STUDIES ON MODIFICATION OF THE MORPHINE ABSTINENCE SYNDROME BY DRUGS

The morphine abstinence syndrome of moderate intensity is sufficiently uniform from the 24th to the 40th hour to permit reasonably accurate prediction of its course from the 30th to 40th hour from data obtained during the preceding 6 hours. A method is described for measuring the effect of drugs administered at the 30th hour of abstinence as percentage deviations from the expected course of the abstinence syndrome. Results by this method confirm the ineffectiveness of thiamine and indicate that prostigmin, pentobarbital, and atropine in the doses given do not ameliorate abstinence syndrome intensity appreciably. Codeine in 26 mgm. dosage also was ineffective. Pyridoxine caused a slight but presumably non-significant reduction. Diethyl-aminomethyl- 3 -phenanthryl carbinol caused a prolonged and probably significant reduction. Significant reductions were caused by 52 and 104 mgm. codeine; 5, 10, and 20 mgm. morphine; 100 and 200 mgm. Demerol; and by 80 mgm. morphine sulfuric ether. The extent of ameliorative effect increased somewhat with dosage. Prostigmin did not potentiate this effect of morphine. The effect of 20 mgm. morphine intravenously was greater and more sustained than an equal amount given subcutaneously. While these results confirm the cross-effectiveness of drugs structurally or pharmacologically similar to morphine, the dose relationships were not the same as found by substitution. Although this method probably will not be useful for studying the duration of action of drugs, the technique offers a quick method for detecting probable addiction liability of drugs.