Contents
I. Introduction
II. Medical Use of Paregoric
III. Background of the Abuse of Paregoric
IV. Occurrence
V. Characteristics of Paregoric Users
VI. Intravenous Injection of Paregoric
VII. Complications
Author: A. Martin LERNER
Pages: 13 to 19
Creation Date: 1966/01/01
I. Introduction
II. Medical Use of Paregoric
III. Background of the Abuse of Paregoric
Legal
Socio-economic
Narcotic
IV. Occurrence
V. Characteristics of Paregoric Users
VI. Intravenous Injection of Paregoric
VII. Complications
Narcotic Addiction
Infections
Thrombophlebitis, Occlusive Venous Sclerosis, and Pulmonary Abnormalities
In 1955 records of the Narcotics Bureau in Detroit showed that there were no paregoric users among 1267 persons arrested for the illicit use of drugs. During the next 8 years paregoric was used increasingly here as an opium or heroin substitute. At the zenith (1963), paregoric claimed 713 of 994 narcotics users. Since at present this medical oddity is again virtually extinct, what is to follow is largely a historical resume of an unusual, and hopefully singular, experience.
In the early eighteenth century LeMort, a professor of chemistry at Leyden, prepared an elixir for asthma and called it "paregoric ", a term derived from the Greek for "soothing ". This needlessly complex pharmacopeial mixture (table 1) of a former day is a camphorated opium tincture, U.S.P., containing four percent opium (0.04 percent morphine). Its other ingredients are benzoic acid, camphor, and anise oil. The average adult dose is 4 ml by mouth which corresponds to 16 mg of opium, or 1.6 mg of morphine. Customarily, paregoric is used for diarrheas in children but it may have some value as an expectorant, particularly when the preparation is somewhat outdated. It was never intended, nor has it ever been used by physicians for intramuscular or intravenous injection. (1)
1From the Departments of Medicine, Microbiology, and Pathology and the Detroit General (Receiving) Hospital, Wayne State University School of Medicine, Detroit, Michigan. Aided by a grant (5 T1 AI 261) from the U.S. Public Health Service.
2The author is grateful to Inspector Joseph Brown, Chief of the Narcotics Bureau of the Detroit Police Department, for his help.
|
Tincture of opium
|
40 cc |
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Oil of anise
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4 cc |
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Benzoic acid
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4 gm |
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Camphor
|
4 gm |
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To make
|
1 000 cc |
*An ounce of paregoric contains 129.6 mg (2 Grs.) of powdered opium, or the equivalent of 13 mg of morphine.
Legal
The first federal law dealing with narcotic addiction in the United States was part of the Internal Revenue Act. The now famous Harrison Narcotic Act, passed in 1914, was intended to police the production and sale of narcotic drugs, and to limit their use to professional and scientific purposes. Therefore, any other usage of these drugs was a crime. (2)
This was in direct opposition to the position taken in Great Britain in 1951 under the Dangerous Drugs Act whereby medical practitioners were allowed to supply or prescribe narcotic drugs as they considered necessary for the treatment of their patients. In England continued provision of supplies to patients who are addicted depends solely on the individual decision made by the medical practitioner in each case. The Home Office in London maintains an index of all known narcotic addicts, and in 1964 there were 635 currently known addicts. "No statistics are available for crimes committed by addicts, but in general, it does appear that the fact that supplies of narcotic drugs may be legally obtained mitigates against the creation of an illicit market on any appreciable scale, or the necessity for resorting to crime in order to support an addiction." (3)
In September 1962, following considerable sentiment in this country for the necessity of a fresh evaluation of narcotic addiction, President Kennedy called a White House Conference on Narcotic and Drug Abuse. (4)In the same year the United States Supreme Court declared unconstitutional legislation that made drug addiction itself a crime. Such legislation was then law in 19 states. (5) In California, Massachusetts, and New York state legislation has since been adopted emphasizing commitment and rehabilitation and after care outpatient programs for narcotics users. (6)
Despite the Harrison Narcotic Act, in most cities of the United States certain narcotic drugs, notably paregoric, could be purchased upon request in pharmacies without prescription. The states in which exempt narcotics did not exist in 1963 are listed in table 2.
