Phencyclidine An Update Editor Doris H. Clouet
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Pharmacol Biochem Behav 1:167-172, 1973. |
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Brady, K.T., and Balster, R.L. Discriminative stimulus |
properties |
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of phencyclidine and five analogues in the squirrel monkey. |
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Pharmacol Biochem Behav 14:213-218, 1981. |
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Brady, K.T.; Balster, R.L.; and May, E.L. Stereoisomers |
of N- |
|
allylnormetazocine: |
Phencyclidine-like behavioral effects-in |
squirrel monkeys and rats." Science 212:178-180, 1982a.
Brady, K.T.; Bolster, R.L.; Meltzer, L.T.; and Schwertz, D. Comparison of phencyclidine and three analogues on fixed-interval performance in rhesus monkeys. Pharmacol Biochem Behav 12:67-
71, |
1980. |
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Brady, K.T.; Balster, R.L.; and Woolverton, W.L. Discriminative |
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stimulus and |
reinforcing properties of etoxadrol |
and dexoxadrol |
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in monkeys. J Pharmacol Exp Ther 220:56-62, 1982b. |
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Carroll, M.E., and Meisch, R.A. |
O r a l phencyclidine |
(PCP) self- |
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administration in rhesus monkeys: Effects of feeding |
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conditions. |
J Pharmacol Exp |
Ther 214:339-346, 1980. |
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Chait, L.D., and Balster, R.L. |
Interaction |
between |
phencyclidine |
||
and |
pentobarbital in several |
species of |
laboratory animals. |
Comm Psychopharmacol 2:351-356, 1978.
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Domino, E.F., and Luby, E.D. Abnormal mental states induced by phencyclidine as a model of schizophrenia. In: Domino, E.F., ed. PCP (Phencyclidine): Historical and Current Perspectives. Ann Arbor: NPP Books, 1981. pp. 4O1-418.
Eastman, J.W., and Cohen, S.N. Hypertensive crisis and death associated with phencyclidine poisoning. JAMA 231:1270-1271, 1975.
Freeman, A.S.; Martin, B.R.; and Balster, R.L. Relationship between the development of behavioral tolerance and the biodisposition of phencyclidine in mice. Pharmacol Biochem Behav 20:373-377, 1984.
Geller, E.B.; Adler, L.H.; Wonjo, C.; and Adler, M.W. The anticonvulsant effect of phencyciidine in rats. Psychopharmacology (Berlin) 74:97-98, 1981.
Hampton, R.Y.; Medzihradsky, F.; Woods, J.H.; and Dahlstrom, P.J. Stereospecific bindina of 3H-phencyclidine in brain membranes. Life Sci 30:2147-2154, 1982.
Hayes, B.H., and Balster, R.L. Anticonvulsant effects of phen- cyclidine-like drugs in mice. Fed Proc 44:724, 1985.
Holtzman, S.G. Phencyclidine-like discriminative effects of opioids in the rat. J Pharmaco1 Exp Ther 214:614-619, 1980.
Johnson, K.M. Phencyclidine: Behavioral and biochemical evidence supporting a role for dopamine. Fed Proc 42:2579-2583, 1983.
Johnson, K.M., and Balster, R.L. Acute chronic phencyclidine administration: Relationship between biodispositional factors and behavioral effects. Subst Alcohol Actions Misuse 2:131-142, 1981.
Kalir, A.; Edery, M.H.; Pelah, Z.; Balderman, D.; and Proath, G. 1-Phenylcycloalkylamine derivatives. II. Synthesis and pharmacological activity. J Med Chem 12:473-477, 1969.
Kanner, M.; Finnegan, K.; and Meltzer, H.Y. Dopaminergic effects of phencyclidine in rats with nigrostriatal lesions. Psychopharmacol Comm 1:393-401, 1975.
Landauer, M.L., and Balster, R.L. The effects of aggregation on the lethality of phencyclidine in mice. Toxicol Lett, 12:171176, 1982.
Landauer, M.L.; Woolverton, W.L.; and Balster, R.L. The effects of chlorpromazine on the lethality of d-amphetamine and phencyclidine in mice. Res Comm Subst Abuse 3:287-295, 1982.
