INSULIN TREATMENT OF MORPHINE ABSTINENCE SYMPTOMS

AN EXPERIMENTAL EVALUATION

¹ From the Department of Pharmacology of the School of Medicine, Western Reserve University, Cleveland, Ohio

The irritability of albino rats addicted to increasing doses of morphine sulfate for a period of five weeks was not significantly or consistently affected by the subcutaneous administration of 0.5, 1, 2, or 5 units of insulin per kilogram as indicated by their struggle response to a uniformly uncomfortable situation before and one hour after injection.

The treatment of addicted rats with 10 units of insulin per kilogram resulted in the death of 75 per cent of the animals so treated within 2 hours after injection. With this dosage the number of struggles remained approximately the same but the magnitude of individual struggles increased. The only quieting effect found occurred between periods of marked activity (probably convulsions?) and was invariably followed by the death of the animal.

Rats injected subcutaneously with 1 unit of insulin per kilogram daily throughout the entire four- to five-week period of daily morphine administration showed an increasing pre-injection irritability which was unaffected by insulin and equivalent to that found in rats receiving morphine and water daily. Likewise, tolerance as determined by the degree of post-morphine tranquilization was not affected by this dosage of insulin.

During permanent withdrawal of morphine sulfate no differences were observed between animals given 1 unit of insulin per kilogram daily and those given water, either in degree of irritability or in rate of return to normal.

Normal animals receiving 1 unit of insulin per kilogram daily for a period of five weeks showed only a decreasing trend of irritability similar to that found with water controls. Rats therefore show no tendency to become addicted to daily insulin at the dosage used.

Rats receiving 1 unit of insulin per kilogram daily failed to increase their weight faster than control animals. The same daily dosage likewise failed to prevent or affect the weight loss which occurred upon daily administration of increasing doses of morphine sulphate.