1. Introduction

piate abuse and dependence is one of the world's major health problems. (7,11). Different therapeutic methods have been presented for the treatment of opiate addiction. Although these drugs have been successful in controlling some of withdrawal symptoms, they have not been able yet to control the symptoms completely, some of them are not available everywhere or are abused in other ways. (5,10). Therefore, herbal medicines can be an excellent option for solving this problem given the high

social acceptance due to the low complications, high effectiveness, their availability and low cost (13). According to the World Health Organization recommendations regarding the use of traditional medicine in health systems (12,14), addiction treatment has been reviewed from the perspective of TIM scientists so that they can play their role in solving this problem. Various therapies for addiction treatment have been introduced in TIM (8). One of these methods is the replacement of opium with natural narcotic drugs (16,2). Several natural narcotic drugs as isolated or in a combination have been introduced in TIM text books (8,16,2,4,15,17,2,3). Hab-o Shefa is a natural combination of drugs which most of TIM scientists have a consensus on the positive effects of this combination in addiction treatment and it has been used for several centuries as a viable alternative for opium in the treatment of opium addiction. This compound contains Datura stramonium, Rheum palmatum, Zingiber officinale and Acacia Arabica (8,16,1,4,15,16). In this study, the efficacy of this drug in controlling morphine withdrawal symptoms was evaluated in rats. 

2. Materials and Methods

Habo- Shefa is a natural combination of Datura stramonium, Heum palmatum, Zingiber officinalea and Acacia arabica which was prepared in the pharmaceutical Laboratory of Traditional Medicine of the Shahed University of Tehran (Iran).

Methadone and morphine were purchased in the form of powder from the Daroupakhsh Company.

2.1. Animals

In this study, 30 male rats of the NMRI strain (Razi Institute of Iran), weighing 250-330 g, were used. These rats were placed in cages quaternary and the temperature was set between 22-25 °C. Ambient light as a 12- hour light 12-hour dark cycle was controlled by a timer. The required amount of water and food was available to each rat. In all the performed experiments the research ethics on animals were fully observed.

2.2. Dependency induction

For creating dependency in animals, morphine at a daily dosage of 10 mg/kg for 8 days was injected i.p. (18).

2.3. Behavioral evaluation

For the study of behavioral dependency after the 8-day morphine injection and 4 to 24 hours after the final injection of morphine to one of the rats in each group, 2.5 mg/kg of naloxone was injected i.p. and the behavioral symptoms were assessed during the following forty minutes. Subsequently, the other rats in each group were also studied one by one. Behavioral indices of withdrawal syndrome including diarrhea, ptosis and teeth chattering are indicative of morphine dependency of such animals. In general, behaviors that occur during the withdrawal syndrome in terms of being countable or non-countable are divided into two categories by the standard agreement; graded signs and chocked signs. Graded signs included jumping, abdominal contraction, wet dog shakes and chocked signs included diarrhea, teeth chattering, salivation, ptosis and genital grooming/ejaculation.

2.4. Experimental groups

In this study, 30 rats were divided into three groups of 10 cases each; the first group named as the control group only received morphine 10 mg/kg daily for 8 days injected i.p.; the methadone group received the same dose of morphine injection plus 25 mg/kg of methadone daily for 8 days by gavage. In the Hab-o Shefa group besides administering the same dose of morphine injection, Hab-o Shefa was prescribed at a dosage of 2000 mg/kg daily for 8 days through gavage.

2.5. Statistical analysis

For data analysis, the graded signs data were
recorded as the number of behaviors occurring in a certain time duration in each rat. After confirming that behaviors of the withdrawal syndrome have a quantitative entity, the number of such behaviors was compared in different groups with ANOVA and Tukey post-hoc test.

3. Results

Figure 1 shows the number of diarrhea, ptosis and salivation in the three groups. Comparing these numbers between the methadone and Hab-o Shefa groups did not reveal a statistically significant difference (p>0.05), but the difference was significant when comparing these two groups with the placebo group (p0.05).

Figure 2 shows the number of jumps in the three groups. Comparing the number of jumps between Hab-o Shefa and methadone with placebo showed a statistically significant difference (p0.05).

4. Discussion

In the previous study by Mohsen Khalili and Mohsen Naseri et al (9), the effectiveness of datura seeds extracts in controlling morphine withdrawal symptoms in rats was studied.  In the latter study, the efficacy of datura seeds extract was significantly superior to placebo, whereas no significant difference was seen in comparison with methadone. Hab-o Shefa acted better than datura extract in controlling symptoms such as diarrhea, salivation and ptosis as compared to methadone. Considering that Hab-o Shefa is a natural compound and datura is its main

Figure 1. Comparison of innumerable withdrawal symptoms in rats. As can be seen, the parameters of diarrhea, ptosis and salivation for Hab-o Shefa and methadone groups as compared together was not significant (p>0.05)  and between these two and placebo was significant (p