifestation of such a sensory effect may have vanished by the time our subjects were examined. Although the findings presented here are provocative, they should be regarded tentatively. Our sample size was small and we cannot be assured that these PCP users might not somehow have been atypical. Drug use and medical histories must be regarded with caution. Although our subjects reported no medical events which might explain their high rate of neuropsychological deficit, we must be mindful of the possibility of distorted memory or motivation. Forgetting may be a particular hazard in PCP users had deficits before they ever took the drug, and selected it to correct perceived cognitive disturbances. Finally, although the Halstead-Reitan method has proven validity in assessing organicity, external criteria of neurological functioning (EEG, CAT scan, neurological exam) would have been helpful in establishing a more certain diagnosis. Despite these limitations, the results of this pilot study suggest the possibility that PCP abuse might carry with it longer term neurological risk. Larger, more comprehensive neurological and neuropsychological investigations seem to be warranted to confirm these preliminary findings, and to define more precisely the nature and time course of possible PCP-related deficit. ACKNOWLEDGMENT
The support of the Services Research Branch of the National Institute on Drug Abuse is gratefully acknowledged.
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Burns, R. S., and Lerner, S. E., Perspectives: Acute phencyclidine intoxication, Clin. Toxicol. 9:477-501(1976). Showalter, C. V., and Thornton, W. E., The increasing abuse of phencyclidine, Ill. Med. J. 151:387-389(1977). Balster, R. L., and hoss, R. S., Phencyclidine: A bibliography of biomedical and behavioral research, J. Psychedelic Drugs 1O:l-15 (1978). Fauman, B., Aldinger, G., Faumen, M.,and Rosen, P., Psychiatric sequelae of phencyclidine abuse, Clin. Toxicol. 9529-538(1976). Cohen, S., Angel dust, J. Am. Med. Assoc. 283515416 (1977). Showalter, C. V.,and Thornton, W. E., Clinical pharmacology of phencyclidine toxicity, Am. J. Psychiatry 134:1234-1238(1977). Dorand, R. D., Phencyclidine ingestion: Therapy review, South. Med. J. 70:117-
119 (1977). Rainey, J. M., and Crowder, M. K., Prolonged psychosis attributed to phencyclidine: Report of three cases, Am. J. Aychiutry 132:1076-1078(1975). Grant, I., Adams, K. M., Carlin, A. S., Rennick, P. M.,Judd, L. L., and Schooff, K., The collaborative neuropsychological study of polydrug users, Arch. Gen. Psychiatry
35:1063-1074(1978). Adams, K., Rennick, P., Schooff, K., and Keegan, J., Neuropsychological measurement of drug effects: Polydrug research, J. Psychedelic Drugs 7:151-160(1975). Grant, I., and Judd, L. L.,Neuropsychological and EEG disturbances in polydrug users, Am. J. Psychhtry 133:1039-1042(1976). Accord, L. D., Hallucinogenic drugs and brain damage, Mil. Med. 137:18-19(1972). Accord, L. D., and Barker, D. D.. Hallucinogogenic drugs and cerebrial deficit, J. Nerv. Ment. Dis. 156:281-283(1973). Cohen, S., and Edwards, A. C., LSD and organic brain impairment, Drug Dependence
2:14 (1969). McClothlin, W. H., Arnold, D. O., and Freedman, D. X., Organicity measures following repeated LSD ingestion, Arch. Gen. Psychiatry 21:704-709(1969). Wright, M.,and Hogan, T. P., Repeated LSD ingestion and performance on neurophyschological tests, J. Nerv. Ment. Dis. 154532438 (1972). Luby, E. D., Cohen, B. D., Rosenbaum, G., Gotlieb, J. S., and Kelley, R.,Study of a new schizophrenomimetic drug-Sernyl, Arch. Neurol. Psychiatry 81 :363-369
(1959). Bakker, C. B., and Amini, F. B., Observations on the psychotometic effects of Sernyl, Compre. Psychium 2:269-280(1961). Beech, H. R., Davies, B. M.,and Morgenstem, F. S., Preliminary investigation of the effects of Sernyl upon cognitive and sensory processes, J. Ment. Sci. 107:509-513
(1961). Morgenstern, F. S., Beech, H. R., and Davies, B. M., An investigation of drug induced sensory disturbances, Psychophurmucologiu 3:193-201 (1962). Luby, E. D., Gottlieb, J. S., Cohen, B. D., Rosenbaum, G., and Domino, E. F., Model psychosis and schizophrenia, Am. J. Psychiutty 119:61-67 (1962). Cohen, B. D., Luby, E. D., Rosenbaum, G., and Gottlieb, J. S., Comparison of phencyclidine hydrochloride (Sernyl) with other drugs, Arch. Gen. Psychhtry
6:395401 (1962). Domino, E. F., Neurobilogy of phencyclidine (Sernyl), a drug with an unusual spectrum of pharmacologicalactivity, Neurobiology 6:303-347(1964).
