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The Effects of Rhodiola rosea L. Extract on
Anxiety, Stress, Cognition and Other Mood
Symptoms
Mark Cropley,
1
*Adrian P. Banks
1
and Julia Boyle
2
1
School of Psychology, University of Surrey, Guildford, Surrey, UK
2
School of Biosciences and Medicine, University of Surrey, Guildford, Surrey, UK
This trial evaluated the impact of a Rhodiola rosea L. extract on self-reported anxiety, stress, cognition, and
other mood symptoms. Eighty mildly anxious participants were randomized into two different groups of either
Rhodiola rosea L (2 × 200 mg dose Vitano®, 1 tablet taken before breakfast and 1tablet before lunch) or a
control condition (no treatment). Self-report measures and cognitive tests were completed at four testing
sessions over a period of 14 days. Relative to the controls, the experimental group demonstrated a significant
reduction in self-reported, anxiety, stress, anger, confusion and depression at 14 days and a significant
improvements in total mood. No relevant differences in cognitive performance between the groups were
observed. Rhodiola rosea L (Vitano®) presented a favourable safety tolerability profile. Although this was a
non-placebo controlled trial, it is unlikely that the findings were the result of placebo effects as changes appeared
gradual and were specific to certain psychological measures. However, we cannot determine a causal
relationship; further investigations are recommended to support the effects of Rhodiola rosea L. extract on stress
related symptoms. Copyright © 2015 John Wiley & Sons, Ltd.
Keywords: Rhodiola rosea L; Stress; Anxiety.
INTRODUCTION
Rhodiola rosea L. (Family Crassulaceae) is a shrub that
has been used in traditional medicine to alleviate the
symptoms of everyday stressors including anxiety, stress,
fatigue and depression (German et al., 1999). The phar-
macological effects of Rhodiola rosea L have been dem-
onstrated in a small number of preclinical (e.g. Chen
et al., 2009; Mannucci et al., 2012; Cayer et al., 2013),
and clinical studies (Darbinyan et al., 2000; Panossian
et al., 2010; Spasov et al., 2000; Darbinyan et al., 2007;
Sarris, 2007; Bystritsky et al., 2008; Sarris et al., 2011).
For example, Edwards et al. (2012) demonstrated that
Rosalin—a proprietary dry extract of the Rhodiola
rosea root—to have significant anti-stress effects after
3 days of treatment. In another study in patients
experiencing stress-related fatigue and burnout, male
and female participants were given an extract SHR-5
of Rhodiola rosea L. for 28 days, with those given the
extract showed increased concentration and a decrease
in fatigue relative to the controls (Olsson et al., 2009).
Such findings support the medicinal use of Rhodiola
rosea in humans.
It is possible that Rhodiola rosea L. may have a
moderating effect on anxiety and mood by inhibiting
physiological stress responsivity. Anxiety, stress and
fatigue are widespread in the Western World. In the
UK, The Office for National Statistics estimate that
4.7 per cent of adults experience diagnosed generalized
anxiety and worldwide; lifetime prevalence of anxiety
disorders is 16.6%. This rate is much higher for mild
anxiety. The primary aim of this trial was to investigate
the effects of Rhodiola rosea L on self-reported mild
anxiety and stress in a sample of university students.
Stress and anxiety are highly prevalent in students, and
it is well documented that students are exposed to a
range of stressors during their studies (Bewick et al.,
2010; Alzahem et al., 2011; Keyes et al., 2012;
Zunhammer et al., 2013). In the present study, mildly
anxious students with scores above 30 on the
Spielberger State–Trait Anxiety Inventory (STAI;
Spielberger, 1983) were randomly allocated to receive
either, a standard dose of Rhodiola rosea L. extract
(Vitano®) for 14days, or to a control group without
treatment. Our primary outcomes were self-reported
anxiety and stress. Secondary outcomes measures
included self-ratings of mood, sleepiness and sleep. In
addition, we also assessed the effects of Rhodiola rosea
L. on cognitive function using standardized speed of
processing cognitive tasks.
MEASURES AND METHODS
Design. The feasibility study was an open-label, ran-
domized (Rhodiola rosea Lvs. control) repeated mea-
sures design. Individuals in the control group did not
receive any investigational medicinal product (IMP).
The Rhodiola rosea L group were given a daily dose of
2 × 200 mg of Vitano® (as recommended in the summary
of product characteristics), 1 tablet taken before
* Correspondence to: Mark Cropley, School of Psychology, University of
Surrey, Guildford, Surrey, GU2 7XH, UK.