Until the specific exclusion of paregoric from its exempt status by the Michigan State Legislature on April 20, 1964 the Narcotics Act, 343 in Michigan stated: "No person shall prescribe, administer, dispense, or sell more than 2 ounces of paregoric to any one person, ... within 48 hours." By visiting several pharmacies daily a paregoric user could thus supply himself with opium freely and inexpensively. 3
Socio-economic
Detroit, the fifth largest city in the United States, is the center of the automobile manufacturing industry and has a population of 2.6 million. Its people are mostly working in this or closely allied industries. Marginal unskilled workers feel small fluctuations in the economy acutely, and even during periods of prosperity a large indigent depressed group is present. From this group come the bulk of narcotics users. 4 They live in the central core of the city extending northward from the Detroit River which separates Windsor, Ontario, in Canada from the United States (figures 1 and 2).
This slum occupies an area of approximately 4 square miles. The present inhabitants of the inner city are predominantly Negro, having replaced former immigrant Caucasians over the past 20 years. This latter group has moved toward the more desirable outer city and suburbs. It is apparent that several low-rent housing developments have not markedly changed the tenor of life in the core of the city. Major efforts in education of the children living here have been underway for some time, and are presently vigorously continuing.
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Arkansas
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Louisiana
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New York
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Utah
|
|
California
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Maryland
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North Dakota
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Vermont
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|
Colorado
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Minnesota
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Oregon
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Washington
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|
Connecticut
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Montana
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Rhode Island
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West Virginia
|
|
Iowa
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Nebraska
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South Dakota
|
|
|
Kansas
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New Jersey
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Texas |
* Paregoric cannot be obtained without a prescription. (On April 20, 1964 the Michigan State Legislature made paregoric a non-exempt narcotic.)
Narcotic
The drug utilized most frequently by narcotics users in the United States is heroin. 5 Heroin is not a recognised drug in this country and its manufacture and importation are prohibited by law. Heroin is, therefore, accessible via an illicit market in coastal cities. Heroin arrives in Detroit from the more cosmopolitan cities, New York or Chicago (figure 1).
3Paregoric users were wont to mix this preparation with the antihistaminic tripelennamine hydrochloride (pyribenzamine hydrochloride). The resultant concoction has a bluish color, and hence was known as "blue velvet." Pyribenzamine is a non-exempt drug in Detroit, but does not require a physician's prescription in Windsor, Canada. Thus, in the immediate Detroit area narcotics users could amply supply their habit and entice new persons to it without violation of the law.
4A few narcotics users on the campuses of Wayne State University and the University of Michigan have been noted.
5Marijuana, cocaine, morphine, dilaudid, pethidine, codeine, dolephine, barbiturate, amphetamine, ... users are also present, but to a much lesser extent.
Heroin is usually preferred by addicts to morphine or other alkaloids because of the resultant intense euphoria which often supplants subjective depression, and the absence of unpleasant side effects such as vomiting and constipation. Relatively pure heroin is regularly " cut", that is " filler", usually lactose is added before sale. In fact, one of the most frequent causes of sudden death in heroin addicts is due to a miscalculation of the strength of an intravenous "dose ".
Due to their distance from the sources Detroit narcotics users in 1955 noted increasing prices for poorer "junk ".
Relative numbers of paregoric and heroin users in Detroit in the decade (1955-1965) are seen in table 3. In 1955 there were 1267 heroin users. No one used paregoric. In 1956 the Narcotics Bureau became aware of a very low level of paregoric abuse. From 1959 until April 1964 when paregoric became a non-exempt narcotic in Michigan, the number of people arrested for paregoric addiction rose geometrically to exceed heroin in 1962. In 1963, the last full year of free access to paregoric, there were 713 people using paregoric to 281 using heroin. Again in 1965, paregoric abuse was insignificant in Detroit.
