A reference work, not a recommendation to use: this profile describes mechanism and evidence and does not replace medical advice. The claims come from marketing and forums and are tested here, not endorsed.

Mechanism of action

Evidence map: Rhodiola rosea

Each line stands for a published finding; line style and color show where it comes from. The filter hides weaker evidence levels. Sources: see references.

About 140 compounds have been isolated from the root and rhizome of Rhodiola rosea, including phenylethanoids such as salidroside and phenylpropanoids such as the rosavins. A review from the research group that has studied the extract SHR-5 extensively names effects on the stress axis (cortisol reduction), the stress kinase JNK, nitric oxide, and protective proteins such as Hsp70 as possible mechanisms [1]. In the laboratory, methanol and water extracts inhibited monoamine oxidases A and B by more than 80%; the most active isolated compound, rosiridin, inhibited mainly MAO-B [2]. In human glial cells, a combination of several adaptogens and salidroside induced the release of neuropeptide Y and Hsp72 [3].

One laboratory finding is of practical importance: extracts from six Norwegian clones inhibited the liver enzyme CYP3A4 and the transporter P-glycoprotein more strongly than St. John’s wort; interactions with medicines are therefore conceivable [4].

Clinically, a systematic review found eleven placebo-controlled RCTs on physical and mental performance and on mental disorders but criticized the lack of independent replication [5]. A second review rated all studies on fatigue as having a high or unclear risk of bias; three of five RCTs on mental fatigue were positive [6]. In a crossover trial with 56 young physicians on night duty, the extract improved a fatigue index in the first two weeks [7]; in stress-related exhaustion, it improved measures of attention and lowered the cortisol awakening response [8]. In mild to moderate depression, it did not differ significantly from placebo or sertraline but caused fewer adverse effects than sertraline [9].

Targets

TargetTypeActionKey dataEvidence
Monoamine oxidase A and BEnzymeInhibitor> 80% inhibition at 100 µg/ml extract; rosiridin pIC50 5.38 (MAO-B, laboratory) Laboratory[2]
CYP3A4 and P-glycoproteinEnzymeInhibitorIC50 1.7–3.1 µg/ml (CYP3A4, laboratory) Laboratory[4]
Neuropeptide Y and Hsp72Signaling pathwayRelease Laboratory[3]

Effect profile

Which signaling systems the compound affects according to current data. ↑ enhanced, ↓ dampened, ≈ modulated, ○ no effect; dots = evidence level.

  • Dopamineunclear · Inhibition of MAO-A and MAO-B in the laboratory; significance in humans unknown[2]
  • Noradrenalineno data
  • Serotoninunclear · Inhibition of MAO-A in the laboratory; significance in humans unknown[2]
  • Acetylcholineno data
  • Glutamate · AMPAno data
  • Glutamate · NMDAno data
  • GABAno data
  • Histamineno data
  • Orexinno data
  • Adenosineno data
  • Opioidsno data
  • Melatoninno data
  • Neurotrophinsno data
  • Blood flowno data
  • Nitric oxideno data
  • Energy metabolismno data
  • Insulin · glucoseno data
  • Inflammation · oxidativeno data
  • Stress axis↓ · lower cortisol awakening response in stress-related exhaustion (RCT); NPY and Hsp72 in cells[3][8]
  • Testosterone axisno data
  • Endocannabinoidsno data
  • Autophagy · senescenceno data
  • Immune systemno data
  • Lipid metabolismno data
  • Coagulation · fibrinolysisno data
  • Methylationno data

Human studies

  • Systematic review of all RCTs

    systematic review of 11 placebo-controlled RCTs · mixed: healthy people and patients · varied

    Measured: physical and mental performance, mental disorders

    Result: Possible benefits, but no independent replication; only a few mild adverse effects.[5]

    Human, randomised

  • Systematic review on fatigue

    systematic review of 10 RCTs and 1 controlled trial · mixed · varied

    Measured: physical and mental fatigue

    Result: Three of five RCTs on mental fatigue positive; all studies at high or unclear risk of bias.[6]

