Posted by psychobot5000 on June 21, 2007, at 9:52:09
So, let me try to summarize a bit of background on Saffron's antidepressant potential. I've quoted all the studies I mention, with the sources' web addresses, at the bottom of this note.
Saffron has recently been found superior to placebo (first abstract below this note) and equivalent to fluoxetine(second abstract), in preliminary studies, and equivalent to imipramine in what may be a slightly higher quality study (third abstract) (these are from Iran [and done in the past three years], where much of the world's saffron is produced, and where it's apparently used traditionally as an antidepressant).
Other work has shown two of Saffron's component chemicals, crocin and safranal, function as antidepressants in rat models (second abstract from bottom), when they're given by injection (the injection detail is important).
Fine, so both saffron components seem to work, and apparently crocin may act on dopamine and noradrenaline reuptake, while safranal allegedly works on serotonin reuptake (I don't have sources for those conjectures, but researchers seem to believe them). And the whole compound has passed a few small studies showing antidepressant action - very good, I say.
From some points of view, there is a problem, however. Here it is: I'm glad of the idea of an herbal source that might act as an antidepressant via norepinephrine and dopamine. On the other hand, we seem to have enough medications that focus on serotonin reuptake. Some might even say too many (I mean that both ironically, and also seriously, in the sense that too much focus on developing carbon-copied SSRIs [that's you, Lexapro!], among other things, takes away resources from developing more innovative treatments). So I greet the news of safranal's apparent antidepressant effect via serotonin with a slight yawn, and the news of crocin's supposed action on dopamine and noradrenaline with somewhat more excitement.
Here's the problem: all the action in humans may come from the safranal. Why? Well, according to more rat studies (quoted at bottom), the crocin isn't absorbed orally. It's converted to crocetin for passage into the blood from the intestine, apparently. No crocin is found in the blood when taken orally (see the last study). No crocin apparently mean no dopamine/norepinephrine action - the rats that responded to Crocin in the other study were given it by injection.
So unless someone comes up with a transdermal patch, or injectable form of crocin, there may be nothing but another serotonergic reuptake inhibition drug/herb here (though one that is likely effective). It's particularly annoying since crocin may even have performed slightly better than safranil in the rat behavioral tests - they had to bump up safranil to a much higher dose to get a response in the climbing section, while crocin showed results at all doses.
So anyway, that's my assessment. Any thoughts are naturally welcome. Also, it does seem that Saffron may be a useful antidepressant herb to try. 30mg, in one or two doses per day, seems to be the standard dose, by the way. The sources are listed below, by the way.
Psychbot5000
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1http://www3.interscience.wiley.com/cgi-bin/abstract/110477939/ABSTRACT?CRETRY=1&SRETRY=0
"Crocus sativus L. in the treatment of mild to moderate depression: a double-blind, randomized and placebo-controlled trial"
Abstract
Depression is a serious disorder in today's society, with estimates of lifetime prevalence as high as 21% of the general population in some developed countries. As a therapeutic plant, saffron is considered excellent for stomach ailments and as an antispasmodic, to help digestion and to increase appetite. It is also used for depression in Persian traditional medicine. Our objective was to assess the efficacy of the stigmas of Crocus sativus (saffron) in the treatment of mild to moderate depression in a 6-week double-blind, placebo-controlled and randomized trial.
Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients had a baseline Hamilton rating scale for depression score of at least 18. In this double-blind, placebo-controlled, single-centre and randomized trial, patients were randomly assigned to receive a capsule of saffron 30 mg[sol ]day (BD) (Group 1) or a capsule of placebo (BD) (Group 2) for a 6-week study. At 6 weeks, Crocus sativus produced a significantly better outcome on the Hamilton depression rating scale than the placebo (d.f. = 1, F = 18.89, p < 0.001). There were no significant differences in the two groups in terms of the observed side effects.
The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified."
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2"Hydro-alcoholic extract of Crocus sativus L. versus fluoxetine in the treatment of mild to moderate depression: a double-blind, randomized pilot trial
Abstract
Depressive disorders are very common in clinical practice, with approximately 11.3 % of all adults afflicted during any a year. Saffron is the world's most expensive spice and apart from its traditional value as a food additive, recent studies indicate several therapeutic effects for saffron. It is used for depression in Persian traditional medicine. Our objective was to compare the efficacy of hydro-alcoholic extract of Crocus sativus (stigma) with fluoxetine in the treatment of mild to moderate depression in a 6-week double-blind, randomized trial. Forty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition for major depression based on the structured clinical interview for DSM-IV and with mild to moderate depression participated in the trial. In this double-blind, single-center trial and randomized trial, patients were randomly assigned to receive capsules of saffron 30 mg/day (BD) (Group 1) and capsule of fluoxetine 20 mg/day (BD) (Group 2) for a 6-week study. Saffron at this dose was found to be effective similar to fluoxetine in the treatment of mild to moderate depression (F = 0.13, d.f. = 1, P = 0.71). There were no significant differences in the two groups in terms of observed side effects. The results of this study indicate the efficacy of Crocus sativus in the treatment of mild to moderate depression. A large-scale trial is justified."
