Arthur Zaks

Naloxone in heroin dependence

Naloxone is a potent and rapidly acting narcotic antagonist, with a duration of action which is shorter (3 to 4 hours) than that of heroin. In a clinical trial of naloxone in the treatment of heroin dependence, a daily oral dose of 100 mg. at 8 A.M. and 7 P.M. effectively blockaded 20 mg. of heroin, with partial blockade of 40 mg., for up to 10 hours after the morning dose. In narcotic antagonism therapy of opiate dependence, naloxone has the advantages of potency, rapid action, absence of secondary effects, and acceptability. It has the disadvantages of brief action and high cost.

MARIJUANA, EEG, AND BEHAVIOR

Studies of EEG effects of Cannabis and related substances (hashish, THC) have been few, and none are definitive. In part, this is a reflection of the lack of availability of standard supplies of Cannabis, difficulties in controlling the duration and rate of inhalation as well as limited EEG quantification. In early studies, Wikler and Lloyd’ and Williams and coworkers2 compared marijuana to synhexyl in volunteer postaddicts. The EEG effects were similar, and were characterized as a decrease in alpha activity and an increase in beta (muscle?) activity. In drug trials up to 39 days, EEG changes were seen during the first four to six days, and then were no longer apparent, implying an adaptation. (This observation has not been confirmed.) Ames3 administered single oral doses of an extract of Cannabis sativa and reported EEG changes in six of ten volunteers. The changes, three hours after ingestion, were principally an increase in beta and theta and a decrease in alpha activity, and accompanied diverse behavioral changes. More recent reports include studies by Miras,4 Rodin and associates? Deliyannakis and colleagues,B Jones and Stone,7 and Hollister and coworkers? Rodin and associates5 observed a shift in the center frequency from 11 H z to 9-10 Hz in 10 volunteers who smoked marijuana in the laboratory until they achieved their usual “high.” The EEG frequency change was carefully quantified by power density spectral analysis. Both Jones and Stone7 and Hollister and coworkers* failed to find consistent EEG changes in volunteers after oral marijuana or THC. Hollister and associates reported some increases in alpha activity, increased synchronization, and occasional paroxysmal activity, which they ascribed to relaxation and the setting. Deliyannakis and coworkerse reported changes after smoking hashish in 18 of 25 Greek chronic drug users. They noted increased alpha activity in 3 of 25, decreased slowing in 3 of 25, and alpha blocking and desynchronization in 11 of 25 subjects. They separated these effects from those of tobacco in these subjects, and compared them to changes reported for LSD and mescaline. Miras4 also reported observations in chronic hashish users, exhibiting sample records with decreased fast activity. Previous experimental studies of the effects of marijuana on perceptual and cognitive functions mostly demonstrated minimal performance decrernenkg EEG and behavioral studies were conducted in several reported experiment^.^,^.^ However, the relations between changes in EEG and behavior as a function of Cannabis dosage have not been directly investigated.

Electrographic effects of diacetylmorphine (heroin) and naloxone in man

Abstract Sixty-three addicts were given heroin intravenously at a rate of 20–40 mg/2 cc/ 2 min, and 8–32 min later received 1–2 mg naloxone. The EEG was recorded in the preheroin, post-heroin and post-naloxone periods. The early response to heroin (first 4 min after the start of the injection) was an increase in alpha amplitudes, decrease of alpha frequency and an occasional increase in alpha spindling. The late response (5–32 min after the start of the injection) was a decrease in alpha abundance, an increase in theta and sometimes delta activities, and paroxysmal EEG activity. Two clinical seizures were seen. The tracings returned to the pre-heroin pattern after the administration of naloxone. These observations of heroin and naloxone are consistent with established theories of association of EEG and behavior in man after psychoactive drugs.

Alcohol use in the opiate use cycle of the heroin addict.

Ninety-six methadone maintained patients selected at random from a private clinic were interviewed to explore lifetime patterns of alcohol use in relation to opiate use. The results indicated that most addicts who ever drank excessively (in alcoholic, problem, or heavy patterns) did so primarily during two periods: prior to becoming addicted to narcotics and during periods of voluntary abstinence from narcotics. Further, most of the addicts who were drinking in excessive patterns while maintained on methadone had pretreatment histories of similar alcohol use.

Opiates and Antagonists

In no period of recent world history-surely in no period of American history-has drug use been so widespread. Tobacco, alcohol, and caffeine are legally “accepted,” and their use is matched by marijuana (cannabis), barbiturates, “minor tranquillizers,” and the opiates. It is the latter drugs that excite a nationwide anxiety. From a know-nothing view that those who develop drug dependence are morally weak and deserve punishment, the nation has gradually begun to pay lip service to a view of the addicted as medically ill, deserving of treatment. Studies of the opiates, the phenomenoma of cross tolerance, and of narcotic antagonists in the treatment of the addicted are now fashionable.

Opiate Antagonists in the Treatment of Heroin Dependence

Opiate addiction is a complex social and psychological disorder of diverse origins that defies conventional therapeutic efforts, both social and medical. Treatment is discouraged by the high rate of recidivism. Rehabilitation programs frequently reduce recidivism either by the careful selection of suitable patients (accepting only those with the best motivation for recovery) or by imprisonment and primitive systems of parole or by methadone substitution, which satisfies opiate craving by cross tolerance. Each treatment program for opiate dependence—whether forced imprisonment, group therapy, reeducation, psychotherapy, or social rehabilitation— requires an adjuvant to “engage” the subject in the treatment schedule. Methadone substitution fulfills such a role, although the addicting properties of methadone is a continuing hazard.

NARCOTIC ANTAGONISTS Another Approach to Addiction Therapy

Currently, the most popular approaches to the treatment of drug addiction are methadone programs and therapeutic communities. Narcotic antagonists, such as cyclazocine and naloxone, may, however, be the answer for the future.