E-mail: mark.cropley@surrey.ac.uk
PHYTOTHERAPY RESEARCH
Phytother. Res. (2015)
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/ptr.5486
Copyright © 2015 John Wiley & Sons, Ltd.
Received 18 March 2015
Revised 30 July 2015
Accepted 15 September 2015
breakfast and one before lunch for 14 days. The active
ingredient of Vitano®
1
is Rosalin (WS® 1375), a propri-
etary dry extract from Rhodiola rosea roots (1.5-5:1)
The trial received approval from the South East Coast,
Brighton and Sussex Research Ethics Committee, the
University of Surrey Committee of ethics and the
Medicines and Healthcare Products Regulatory Agency
(MHRA).
Participants and procedure. Students were screened for
inclusion and if eligible were randomized to either the
treatment (Rhodiola rosea L) or control group. The
study had four phases. The baseline visit and completion
of the validated baseline questionnaires and cognitive
tests took place between 7 AM and 8 AM (Time
1 = T1). Following the baseline measures the experimen-
tal group received their first intake of the IMP. Dosing
took place 30 min before breakfast, and another dose
took place 30 min before lunch. Participants revisited
the laboratory 4 h later on the same day (T2) and com-
pleted the same batch of questionnaires and cognitive
tests (apart from the sleep measure). They returned to
the laboratory again at 7 days (T3) and at 14 days (T4)
and completed the same questionnaires and cognitive
tests. Participants in the treatment group were
telephoned each day to check IMP compliance, whilst
participants in the control condition were telephoned
to remind them of their next visit the day before their
visit. To monitor compliance, participants were asked
to bring back their used study medication packets.
Participants were compensated for their time and were
informed that they could voluntarily discontinue partic-
ipation in this study at any time.
Inclusion criteria. In order to satisfy the inclusion
criteria participants (1) had to be able to read, under-
stand and sign the Informed Consent Form, and under-
stand study procedures; (2) had to be healthy (on the
basis of medical history, vital signs and the results of
routine laboratory tests), male or female aged
18–35 years inclusive; (3) had reported a screening score
above 30 on the STAI; (4) agreed to use suitable
methods of contraception during the study and for
3 months afterwards; and (5) were non-smokers.
Exclusion criteria. Participants were not eligible for the
study if (1) they were pregnant or breast feeding; (2)
were consuming more than five caffeine-containing bev-
erages per day; (3) were colour blind; (4) received clin-
ically significant hepatic or renal abnormality as
determined by laboratory tests; (5) had a BMI above
33; (6) had a history of alcohol, narcotic, benzodiaze-
pine, or other substance abuse or dependence within
the 12 months preceding; (7) had a positive alcohol
breath test at any visit; (8) used any other medication
which may interfere with study outcome and/or inter-
fere with IMP within the 2 weeks or five half-lives pre-
ceding the first treatment phase; (9) currently
participated in another clinical trial with an investiga-
tional or non-investigational drug or device, or partici-
pated in another clinical trial within the 3 months
preceding Visit 1 (screening visit); or (10) had any
condition that could compromise the subject’s ability
to meet protocol requirements or to complete the study.
Primary outcomes measures
Anxiety. Anxiety was assessed using the STAI. This
measure has 20 items each scored on a scale of 1
(‘almost never’)to4(‘almost always’), which relate to
how patients feel generally. Some items are specific to
anxiety (e.g. ‘I feel nervous and restless’), and others
relating to more general symptoms of psychological
distress (e.g. ‘I feel like a failure’) (Spielberger, 1983).
Stress. Stress was assessed using the Perceived Stress
Scale (Cohen et al., 1994; Cohen et al., 1995). This is
the most widely used and cited psychological instrument
for measuring perception of stress. Participants rate the
degree to which situations in their life are appraised as
stressful using a 5-point scale (0 = Never, 1 = Almost
Never, 2 = Sometimes, 3 = Fairly Often, 4 = Very Often),
e.g. ‘In the last month, how often have you been upset
because of something that happened unexpected?’