A few paregoric addicts apparently exist in other large cities of the United States, for example, St. Louis, Missouri and Miami, Florida. These occurrences are apparently very unusual, however. In other cities such as New York and Louisville, Kentucky, paregoric users do not exist. (7)
|
Persons using |
|||
|---|---|---|---|
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Year |
Paregoric |
Heroin |
% Paregoric |
| 1955 | 0 | 1 267 | 0 |
| 1956 | 3 | 1 388 | 0.2 |
| 1957 | 4 | 1 209 | 0.3 |
| 1958 | 4 | 924 | 0.4 |
| 1959 | 10 | 648 | 1.5 |
| 1960 | 64 | 673 | 8.8 |
| 1961 | 245 | 378 | 39.2 |
| 1962 | 318 | 202 | 51.1 |
| 1963 | 713 | 281 | 70.7 |
| 1964 | 428 | 378 | 52.3 |
| 1965 | 10 | 328 | 3.0 |
The sex, race, and age of paregoric users during the peak year of incidence are indicated in tables 4 and 5. The mean age was in the early thirties (tables 4 and 6) but nineteen were 17-20 years old, and forty-four of them were in the 20-23 age group. Negroes, Caucasians, Mexicans, and Orientals used paregoric. There were about 5 Negroes to 1 of all other races, and 9 men to every woman.
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Years |
Number |
|---|---|
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<15
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0 |
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15-16
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0 |
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17-20
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19 |
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21-23
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44 |
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24-26
|
105 |
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27-30
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140 |
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31-35
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165 |
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36-40
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151 |
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>40
|
89 |
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Race |
|||||
|---|---|---|---|---|---|
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Sex |
Negro |
Caucasian |
Mexican |
Oriental |
Number of persons |
|
Male
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970 | 90 | 18 | 1 | 1 079 |
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Female
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85 | 52 | 0 | 0 | 137 |
Detailed habituation and sociologic data from 21 paregoric users admitted to the Detroit General Hospital who were interviewed by Dr. F. J. Oerther are shown in table 6. The men could not hold responsible jobs and were unemployed or worked irregularly. The women were prostitutes. Most of them had been heroin addicts for several years who had recently switched to paregoric. Primary paregoric usage was becoming increasingly evident until the abrupt end of this practice with the sudden unavailability of this mixture in April, 1964. Most paregoric users processed and injected 1-7 ounces of the medication a day, but as many as 30 ounces (equivalent to 390 mg morphine) were occasionally employed. Other drugs notably pyribenzamine or a barbiturate were frequently concomitantly infused.
Most had been in prison. They occasionally were hospitalized voluntarily in Lexington, Kentucky, for controlled withdrawal of drugs in order to decrease their acquired tolerance. Family histories revealed that 84 % of them were separated or divorced.
Administration of paregoric is described in a report from the Narcotics Bureau, Detroit Police Department, November 8, 1962: "Addicts do not drink this drug, but instead, boil it down, strain it to remove camphor, and then inject the remaining liquid containing the narcotic directly into the blood stream."
A more detailed description from one of the more articulate paregoric users follows. A bottle containing 2 ounces of paregoric is emptied into a small pan, and heated on a stove. Simultaneously, the top of the liquid is ignited. It might then be boiled to dryness and reconstituted with a small amount of water. Other users boiled the original paregoric solution to a turbid constituency. It is then allowed to cool. Camphor (no longer in solution) floats to the top of the mixture, and is removed with cotton. The remaining fluid is aspirated through cotton into a medicine dropper or insulin syringe. A 24-26 gauge needle is usually employed.
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Number of Persons |
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|---|---|
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Age
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|
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20-24 yrs.
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4/21
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25-30 yrs.
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5/21
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31-40 yrs.
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11/21
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>41 yrs.
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1/21
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Mean age (yrs.)
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31.3 |
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Sex
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|
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Male
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18/21
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Female
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3/21
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Occupation
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Unemployed
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18/21
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Prostitutes
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3/21
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Years of Addiction
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1-5 yrs.
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4/21
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6-10 yrs.
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6/21
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11-15 yrs.
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11/21
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Paregoric/Pyribenzamine Habit
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0.1 yr.
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6/21
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1-2 yrs .
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5/21
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3-4 yrs .
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6/21
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>4 yrs.
