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A NEW TREATMENT OF ALCOHOLISM WITH

CYANAMIDE (H 2 NCN)

 

HIROSHI MUKASA. TAKASI ICHIHARA

and AKIRA ETO

Department of Neuropsychiatry, Kurume University ,

School of Medicine , Kurume

 

INTRODUCTION

 

The most important and difficult problems in the treatment of alcoholism are how to relieve alcoholics from addiction, and how to keep them from addiction for a long time until they are completely cured.

Practically, however, in many cases, the abstinence forced on heavily-addicted alcoholics ends in failure even though it may be successful temporarily. This shows how difficult abstinence is for alcoholics. Therefore, we must try to find some other effective therapy. If it is possible to reduce the alcohol tolerance of the patient and if allowed to drink as much as ordinary people do instead of depriving him of the pleasure of drinking entirely, such a therapy probably is the most reasonable one.

For this purpose, the authors worked out a new therapy for reforming the problematical drinking habit by administering cyanamide to alcoholics, and named it “Sesshu Ryoho” or the temperance therapy.

 

MATERIALS AND METHODS

 

Although the treatment of alcoholism may be divided into well known categories: psychotherapy and drug therapy, the final purpose of therapy must be abstinence, temperance or to rid of the alcohol drinking habit. Alcohol deterrent drugs used heretofore as aids in the treatment of alcoholism were emetics, natrium thiosulfate and disulfirum introduced by Jacobsen 2) . In the disulfirum treatmet, however, several disadvantages have been reported: 1) its effect appears very slowly, 2) due to excessive disulfirum-alcohol reaction, some highly unpleasant side-effects are caused when the administration of disulfirum is followed by giving a small amount of alcohol for trial drinking, 3) as it is an abstinence treatment, it often gives the patients an unpleasant experience, 4) tolerant quantity of alcohol is difficult to determine, 5) that the patients are rehabilitated by the administration of the drug is difficult and that it is used for temperance treatment is impossible.

To off- set these short-comings of disulfirum, the nitro-lime treatment was introduced. Many advantages have been reported with regard to this treatment. But some foreign components, such as caustic lime and carbon, containing in nitro-lime aside from calcium cyanamide, its essential component, might develop the irritant action on the skin and mucous membran and cause unpleasant odor and bad taste. Therefore, nitro-lime is not suitable for oral use. Many studies and experiments have been carried out in order to purify calcium cyanamide and to make it fit for oral use. From the results obtained by many experiments, the authors ascertained that the alcohol detaining effect of cyanamide was due to the mechanism that cyanamide was absorbed by the stomach, following the transformation from calcium cyanamide by acid in the stomach.

 

CaCN 2 + 2 HCl a CaCl 2 + HN – C – HN

After further experiments, cyanamide was proved to have many merits as a medicament for temperance and also for abstinence in the form of stable solution for oral use. It is now offered as an alcohol deterrent under the name “CYANAMIDE SOLUTION YOSHITOMI”.

Cyanamide is a white, odorless needle crystal. It has a low melting point (42.9 o C), and is unstable in nature. Progress in the use of cyanamide has reached such a point that a 1% solution trial-manufactured by the Yoshitomi Pharmaceutical Company can be used to create stable effect.

Cyanamide has sure and prompt anti-alcoholic effect. It has a safe and almost no harmful side-effect, and can be used in a simple manner. Furthermore, the use of a small dose (10-60 milligrams) of cyanamide prevents morbid alcoholism, and permits the adjustment of the patient's alcohol tolerance by an appropriate dosage without greatly affecting his enjoyment of alcohol. The appropriate dosage of cyanamide differs with individuals, and cannot be fixed categorically. Roughly, however, we can fix it at best at 10 to 60 milligrams. Since this medicine is effective for at least 12 hours, starting 10 minutes after administration of the alcoholic, it is enough to use it only once a day. The patient must learn as soon as possible to drink the appropriate quantity of alcohol while using cyanamide regularly, and must make it a habit. In Japan , cyanamide dosage is determined so as to turn alcoholics into moderate drinkers whose tolerance is about 200cc of “Sake” with a 15% alcohol content. Experience shows that the period of treatment should be at least five months. The longer the period, the better the result. As this gives little pain to alcoholics, it can easily be applied to out-patients.

 

RESULTS

 

Summarizing the results of temperance therapy, which was used in 250 cases during the past three years or so, the authors find that the therapy has a favorable social rate of cure at 76 per cent. Successful use of this therapy, needless to say, presupposes a good attitude on the part of the alcoholic, good understanding and cooperation in the treatment on the part of this family, and close contact between the doctor and the patient including proper interviews and guidance. Some alcoholics, however, start problematical drinking again by arbitrary adjustment of their dosages of the medicine during the period of treatment or by ceasing to use it. Some other alcoholics, having no intention at all to be treated are putting their family and community to trouble. Therapy for these people is an urgent need.

