Intranasal Oxytocin Blocks Alcohol Withdrawal in Human Subjects

Abstract

Background The neuropeptide, oxytocin, 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 oxytocin administered by the intranasal route penetrates into and exerts effects within the brain. Methods In a randomized, double-blind clinical trial, intranasal oxytocin (24 IU/dose, N=7)) or placebo (N=4) was given BID 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 (PACS), 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. Oxytocin 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=.0015), lower mean CIWA scores on admission day 1 (4.3 [2.3] vs. 11.8 [0.4], p<.0001) and day 2 (3.4 [2.2] vs. 11.1 [3.6], p<.002), lower AWSC scores on days 1 and 2 (p<.02; p=.07), lower ACVAS ratings (p=.01) and lower POMS Tension/Anxiety subscale scores on day 2 (p<.01). Conclusions This is the first demonstration that oxytocin treatment may block alcohol withdrawal in human subjects. Our results are consistent with previous findings in rodents that oxytocin inhibits neuroadaptation to and withdrawal from alcohol. Oxytocin 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 oxytocin treatment is effective in reducing drinking in alcohol dependent outpatients.

Economic demand predicts addiction-like behavior and therapeutic efficacy of oxytocin in the rat

“…There is strong preclinical evidence for oxytocin as a treatment for psychostimulant addiction (34,35,37), and early clinical studies have confirmed that oxytocin reduces craving for marijuana and alcohol (38,39). We found that oxytocin dramatically reduced cocaine demand in animals with a standard self-administration history; this finding, in view of the relationship between demand and addiction-like behavior reported here, predicts that oxytocin may effectively treat psychostimulant dependence in the clinic.…”

“…There is no current Food and Drug Administration-approved pharmacotherapy to evaluate the predictive validity of our economic demand procedures; however, oxytocin is a promising candidate (34,35). In preclinical testing oxytocin attenuates self-administration of psychostimulants as well as reinstatement to drug seeking (36,37), and early clinical testing confirmed that oxytocin attenuates drug craving (38,39). We tested the effect of oxytocin pretreatment on cocaine demand and reinstatement of cocaine seeking to evaluate its potential as a cocaine addiction treatment as well as to demonstrate utility of this economic approach.…”

Oxytocin prevents ethanol actions at δ subunit-containing GABA A receptors and attenuates ethanol-induced motor impairment in rats

“…In contrast, OT has a well-characterized anxiolytic effect (9) and, when dosed at a specific level, powerfully reduces seizures and lethality during ethanol withdrawal in mice (11). In a recent preliminary clinical study, OT also attenuated symptoms of alcohol withdrawal in dependent humans to the point where a standard clinical intervention for anxiety and seizures (lorazepam) was not required (13).…”

“…Early preclinical studies suggested that OT can prevent the development of tolerance to the sedative and ataxic effects of ethanol in rodents (10) and also modulate the severity of ethanol withdrawal (11). More recent studies show that OT reduces alcohol intake in rats (12) and reduces the severity of alcohol withdrawal and craving in dependent humans during detoxification (13). However, the mechanism underlying these actions is largely uncharacterized, including whether the modulation of various alcohol-related effects by OT involves the OT receptor (OTR).…”

Oxytocin und die suchterhaltenden Mechanismen der Alkoholabhängigkeit

“…Dazu wurden zweimal pro Tag 24 IU Oxytocin intranasal verabreicht. Limitierend für die Aussagekraft der Studie ist jedoch die geringe Anzahl von lediglich 11 Testper-review sonen [46]. Dennoch bestätigt dies, dass Oxytocin synergistisch mit Benzodiazepinen wirkt.…”