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4/21
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Ounces of Paregoric/Day
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|
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1-2
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2/21
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3-4
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1/21
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5-6
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4/21
|
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7-8
|
1/21
|
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9-10
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7/21
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11-12
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3/21
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| 16 |
2/21
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| 30 |
1/21
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Tablets Pyribenzamine/Day
|
|
| 0 |
2/21
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1-5
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4/21
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6-10
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10/21
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10-16
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5/21
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Other Drugs (infused occasionally)
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|
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Seconal/Tuinal
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20/21
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Doriden
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20/21
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Amphetamine
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11/21
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Prison Record
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12/20
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Hospitalization, Lexington, Ky.
*
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2/17
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Family History
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|
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Married (stable)
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2/19
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Separated
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15/19
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Divorced
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1/19
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Widowed
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1/19
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Children
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10/19
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Purpose of hospitalization was to break narcotics habit.
Amphetamine, seconal, doriden, one of several barbiturates, or pyribenzamine tablets are sometimes crushed, dissolved in water, and added to the paregoric distillate. The mixture was then infused.
Most heroin addicts prefer the antecubital veins. These can be repeatedly used, and despite the apparent lack of aseptic technique in administration, infection is relatively infrequent. Benzoic acid, camphor, and anise have limited solubilities, are irritants and rapidly lead to occlusive sclerosis of veins into which they are instilled. Larger vessels were sought, and sequentially the femoral, popliteal, axillary, superficial veins of the saphenous system, and the jugular vein are used Occasionally the carotid or radial arteries were used. The jugular vein because of its large size and ready accessbility was finally regularly chosen. A characteristic scar in the supraclavicular region of the neck is the pathognomonic sign of the habit. Users of paregoric injected themselves or, in other cases, experts were available (see pictures, p. 18).
Narcotic Addiction
The classic concept of narcotic addiction includes three factors:(8) 1) compulsion - an overwhelming desire to continue taking the drug, 2) tolerance- a tendency to increase the dose, and 3) Withdrawal syndrome physical dependence on the drug with illness when it is withheld. Users, however, often are emotionally rather than physically dependent. Only about sixty percent of narcotic users seem to have any tolerance or subsequent withdrawal symptoms.(8)
This seems to have been remarkably substantiated in Detroit following the sudden unavailability of the drug with the acquisition of a non-exempt status. In 1963 there were 994 heroin or paregoric users in Detroit. In 1965 there were only 338. Since permanent cure of true addiction is rare, most of the paregoric users were not physically dependent.
Infections
One of 7 paregoric users had infective complications. Homologuus serum hepatitis, septicemia, abscesses and/ or cellulitis at injection sites (submandibular, region neck, leg or groin) were seen. In addition, purulent meningitis, brain abscess, septic arthritis pyopneuomothorax, and bacterial endocarditis were observed. Tetanus, mycotic, infections, and malaria did not occur as have been recorded in reports of other drug abuses. (10-13) All of the deaths were in patients with bacterial endocarditis.
Local or distant abscesses and bacteremias were predominantly due to Staphylococcus aureus, but β-hemolytic streptococci, and Bacteroides species were also cultured. Vegetations of bacterial endocarditis occurred on normal or abnormal valves (mitral, aortic, or Starr-Edwards prostheses). (14) These latter cases were also usually due to Staphylococcus aureus, but occasionally the leaflet of rheumatic heart was infected with a strain of Streptococcus viridans.
Vigorous therapy with antibiotics specifically suited to the bacterial pathogen in each case was needed to save the lives of many of these severely ill people. Bacterial cultures and sensitivity studies of organisms obtained from abscess sites, blood, cerebrospinal fluid, or joints were keys to a successful outcome. Although the infections were not nosocomial, these strains of staphylococci were usually resistant to penicillin suggesting that this antibiotic had been used before hospitalization.
Thrombophlebitis, Occlusive Venous Sclerosis, and Pulmonary Abnormalities
Thrombophlebitis and occlusive sclerosis of peripheral veins regularly follow the intravenous injection of paregoric.
In addition, several functional and pathologic pulmonary abnormalities have been noted among paregoric users. (15-19) Dyspnea and vague chest discomfort have occurred. Drs. Benjamin Lewis and Burleigh DeTar of this university have begun pulmonary function studies in a group of these patients, and preliminary data suggest that these individuals have definite decreased lung volumes and diffusing capacities. Other studies have found pulmonary hypertension. No obstruction to the rate of air flow has been found. These data are consistent with an alveolar-capillary block, and have not previously been noted afters multiple minute non-inflammatory pulmonary emboli of the usual variety.