Cyanamide is prepared in the form of tasteless, odorless solution. It is very easy to administer, mixing it in food without the patient's knowledge. Furthermore, cyanamide is much safer than Antabuse and fertilizer nitro-lime, and no danger is involved if the patient drinks alcohol after taking 5 to 10 milligrams of cyanamide without knowledge. The patient's alcohol tolerance can thus be reduced safely.

A proper method of reforming problematical drinking without the patient's knowledge, therefore, is to administer cyanamide in a quantity as small as 5 to 10 milligrams of cyanamide unwares. The patient's drinking capacity can thus be reduced safely.

The method for rectifying the problematical drinking habit in doses as small as 5 to 10 milligrams at the start and then to increase the dosage gradually. In cases where temperance therapy is adopted, the authors proceed with the same dosage without the patient's knowledge. Thus, the authors can treat successfully those alcoholics who refuse to take the medicine or who have no intention of temperance. The authors name this “Special Therapy” for alcoholism.

In the past few years, the authors had been trying this therapy in 110 cases. In 43 of the 110 cases, the authors asked their family to treat the patient by their physicians and recognized the patient's adaptability to the therapy after obtaining information about their health conditions from their families. In these cases, the authors adopted the special therapy from the start. In the remaining 67 cases, the patients voluntarily desired to be treated, and in the course of the treatment a switchover was made to special therapy. These alcoholics were first given placebo (distilled water) temporarily so that special therapy could be effected smoothly.

The alcoholics were engaged in occupations as shown in Table I. They were all breadwinners for their families. In age, they ranged from 20 to over 70, as shown in Table II. Those in their thirties accounted for the highest percentage. The cyanamide dosage was from 10 to 60 milligrams, as shown in Table III. As seen in Table III, there were many cases in which the dosage was maintained between 20 to 30 milligrams so that patients would become moderate drinkers. The

Occupation

Clinical Case
Merchants
25
Farmers
25
Public
24
Officials
20
Employees of company Enterprisers
3
Buddhist
3
priests
3
Shopmen
4
Others
110

 

Difference by Age

Clinical Case

20-29 Yrs.
19
30-39 Yrs.
40
40-49 Yrs.
24
50-59 Yrs.
21
60-69 Yrs.
5
70-79 Yrs.
1

Others

 

Total

110



Cyanamide

10mg.

15 mg.

20 mg.

25 mg.

30 mg.

40 mg.

50 mg.

60 mg.

 

Clinical Case

4

9

25

20

32

12

6

2

110
total



Продолжительность

Клинический случай

Прекращение (Good. Unclear)

 

3-5 Mon

? - 1 Yrs.

1-2 Yrs.

2-3 Yrs.

3-4 Yrs.

Total

 

27

18

22

5

4

76

 

15 (7. 8)

8 (4. 4)

8 (4. 2)

3 (3. 0)

 

34 (18. 14)


period of treatment ranged from three months up to four years as shown in Table IV. In 76 cases shown in the Table, which are in a state of social cure, the treatment is still being continued. In 34 cases, the treatment was discontinued after three months to three years. In 20 of these cases, a state of social cure was maintained, while in the remaining 14 cases the treatment proved to be effective, but nothing is known about their post-treatment condition.

DISCUSSION 

Since the description of Disulfirum (Antabuse) by Hald and Jacobsen 2) in 1948, as a substance of anti-alcoholic action the pharmacotherapy has completely changed and progressed remarkably 1)7)9)10) .

However, during the clinical application of antabuse, such defects as the increased difference of the effectiveness were pointed out by some investigators 1)5)7)10) . In order to improve these defects, anti-alcoholic therapy with nitro-lime was advocated by Usuba 10) . In the United States of America , on the other hand, citrated calcium carbamide (Temposil containing extremely purified calcium cyanamide 50 mg., citrate 100mg. in one tablet) was invented by Furguson 1) . One of the authors, Mukasa 5)6)7) advocated cyanamide for alcoholic therapy as clinical use. Practically, however, abstinence is difficult for alcoholics to keep with these drugs for a long period.

Jacobsen 3) described that the ideal therapy for the chronic alcoholic is not to deprive him of the drinking pleasure, but to put him back to the moderate drinking taste, which is his ideal, but unfortunately, such method has not yet found, and the best possible method is to make him continue absolute abstinence.

