Planta Med 2009; 75(2): 105-112
DOI: 10.1055/s-0028-1088346
Clinical Study
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

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

Erik M. G. Olsson1 , 2 , Bo von Schéele2 , 3 , Alexander G. Panossian4
  • 1Department of Psychology, Uppsala University, Uppsala, Sweden
  • 2PBM Stress Medicine AB, Stockholm, Sweden
  • 3School of Innovation, Design and Engineering, Mälardalen University, Västerås, Sweden
  • 4Swedish Herbal Institute Research and Development, Åskloster, Sweden
Further Information

Publication History

Received: July 8, 2008 Revised: September 23, 2008

Accepted: September 29, 2008

Publication Date:
18 November 2008 (online)


The aim of the study was to assess the efficacy of the standardised extract SHR-5 of roots of Rhodiola rosea L. in the treatment of individuals suffering from stress-related fatigue. The phase III clinical trial took the form of a randomised, double-blind, placebo-controlled study with parallel groups. Participants, males and females aged between 20 and 55 years, were selected according to the Swedish National Board of Health and Welfare diagnostic criteria for fatigue syndrome. A total of 60 individuals were randomised into two groups, one (n = 30) of which received four tablets daily of SHR-5 extract (576 mg extract/day), while a second (n = 30) received four placebo tablets daily. The effects of the extract with respect to quality of life (SF-36 questionnaire), symptoms of fatigue (Pines’ burnout scale), depression (Montgomery-Asberg depression rating scale – MADRS), attention (Conners’ computerised continuous performance test II – CCPT II), and saliva cortisol response to awakening were assessed on day 1 and after 28 days of medication. Data were analysed by between-within analyses of variance. No serious side effects that could be attributed to the extract were reported. Significant post-treatment improvements were observed for both groups (placebo effect) in Pines’ burnout scale, mental health (SF-36), and MADRS and in several CCPT II indices of attention, namely, omissions, commissions, and Hit RT SE. When the two groups were compared, however, significant effects of the SHR-5 extract in comparison with the placebo were observed in Pines’ burnout scale and the CCPT II indices omissions, Hit RT SE, and variability. Pre- versus post-treatment cortisol responses to awakening stress were significantly different in the treatment group compared with the control group. It is concluded that repeated administration of R. rosea extract SHR-5 exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome.


