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Rhodiola Rosea's pharmacological mode of action

c0rt3x

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Rhodiola Rosea

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Rhodiola rosea (commonly golden root, rose root, roseroot, Aaron's rod, arctic root, king's crown, lignum rhodium, orpin rose) is a plant in the Crassulaceae family that grows in cold regions of the world. These include much of the Arctic, the mountains of Central Asia, the Rocky Mountains, and mountainous parts of Europe, such as the Alps, Pyrenees, and Carpathian Mountains, Scandinavia, Iceland, Great Britain and Ireland. The perennial plant grows in areas up to 2280 meters elevation. Several shoots grow from the same thick root. Shoots reaches 5 to 35 cm in height. Rhodiola rosea is dioecious – having separate female and male plants.
Contents

1 Uses
2 Phytochemicals and potential health effects
3 References
4 External links
5 Further reading

Uses
Plant

Rhodiola rosea may be effective for improving mood and alleviating depression. Pilot studies on human subjects[2][3][4] showed it improves physical and mental performance, and may reduce fatigue.

It has been hypothesized that Rhodiola rosea's effects are mediated by changes in serotonin and dopamine levels due to monoamine oxidase inhibition and its influence on opioid peptides, such as beta-endorphin,[5] although these specific neurochemical mechanisms have not been clearly documented with scientific studies.

Rhodiola is included among a class of plant derivatives called adaptogens which differ from stimulants, such as nicotine and amphetamine. Adaptogens have less efficacy and different physiological effects than stimulants. Adaptogens are absent from mainstream medicine, but are popular in energy drinks.[6] On the other hand, stimulants are widely used in mainstream medicine to treat conditions like narcolepsy, obesity, and attention-deficit hyperactivity disorder.[7]

In Russia and Scandinavia, R. rosea has been used for centuries to cope with the cold Siberian climate and stressful life.[8] Such effects were provided with evidence in laboratory models of stress using the nematode C. elegans,[9] and in rats in which Rhodiola effectively prevented stress-induced changes in appetite, physical activity, weight gain and the estrus cycle.[10]

The plant has been used in traditional Chinese medicine, where it is called hóng jǐng tiān (红景天).
Wikimedia Commons has media related to: Rhodiola rosea
Phytochemicals and potential health effects
Withering flower

Rhodiola rosea contains a variety of compounds that may contribute to its effects,[11] including the class of rosavins which include rosavin, rosarin, and rosin. Several studies have suggested that the most active components are likely to be rhodioloside and tyrosol,[12] with other components being inactive when administered alone, but showing synergistic effects when a fixed combination of rhodioloside, rosavin, rosarin and rosin was used.[13] Authentication, as well as potency, of Rhodiola rosea crude material and standardized extracts thereof are carried out with validated high-performance liquid chromatography analyses to verify the content of the marker constituents salidroside, rosarin, rosavin, rosin and rosiridin.[14]

Although rosavin, rosarin, rosin and salidroside (and sometimes p-tyrosol, rhodioniside, rhodiolin and rosiridin) are among suspected active ingredients of Rhodiola rosea, these compounds are mostly polyphenols. There is no evidence that these chemicals have any physiological effect in humans that could prevent or reduce risk of disease.[15]

Although these phytochemicals are typically mentioned as specific to Rhodiola extracts, there are many other constituent phenolic antioxidants, including proanthocyanidins, quercetin, gallic acid, chlorogenic acid and kaempferol.[16][17]

While animal tests have suggested a variety of beneficial effects for Rhodiola rosea extracts,[18] there is scientific evidence only for depression as a benefit in humans. A 2007 clinical trial from Armenia showed significant effect for a Rhodiola extract in doses of 340–680 mg per day in male and female patients from 18 to 70 years old with mild to moderate depression. No side effects were demonstrated at these doses[19] Another study also found antidepressant properties,[20] possibly via the plant's inhibition of MAO-A and MAO-B.[21]

R. rosea promotes the release of norepinephrine from rat penile corpus cavernosum smooth muscle cell and artery endothelium cell, which was correlated with its effect to resist senility.[22]