Lemere 4) advocated that the most generally employed and effective treatment for alcoholism is a combined approach in U.S.A. The use is made of medical care, alcoholic anonymous, disulfirum, and definitive psychotherapy in varying degrees.

From the psychoanalytical standpoint of view, Navratil 8) advocated that the heavy drinker together with his wife should receive the anti-alcoholic therapy.

Alcoholics are in various circumstances, and the special therapy of the authors should be used in a manner suited to the condition of each alcoholic, with the understanding and earnest cooperation of their families. In practice, the rate of effectiveness of the temperance therapy is very high. The alcoholic is relieved the painful thought that he must take anti-alcoholic medicine every day. He becomes to believe that he has been cured, and become to be able to live in peace. It should to believe that, in the course of treatment, the alcoholic brinks only a little alcohol and his alcoholic addiction totally disappears as he becomes to be used to limited drinking.

The new temperance therapy has an advantage over the conventional prohibition therapy with anti-alcoholic medicine in which it gives less pain to the alcoholic, that is easier, and that it has a higher effectiveness. From these facts, the authors believe that this temperance therapy is applicable to alcoholism.

SUMMARY 

The authors found a new anti-alcoholic treatment through the administration of cyanamide which does not take away the pleasure of drinking from chronic alcoholics but leads them to become moderate drinkers. The subjects were chronic alcoholics who had some troubles in their health and in their family or social life.

The administrative quantity of cyanamide used was 10-60 mg. At the first stage, about 20 mg. of cyanamide was used and if the anti-alcoholic reaction was not fully realized, the dose of cyanamide was gradually increased.

As to the method of application of cyanamide, it was sufficient to give a dose of cyanamide once a day in the morning o at noon . However, it was a necessary factor that this application should always be given before drinking “Sake”.

At the time of drinking Sake after cyanamide, it was desirable to drink slowly and avoid the discomfort which comes as the result of over-drinking. For this purpose, it was most desirable to drink 100 cc of Sake with a 15% alcohol content within a period of 10-15 minutes.

As the length of treatment period, it was necessary to dose continuously for at least five months, and the longer the treatment continued, the better was the anti-alcoholic action obtained.

The safety of anti-alcoholic treatment with cyanamide is very high and its procedure is so simple that the application of this treatment for the out-patient is very easy. Moreover, the long term hospitalization is not so significant, although some patients are required to be hospitalized, during the early stage of treatment.

Cyanamide has no taste or smell when it is used in a mixture. It is very easy to administer without the knowledge of the subject. Cyanamide is comparatively safer than Antabuse and Nitrolime, so its therapeutic effects upon the chronic alcoholics and the addicts who refuse its intake or do not wish absolutely to achieve temperance can be brought by administering secretly a small amount of cyanamide at first and then gradually increasing the amount. The authors called it “special therapy” for alcoholism. If this is done, the effective ratio is very high as shown in the clinical results of 110 cases and can be expectable treatment from now on.

The successful use of this anti-alcoholic treatment depends on the following three points; namely, the patient's attitude to the treatment, the full understanding and cooperation of relatives and finally, the appropriate guidance by the doctor.

REFERENCES 

  1. Ferguson , J.K.W.: A new drug for the treatment of alcoholism. Canad. M.A.J., 74 , 793, 1956.
  2. Hald, J. & Jacobsen, E.: A drug sensitizing the organism to ethyl-alcohol. Lancet, 255 , 1001, 1948.
  3. Jacobsen, E.: The treatment of alcoholism in Denmark . Transactions of the 16 th Genera. Assembly of the Japan Medical Congress, 1959, Tokyo .
  4. Lemere, F.: A comparison of the various methods of treating alcoholism. The joint meeting of the Japanese Society of psychiatry and neurology and the America psychiatric Association. May, 1963, Tokyo .
  5. Mukasa, H.: Clinical study on the anti-alcoholic action of Cyanamide (I). The Journal of the Kurume Medical Association, 22 , 1632, 1959.
  6. Mukasa, H.: Clinical study on the anti-alcoholic action of Cyanamide (II). Clinical Psychiatry, 2 , 23, 1960.
  7. Mukasa, H.: Studies on the physiological anti-alcoholic effects of Cyanamide and its clinical application. Psychiatr. Neurol. Jap., 64 , 469, 1962.
  8. Navratil, L.: Die Rolle der Ehefrau in der pathogenese der Tranksucht. Wien 2, Nerv., 14 , 90, 1957.
  9. Takahashi, H.: Etude Psychiatruqye sue les Toxicomanes Alcooliques. Psychiatr. Neurol. Jap. 62 , 592, 1960.
  10. Usuba, M.: Nitrolime – treatment of Alcoholism. Psychiatr. Neurol. Jap. 58 , 93, 1956.