Secondary outcomes measures
Mood. The Profile of Mood States Inventory (McNair
et al., 1971) was employed to assess mood. This is a
widely used measure of affective state, particularly ap-
propriate for assessing fluctuations in mood. It com-
prises 65 items that measure six mood factors. These
subscales assess (a) depression–dejection, (b) tension–
anxiety, (c) anger–hostility, (d) confusion–bewilderment,
(e) fatigue–inertia and (f) vigour–activity. Each item is
an adjective describing a mood or feeling for which the
participant has to indicate on a 5-point Likert-type scale
the extent to which they are experiencing that feeling,
i.e. not at all (0) to extremely (4). The Profile of Mood
States yields six subscale scores and a total mood score,
labelled total mood disturbance, which is derived from
totalling the six subscales. The vigour subscale carries a
negative weighting because it is the only positive mood
characteristic.
Sleepiness. The Milford Epworth Sleepiness Scale
(Johns, 1992) was used to assess daytime sleepiness.
Sleepiness is assessed using a visual analogue scoring
technique. Participants are required to rate their likeli-
hood of them falling asleep in a number of everyday
situations, and their overall mean score gives a measure
of daytime sleepiness.
Sleep. The Leeds Sleep Evaluation Questionnaire
(LSEQ) assesses the effects of psychoactive compounds
on sleep and early morning behaviour (Parrott and
Hindmarch, 1980). Participants mark a series of
100 mm line analogue scales, indicating the direction
and magnitude of any changes in behavioural state they
experience following administration of the drug. More
specifically, the LSEQ considers the perceived ease of
going to sleep, the quality of sleep, and any hangover
effect the following morning. Scores are represented in
millimetres.
1
The international brand name in most countries is Vitango®. The
product is manufactured by Dr Willmar Schwabe GmbH & Co. KG.
M. CROPLEY ET AL.
Copyright © 2015 John Wiley & Sons, Ltd. Phytother. Res. (2015)
Cognitive tests. Simple reaction time. Simple reaction
time was measured using a computer-based task. Partic-
ipants looked at a blank computer screen. When the
word ‘YES’appeared they responded by pressing a but-
ton as quickly as possible.
Choice reaction time. Choice reaction time was mea-
sured using a computer-based task. Participants looked
at a blank computer screen and responded quickly to a
word, but for this task there is a choice of words. The
participant was instructed to press one button when
the word YES appears and a different button when the
word ‘NO’appears.
Sustained Attention to Response Test (SART). The
SART measures concentration. Participants sat at a
computer, whilst numbers between one and nine
appeared on the screen at a regular pace in a random or-
der. They pressed the number on the keyboard corre-
sponding to each number as it appeared on the screen.
However, they were asked not to respond to the number
‘3’. The number of mistakes made indicates their ten-
dency to drift off into an automatic, error prone style
of responding as they lose concentration.
Symbol Digit Processing. Symbol digit processing mea-
sures speed of thinking. Participants were shown a key
on the computer screen linking nine nonsense symbols
with the numbers one to nine. Beneath the key, these
symbols were displayed one at a time in a random order.
The aim of this task was to press the number corre-
sponding to the symbols as quickly and as accurately
as possible.
Statistical analysis. Between groups characteristics were
assessed by t-tests and chi-squared tests. Subjective
questionnaire measures and cognitive tests were
analysed using repeated measures analysis of co-
variance with group (treatment/control) as between
group factors and testing session as the within subject
factor, controlling for baseline scores. Where significant
interactions were found these were broken down using
t-tests in a series of planned comparisons. Cognitive per-
formance was analysed as mean response latencies and
percentage of errors.
RESULTS
As shown in Table 1, there was no significant difference
between the groups on any of the demographic charac-
teristics. In total, 216 students were screened for inclu-
sion into the study of which 81 were randomized into
one of two conditions: treatment = 40; control = 41 volun-
teers. Compliance was 100% for the treatment group.
Every individual presented with a negative alcohol
breath test over each of the testing phases. During the
study, one participant in the treatment group terminated
the study prematurely because of concomitant medica-
tion. As this individual had no measurement during the
active study period, she was excluded from the analyses
of effectiveness measures, but was analysed with regard
to safety measures [adverse events (AE)]. Forty-one
subjects were in the non-dosing arm (control group).
Of the 40 subjects that were randomized to treatment
(dosing) group, 4 subjects reported one treatment emer-
gent AE each. Reported AEs were observed within
several system organ classes (SOC). The reported event
‘forgetfulness,’which was assigned to the SOC ‘Nervous
system disorder’as well the event ‘loss of appetite’
attributed to the SOC ‘Metabolism and nutrition disor-
ders’, were known symptoms of the condition under
investigation. The two other events ‘food poisoning’
(SOC ‘Gastrointestinal disorders’) and ‘pelvic infection’
(SOC ‘Infections and infestations’) seemed to be
because of an independent concomitant condition. For
two participants of the control group one AE was
recorded in each case. For one subject who reported
numbness and slight tingling in his left little finger, the
preferred term was ‘hypoaesthesia’, this incident was
coded within the SOC Nervous system disorders. In
the second subject the event ‘increased stress’attributed
to the SOC ‘Psychic disorders’was because of an inde-
pendent exaggeration of everyday stress.