Lasagna, L., and Pearson, J.W. Analgesic and psychotomimetic properties of dexoxadrol. Proc Soc Exp Biol Med 118:353-354, 1965.
Lukas, S.E.; Griffiths, R.R.; Brady, J.V.; and Wurster, R.M. Phencyclidine-analogue self-injection by the baboon. Psychopharmacology (Berlin) 83:316-320, 1984.
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dine, pentobarbital, and d-amphetamine on the acquisition and performance of conditional discriminations in monkeys. Pharmacol Biochem Behav 13:887-894, 1980a.
Moerschbaecher, J.M., and Thompson, D.M. Effects of d-ampheta- mine, cocaine, and phencyclidine on the acquisition of response sequences with and without stimulus fading. J Exp Anal Behav 33:369-381, 1980b.
Petersen, R.C., and Stillman, R.C., eds. Phencyclidine (PCP)
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Pollard, J.C.; Uhr, L.; and Stern, E. Drugs and Phantasy: The Effects of LSD Psilocybin and Sernyl on College Students. Boston: Little, Brown and Co., 1965. 205 pp.
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Slifer, B.L., and Balster, R.L. Reinforcing properties of stereoisomers of the putative sigma agonists N-allylnormetazocine and cyclazocine in rhesus monkeys. J Pharmacol Exp Ther 225:522528, 1983.
Slifer, B.L., and Balster, R.L. Phencyclidine-like discriminative stimulus properties of the stereoisomers of dioxadrol. Subst Alcohol Actions Misuse, in press.
Slifer, B.L.; Balster, R.L.; and Woolverton, W.L. Behavioral dependence produced by continuous phencyclidine infusion in rhesus monkeys. J Pharmacol Exp Ther 230:399-406, 1984.
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161
ACKNOWLEDGEMENTS
My colleagues whose names appear as my co-authors on the papers cited for this report are due a substantial portion of the credit for most of the research described herein. The research has been supported by National Institute on Drug Abuse Grant DA-01442.
AUTHOR
Robert L. Balster, Ph.D.
Department of Pharmacology and Toxicology
Medical College of Virginia
Virginia Commonwealth University
Richmond, VA 23298
162
Phencyclidine: Changing
Abuse Patterns
Raquel Crider
GENERAL TRENDS 1973 TO 1984
Phencyclidine (PCP), one of the arylcyclohexylamines. was developed and originally used as a general anesthetic for humans. Due to psychotic and hallucinogenic reactions, use of the drug for humans was discontinued. It is now used legally only in veterinary medicine as an animal immobilizing agent.
Currently, trends in PCP abuse are monitored through emergency room visits, deaths, initiates entering drug abuse treatment programs, and surveys, as shown in table 1 and figures 1 and 2. The years between 1973 and 1984 have been divided into three periods: during the years between 1973 and 1978/1979, the indicators of PCP
use increased; the period 1978/1979 through |
1981 |
marked |
a |
decline |
||
in the PCP indicators; 1981 to the present |
time |
are |
years |
in |
which |
|
PCP indicators have shown resurgence. |
|
|
|
|
|
|
Indicators of PCP abuse, i.e., emergencies, |
deaths, |
and |
the |
number |
of initiates entering treatment, increased between 1973 and 1978/ 1979. Between 1973 and 1975, the rate of initiates, based on treatment year-of-first-use records, increased more rapidly than the number of emergencies. This phenomenon may be explained, in part, by a change in the route of administration. Beginning about 1972, PCP users changed from administering the drug orally in tablet or capsule form to smoking the drug on leaf material, such as
marijuana, |
tobacco, or |
parsley. By smoking, |
PCP users |
were |
able |
|
to |
control |
the dosage |
more effectively, thus |
decreasing |
the |
chance |
of |
overdose. |
|
|
|
|
By 1978/1979, indicators of PCP abuse leveled off and started to decline. This trend is thought to be related to a variety of activities initiated by health and law enforcement officials, including a nationwide education campaign in which 18,000 letters
163
were mailed to treatment programs, emergency rooms, health agencies, and medical examiner/coroner offices describing the typical reactions to PCP, and treatment procedures. In addition, PCP was rescheduled from Schedule III to Schedule II of the Controlled Substance Act, a highly restrictive category reserved for substances with limited legitimate use and/or significant abuse potential. The PCP analogues, PCE, PHP, and TCP were placed in Schedule I. Required reporting of production of the precursor, piperidine, began in 1979. Penalties for possession of PCP with intent to sell were increased at about the same time. As a result of these and other efforts, the number of emergencies, deaths, and PCP initiates entering treatment began to decline.
