Background. Dextromethorphan is a noncompetitive N-methyl D-aspartate receptor antagonist that is clinically feasible for relieving the opioid withdrawal symptoms. This study compares the efficacy of a combination therapy with dextromethorphan and clonidine to treatment with clonidine alone. Methods and Materials. In this double-blind randomized clinical trial, patients were selected from inpatients of detox and rehabilitation ward of Razi Hospital, Tabriz, Iran. They were randomly allocated to two groups receiving either clonidine (0.4–1.2？mg/day) or clonidine and dextromethorphan (300？mg/day). Withdrawal symptoms were evaluated in the first day of admission and again 24, 48, and 72 hours later. Results. Thirty male patients completed the trial in each group. Withdrawal symptoms began to decrease in the second day in patients receiving dextromethorphan and clonidine while patients receiving clonidine experienced the more severe symptoms in 72 hours. Analysis of variance of the symptom severity score revealed a significant group time interaction ( ; ), so that patients receiving dextromethorphan plus clonidine had milder symptoms during three days in all of the measurements compared to clonidine group. Conclusion. Combination therapy of dextromethorphan and clonidine would result in milder opioid withdrawal symptoms compared to clonidine alone with a reduction beginning at the second day. 1. Introduction Addiction is one of the most disturbing and problematic social phenomena in current years with known social, economic, and individual detriments. Unfortunately this problem has been rising in Iran during the last two decades. Documented reports have shown that there are 1200000 to 2000000 substance abusers in Iran. Mokri et al. report the number to be 4000000 abusers in 2002 [1]. These researches demonstrated that opium and heroin are the main substances being abused while achieving a complete abstinence is the main expected outcome for treatment of addiction. Detoxification is the first step of substance abuse/dependence treatment and researches about brief and cost-effective methods receive a lot of interest in Iran [2]. Long-term opioid use would increase the cyclic Adenyl cyclase in noradrenergic system of the locus coeruleus. Hence this compensatory increase in cyclic Adenyl cyclase would result in adrenergic withdrawal symptoms during rapid opioid cessation. Some pharmacological agents (opioid agonists, opioid agonist-antagonists, opioid antagonists, and alpha-2 agonists) are studied and used in opioid detoxification [2]. The efficacy of clonidine
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