Pharmacological investigation and evaluation of the effects of combined barbiturate and heroin inhalation, by addicts

Abstract

Initial observations of addicts who employ barbiturates as a base powder during the smoking of heroin suggested that some of these individuals might suffer from the deleterious effects of chronic barbiturate intake, or in fact be addicted to both barbiturates and heroin. Therefore, an investigation was undertaken to determine (1) the nature of the base powder, (2) the amount of base powder used by addicts, (3) the effect of volatilization of the base powder and (4) the amount of volatilized base powder inhaled by the addicts. On the basis of these results, previous published information and clinical observations, an evaluation has been made of the effects of combined barbiturate and heroin inhalation in addicts who " chase the dragon ".

Details

Author: Carl C. Gruhzit
Pages: 8 to 11
Creation Date: 1958/01/01

Pharmacological investigation and evaluation of the effects of combined barbiturate and heroin inhalation, by addicts [1]

Dr. M.D., Ph.D., Carl C. Gruhzit Lecturer in Pharmacology, University of Hong Kong

Initial observations of addicts who employ barbiturates as a base powder during the smoking of heroin suggested that some of these individuals might suffer from the deleterious effects of chronic barbiturate intake, or in fact be addicted to both barbiturates and heroin. Therefore, an investigation was undertaken to determine (1) the nature of the base powder, (2) the amount of base powder used by addicts, (3) the effect of volatilization of the base powder and (4) the amount of volatilized base powder inhaled by the addicts. On the basis of these results, previous published information and clinical observations, an evaluation has been made of the effects of combined barbiturate and heroin inhalation in addicts who " chase the dragon ".

Analysis of Substances used by Addictswho "Chase the Dragon"

Four samples of base powder or " daai fan " were chemically tested and assayed according to the procedure in the British Pharmacopoeia (1953). Relatively pure sodium barbitone powder (May & Baker) was employed as a control of the methods of identification and assay. All samples of base powder were identified chemically as barbitone base and assayed at 97 ± S.D. 3%. It is suspected that the colouring matter employed in at least one of the samples was litmus, but this matter was not investigated further (appendix 1).

The base powder (dissolvedin weak alkali) was tested biologically in eight rabbits, and the results were compared with those produced by the administration of sodium barbitone. The effects produced by the administration of base powder were indistinguishable from those produced by the administration of an equivalent amount of sodium barbitone (appendix 2).

Twelve packets of heroin tested according to the method in the British Pharmacopoeia were determined to contain diacetylmorphine hydrochloride. The melting-points ranged between 222°C and 229°C indicating that the samples were not highly purified. Assay of the samples indicated that they contained 92 ± S.D. 5% heroin hydrochloride (appendix 3).

These results obtained by chemical and biological assay are in close agreement with the findings of the government chemists, except that on occasion they have found phenobarbitone employed as the base powder. Since barbitone and phenobarbitone have similar pharmacological effects, the results with barbitone are applicable to both drugs.

Volatilization and Condensation of the Base Powder

Twenty-seven one-gramme samples of the base powder were volatilized by gentle heating. The vapour was collected and condensed by a cooling jacket and the condensate was dissolved in warm alcohol. The alcoholic solution was evaporated to dryness and the residue was weighed and tested chemically and biologically for activity. Following volatilization, 57-95% of the barbitone could be recovered (appendix 4). The degree of recovery was primarily dependent on the nature of heating. Very gentle heat gave high recovery yields, while stronger heat resulted in partial decomposition of barbitone to carbon, carbon dioxide, ammonia and other unidentified by-products. The residue left in the flask after heating formed a black stain similar to that observed on the tinfoil used by addicts.

Biological testing of the material collected after volatilization produced results which were in close agreement with those obtained by chemical assay (appendix 5).

The time required by addicts to volatilize the combined base-powder-heroin mixture and the formation of the residue on the tinfoil indicate that a significant, but not excessive, portion of the base powder used by addicts is decomposed. Although no actual data can be obtained, it is estimated, on the basis of these observations, that approximately 15-25% of the base powder is broken down by heating during the process of " chasing the dragon". The exact amount which is decomposed will certainly vary with the habits of the individuals.

