Joseph W. Ternes

CLINICAL PHARMACOLOGY OF NARCOTIC ANTAGONISTS

Both naloxone and naltrexone are effective narcotic antagonists with minimal agonistic effects and a wide margin of safety. Naloxone is useful in the treatment of narcotic overdose and it is helpful in the quantification of physical dependence. Naltrexone is pharmacologically successful as an orally effective, long-acting antagonist but its clinical usefulness in the prevention of relapse is still being determined.

An electrodermal measure of arousal in opiate addicts to drug-related stimuli.

Frequency per minute of spontaneous skin resistance responses (SSRRs), an inferred measure of arousal, was compared for three groups of subjects when exposed to drug-related and neutral stimuli. The three groups were a recently detoxified opiate addict group, a group maintained on methadone, and a non-addict control group. Stimuli consisted of slides, objects, and video-tapes, all showing either items used in drug-preparation for self-injection, or neutral items. Results showed clear evidence of an increase in rate of response to drug-related cues in the detoxified drug-free group as compared to the other two groups. No differences were found in response to the neutral stimuli. It is concluded that the present finding of increased arousal to drug-related cues in recently detoxified patients may be an important component of withdrawal, which in turn is regarded as a conditioned autonomic response leading to instrumental behavior of readdiction.

Cynomolgus monkeys do not develop tolerance to opioids.

In order to examine the development of tolerance to opioids, eight cynomolgus and two rhesus monkeys were trained to press a lever for food reinforcement and then were catheterized so that drugs could be infused. Three doses of hydromorphone and six different interdose intervals were studied. Hydromorphone infusions initially suppressed lever pressing for food in both species. The rhesus monkeys acquired tolerance to these sedative effects after 14 exposures to the opioid. However, the cynomolgus monkeys failed to acquire tolerance after more than 100 exposures. Naloxone challenge elicited withdrawal symptoms from the rhesus monkeys but not from the cynomolgus monkeys. This differential response to sustained opioid administration in these closely related species suggests that a genetic mechanism may underlie tolerance to and physical dependence on opioids.

A software system for real-time control of psychological experiments

This paper describes an all-purpose experimental system, “APES,” for use in a microprocessor-controlled behavioral pharmacology laboratory. APES is an assembly language program that can run on any of the DEC PDP-11 family processors under an RT-11 single-job operating system. Its main purpose is the real-time control of psychological experimentation. The capabilities of the system are: (1) system generation of all operant or Pavlovian conditioning paradigms, (2) collection and storage of both behavioral and physiological data in a machine-readable format for later statistical analysis, and (3) operation that can be accomplished by individuals who have no computer programming experience.

Applications of Human Behavioral Pharmacology to the Problems of Drug Addicts: A Brief Review

The work of Abraham Wikler (1973) over the past three decades has called attention to the importance of conditioned responses in the addictive process. Drugs act as powerful forces in shaping behavior, both by their direct pleasant effects (positive reinforcement) and by their effects in relieving withdrawal symptoms (negative reinforcement). Wikler theorized that the environmental cues which have been repeatedly paired with drug-induced states may become conditioned stimuli. He observed that former addicts who are free of drugs often develop tearing and yawning (opiate withdrawal signs) when they discuss drugs in group therapy. He and others subsequently showed that withdrawal signs could become conditioned in animals (Wikler and Pescor, 1967; Goldberg and Schuster, 1970). More recently, conditioned withdrawal has been demonstrated in humans (O’Brien et al, 1975; O’Brien et al, 1977). These conditioned withdrawal responses are thought to be partly due to simple pairing of pharmacological withdrawal with environmental cues, and partly due to pairing of environmental stimuli with the body’s homeostatic mechanisms adapting to the onset of drug effects (Wikler, 1973; Siegel, 1974). Eventually the environmental stimuli themselves can elicit the adaptative response and this can be perceived as withdrawal.