Friday, March 15, 2019

I'm just mad about saffron

The popular and expensive spice saffron (Crocus sativus L), appears to be as effective as the stimulant methylphenidate (MPH) in treating symptoms in youngsters with attention deficit hyperactivity disorder (ADHD), new research suggests.

In a randomized 6-week trial, a team of investigators from Tehran University of Medical Sciences in Iran, found there were no significant differences in efficacy or adverse events in the saffron vs MPH group.

"From this preliminary study, the main point is that we can consider saffron as an alternative [to stimulants] in patients with ADHD," senior author Shahin Akhondzadeh, PhD, FBPhS, DSc, professor of clinical psychopharmacology, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Iran, told Medscape Medical News.

"Short-term efficacy of saffron demonstrated the same efficacy as methylphenidate, although larger, controlled studies with longer treatment periods are necessary to verify the findings," he said. "Many antidepressants have been used as alternatives to stimulants in patients with ADHD that cannot tolerate Ritalin or do not respond to Ritalin," Akhondzadeh said.

However, antidepressants are also associated with adverse events, with results that are "often unsatisfactory," the authors note.

This leaves an "empty place to be filled by alternative medications, in particular herbal medications," they add.

Saffron has traditionally been used for a variety of medicinal purposes, including its antispasmodic, antiseptic, anticancer, and anticonvulsant effects. 

Saffron and its active constituents appear to increase the reuptake inhibition of dopamine and norepinephrine and are N-methyl D-aspartic acid (NMDA) receptor antagonists and GABA-α agonists.

"As you may know, my country is the main producer of saffron and about 90% of saffron is from Iran — indeed, saffron is a Persian herb with history as long as the Persian Empire," Akhondzadeh noted.

"There are solid documents in the Persian traditional medicine about the psychotropic effects of saffron, but we need evidence-based medicine in traditional medicine as well.

"My research group at Roozbeh Psychiatry Hospital has studied the psychotropic effects of saffron since early 2000, and we have documented its antidepressant effects," he added…

No significant difference was found in Parent ADHD Rating Scale scores at baseline between the saffron and the MPH groups (34.20 ± 4.69 vs 33.56 ± 6.48, respectively; mean difference [MD], 0.64; 95% confidence interval [CI], –2.58 to 3.86; t = –0.400; df = 48; P = .691).

Moreover, general linear model repeated measures also showed no significant effect for treatment (between-subject factor; F = 0.672; df = 1; P = .416).

A time × treatment calculation showed a similar trend of the two treatment groups across time in both hyperactivity and inattention.

Moreover, a significant effect of both treatments on improving Parent ADHD Rating Scale scores was demonstrated (P < .001).

Post hoc comparisons of the Parent ADHD Rating Scale showed a significant reduction as soon as week 3 (P < .001) in both groups, and there was no significant difference between the treatment groups at endpoint (P = .975).

Similar findings were obtained in the Teacher ADHD-RS-IV scores, with no significant difference in baseline total scores between the saffron and the MPH groups (24.16 ± 8.32 vs 23.64 ± 8.16, respectively; MD, 0.52; 95% CI, –4.16 to 5.20; t = ­–0.223; df = 48; P = 0.824), time to improvement, and reduction in symptoms at study endpoint.

No serious adverse event was recorded in any of the patients, and non-serious events (eg, headache, dry mouth, insomnia, decreased appetite) were similar between the two groups.

"This study provides evidence for satisfactory outcomes with saffron in treatment of ADHD," the authors write.

However, Akhondzadeh acknowledged that the cost of saffron is a concern.

"Although saffron is the most expensive spice, the daily dosage that we used in this study is equal to 60 mg pure saffron," he reported…

Although saffron is available as a spice in the United States, "there is no guaranty that it will have the same medicinal effect if used in a meal, since the main component of our extract is crocin," he added.

Commenting on the study for Medscape Medical News, Patricia L. Gerbarg, MD, assistant clinical professor in psychiatry, New York Medical College, Valhalla, and Richard P. Brown, MD, associate professor in clinical psychiatry at Columbia University College of Medicine, New York, NY, called it a "credible" and "well-done randomized controlled trial."

The authors "appropriately note that this is positive preliminary evidence and that additional trials are needed to replicate these initial very positive findings," Gerbarg and Brown, who were not involved with the study, told Medscape Medical News via email.

The study was conducted in Iran, "where ethnic populations may have genetic variants that enable them to respond more positively or more robustly to saffron than other populations," which has been "noted with other herbs."

It is therefore "particularly important to replicate this study in a population that is not Iranian, to verify efficacy in other countries," noted Brown and Gerbarg, who are coeditors of Complementary and Integrative Treatments in Psychiatric Practice (Washington, DC: American Psychiatric Association Publishing; 2017), which has a chapter on saffron.

"Each practitioner must decide whether they feel that this evidence is promising enough to justify a trial of optimized saffron on a case-by-case basis [that] takes into account the observation that saffron is very low in side effects, so the risks are minimal," they said.

Moreover, "if the saffron is beneficial, it may be possible to reduce the dose or discontinue a prescription stimulant, which could spare the patient who may be experiencing side effects," Gerbarg and Brown add.

Batya Swift Yasgur. Popular Spice Rivals Stimulant for ADHD - Medscape - Mar 11, 2019.

Baziar S, Aqamolaei A, Khadem E, Mortazavi SH, Naderi S, Sahebolzamani E, Mortezaei A, Jalilevand S, Mohammadi MR, Shahmirzadi M, Akhondzadeh S. Crocus sativus L. Versus Methylphenidate in Treatment of Children with Attention-Deficit/Hyperactivity Disorder: A Randomized, Double-Blind Pilot Study. J Child Adolesc Psychopharmacol. 2019 Feb 11. doi: 10.1089/cap.2018.0146. [Epub ahead of print]


Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders of childhood and adolescence. About 30% of patients do not respond to stimulants or cannot tolerate their side effects. Thus, alternative medication, like herbal medicine, should be considered. The aim of this trial is to compare the safety and efficacy of Crocus sativus (saffron) versus methylphenidate in improving symptoms of children with ADHD.

In a 6-week randomized double-blind study, 54 patients (children 6-17 years old) with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of ADHD were randomly assigned to receive either 20-30 mg/d (20 mg/d for <30 kg and 30 mg/d for >30 kg) methylphenidate (MPH) or 20-30 mg/d saffron capsules depending on weight (20 mg/d for <30 kg and 30 mg/d for >30 kg). Symptoms were assessed using the Teacher and Parent Attention-Deficit/Hyperactivity Disorder Rating Scale-IV (ADHD-RS-IV) at baseline and weeks 3 and 6.

Fifty patients completed the trial. General linear model repeated measures showed no significant difference between the two groups on Parent and Teacher Rating Scale scores (F = 0.749, df = 1.317, p = 0.425, and F = 0.249, df = 1.410, p = 0.701, respectively). Changes in Teacher and Parent ADHD Rating Scale scores from baseline to the study end were not significantly different between the saffron group and the MPH group (p = 0.731 and p = 0.883, respectively). The frequency of adverse effects was similar between saffron and MPH groups.

Short-term therapy with saffron capsule showed the same efficacy compared with methylphenidate. Nevertheless, larger controlled studies with longer treatment periods are necessary for future studies.

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