Narcotics research, rehabilitation, and treatment. Hearings, Ninety ...

436The first drug that we studied with this end in view was cj'chizocine,which is a very potent drug, but ])roduces some undesirable side effectsAvliich has made it necessary for physicians to be both knowledgeableof its pharmacology and skilled in its use. The second drug thatwas studied was naloxone, which iproved to bo a pure antagonist withoutimdesirable side effects, but which suffered from the disadvantagesthat it was short acting and quite ineffective by the oral route. We havecontinued to study other narcotic antagonists and have recently investigatedEN-1639A, which combines the structural features of bothnaloxone and c3^clazocine, and have found that this agent is two tothree times more potent than naloxone and cyclazocine and that ithas a longer duration of action than naloxone. We have further foundthat we can, for all intents and pur])ose, antagonize both tlie euphorogenicand the dejjendence-producing effects of large doses of morphinewith an oral dose level of 50 milligrams per day. Thus, we feel that wehave made substantial progress in finding the ideal narcotic antagonistwhich meets the criteria of: (1) Being potent, 10-50 milligrams perday; (2) having a long duration of action; (3) having no side effects,being a pure antagonist; (4) being orally effective; and (5) beingsuitable for depot administration.Additional efforts need to be undertaken to develop not only longeracting pure antagonists, but depots which will allow antagonists andmethadone-like drugs to be administered at 2-week to monthly intervalsand which will provide effective levels of the drug for this period oftime. If we can achieve these goals, I believe that certain motivatedaddicts can be benefited by this a])proach. Because the antagonists donot produce physical dependence and are nontoxic, they may find arole in the treatment of the juvenile experimenter.Turning now from the anatgonists to the general problem of drugdependence, it is my personal, though professional, oi)inion thatmounting an effort to deal effectively with drug abuse problemsspecifically and the problem of psychopathy generally should startAnth the assumptions that we do not have an understanding of thebasic psychopathology or ]:>athophysiology of these disease ])rocessesand that we do not have effective and nontoxic therapeutic measuresto deal with all except a small proportion of the patients incapacitatedwith this disease process.It is further my conviction that both the size of the problem and itsimpact on society will continue to increase until we find definitivesolutions. The reasons for this conviction are: (1) The number ofabusable drugs will increase because of the growth of the chemical andpharmaceutical industries, (2) the impact of psychopathic behavioron society will become less tolerable as our society increases in sizeand complexity, and (3) the complexity and stabilit}^ of our societylessens the im})act of social controls on i)sychopathic behavior. Becauseof the imminence of the i)roblem, I would recommend that thefollowing stei)s be taken: (1) Increase our efforts to identify drugswith an abuse potentiality early and to utilize ap])ropriate controlmeasures, (2) increase our efl'orts to understand the psychopathologyand pathophysiology of psychopathy and through this efl"ort to rationallyi'ornndiii(» therai)eutic processes, (3) aggressively search fornontoxic, nonaddicting drugs that may be effective in the treatmentof psychopathy.Thank you, sir.