Rhodiola rosea extract exerts an antifatigue effect that increases mental performance, particularly the ability to concentrate in healthy subjects[3][23][2] and burnout patients with fatigue syndrome.[24] Rhodiola significantly reduced symptoms of fatigue and improved attention after four weeks of repeated administration.[24] Because of its stimulating properties and potential to interfere with sleep, Rhodiola rosea should be taken early in the day.
Dried Rhodiola rosea root

Studies on whether Rhodiola improves physical performance have been inconclusive, with some studies showing some benefit,[25] while others show no significant difference.[26]

Inhibitory activities against HIV-1 protease have also been studied.[27]


Even though wikipedia mentions it increases the release of noradrenaline - it feels like its actions must be more complex than this.
For example the first effects I remember were feeling much more harmonic and balanced emotionally and in my mind in general.

The first time I took about 20x200mg of extract but did not realize those effects before the early morning hours after a sleepless night. (even one night of sleep withdrawal makes me feel very stressed in most cases...)

Interestingly the only comparable experiences I had before were on combinations of stimulants and benzodiazepines.

Somewhere I read that Rhodiola had anxiolytic properties, too, so maybe this comparison is not that wrong...
 
Wow this sounds like an amazing plant/remedy. I don't know if this would be considered sourcing, I hope not, but what extract or in what form would you suggest I get? I would be attempting to use this plant in order to give me some energy and motivation, after coming off of methadone and several years of opiate abuse/dependence and now being on suboxone I have been having some major problems with motivation and energy, also depression and anxiety so thus plant seems quite amazing. Also I had no idea that there was a separate drug class called adaptogens, i assumed all these plants and some of the one used in energy drinks were just considered stimulants.
Thanks for posting this
Sincerely YN:)
 
The "active" components in Rhodiola are mostly polyphenols - which have exttraordinarily poor bioavailibility most of the time.

Green tea is probably a better source...
 
Sekio, do you know of any methods that could be used to enhance absorption/bioavailability? I mean its a stretch, but if one could figure a way to increase the BA it would make these compounds much more useful and viable for human consumption.
 
No, it's a limitation of the physical properties of the molecules. The polyphenols just have such high water solubility (highly polar, multiple phenolic hydroxyls does that...) and such poor metabolic stability that acchieving pharamcologically significant levels is kind of difficult without taking megadoses. Look at the BBB permeability of dopamine versus that of amphetamine if you need an example (BBB penetration decreases with more hydroxyl groups, methamp>amphetamine>ephedrine>dopamine>noradrenaline) (Most of the antioxidant potential of polyphenols comes from the presence of these multiple hydroxyl groups because they can soak up radicals a la BHT.)

If you start masking the hydroxyl groups to change pharmacokinetics, suddenly you don't have polyphenols anymore. They're different molecules and probably will lose activity at your target. You can't just "make" molecules cross the BBB without changing any of their other properties (without direct-brain injection)

Really most of my research has been into the MAO inhibitory properties of Rhodiola, w.r.t rosiridin and such. They're MAO inhibitors in cell culture, sure, but on the order of 1000 times less active than pharmaceutical selective MAOIs. I cannot imagine that concentrations would build that high in the brain.

Moreover I have not heard of very many studies, controlled or not, suggesting Rhodiola is a blow-you-away miracle adaptogen. I don't think it's active as a DMT/ayahuasca additive, and...
There is no evidence that these chemicals have any physiological effect in humans that could prevent or reduce risk of disease. [...]
Studies on whether Rhodiola improves physical performance have been inconclusive, with some studies showing some benefit, while others show no significant difference.

Until more studies have been done I would not neccesarily be spending my time and money on Rhodiola, I imagine drinking more tea and eating more colored/leafy vegetables (anthocyanins/polyphenols/etc) would be just as well.
 
Some people claim efficacy from homeopathic medicines, too. All I'm saying is I know it's not really super effective as a MAOI.
Maybe I'm just a cynic though.

