Clinical Assistant Professor, Department of Family Medicine, University of Wisconsin; Clinical Assistant Professor of Medicine, Arizona Center for Integrative Medicine, University of Arizona, Tucson

Dr. Kiefer reports no financial relationships relevant to this field of study.

SYNOPSIS: A small, poorly designed study hints at some adjunctive treatment benefit for saffron powder in people weaning off narcotic medications.

SOURCE: 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 2017;2017:1079132. doi: 10.1155/2017/1079132. Epub 2017 Nov 21.

Saffron is the quintessential flavor in the Mediterranean rice and seafood dish called paella, but the researchers of this clinical trial moved beyond dinner. They used an extract of the spice as adjunctive therapy in people trying to wean themselves off narcotic medications.

The topic is compelling, but the prose and methodology made it a challenge to tease out results and draw firm conclusions about the intervention. Patients of an addiction treatment center in Sabzevar parish, Iran, were selected randomly to participate in this intervention, and then randomly assigned to either saffron capsules (30 mg of saffron powder per capsule) or placebo capsules. The authors stated once that this intervention was offered once weekly, but it is unclear how many patients were in each arm of the clinical trial. They only mentioned that “44 clients” participated in this study in the abstract. Further, they stated that if the study participants “… did not have the ability to continue the process of intervention, they would be excluded from the research.” This seems to indicate that an important methodological characteristic, intention-to-treat analysis, was not at play.

Regarding inclusion criteria, the patients had to be stable on maintenance methadone dosing without “physical and mental symptoms.” Patients presented to the clinic once weekly, at which time their methadone dosing was decreased by 5 mg, and the week’s worth of saffron or placebo capsules (one capsule weekly) were prescribed. Telephone calls (unclear how often) monitored the patients for withdrawal symptoms and treatment adherence. Baseline methadone dose was not described, nor was the reason for maintenance methadone treatment.

The authors followed withdrawal symptoms, including loss of appetite, diarrhea, rhinorrhea, myalgia, and “temptation.” Over the eight-week intervention period, the percentage of patients experiencing each of these symptoms was displayed on graphs for the saffron and placebo groups. Numbers on the graphs also were included, which might represent the number of patients reporting each of those symptoms, but that is merely conjecture; it was not labeled as such. A “downward trend” in loss of appetite, diarrhea, and temptation; a “lagging downward trend” for rhinorrhea; and a “serious downward trend” for myalgia were described for the saffron group. People in the placebo group either had stable symptoms or increased symptoms over the study period. No statistical analyses were offered other than in the abstract with this statement: “The results showed that the use of saffron and methadone alleviated the symptoms of withdrawal syndrome (P < 0.001).”

The opioid crisis is just that, a crisis. The desperate attempts to establish evidence-based adjunctive therapies for opioid withdrawal symptoms probably explain why this article was published in an open-access journal, when, mostly because of serious methodological flaws, it should not have been published. The title and abstract likely raise the hopes of any clinicians working in this field, and, indeed, saffron might be the correct herbal medicine to have been chosen to fill this public health need. Saffron has a relevant mechanism of action, with centrally acting neurotransmitter effects that could address comorbid psychological conditions in people with chronic pain or narcotic addiction.¹ The authors also mentioned that saffron, as with methadone, affects the reuptake of serotonin, but no references were provided for this statement. In addition, prior clinical trials have used 30 mg daily (or 15 mg twice daily), so the participants in this study either were under-dosed markedly, or there was an error in the reporting of the data.

Do the results of this study change our management of chronic pain, opioid addiction, and related conditions? Not yet. Tried and true methods of integrative, individualized, team-based care are still the best approach. Why mention a study like this, given its marginal design and results? Mostly to help saffron appear on our clinical radar as we creatively approach the opioid crisis and extend beyond the antidepressant use of this herbal medicine. It’s unclear whether saffron is efficacious as the authors of this study claim, but it seems to represent the beginning of unique therapies being studied to help this demographic in diverse and interesting ways. Pending a large-scale clinical trial or two to corroborate efficacy and safety, saffron may indeed have a role for weaning off maintenance opioid therapy in the not-too-distant
future.

REFERENCE

1. Modabbernia A, Akhondzadeh S. Saffron, passionflower, valerian and sage for mental health. Psychiatr Clin North Am 2013;36:85-91.