Effect of dehydroepiandrosterone add-on therapy on mood, decision making and subsequent relapse of polydrug users David Ohana 1,2 , Rachel Maayan 3 , Yael Delayahu 3,4 , Paola Roska 5,6 , Alexander M. Ponizovsky 5 , Abraham Weizman 3 , Gal Yadid 2 & Eldad Yechiam 1 Max Wertheimer Minerva Center, Technion—Israel Institute of Technology, Israel 1 , Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Israel 2 , Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Research Unit, Geha Mental Health Center, Tel-Aviv University, Israel 3 , Abarbanel Mental Health Center, Israel 4 , Department for the Treatment of Substance Abuse and Mental Health Services, Israeli Ministry of Health, Israel 5 and Hebrew University, Israel 6 ABSTRACT A major problem in the treatment of addiction is predicting and preventing relapse following a rehabilitation program. Recently, in preclinical rodent studies dehydroepiandrosterone (DHEA) was found to markedly improve the resistance to drug reuse. In a double-blind, placebo-controlled study, we examined the effect of DHEA on relapse rates in adult polydrug users taking part in a detoxification program enriched with intensive psychosocial interventions and after- care. During treatment, participants (79 percent males, mean age 28) consumed DHEA (100 mg/day) or placebo daily for at least 30 days. Of the 121 initial volunteers, 64 participated for at least 1 month. While in treatment, DHEA reduced negative affect on the Positive and Negative Affect Scale (F = 4.25, P = 0.04). Furthermore, in a 16-month follow-up, we found that reuse rates in the DHEA condition were about a third compared with placebo (12 versus 38 percent; χ 2 = 5.03, P = 0.02). DHEA treatment also resulted in an increase in DHEA sulfate (DHEA-S) 1 month following treatment, and the level of DHEA-S predicted relapse in the follow-up assessment. Keywords Cortisol, decision making, DHEA, drug addiction, relapse. Correspondence to: Gal Yadid, Gonda Multidisciplinary Brain Research Center, Bar Ilan University, Ramat Gan 5290002, Israel. E-mail: yadidg@ mail.biu.ac.il; EldadYechiam, Max Wertheimer Minerva Center for Cognitive Studies,Technion, Haifa 3200003, Israel. E-mail: yeldad@tx.technion.ac.il INTRODUCTION A major problem in the treatment of addiction is high rates of relapse to drug use after periods of forced or self-imposed abstinence. Prolonged abstinence from substances of abuse is characterized by dysphoria, depression and anxiety, coupled with high stress and craving, which provides a backdrop for the decision to reuse drugs (Lovallo 2007; Froeliger et al. 2012; Yadid et al. 2012). Most medications currently used for the maintenance of abstinence over time are opioid agonists, such as methadone (Clark et al. 2002; Mattick et al. 2008), or opioid antagonists such as naltrexone (Ferri, Davoli & Perucci 2006, 2011), and these medica- tions have some effect on reducing stress and anxiety of heroine addicts (Emrich, Vogt & Hertz 1982; Dyer et al. 2001). However, relapse rates tend to be quite high even with these medications (Drake et al. 1998; Wasserman et al. 1998). The present study examined a novel approach for the treatment of addiction through the administration of dehydroepiandrosterone (DHEA), an endogenous neuro-steroid hormone, which is marketed as a food supplement. This approach focuses on boosting the participants’ emotional and cognitive resources during the period of treatment. We examined whether DHEA administration affects decision making, mood and quality of life during treatment and has a long-lasting effect on subsequent relapse. In a simple view, DHEA can be understood as a pro- hormone for the sex hormones. Sex hormones modulate the reward system (Trainor 2011), partly by increasing the density of dopamine (D2) receptors at the striatum and the density of 5-HT binding sites in anterior frontal, cingulate and primary olfactory cortex, and in the nucleus accumbens (Fink et al. 1995). Furthermore, DHEA negatively modulates the level of the stress ORIGINAL ARTICLE Addiction Biology doi:10.1111/adb.12241 © 2015 Society for the Study of Addiction Addiction Biology