Clinical Trial Studies Effectiveness of Saffron in Treating Opioid Withdrawal Symptoms

Opioid addiction has reached epidemic levels, and withdrawal from the use of drugs such as heroin or prescription opioids can cause acute physical and mental distress. Methadone is often used as replacement therapy in the treatment of opioid dependence since it is slow-acting and able to treat withdrawal symptoms while blocking the high associated with other opioids. Since methadone is itself an opioid, there is still the potential for abuse and addiction, so the search for non-addictive alternative treatments is ongoing. Saffron (Crocus sativus, Iridaceae) stigma may work similarly to methadone in preventing serotonin reuptake, while also having anti-inflammatory and analgesic effects. Its use, therefore, might allow patients to reduce their methadone dose.

The authors conducted a parallel, eight-week, double-blind, placebo-controlled clinical trial to study the effect of saffron on patients undergoing methadone treatment for opioid addiction. The study took place in Sabzevar county, Iran from 2016-2017 and recruited patients from regional addiction treatment centers. Forty-four patients who were stable (without severe physical or mental withdrawal symptoms) and had been receiving a fixed dose of methadone for several months were selected for the trial. They were randomly assigned to either Group A (saffron) or Group B (placebo). The study methodology was not fully described. Patients received methadone syrup once per week for eight weeks, with a “decrease in methadone dose during the study period (5 mg per week).” Group A patients additionally received 30 mg saffron powder capsules (composition not given; prepared by the authors), while Group B patients received placebo capsules (composition not given). The authors are not clear about how saffron was dosed, but it appears that as the methadone dose was decreased by 5 mg each week, the saffron dose was increased by 30 mg each week. It is unclear if the saffron dose was taken once daily or once weekly. This treatment regimen provided a lower dosage of methadone than patients had been receiving prior to the trial; therefore, patients had 24-hour telephone access to their treating physician in case withdrawal symptoms worsened. Additionally, patients had weekly in-person checkups to make sure that they were compliant and to assess their symptoms. No patients experienced worsening symptoms severe enough to end their participation in the trial. The results were analyzed using the Statistical Package for Social Sciences (SPSS) v20.

Forty-four male patients completed the study. [Note: Elsewhere in the article, the authors state that 100 patients completed the trial.]  Patient recovery was assessed using the following withdrawal symptoms: loss of appetite, rhinorrhea, diarrhea, myalgia, and temptation. The authors did not specify the parameters of the assessment or what scale was used to measure the change in withdrawal symptoms. In the saffron group, loss of appetite decreased from 50% of patients reporting the loss of appetite at week one to 31.8% at week eight. Similar trends were seen in the other categories, with myalgia showing the sharpest decline from 14 patients (63%) experiencing muscle pain at the start to only two (9%) reporting it at the conclusion of the trial. Diarrhea showed little change over the course of the study within the saffron group.

In the placebo group, most symptoms remained fairly stable throughout the trial or had a slight increase by week eight. Ten patients (45.5%) in the placebo group reported experiencing myalgia at week one, while 15 (68%) reported it by the end of the trial. Diarrhea showed a similar trajectory. Reports of loss of appetite and temptation showed a slight decrease by the end of the study. [Note: Evident errors in data figures make the absolute effect unclear. No statistical analysis for significance was provided; the abstract quotes a single P value of <0.001, without clarifying to what comparison it refers.]

In view of the small sample size, reporting errors, and lack of analysis to determine significance, it is difficult to gauge the effect that saffron had on methadone treatment for opioid addiction in this trial. The data reported by the authors indicate that saffron may help to reduce withdrawal symptoms associated with opioid addiction when taken as part of a methadone treatment program, but further studies with larger sample sizes that include women and more thorough statistical analysis will be required.

The authors declare that they have no conflicts of interest.


Nemat Shahi M, Asadi A, Behnam Talab E, Nemat Shahi M. The impact of saffron on symptoms of withdrawal syndrome in patients undergoing maintenance treatment for opioid addiction in Sabzevar Parish in 2017. Adv Med. November 2017;2017:1079132. doi: 10.1155/2017/1079132.