Intranasal oxytocin blocks alcohol withdrawal in human subjects.

BACKGROUND: The neuropeptide, oxytocin (OT), has been reported to block tolerance formation to alcohol and decrease withdrawal symptoms in alcohol-dependent rodents. Numerous recent studies in human subjects indicate that OT administered by the intranasal route penetrates into and exerts effects within the brain. METHODS: In a randomized, double-blind clinical trial, intranasal OT (24 IU/dose, N = 7) or placebo (N = 4) was given twice daily for 3 days in alcohol-dependent subjects admitted to a research unit for medical detoxification using Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score-driven PRN administration of lorazepam. Subjects rated themselves on the Alcohol Withdrawal Symptom Checklist (AWSC) each time CIWA scores were obtained. Subjects also completed the Penn Alcohol Craving Scale, an Alcohol Craving Visual Analog Scale (ACVAS) and the Profile of Mood States (POMS) on inpatient days 2 and 3. RESULTS: All subjects had drunk heavily each day for at least 2 weeks prior to study and had previously experienced withdrawal upon stopping/decreasing alcohol consumption. OT was superior to placebo in reducing alcohol withdrawal as evidenced by: less total lorazepam required to complete detoxification (3.4 mg [4.7, SD] vs. 16.5 [4.4], p = 0.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p < 0.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p < 0.002), lower AWSC scores on days 1 and 2 (p < 0.02; p = 0.07), and lower ACVAS ratings (p = 0.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p < 0.01). CONCLUSIONS: This is the first demonstration that OT treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that OT inhibits neuroadaptation to and withdrawal from alcohol. OT could have advantages over benzodiazepines in managing alcohol withdrawal because it may reverse rather than maintain sedative-hypnotic tolerance. It will be important to test whether OT treatment is effective in reducing drinking in alcohol-dependent outpatients.

Centrally-mediated sensory information processing is impacted with increased alcohol consumption in college-aged individuals.

Alcohol consumption can have an impact on a variety of centrally-mediated functions of the nervous system, and some aspects of sensory perception can be altered as a result of long-term alcohol use. In order to assess the potential impact of alcohol intake on sensory information processing, metrics of sensory perception (simple and choice reaction time; static and dynamic threshold detection; amplitude discrimination with and without pre-exposure to conditioning stimulation) were tested in college-aged subjects (18 to 26 years of age) across a broad range of levels of alcohol consumption. The analysis indicated no detectable associations between reaction time and threshold measures with alcohol consumption. However, measures of adaptation to short duration (0.5s) conditioning stimuli were significantly associated with alcohol consumption: the impact of a confounding conditioning stimulus on amplitude discriminative capacity was comparable to values reported in previous studies on healthy controls (28.9±8.6) for light drinkers while the same adaptation metric for heavy drinkers (consuming greater than 60 drinks per month) was significantly reduced (8.9±7.1). The results suggest that while some of the sensory perceptual metrics which are normally impacted in chronic alcoholism (e.g., reaction time and threshold detection) were relatively insensitive to change with increased alcohol consumption in young non-alcoholic individuals, other metrics, which are influenced predominantly by centrally-mediated mechanisms, demonstrate a deviation from normative values with increased consumption. Results of this study suggest that higher levels of alcohol consumption may be associated with alterations in centrally-mediated neural mechanisms in this age group.