Primary outcome variable
Significant interaction effects were found for both Anx-
iety and Stress (Table 2). Relative to the control group,
and controlling for baseline ratings, the treatment
group showed a significant reduction in anxiety at T4,
(p<0.01), and a reduction in anxiety that approached
significance at time T3 (p= 0.08), but there was no
difference in ratings of anxiety between the groups at
T2. For perceived stress the treatment group showed
a non-significant trend to report less stress at T2,
(p=0.08), and T3 (p= 0.06), but reported significantly
less stress at T4 (p<0.01), relative to the control group.
There were also main group effects with the treatment
group reporting lower levers of anxiety and stress rela-
tive to the controls. Thus, both self-reported anxiety
and perceived stress were significantly reduced in the
treatment group.
Secondary outcome variables
With respect to the other mood factors, there were sig-
nificant main group effects for Confusion, Depression
Table 1. Demographic data (frequency and p-values of the
two-tailed χ
2
-test or mean (SD), and p-value of the two-tailed
t–test respectively)
Rhodiola rosea
L. (Vitano®) Control p
Sex Male 19 13 0.09
Female 20 28
Age (years) 21.21 (2.46) 21.17 (3.03) 0.95
Height (cm) 173.02 (8.32) 170.92 (9.11) 0.28
Weight (kg) 67.89 (10.75) 64.41 (9.38) 0.12
Hip (cm) 98.76 (7.09) 98.12 (5.56) 0.65
Waist (cm) 78.23 (7.66) 75.87 (6.94) 0.15
Hip-to-waist ratio 0.78 (0.05) 0.77 (0.04) 0.21
BMI 22.59 (2.56) 22.00 (2.42) 0.30
RHODIOLA ROSEA, MOOD AND COGNITION
Copyright © 2015 John Wiley & Sons, Ltd. Phytother. Res. (2015)
and Total Negative Mood. In each case, this was due to
lower ratings of Confusion, Depression and Total
Negative Mood for the treatment group. Significant
interaction effects were found for ratings of Anger,
Confusion, and Total Negative Mood. Relative to the
control group, and controlling for baseline ratings, the
treatment group showed a significant reduction in anger
at time T4 (p<0.05), but there was no difference in
ratings of anger between the groups at T2 and T3. For
Confusion, the control group gave higher ratings at T4
(p<0.01), but there was no difference in ratings of
confusion between the groups at T2 and T3. For Total
Negative Mood relative to the control group, and
controlling for baseline ratings, the treatment group also
gave lower ratings of Total Negative Mood at T4
(p<0.01). No significant effects were found for the af-
fective states of fatigue and tension.
Thus, the treatment (Vitano®) group demonstrated
lower significant ratings of self-reported anger, confu-
sion, and depression relative to the controls and showed
significant improvements in total mood, over the course
of the study. The analysis of the three sleep subscales
revealed no significant differences between the two
groups, and this was probably because of the partici-
pants reporting good sleep at baseline. Daytime sleepi-
ness did not differ between the two groups (Table 3).
Table 2. Results, means (SD), and p-value for self-reported Stress and Anxiety for the Control and Vitano® groups
Measure T1 T2 T3 T4
Time
F-value
Group
F-value
G×T
F-value
Anxiety
Control 41.68 (7.61) 38.85 (7.37) 40.60 (9.57) 41.44 (9.43) 0.70 5.02* 3.06*
Vitano® 40.24
a
(6.71) 37.33 (7.13) 37.07 (7.65) 35.81
a
(7.92)
Stress
Control 18.78 (5.82) 18.68 (5.96) 19.14 (6.83) 18.97 (6.68) 2.56 7.11** 4.33**
Vitano® 17.69
a
(6.58) 16.68 (5.80) 16.43 (6.44) 15.25
a
(5.35)
Values on each line sharing the same superscript were significantly different from one another.
*p=<0.05.