Estimation of the Amount of Heroin and Barbiturates inhaled by Addicts

It is naturally difficult to obtain information regarding the actual intake of base powder by addicts. The base powder is freely available and, in general, can be used in any quantity which the smoker desires. Observation of the addicts during the process of " chasing the dragon " is, in general, unsatisfactory, because under surveillance they avoid the use of heroin. Estimates by addicts (prisoners), however, indicate that they usually use about four granules of base powder per granule of heroin. This is approximately the ratio utilized when heroin was given to addicts for observational purposes. This is also the approximate ratio of base powder and heroin contained in " prepared packets " sold to some addicts.

The average addict spends approximately HK $ 3-4 per day on heroin, and an occasional addict spends more than HK $10 per day on heroin. At the current prices, this is the equivalent of the smoking of approximately 0.2-0.25 g of heroin per day by the average addict and more than 0.75 g per day by the addict with a large consumption. If only 50% of the fumes are inhaled, the average addict inhales over 0.1 g of heroin per day, and some individuals take in over 0.3 g per day.

If one assumes that the addict who " chases the dragon" uses four times as much base powder as heroin, the average addict would use about 1.0 g per day of barbitone. Depending on the amount of decomposition with heating, and the skill of the addict in inhaling the fumes, the average total intake would probably be only 50-75% of this amount. However, the addict who consumes large quantities of heroin also uses large quantities of base powder, and under these conditions the daily intake of base powder may exceed 1.5 g.

These estimates of drug intake are confirmed by clinical observations (vide infra) and results of the determination of barbiturate levels in the blood and urine specimens obtained from newly admitted prisoners who " chased the dragon " just prior to their arrest (appendix 6).[2]

Evaluation of the Effect of Drug Intake

The results of controlled studies and the study of the withdrawal symptoms induced by the administration of nalor-phine indicate that the daily intake of even less than 0.02-0.04 g of heroin may produce addiction. Even the least adroit person who " chases the dragon " probably inhales far in excess of this amount. Therefore, an individual who "chases the dragon" repeatedly will become addicted to heroin. This fact is confirmed by observing individuals at liberty and by the medical examination of individuals committed to prison. One can detect the addicts by their characteristic withdrawal symptoms even prior to questioning. Even the addicts who claim to smoke only one to two HK dollars' worth of heroin per day show definite withdrawal signs.

The addicting dose of barbiturates is also variable. However, controlled studies and clinical observations indicate that the continued intake of 0.6-0.8 g per day of the short-acting barbiturates - e.g., pentobarbitone - produces addiction in the majority of individuals. The addicting dose of the barbiturates varies with the potency of the compound, and therefore larger amounts of barbitone would be required to produce addiction. The total intake of barbitone by the average individual who " chases the dragon " is not sufficient to produce barbiturate addiction. Individuals who consume large quantities of heroin, and therefore consume large quantities of barbitone are, however, likely to become addicted to barbiturates. Addiction is also likely to occur in individuals with renal disease who have impaired excretion of barbitone. It is also probable that many individuals who have insufficient funds to purchase heroin use barbitone as a substitute and thus become addicted to the latter drug. Even non-addicting amounts of barbitone would be likely to produce some degree of sedation, and in higher doses, mental confusion, a staggering gait, and slurred speech.

This theoretical evaluation based on the estimate of drug intake is adequately confirmed by observing addicts and individuals during their withdrawal period. The majority of heroin addicts do not show signs of chronic barbiturate intoxication. Nevertheless individuals have been observed who do show signs of barbiturate addiction (vide supra). Unfortunately, severe heroin addiction may also produce similar signs, and it is difficult to attribute the correct proportion of signs to each of the two drugs.