    Human, randomised

  • Physicians on night duty

    RCT, double-blind, crossover · healthy (young physicians) · n = 56 · 2 × 2 weeks

    Measured: Fatigue index from five tests

    Result: Significant improvement in the first treatment phase; no adverse effects reported.[7]

    Human, randomised

  • Stress-related exhaustion

    RCT, double-blind, placebo-controlled · Patients: stress-related exhaustion syndrome · n = 60 · 28 days

    Measured: Burnout scale, attention (CCPT II), cortisol

    Result: Better than placebo on the burnout scale and some measures of attention; lower cortisol awakening response.[8]

    Human, randomised

  • Mild to moderate depression

    RCT, placebo-controlled, comparison with sertraline · Patients: major depression · n = 57 · 12 weeks

    Measured: HAM-D, BDI, CGI

    Result: No significant difference between the groups; fewer adverse effects than with sertraline.[9]

    Human, randomised

Risks and warnings

  • Drug interactions via CYP3A4 and P-glycoprotein

    In the laboratory, rhodiola inhibited CYP3A4 more strongly than St. John’s wort; clinically relevant interactions are possible but have not been studied in humans [4].

    Laboratory

  • Adverse effects

    Only a few mild adverse effects in the RCTs [5]; less frequent than with sertraline in the depression trial [9].

    Human, randomised

  • MAO inhibition

    In the laboratory, extracts inhibit MAO-A and MAO-B [2]; whether this causes interactions in humans, for example with serotonergic medicines, has not been studied.

    Laboratory

Interactions

  • Substrates of CYP3A4 and P-glycoprotein: Possible increase in levels through inhibition in the laboratory [4]; not tested in humans.

Fact check: common claims

  • partly supported

    “Rhodiola reduces mental exhaustion under stress”

    Some small RCTs positive, for example on night duty [7] and in stress-related exhaustion [8]; reviews criticize risks of bias and the lack of replication [5][6].

  • not supported

    “Rhodiola improves concentration and memory in well-rested healthy people”

    The positive studies examined fatigue or stress [7][8]; independent evidence for an effect without strain is lacking [6].

  • not supported

    “Rhodiola has an antidepressant effect like an antidepressant”

    In one RCT, no significant difference from placebo or sertraline [9]; MAO inhibition shown only in the laboratory [2].

  • not supported

    “Rhodiola has no interactions with medicines”

    Strong inhibition of CYP3A4 and P-glycoprotein in the laboratory [4]; a review by the SHR-5 group, by contrast, describes a lack of interactions in clinical studies [1].

Pharmacokinetics

Absorption
By mouth as a standardized root extract.
Half-life
Not verified.
Metabolism
Not verified; the extract inhibits CYP3A4 in the laboratory [4].
Entry into the brain
Not verified.

Legal status

Germany
Not verified.
EU
Not verified.
USA
Not verified.
Other countries
Traditionally used in Eastern Europe and Asia against fatigue, stress, and low mood [2]; approval status not checked.

Related compounds

Bacopa monnierisame classGinkgo bilobasame class

Open questions

  • Can independent groups with a low risk of bias replicate the effects on mental fatigue?
  • Are the CYP3A4 inhibition and the MAO inhibition clinically relevant at usual intake?
  • Which constituents are responsible for the effect, and how comparable are different extracts?