CCCPT II:Conners’ computerised continuous performance test II


ICD:International Classification of Diseases

MADRS:Montgomery-Asberg depression rating scale

Qol:quality of life


  • 1 National Board of Health and Welfare. Utmattningssyndrom – Stressrelaterad psykisk ohälsa. 2003 – 123 – 18. Stockholm; National Board of Health and Welfare 2003
  • 2 Linné C. Materia medica – Liber I. de plantis. Stockholm; Lars Salvius 1749: 168
  • 3 Sparschuch H. Pharmacopoeia Svecia. Stockholm; Holmia 1775: 39
  • 4 Virey J -J. Racine de roses. Rhodiola rosea L. Traité de pharmacie théorique et pratique,. Vol 1 Paris; Remont-Ferra 1811: 92
  • 5 Saratikov A S, Krasnov E A. Rhodiola rosea (Golden root). Tomsk; Tomsk University Publishing House 2004: 292
  • 6 Aksenova R A, Zotova M I, Nekhoda M F, Cherdantsev S G. Comparative characteristics of the stimulants and adaptogenic effects of Rhodiola rosea preparations. In: Saratikov AS, editor Stimulants of the central nervous system. Vol. 2 Tomsk; Tomsk University Publishing House 1968: 3-12
  • 7 Saratikov A S, Krasnov E E, Chnikina L A, Duvidson L M, Sotova M I, Marina T F. et al . Rhodiolosid ein neues Glykosid aus Rhodiola rosea und seine pharmakologischen Eigenschaften.  Pharmazie. 1968;  23 392-5
  • 8 Komar V V, Kit S M, Sishchuk L V, Sishchuk V M. Effect of Rhodiola rosea on human mental activity.  Pharm J (Kiev). 1981;  36 62-4
  • 9 Sokolov S Ya, Ivashin V K, Zapesochnaya G G, Kurkin V A, Shchavlinskii A N. Studies of neurotropic activity of new compounds isolated from Rhodiola rosea L.  Chem Pharm J (Moscow). 1985;  19 1367-71
  • 10 Panossian A, Wagner H. Stimulating effects of adaptogens: an overview of clinical trials of adaptogens with particular reference on their efficacy at single dose administration.  Phytother Res. 2005;  19 819-38
  • 11 Müller-Dietz H. Arzneipflanzen in der Sowietunion.  Berlin: Berichte des Osteuropa-Instituts an der Freien. Universität;  1969 44, 91-3
  • 12 USSR Ministry of Health. Pharmacopoeia paper 75 – Rhizome and roots of Rhodiola rosea. National pharmacopoeia of the USSR, 11th edition. Moscow; Meditsina 1990 2: 317-9 (update No. 2 of 19 – 05 – 1999)
  • 13 Estonian Ministry of Health Affairs. Regulation No. 7, Annex 1, 21 – 01 – 1998. Tallin; Government of Estonia 1998
  • 14 Sandberg F. Herbal remedies and herb magic. Stockholm; Det Basta 1998: 223
  • 15 Mattioli L, Perfumi M. Rhodiola rosea L. extract reduces stress- and CRF-induced anorexia in rats.  J Psychopharmacol. 2007;  21 742-50
  • 16 Petkov V D, Yonkov D, Mosharoff A, Kambourova T, Alova L, Petkov V V. et al . Effects of alcohol aqueous extract from Rhodiola rosea L. roots on learning and memory.  Acta Physiol Pharmacol Bulg. 1986;  12 3-16
  • 17 Perfumi M, Mattioli L. Adaptogenic and central nervous system effects of single doses of 3 % rosavin and 1 % rhodioloside Rhodiola rosea L. extract in mice.  Phytother Res. 2007;  21 37-43
  • 18 Panossian A, Nikoyan N, Ohanyan N, Hovhannisyan A, Abrahamyan H, Gabrielyan E. et al . Comparative study of Rhodiola preparations on behavioral despair of rats.  Phytomedicine. 2008;  15 84-91
  • 19 Darbinyan V, Kteyan A, Panossian A, Gabielian 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;  7 365-71
  • 20 Spasov A A, Wikman G K, Mandrikov V B, Mironova I A, Neumoin V V. A double-blind, placebo-controlled pilot study of the stimulating and adaptogenic effect of Rhodiola rosea SHR-5 extract on the fatigue of students caused by stress during an examination period with a repeated low-dose regimen.  Phytomedicine. 2000;  7 85-9
  • 21 Shevtsov V A, Zholus B I, Shervaly V I, VolŽskij V B, Korovin Y P, Khristich M P. et al . A randomized trial of two different doses of a SHR-5 Rhodiola rosea extract versus placebo and control of capacity for mental work.  Phytomedicine. 2003;  10 95-105
  • 22 Grossi G, Perski A, Ekstedt M, Johansson T, Lindstrom M, Holm K. The morning salivary cortisol response in burnout.  J Psychosom Res. 2005;  59 103-11
  • 23 World Medical A ssociation. Declaration of Helsinki: ethical principles for medical research involving human subjects.  J Postgrad Med. 2002;  48 206-8
  • 24 World Health Organisation. ICD-10 – International statistical classification of diseases and related health problems. Arlington; American Psychiatric Publishing 1992
  • 25 Pines A, Aronson E, Kafry D. Burnout: from tedium to personal growth. New York; Free Press 1981