The majority of individuals who cease " chasing the dragon " (because of incarceration) do not show typical signs of barbiturate withdrawal. There is no skin rash (which may result from chronic barbiturate administration), nystagmus or tremors in most addicts during withdrawal. Nevertheless, a significant percentage (about 1%) of prisoners who formerly " chased the dragon " develop convulsions during the withdrawal phase. These convulsions are not usually produced in individuals addicted to the opium alkaloids or their derivatives, but are characteristic of the withdrawal signs in individuals severely addicted to barbiturates. The percentage of individuals showing convulsions probably represents only a minimal figure for barbiturate addiction. It is likely that many individuals who have only tremors or minor twitches during their withdrawal period are not observed during their attacks and are therefore not reported to the medical officer. It is therefore likely that at least about 5-10% of individuals who " chase the dragon " have combined heroin and barbiturate addiction.

In many respects barbiturate addiction is a greater danger than addiction to the " narcotic " group of drugs. The depression of mental facilities which it produces is usually greater than one observes in " straight " morphine or heroin addicts. In addition, the effects produced by barbiturate withdrawal are considered by most workers in the field to be more severe and more likely to cause death than those produced following " narcotic " withdrawal. In fact, the withdrawal signs may be so severe that from a medical standpoint abrupt withdrawal is counterindicated in any individual who is suspected of being a barbiturate addict. Certainly the relatively high incidence of convulsions which has been observed in prisoners indicates the wisdom of this advice.

The combined use of heroin and barbiturates produces a particularly odious form of drug addiction. The central nervous system depression produced by these drugs is additive and may result in marked stupor. Furthermore, the individual has physical dependence on two distinct types of depressants, and continued intake of both drugs is necessary to prevent withdrawal symptoms. From a medical standpoint the combined use of heroin and barbiturates represents a great danger to the individual.

10 BULLETIN ON NARCOTICS l JULY-SEPTEMBER 1958

APPENDICES

Appendix 1

Four samples of base powder were subjected to the following chemical tests for the identification of barbitone. The results obtained were identical to those obtained using known samples of barbitone base.

  1. Solubility in water, 95% alcohol, solvent ether, chloroform and alkali hydroxides.

  2. A gelatinous precipitate was produced when several drops of mercury nitrate solution were added to a saturated aqueous solution of the test substance acidified with nitric acid.

  3. The addition of 1 ml of solution of copper sulphate with pyridine to a solution containing 0.1 g of the test substance dissolved in 1.5 ml of N/1 sodium hydroxide and 10 ml of 10% w/v pyridine in water produced a lilac-coloured precipitate.

  4. Fusion of the test substance with caustic alkali or boiling of a strong caustic alkali solution of the test substance resulted in the production of ammonia.

Melting-point determinations on the base powder ranged between 185°C and 191°C. Melting-point determinations on known samples of barbitone base ranged between 190°C and 192°C.

Base powder

Test 1

Test 2

Test 3

Average

1.
187 185 188 187
2.
188 190 185 188
3.
190 191 186 189
4.
188 185 188 187
Average
 
 
 
188
Barbitone base
192 190 190 191

Assay of the base powder showed the following percentage barbitone content:

Base powder

Test 1

Test 2

Test 3

Average

1.
102 94 97
97.7%
2.
95 101 96
97.3%
3.
100 93 93
95.3%
4.
98 102 97
99.0%
Average
 
 
 
97% ± S.D. 3%
Sodium barbitone
103 100 101
101.3%

Appendix 2

The intraperitoneal injection in rabbits of 200 mgm/kgm base powder (dissolved in weak alkali) produced effects which were indistinguishable from those produced by the injection of an equivalent amount of sodium barbitone (calculated as base).

Rabbit

Base powder

Latent period of anaesthesia (Minutes)

Duration of anaesthesia (Minutes)

1 1 38 490
2 1 27 330
3 2 33 380
4 2 48 460
5 3 46 420
6 3 29 360
7 4 37 320
8 4 39 370
 
 
Average 37
390

Comparable experiments employing sodium barbitone gave an average latent period of 34.5 min. and a duration of anesthesia of 420 min.

