STUDIES OF THE DEPENDENCE-PRODUCING POTENTIAL OF THE NARCOTIC ANTAGONIST 2-CYCLOPROPYLMETHYL-2'-HYDROXY-5,9-DIMETHYL-6,7-BENZOMORPHAN (CYCLAZOCINE, WIN-20,740, ARC II-C-3)

¹ National Institute of Mental Health, Addiction Research Center, U. S. Public Health Service, Lexington, Kentucky

The effects of single doses and chronic administration of cyclazocine have been studied in nontolerant postaddicts, as well as in postaddicts physically dependent upon morphine. In addition, cyclazocine has been compared with morphine sulfate and nalorphine hydrochloride.

Single dose studies indicate that cyclazocine produces a degree of euphoria, and that maximal euphoric effects are produced with doses of the order of magnitude of 1 mg/70 kg. The subjective effects produced by cyclazocine, however, are qualitatively different from those produced by morphine and most closely resemble those of nalorphine. In addition, larger doses of cyclazocine (1.0 and 2.0 mg/70 kg) produced certain effects which resembled, at least superficially, those produced by barbiturates.

Cyclazocine does not suppress abstinence in subjects physically dependent on morphine; on the contrary, it precipitates abstinence in a manner similar to that of nalorphine.

Subjects chronically intoxicated with 13.2 mg/70 kg/day of cyclazocine, using a gradually progressing dose schedule, showed definite evidence of tolerance to cyclazocine, cross tolerance to nalorphine, and exhibited a definite abstinence syndrome when cyclazocine was withdrawn. The predominant signs of abstinence from cyclazocine consisted of an increase in body temperature, mydriasis, loss of appetite, decrease in body weight, and tachycardia. The abstinence syndrome was slow in developing, first becoming apparent on the third or fourth day following withdrawal, and reaching a maximum on the seventh day of abstinence. Minimal signs of abstinence were seen as long as 6 weeks following withdrawal. The abstinence syndrome was qualitatively different from that from morphine. Although cyclazocine produces a type of euphoria, tolerance, and physical dependence, the bulk of evidence indicates that this agent is qualitatively different from morphine. In general, the effects of cyclazocine most closely resembled those of nalorphine.

In conclusion, cyclazocine should not be classified as a morphine-like analgesic and its potential for abuse by narcotic addicts is regarded as being very low. Whether it would be abused on the basis of other pharmacologic properties, particularly for its sedative characteristics, cannot be predicted on the basis of these experiments.

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