Several of these patients have been autopsied. Lesions in the lungs were thrombosis of small pulmonary arteries, arterioles, and capillaries with starch granules or talc 6 crystal within the thrombi. Talc crystals were surrounded by granulomatous reactions and may well be responsible for much of the functional derangement.
The lesions have recently been reproduced after intravenous injections in rabbits. Paregoric alone is associated with passive hyperemia of the lung, starch with bland pulmonary thromboses, and talc with pulmonary thromboses with surrounding pulmonary granulomata.
6 Talc is the magnesium salt of metasilicic acid , Mg3H3(SiO3)4.It is the filler in pyrabenzamine tablets. Starch is the filler in seconal capsules.
The legal, socio-economic, and narcotic milieu of the intravenous use of paregoric in Detroit between 1956-1965 has been recorded. Its occurrence, the, characteristics of the users, and its sociologic and medical complications have been reviewed.
Goodman, L.S., and Gilman, A., The Pharmacological Basis of Therapeutics (Second Edition), 1830 pp.; pp. 216-280, The MacMillan Company, New York, 1955.
002Lewis, D.C., and Zinberg, N.E., "Narcotic usage II. A historical perspective on a difficult medical problem" New Engl. J. Med . 270: 1045-1050, 1964.
003Deke, A.L., H.M. Chief Inspector, Dangerous Drugs, London. - 5, June, 1964 (personal communication).
004United States Treasury Department. Remarks of Douglas Dillon, Secretary of Treasury, at White House Conference on Narcotic and Drug Abuse, Washington, D.C.; September 27, 1962. 3 pp. Washington, D.C. (Government Printing Office, 1962).
005Curran, W.J., " Narcotics, treatment and crime ", New Engl. J.Med. 271: 309-310,1964.
006Curran, W.J., " Massachusetts drug addiction act: legislative history and comparative analysis ", Harvard J. Legislation 1 : 89-114, June, 1964.
007Personal communications with narcotics officers of several cities, notably St. Louis, Mo.; Miami, Fla.; New York, N.Y.; and Louisville, Ky.
008Zinberg, N.E., and Lewis, D.C., "Narcotic usage II. A spectrum of a difficult medical problem ", New Engl. J. Med . 270: 989-993, 1964.
009Oerther, F.J., Goodman, J.L., and Lerner, A.M., " Infections in paregoric addicts " J.A.M.A. 190: 683-686, 1964.
010Doane,.J.C., " Tetanus as complication in drug inebriety ", J.A.M.A. 82: 1105-1106, 1924.
011Levinson, A., Marske, R.L., and Shein, M.K., "Tetanus in heroin addicts", J.A.M.A. 157: 658-660, 1955
012Wikler, A., et al ., "Mycotic endocarditis: report of case", J.A.M.A 119: 333-336, 1942.
013Most, H., " Falciparum malaria among drug addicts: epidemiologic studies ", Amer. J. Public Health 30: 403-410, 1940.
014Starr, A., and Edwards, M.L., " Mitral replacement: clinical experience with a ball-valve prosthesis ", Ann. Surg . 154: 726-740, 1961.
015Wendt, V.E., Puro H.E., Shapiro, J., Mathews, W., and Wolf, P.L., "Angiothrombotic pulmonary hypertension in addicts ", J.A.M.A 188: 755-757, 1964.
016Burton, J.F., Zawadski, E.S., Wetherell, H.R., and Moy, T.W., " Mainliners and blue velvet ", J. Forensic Sciences 10: 466-472, 1965.
017O'driscoll, W.G., and Lindley, G.R., "Self administration of tripelennamine by a narcotic addict ", New Engl. J. Med . 257: 376-377, 1957.
018Krainer, L., Berman, E., and Wishnick, S.D., "Parenteral talcum granulomatosis: a complication of narcotic addiction", Lab. Invest . 11: 671, 1962.
019Puro, H., Wolf, P.L., Skirgaudas, J., and Vasquez, J., "Experimental production of human blue velvet and red devil lesions" (submitted for publication).