Appendix 3

The following chemical tests were used to confirm that twelve packets of "heroin" contained diacetylmorphine hydrochloride:

  1. Solubility in water, 90 % alcohol and solvent ether.

  2. Contact with nitric acid produced a yellow colour which changed to bluish-green on heating.

  3. Heating following the addition of 1 ml of sulphuric acid to a 2 ml solution of 90 % alcohol in which 0.1 g of heroin was dissolved produced the characteristic odour of ethyl acetate.

  4. The samples gave positive tests for chlorides.

  5. The yellow colour produced by the addition of 2 ml of 1% w/v sodium nitrate in water followed by the addition of 3 ml dilute ammonium hydroxide to 0.5 ml of 0.1% w/v heroin solution in N/10 hydrochloric acid was less than when 0.0015 % w/v anhydrous morphine in N/10 hydrochloric acid was treated in a similar fashion.

As shown in the following table, the melting-point determinations of the heroin samples ranged between 222°C and 229°C. The melting-point of pure diacetylmorphine hydrochloride is listed at 229-233°C. Because of the size of the packets it was necessary to use different samples of heroin for identification tests, melting-point determinations and assay procedures.

Packet

Test 1 (° C)

Test 2 (° C)

Average

13 226 223 224.5
14 222 224 223
15 229 227 228
16 224 223 224.5
17 227 223 225

Uncontrolled assay of samples of heroin indicated that they contained 92% ± S.D. 5 % diacetylmorphine hydrochloride. The packet size did not allow for duplicate determinations to evaluate the variations in the test methods. It is likely that the large standard deviation is due in part to variations in the testing and in part to variations in the samples tested.

Packet

% diacetylmorphine hydrochloride content

Packet

% diacetylmorphine hydrochloride content

18 98 24 99
19 84 25 80
20 88 26 93
21 87 27 88
22 96 28 95
23 92 29 93

Appendix 4

One-gramme samples of base powder were volatilized and the vapours were collected and condensed by a cooling jacket. The condensate was dissolved in warm alcohol and evaporated to dryness, and the residue was weighed and tested chemically and biologically for activity.

Sample

Volatilization time (Minutes)

Recovery (%)

1
22 92
2
18 97
3
17 90
4
15 82
5
15 80
6
13 83
7
12 79
8
11 78
9
11 86
10
11 77
11
11 74
12
10 82

Sample

Volatilization time (Minutes)

Recovery (%)

13 10 84
14 10 78
15 10 69
16 10 78
17 10 78
18 10 74
19 9 68
20 9 71
21 8 69
22 7 68
23 7 59
24 5 66
25 5 62
26 5 57
27 5 57

Appendix 5

The intraperitoneal injection in rabbits of 200 mgm/kgm of the condensate (dissolved in weak alkali) obtained after volatilization of the base powder produced results comparable to those obtained following the injection of an equivalent amount of sodium barbitone (dose calculated as base).

Sample

Latent period of anaesthesia (Minutes)

Duration of anaesthesia (Minutes)

15 33 370
16 44 380
17 30 420
18 37 430
Average
36 400

Appendix 6

Blood and urine specimens were obtained from each of two prisoners by Dr. C. O. Lee and were analysed by Dr. E. G. N. Greaves, Government Chemist. Both patients had been deprived of drugs for three to five days prior to the sampling. Barbiturates were not detected in one patient, who, it is estimated, inhaled only 0.3-0.4 g of barbitone per day. The majority of barbitone is excreted within 48-72 hours following cessation of drug intake, and in this individual presumably only undetectable traces remained in the blood and urine at the time of sampling. In the second patient significant amounts of barbitone were detected in the blood, indicating a high level of barbiturate intake, which is compatible with the relatively large amounts of money which this patient spent on " chasing the dragon " prior to his arrest.

Although technical difficulties prevent an accurate quantitative determination of the blood and urine barbitone level in the second patient, it is likely that he was inhaling sufficient barbitone to develop combined heroin and barbiturate addiction as the result of " chasing the dragon ".

1

See preceding article.

2

The blood and urine samples where obtained from prisoners by Dr. C. O. Lee and were analysed by Dr. E. G. N. Greaves, Government Chemist.