TABLE |
1. |
PCP indicators |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Number |
Percent |
Percent |
|
|
|
PCP Emergencies |
PCP |
“Ever Use” |
30-Day Use |
Age |
12-17 |
|
PCP Related |
|
|
Initiate |
in |
In High |
"Ever |
Use" |
|
Deaths |
National2 |
In Panel3 |
Treated4 |
Households5 |
School |
Households7 |
||
|
|
|
|
|
|
|
|
|
1973 |
|
1.400 |
|
3.42 |
|
|
|
|
1974 |
|
1.934 |
|
4.24 |
|
|
|
|
1975 |
|
1.768 |
|
5.49 |
|
|
|
|
1976 |
|
2.799 |
|
6.32 |
|
|
3.0 |
|
1977 |
8.1 |
4.993 |
|
7.16 |
6.98 |
|
5.8 |
|
1970 |
12.3 |
9.877 |
|
9.13 |
|
|
|
|
1979 |
10.5 |
10.288 |
|
5.67 |
7.01 |
2.4 |
3.9 |
|
1980 |
8.5 |
7.154 |
3.781 |
2.88 |
|
1.4 |
|
|
1981 |
9.4 |
5.840 |
2.722 |
1.27 |
|
1.4 |
|
|
1982 |
16.4 |
8.067 |
3.383 |
|
8.28 |
1.0 |
2.2 |
|
1983 |
23.8 |
9.782 |
4.376 |
|
|
1.3 |
|
|
1984 |
21.7 |
|
4.526 |
|
|
1.0 |
|
|
1. Number of PCP related deaths x 10-1 reported to DAWN. Newark and New York exeluded after 1981. The 1984 data are preliminary (National lnstitute on Drug Abuse 1985c).
2.Number of PCP related emergencies x 10-3 reported to DAWN projected to the Nation (Hinkley and Greenwood 1982).
3. Number of imputed PCP related emergencies x 10-3 reported to a consistent panel of hospitals In DAWN (National lnstitute on Drug Abuse 1985a).
4.Number of PCP lnitiates x 10-2 starting use 1973-1983 admitted to a consistent panel of 402 treatment programs In 1977 through 1981.
5.Number of persons in households x 10-6 having ever used PCP 1970, 1979, and 1982 (Miller et al. 1983).
6.Percent of high school seniors using PCP In the 30 days prior to the survey (Johnston et al. 1985).
7.Percent ages 12 to 17 years In households reporting ever having used PCP (Miller et al. 1983).
164
KEY: |
= |
PCP |
ralated |
mortalities (NY |
and |
Newark |
excluded) x 10-1; |
= P C P |
emergencies |
projected to |
nation x 10-3; |
= |
PCP |
emergencies reported |
to con- |
||
sistent |
panel |
x 10-3. |
|
|
|
|
|
FIGURE 1. The number of PCP-retated emergencies projected to the Nation, and the number of PCP-related deaths, peaked in 1978/1979, declined through 1980/1981, then increased in 1981 through 1984
By 1981, some of the indicators of PCP abuse began to increase again. The number of PCP-related emergencies projected to the Nation from the Drug Abuse Warning Network (DAWN) data showed an increase from 5,840 in 1981 to 9,782 in 1983 (Hinkley and Greenwood 1984). Data from a consistent panel of reporting hospitals indicate that the number of emergencies continued to increase through 1983. The number of PCP-related deaths reported to DAWN increased from 96 in 1981, to 154 in 1983 (National Institute on Drug Abuse 1984). The estimated number of persons reporting ever having used PCP increased from 7.01 million in 1979 to 8.28 million in 1982 (Miller et al. 1983).