  • 26 International Conference on Harmonisation. ICH Topic Q2B Validation of Analytical Procedures: Methodology, Step 4, Consensus Guidelines,. 6 November, 1996 []
  • 27 International Organisation for Standardisation. EN ISO/IEC 17 025 : 2001 Standard Accreditation Requirements for QC Laboratories Operating under the GxP Compliance Requirements. 2001 []
  • 28 Conners C K. Conners' continuous performance test II: Computer program for Windows – Technical guide and software manual. Toronto; Multi-Health Systems 2003
  • 29 Hallsten L, Bellaagh K, Gustafsson K. Utbränning i Sverige - en populationsstudie. Arbete och Hälsa; Arbetslivsinstitutet 2002
  • 30 Montgomery S A, Asberg M. A new depression scale designed to be sensitive to change.  Br J Psychiatry. 1979;  134 382-9
  • 31 Sullivan M, Karlsson J, Ware J. The Swedish SF-36 health survey – I. Evaluation of data quality, scaling assumptions, reliability and construct validity across general populations in Sweden.  Soc Sci Med. 1995;  41 1349-58
  • 32 Persson L -O, Karlsson J, Bengtsson C, Steen B, Sullivan M. The Swedish SF-36 health survey – II. Evaluation of clinical validity: Results from population studies of elderly and women in Gothenburg.  J Clin Epidemiol. 1998;  51 1095-103
  • 33 Sullivan M, Karlsson J. The Swedish SF-36 health survey – III. Evaluation of criterion-based validity: Results from normative population.  J Clin Epidemiol. 1998;  51 1105-13
  • 34 Pruessner J C, Hellhammer D H, Kirschbaum C. Burnout, perceived stress, and cortisol responses to awakening.  Psychosom Med. 1999;  61 197-204
  • 35 de Vente W, Olff M, van Amsterdam J G, Kamphuis J H, Emmelkamp P M. Physiological differences between burnout patients and healthy controls: blood pressure, heart rate, and cortisol responses.  Occup Environ Med. 2003;  60 (1) i54-61
  • 36 Levin E D, Conners C K, Silva D, Canu W, March J. Effects of chronic nicotine and methylphenidate in adults with attention deficit/hyperactivity disorder.  Exp Clin Psychopharmacol. 2001;  9 83-90
  • 37 Vercoulen J H, Bazelmans E, Swanink C M, Galama J M, Fennis J F, van der Meer J W. et al . Evaluating neuropsychological impairment in chronic fatigue syndrome.  J Clin Exp Neuropsychol. 1998;  20 144-56
  • 38 StatSoft. STATISTICA (data analysis software system). Tulsa; StatSoft 2004
  • 39 Zotova M I. The effect of Rhodiola rosea extract on mental working activity in man. Collection of reports at 3rd scientific conference of physiologists. Tomsk; Biochemists and Pharmacologists of Western Siberia 1965: 298-9
  • 40 Marina T F, Mikhaleva L K, Suslov N I. Comparative effects of para-tyrosol and Rhodiola extract on the central nervous system. Proceedings of a Joint Plenary Session of Pathophysiologists and Pharmacologists of Siberia and the Far East on Mechanisms of the Development of Pathological Processes. Kemerovo; Kemerovo State University Press 1994: 66-8
  • 41 Munk A. Corticosteroids and stress. In: Fink G, editor Encyclopedia of stress. Vol 1 San Diego; Academic Press 2000: 570-7
  • 42 Young A H. Cortisol in mood disorders.  Stress. 2004;  7 205-8
  • 43 Panossian A G. Adaptogens: Tonic herbs for fatigue and stress.  Altern Compliment Therapies. 2003;  9 327-32
  • 44 Panossian A, Hambartsumyan M, Hovanissian A, Gabrielyan E, Wikman G. The adaptogens Rhodiola and Schizandra modify the response to immobilization stress in rabbits by suppressing the increase of phosphorylated stress-activated protein kinase, nitric oxide and cortisol.  Drug Target Insights. 2007;  1 39-54 Available at = 260. Accessed June 26, 2008
  • 45 Kirschbaum C, Hellhammer D H. Salivary cortisol in psychoneuroendocrine research: recent developments and applications.  Psychoneuroendocrinology. 1994;  19 313-33
  • 46 Schmidt-Reinwald A, Pruessner J C, Hellhammer D H, Federenko I, Rohleder N, Schürmeyer T H. et al . The cortisol response to awakening in relation to different challenge tests and a 12-hour cortisol rhythm.  Life Sci. 1999;  64 1653-60
  • 47 Holsboer F. The corticosteroid receptor hypothesis of depression.  Neuropsychopharmacology. 2000;  23 477-501
  • 48 Darbinyan V, Aslanyan G, Amroyan E, Gabrielyan E, Malmström C, Panossian A. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression.  Nord J Psychiatry. 2007;  61 343-8
  • 49 Herbert J, Goodyer I M, Grossman A B, Hastings M H, de Kloet E R, Lightman S L. et al . Do corticosteroids damage the brain?.  J Neuroendocrinol. 2006;  18 393-411

Erik M. G. Olsson

Department of Psychology

Uppsala University

Box 1225

751 42 Uppsala


Phone: +46 70 359 27 59