If it boils down to 'this is a herb, that makes you feel good, we don't know why though' I don't see a lot of reason to take it, personally. If it's the flavonoids/polyphenols that are the actives then there are better sources anyway.

A good big cup of strong green or black tea has probably 100-200mg of polyphenols in it. Plus theanine et cetera, whuich mild as they may be, actually have a body of evidence for their mode of action & an established safety/tox profile.
 
...but what extract or in what form would you suggest I get?

@YellowNikes:

That depends on where you live. In my country there is a discounter called "Norma" which just introduced a new cheap product labeled "Anti-Stress Pills" which contains 32x200mg Rodiola Rosea extract and some vitamins. A box is about 4€ - which is quite cheap compared to the prices in the pharmacy stores here (if they can get it at all).

In Russia Rhodiola Rosea is far more spread then elsewhere - as far as I know.


...do you know of any methods that could be used to enhance absorption/bioavailability?

@Hiltoniano:

Piperine (or simply Black Pepper) can greatly increase the absorption of many substances:

http://en.wikipedia.org/wiki/Piperine#Biological_activity

Furthermore it has some Anti-Depressive effects itself.


Some people claim efficacy from homeopathic medicines, too. All I'm saying is I know it's not really super effective as a MAOI.
Maybe I'm just a cynic though.

@sekio:

Medical herbs have nothing to do with "homeopathic" sugar pills.

However I agree with the assumption that it is not a potent MAOI.

But this changes nothing about the widely documented fact that it has very beneficial effects on mood, motivation and can increase one's inner harmony!

At doses as high as mentioned in my opening post it really keeps one awake for a whole night for sure - but without causing unpleasant come-downs like many synthetic stimulants usually do.


PS:
As I collected more experience with this plant extract, I actually came to the conclusion that lower doses are more suitable for my every day life, since I react very negatively to sleep withdrawal in general and more than 4x200mg once in the morning keep me awake too long.
 
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In regard to sekio's comments, even though it may have poor bioavailability to the brain, its utilization in other parts of the body (where bioavail may not be an issue) may be highly significant. There's a form of scopolamine — the butylbromide salt — that doesn't or barely pass the BBB; but it's used medically because of its effects on other parts of the body.

Rehmannia Dean Thomas and Ron Teeguarden reccommend Rhodiola crenulata and Rhodiola sacraa over rosea.
 
Just dropping by to say that I use Rhodiola rosea for depression/anxiety/energy/motivation, and I notice a difference when I'm on it vs. off it. I've been using it for a few years now. Tried stopping a few times and started to notice my days lagging, so I went back on it.
 
In regard to sekio's comments, even though it may have poor bioavailability to the brain, its utilization in other parts of the body (where bioavail may not be an issue) may be highly significant. There's a form of scopolamine — the butylbromide salt — that doesn't or barely pass the BBB; but it's used medically because of its effects on other parts of the body.

Not to nitpick but bio-availability has to do with the amount of substance absorbed by whatever ROA, so if it has terrible bio-availability then it doesn't get utilized anywhere , it has nothing to with how much actually reaches your brain, though if a drug can get into your brain then a higher BA will allow more to reach the receptors in the brain because there is more total amount absorbed.

It's essentially just the % of the drug absorbed by your body. There is the whole other side of how permeable the drug is to the BBB, that is what determines if it's psychoactive or just a drug that bonds to receptors elsewhere in the body. Correct me if I'm wrong though, but I think that's how it works.
 
I've been using Rhodiola extract (New Chapter has the good stuff with standardized levels of Rosavins and Salidrosides) for 4 months now. It's a special plant for sure. It really shines in conditions of sleep dep or mental fuzziness.

I'm going to figure out how to cheaply make a full spectrum extract so I don't have to keep paying out the ass for it. The whole herb is nice but has the potential for more sedation- though I haven't used that form long enough to know what it's true colors are.
 
rhodiola is a serious COMT inhibitor. be careful with that crap. i induced parkinson like effects with it in mild doses combined with random MAOIs that suprisingly enough you can get from any substance out there, natural or synthetic.
 
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