Effects of Intranasal Oxytocin on Stress-Induced Cigarette Craving in Daily Smokers.

BACKGROUND: Cigarette smoking is a well-known public health concern, and there is an urgent need to develop new treatments to reduce smoking or facilitate abstinence. One factor that is known to contribute to relapse is stress, making the stress response an important target for treatment. The neuropeptide oxytocin (OT) is believed to have stress-reducing effects, and in addition there is evidence that it reduces drug craving. The purpose of the present study was to examine the effects of intranasal OT on stress-induced cigarette craving in regular smokers after 12 h of abstinence. METHOD: Daily smokers (n = 48) completed a stress induction task and a nonstressful control task at two different sessions, receiving intranasal OT (40 IU) or placebo (PBO) before or after the task. Subjects were randomly assigned to one of three groups: Group PP (n = 16) received PBO before and after the stress/control tasks, Group OP (n = 16) received OT before the tasks and PBO after, and Group PO (n = 16) received PBO before the tasks and OT shortly after completing the tasks. Cigarette craving as well as subjective and physiological responses to stress was assessed. RESULTS: OT did not alter responses to stress, whether it was administered before or after the stressful task, on measures of cigarette craving, anxiety, heart rate, blood pressure, and cortisol levels. CONCLUSIONS: The current study findings do not support several previous reports that OT reduced either stress or drug craving. IMPLICATIONS: This study finds a null result of the neuropeptide oxytocin on stress-induced cigarette craving. Reporting null findings is part of the process of identifying potential treatments for addictive disorders.

Pharmacological challenge studies with acute psychosocial stress.

Chronic stress is known to affect many psychiatric disorders, and studies of responses to acute stress may reveal processes that ultimately lead to maladaptive responses to chronic stress. Many studies have used simulated public speaking tasks to induce stress in the laboratory and, of interest to this review, the tasks have been used to assess the effects of both therapeutic and nonmedical drugs on stress reactivity. Here we review 38 studies that examined effects of single doses of drugs on subjective, cardiovascular and hormonal responses to an acute social stressor in healthy volunteers. Most studies have used the Trier Social Stress Test (TSST), or variations on it involving public speaking or mental arithmetic. Pharmacological studies with the TSST (ph-TSST) have been conducted for three main reasons: i) to determine the clinical effectiveness of psychiatric medications to reduce stress responses, ii) to investigate the neurochemical mechanisms involved in the stress response, and iii) to determine whether drugs of abuse relieve, or occasionally worsen, responses to acute stress. The review indicates that standard anxiolytic medications consistently reduce subjective responses to the TSST, whereas single doses of antidepressants produce mixed effects. Mechanistic studies indicate that several neurotransmitter systems are involved in the stress response, including serotonin, norepinephrine, GABA, glutamate, opioids, and endocannabinoids. Among drugs of abuse, alcohol and cannabinoids exert some stress-dampening effects, whereas caffeine, nicotine, and amphetamines tend to increase stress responses. Comparing outcome measures of the responses to stress, subjective ratings of anxiety are among the most sensitive indices of the stress response, with cortisol levels second and cardiovascular responses least sensitive. We conclude that the TSST is a valuable tool to study the clinical effectiveness of medications for stress-related disorders, and that it is important to use standardized procedures to enable comparisons across studies.