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3http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=517724
"Comparison of Crocus sativus L. and imipramine in the treatment of mild to moderate depression: A pilot double-blind randomized trial [ISRCTN45683816]
Background
The morbidity and mortality associated with depression are considerable and continue to increase. Depression currently ranks fourth among the major causes of disability worldwide, after lower respiratory infections, prenatal conditions, and HIV/AIDS. Crocus sativus L. is used to treat depression. Many medicinal plants textbooks refer to this indication whereas there is no evidence-based document. Our objective was to compare the efficacy of stigmas of Crocus sativus (saffron) with imipramine in the treatment of mild to moderate depression in a 6-week pilot double-blind randomized trial.Methods
Thirty adult outpatients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition for major depression based on the structured clinical interview for DSM IV participated in the trial. Patients have a baseline Hamilton Rating Scale for Depression score of at least 18. In this double-blind, single-center trial, patients were randomly assigned to receive capsule of saffron 30 mg/day (TDS) (Group 1) and capsule of imipramine 100 mg/day (TDS) (Group 2) for a 6-week study.Results
Saffron at this dose was found to be effective similar to imipramine in the treatment of mild to moderate depression (F = 2.91, d.f. = 1, P = 0.09). In the imipramine group anticholinergic effects such as dry mouth and also sedation were observed more often that was predictable.Conclusion
The main overall finding from this study is that saffron may be of therapeutic benefit in the treatment of mild to moderate depression. To the best of our knowledge this is the first clinical trial that supports this indication for saffron. A large-scale trial with placebo control is warranted."_______________________________________________________________________________
4http://www.actahort.org/members/showpdf?booknrarnr=650_54
"ANTIDEPRESSANT EFFECT OF CROCUS SATIVUS L. STIGMA EXTRACTS AND THEIR CONSTITUENTS, CROCIN AND SAFRANAL, IN MICE
Authors: H. Hosseinzadeh, G. Karimi, M. Niapoor
Keywords: antidepressant activity, Crocus sativus, crocin, safranal
Abstract:
The effects of aqueous and ethanolic extracts of Crocus sativus L. stigma and their constituents safranal and crocin were studied for the antidepressant activity using forced swimming test in mice. The extracts and constituents were injected intraperitoneally to mice. The aqueous and ethanolic extracts of stigma (0.2-0.8 g/kg) decreased immobility time in comparison to normal saline. Safranal (0.15-0.5 ml kg) and crocin (50-600 mg/kg) also reduced immobility time. Swimming time was increased by fluoxetine and both extracts. Safranal increased swimming time. Climbing time was increased by imipramine and both extracts. Safranal with a higher dose (0.5 mg/kg) and crocin at doses 50 and 600 increased climbing time. In the open field activity test, the ethanolic extract and safranal increased stereotypic activities. On the basis of these results, the antidepressant effect of C. sativus stigma extracts may be mediated via safranal and crocin. Crocin may act via the uptake inhibition of dopamine and norepinephrine, and safranal via serotonin."________________________________________________________________________________________
5http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&list_uids=17215113&cmd=Retrieve&indexed=google
"Pharmacokinetic properties of crocin (crocetin digentiobiose ester) following oral administration in rats.
Xi L, Qian Z, Du P, Fu J.Department of Pharmacology, China Pharmaceutical University, P.O. Box 46, 24 Tongjia Xiang, Nanjing 210009, PR China.
This study investigated the pharmacokinetic properties of crocin following oral administration in rats. After a single oral dose, crocin was undetected while crocetin, a metabolite of crocin, was found in plasma at low concentrations. Simultaneously, crocin was largely present in feces and intestinal contents within 24h. After repeated oral doses for 6 days, crocin remained undetected in plasma and plasma crocetin concentrations were comparable to the corresponding data obtained after the single oral dose. Furthermore, the absorption characteristics of crocin were evaluated in situ using an intestinal recirculation perfusion method. During recirculation, crocin was undetected and low concentrations of crocetin were detected in plasma. The concentrations of crocin in the perfusate were reduced through different intestinal segments, and the quantities of drug lost were greater throughout the colon. These results indicate that (1) orally administered crocin is not absorbed either after a single dose or repeated doses, (2) crocin is excreted largely through the intestinal tract following oral administration, (3) plasma crocetin concentrations do not tend to accumulate with repeated oral doses of crocin, and (4) the intestinal tract serves as an important site for crocin hydrolysis."
For a similar result on crocin absorbtion, see also:
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16131146&dopt=Abstract
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poster:psychobot5000
thread:764706
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