Opium is the dried latex obtained from the opium poppy. Opium addiction is the most prevalent addiction in Iranian society. During the last two decades "congress 60" a nongovernmental organization, has been performed a taper off treatment of opium associated with a package of psychological treatment group classes. While the effectiveness of taper off method in opium addiction has been confirmed, molecular mechanisms of this treatment in addicts are not clarified. BDNF gene is a brain-derived neurotrophic factor which is related to several molecular mechanisms of the brain including memory. 5-HTTPLR is a transporter of serotonin that is related to the decision-making process. In present study mRNA level of BDNF and 5-HTTPLR genes in peripheral blood of 20 non-psychiatric persons and 79 opium addicted individuals before and after six months period of taper off treatment was examined by using Real-Time PCR and confirmed by protein level analysis using Western blotting. In addition, executive functions including memory and decision making were analyzed in all participants. Results showed significant down expression of BDNF and 5-HTTPLR in addict persons vs. non psychiatric persons. Also significantly increase detected in BDNF (p<0.01) and5-HTTPLR (p<0.01) expression level in addicts after six months of therapy period. Similar results with gene expression results revealed in protein level analysis. Also, significant improvements in memory and decision making were revealed in addicts after therapy and these improvements were correlated with the expression level of BDNF and 5-HTTPLR. Findings revealed the effect of opium abuse and taper off treatment on the expression of BDNF and 5-HTTPLR. In addition, the association of BDNF mRNA level with psychological states of addict's individuals detected. Results of the present study may help to a better understanding of molecular and neuropsychological mechanisms of opium addiction and taper off treatment. Also, present BDNF and 5-HTTPLR as potential markers for screening the effectiveness of different kinds of addiction treatment.