Tehran University of Medical Sciences Journal of Craniomaxillofacial Research 2345-5489 8 1 2021 07 07 29 34 Abdollah Farhadi Nasab Behavioral Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Safoura Raoufi Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Naghmeh Bahrami Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Craniomaxillofacial Research Center, Tehran University of Medical Sciences, Tehran, Iran. 2021 02 27 2021 04 18 Introduction: Today, drug addiction is an important healthcare issue. Any helps to drug withdrawal may decrease its prevalence in the society. Ascorbic acid is a component, which can affect neurotransmitter systems as a regulator along with its cofactor role. Noradrenergic and dopaminergic systems are two important neurotransmitter systems in the opiate withdrawal syndrome. It seems that ascorbic acid can decrease the symptoms of opiate withdrawal through regulating the related systems. In this regard, the current study aimed to evaluate the effect of ascorbic acid on the symptoms of morphine withdrawal in Syrian mice. Materials and Methods: Male Syrian mice in eight experimental groups received incremental doses of morphine as 10, 20, 30 and 40mg/kg within the first, second, third, and fourth days of the experiment, respectively, through intraperitoneal injection, twice a day, and the control group received and equal amount of saline. On the fifth day, six groups of morphine addicts received ascorbic acid with six doses of 10, 50, 100, 200, 400 and 800mg/kg through intraperitoneal injection. Then, naloxone 2mg/kg was injected to all groups including morphine alone and morphine with acute does of ascorbic acid. Then, withdrawal symptoms were evaluated for 30 minutes. Results: Administration of an acute dose of ascorbic acid reduced dose dependent withdrawal symptoms in such a way that 10, 50, and 100mg/kg doses of ascorbic acid reduced “writhing” symptom, 200mg/kg reduced “jumping” symptom, and 400 and 800mg/kg reduced “climbing, jumping, and standing” symptoms. Conclusion: It seems that ascorbic acid administration can improve the symptoms of opiate withdrawal syndrome. More studies on human population can also indicate the therapeutic effect of ascorbic acid on drug withdrawal. Keywords: Addiction; Morphine; Withdrawal syndrome; Ascorbic acid. https://jcr.tums.ac.ir/index.php/jcr/article/view/365 https://jcr.tums.ac.ir/index.php/jcr/article/download/365/319