Oxytocin Blocks Opioid Withdrawal Symptoms Only When Combined with Group Therapy: A Double-Blind, Randomized Controlled Clinical Trial

Background: Oxytocin is a well-known central nervous system mediator in social-related behaviors and stress management. Oxytocin has also been shown to prevent withdrawal symptoms of opioids in animal studies. Group interactions with emotion sharing have been shown to result in an increase in endogenous oxytocin. Although abrupt discontinuation of methadone in opioid substitution therapy is not routinely recommended, it might result in severe withdrawal symptoms and relapse in cases that there is a clinical justification for quitting methadone. Objectives: To evaluate and compare the role of oxytocin and group interactions, combined or independently, in abrupt discontinuation of methadone in methadone maintenance treatment (MMT) cases, where there had been a reasonable clinical judgment to cease medication. Methods: In a double-blind randomized clinical trial, four groups of participants who were on methadone treatment for more than six months received either oxytocin or placebo and marathon group therapy or routine group therapy upon abrupt discontinuation of methadone. The participants were monitored for opioid withdrawal symptoms, depression, and anxiety during a four-month follow-up program. The participants were also screened by urine tests for lapses. Results: Administration of oxytocin combined with marathon group activity, with highly emotional content, resulted in less craving (P < 0.000) and withdrawal symptoms (P < 0.000) compared to placebo and non-marathon group intervention in different combinations, irrespective of methadone dose and age. The same combination also resulted in continued participation in group therapy for a longer period (P < 0.000). Additionally, the same combination was effective in improving mental health, as measured by the Beck Anxiety (P < 0.002) and Beck depression (P < 0.014) inventories. Conclusions: In order to prevent methadone craving and withdrawal symptoms and sustained abstinence, group therapy with a highly emotional theme appears to be an essential factor for the manifestation of oxytocin effects in the brain.