References

  1. Panossian A, Wikman G, Sarris J. Rosenroot (Rhodiola rosea): traditional use, chemical composition, pharmacology and clinical efficacy. Phytomedicine. 2010;17(7):481–93. doi:10.1016/j.phymed.2010.02.002 · PubMed
  2. van Diermen D, Marston A, Bravo J, Reist M, Carrupt PA, Hostettmann K. Monoamine oxidase inhibition by Rhodiola rosea L. roots. J Ethnopharmacol. 2009;122(2):397–401. doi:10.1016/j.jep.2009.01.007 · PubMed
  3. Panossian A, Wikman G, Kaur P, Asea A. Adaptogens stimulate neuropeptide Y and Hsp72 expression and release in neuroglia cells. Front Neurosci. 2012;6:6. doi:10.3389/fnins.2012.00006 · PubMed
  4. Hellum BH, Tosse A, Hoybakk K, Thomsen M, Rohloff J, Georg Nilsen O. Potent in vitro inhibition of CYP3A4 and P-glycoprotein by Rhodiola rosea. Planta Med. 2010;76(4):331–8. doi:10.1055/s-0029-1186153 · PubMed
  5. Hung SK, Perry R, Ernst E. The effectiveness and efficacy of Rhodiola rosea L.: a systematic review of randomized clinical trials. Phytomedicine. 2011;18(4):235–44. doi:10.1016/j.phymed.2010.08.014 · PubMed
  6. Ishaque S, Shamseer L, Bukutu C, Vohra S. Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complement Altern Med. 2012;12:70. doi:10.1186/1472-6882-12-70 · PubMed
  7. Darbinyan V, Kteyan A, Panossian A, Gabrielian E, Wikman G, Wagner H. Rhodiola rosea in stress induced fatigue – a double blind cross-over study of a standardized extract SHR-5 with a repeated low-dose regimen on the mental performance of healthy physicians during night duty. Phytomedicine. 2000;7(5):365–71. doi:10.1016/S0944-7113(00)80055-0 · PubMed
  8. Olsson EM, von Schéele B, Panossian AG. A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract SHR-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue. Planta Med. 2009;75(2):105–12. doi:10.1055/s-0028-1088346 · PubMed
  9. Mao JJ, Xie SX, Zee J, Soeller I, Li QS, Rockwell K, et al. Rhodiola rosea versus sertraline for major depressive disorder: a randomized placebo-controlled trial. Phytomedicine. 2015;22(3):394–9. doi:10.1016/j.phymed.2015.01.010 · PubMed
How this profile was checked

Last reviewed: 2026-10-23. All sources with a DOI or PMID were resolved automatically via Crossref or doi.org and PubMed.

Translated from the German profile (version of 2026-10-23); translation checked on 2026-10-26.

Checked

  • All DOIs resolved via Crossref; PMIDs match the DOIs.
  • From the abstracts: about 140 compounds, mechanisms, statement on the lack of interactions [1]; MAO-A/B inhibition > 80%, rosiridin pIC50 5.38 [2]; NPY and Hsp72 in glial cells, combination product ADAPT-232 [3]; IC50 1.7–3.1 µg/ml for CYP3A4 [4]; 11 RCTs, no independent replication [5]; 11 studies, 3 of 5 RCTs on mental fatigue positive, high/unclear risk of bias [6]; 56 physicians, crossover [7]; 60 people, CCPT II, cortisol [8]; 57 people, no significant difference, adverse event rates [9].
  • ClinicalTrials.gov: 44 entries (October 23, 2026).
  • October 26, 2026, precision flags (m004; rules in the guideline under “Number rule and precision flags,” implementation by Claude pending confirmation by Tilman): “Better mental performance in healthy people”: “inkonsistent” (inconsistent) – according to the abstract of [6], 3 of 5 RCTs on mental fatigue were positive and the rest were not; [7] positive. No “kleine_studien” (small studies) flag because the participant numbers of the studies in [6] are missing from the abstract. Cross-check of October 26, 2026: the evidence behind the flags (participant numbers, direction, funding) was incorporated into the “begruendung” and rechecked against abstracts or full texts.

Not verified

  • Legal status (e.g., traditional herbal medicinal product in the EU) not checked; EMA pages not reachable.
  • Whether the working group around Panossian and Wikman has a financial connection to the manufacturer of SHR-5; cannot be determined reliably from the abstracts.
  • Pharmacokinetics of salidroside and rosavins in humans.
  • Participant numbers of the studies in [6] not determined (abstract only, which has no numbers); therefore no “kleine_studien” flag for “Better mental performance in healthy people” (October 26, 2026).

No dosages, no sources of supply. This information does not replace medical advice.

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