The recent increase, however, appears to be concentrated primarily in the metropolitan areas of Los Angeles, Washington, D.C., and New York City. These three areas accounted for 76.0 percent of the emergencies reported to DAWN in 1983, while Los Angeles and Washington, D.C. accounted for 81.8 percent of the PCP-related deaths2. Rates of PCP emergencies per 100,000 total emergencies are available for 26 major metropolitan areas in 1983, based on DAWN data (National Institute on Drug Abuse 1985d). The areas of Los Angeles, Washington, D.C., and New York City show the highest rates at 2.52, 2.03 and 0.53 per 100,000 emergencies, respectively, in 1984.
165
KEY: |
= Percent of |
household |
residents |
ages 12 |
to 17 |
years |
reporting |
"ever |
use” |
|||
of PCP; |
= |
Percent |
of |
high school seniors |
using |
PCP In past 30 days; |
= |
PCP |
||||
lnitiates |
In |
treatment |
x 10-2, |
corrected |
for |
lag |
between |
first |
use and |
treatment. |
FIGURE 2. The increase in PCP indicators starting in 1981 does not reflect an increase for new or young users. The number of PCP initiates first admitted to treatment, the percent of high school seniors using the drug in the 30 days prior to the survey, and the percent of persons ages 12 to 17 years in households reporting ever having used PCP declined in the late 1970s and remained at low levels since the early 1980s.
Table 2 shows the number of PCP-related emergencies for the period of 1982 to 1984 by quarter for New York, Los Angeles, and Washington, D.C. For New York and Washington, D.C., the average number of mentions increased significantly between 1983 and 1984.
The decline in Los Angeles between 1983 and 1984 cannot immediately be interpreted as a decline in PCP use for that city. In 1981, during an investigation of PCP trends in Los Angeles, it was discovered that many PCP emergencies were diverted to psychiatric units, better equipped to handle the violent behavior sometimes accompanying PCP reactions. These psychiatric units were not participating in the DAWN network at that time (Kozel and Husson 1981). It is possible that similar systemic problems may have occurred in 1984.
166
TABLE 2. Number of PCP-related emergencies from a consistent panel of emergency rooms in New York, Washington, D.C., and Los Angeles, 1982-1984
Time |
Frame |
New York |
Washington, D.C. |
Los Angeles |
|
|
|
|
|
1982 |
Q1 |
93 |
49 |
567 |
|
Q2 |
147 |
68 |
660 |
|
Q3 |
147 |
68 |
660 |
|
Q4 |
125 |
96 |
589 |
1983 |
Q1 |
142 |
104 |
568 |
|
Q2 |
173 |
97 |
807 |
|
Q3 |
214 |
130 |
910 |
|
Q4 |
303 |
179 |
910 |
1984 |
Q1 |
267 |
190 |
641 |
|
Q2 |
217 |
285 |
635 |
|
Q3 |
237 |
285 |
635 |
|
Q4 |
239 |
229 |
493 |
Mean |
1982 |
121.6 |
70.0 |
600.6 |
Mean |
1983 |
207.9 |
127.6 |
751.8 |
Mean |
1984 |
240.0 |
241.4 |
621.0 |
|
|
|
|
|
SOURCE: National institute on Drug Abuse 1985b.
Potential problems in PCP abuse were also reported in New Orleans and St. Louis (National Institute on Drug Abuse, in preparation), although the quarterly frequencies of emergency room mentions in
those |
SMSAs |
were small compared to New York, Washington, D.C., and |
|
Los |
Angeles. |
|
|
NEW |
OR |
YOUNG |
USERS |
Based on data from national surveillance systems, the increase between 1981 and 1983 does not appear to reflect substantial increased use among new or young users, as occurred during the early and mid-1970s, although there may be regional variations. In general, the number of initiates declined sharply after 1977 and remained at low levels through 1981. Table 1 and figure 2 show
that |
there were 913 initiates starting use in 1978, first treated |
in a |
panel of 402 consistently reporting treatment programs. The |
167