**p=<0.01.
Table 3. Results, means (SD), and p-value for self-reported mood, sleep and sleepiness for the Control and Vitano® groups
Time Group G × T
Measure T1 T2 T3 T4 F-value F-value F-value
Anger
Control 16.8 (4.07) 15.8 (4.33) 17.3 (5.99) 17.0 (5.70) 0.33 1.39 4.61*
Vitano® 16.4
a
(4.20) 15.4 (4.62) 16.3 (5.12) 15.0
a
(3.75)
Confusion
Control 13.1
a
(3.80) 12.4 (3.82) 12.6 (4.70) 13.6
a
(4.42) 0.60 7.40** 3.05*
Vitano® 12.7 (4.0) 11.5 (3.73) 11.2 (4.01) 11.0 (3.63)
Depression
Control 22.0 (5.94) 21.1 (5.75) 23.0 (8.90) 23.1 (7.10) 1.74 6.11** 2.25
Vitano® 22.8 (7.98) 20.4 (5.66) 20.8 (6.74) 19.6 (6.26)
Fatigue
Control 15.5 (4.86) 13.0 (3.77) 12.5 (4.90) 13.5 (5.15) 0.68 2.48 0.68
Vitano® 16.0 (5.78) 12.6 (4.59) 12.1 (4.85) 11.9 (4.73)
Tension
Control 14.5 (3.24) 14.2 (3.67) 15.0 (4.74) 14.5 (3.89) 1.56 3.45 0.56
Vitano® 15.5 (4.57) 14.0 (4.06) 13.9 (3.75) 13.9 (4.30)
Vigour
Control 17.8 (4.77) 20.4 (5.32) 20.9 (5.08) 21.0 (5.80) 4.03* 1.55 0.67
Vitano® 18.5(4.97) 21.2 (5.17) 21.7 (5.03) 22.8 (5.08)
TNMood
Control 112.0(19.1) 104.2 (11.4) 107.8 (27.4) 108.9 (23.1) 0.86 6.93** 4.90*
Vitano® 113.1
a
(23.1) 106.8 (18.8) 100.7 (21.2) 98.2
a
(18.2)
Sleepiness
Control 8.21 (3.57) 7.85 (4.02) 7.56 (3.78) 8.04 (4.78) 3.51* 0.01 2.52
Vitano® 7.05 (3.59) 7.30 (3.79) 6.76 (3.44) 6.41 (3.69)
Sleep Qual
Control 4.95 (1.45) 4.94 (1.43) 4.94 (1.28) 0.91 0.32 0.36
Vitano® 4.77 (1.22) 5.02 (1.44) 5.17 (1.73)
Values on each line sharing the same superscript were significantly different from one another.
TNMood, Total Negative Mood; Sleep Qual, Sleep Quality.
*p=<0.05.
**p=<0.01.
M. CROPLEY ET AL.
Copyright © 2015 John Wiley & Sons, Ltd. Phytother. Res. (2015)
Cognitive tests
The performance on each of the cognitive tests is pre-
sented in Table 4. There was no difference in simple re-
action times, choice reaction times, the mean number of
errors on the SART, or errors on the symbol-digit cod-
ing task between the Vitano® group and control group.
Thus across a range of cognitive tests no reduction in
cognitive processing was found in the treatment group.
DISCUSSION
The purpose of this feasibility study was to evaluate the
impact of Rhodiola rosea L extract (Vitano®) on self-
reported stress and anxiety and concomitant mood
symptoms in healthy individuals with mild anxiety. Fol-
lowing 14 days, the treatment group demonstrated a sig-
nificant reduction in self-reported anxiety and stress.
This finding supports previous evidence and research
(Darbinyan et al., 2000; Panossian et al., 2010; Spasov
et al., 2000; Darbinyan et al., 2007; Sarris, 2007). Al-
though Rhodiola rosea has been used traditionally to re-
lieve a range of symptoms of stress related disorders, to
our knowledge this is the first study to demonstrate the
efficacy of Rhodiola rosea L. in the treatment of mild
anxiety.
Regarding the secondary measures, the analyses re-
vealed significant reductions in self-reported Anger,
Confusion, Depression and Total Negative Mood in
the treatment group. These findings are interesting in
particular as the participants were recruited solely on
their anxiety scores and not other measures of mood.
Vitano® appeared therefore to have a general positive
effect on mood.
With regard to the cognitive tasks, no relevant differ-
ences between the groups could be observed. Vitano®,
therefore appears not to affect cognition. In addition,
consistent with previous research (Darbinyan et al.,
2000; Darbinyan et al., 2007; Panossian and Wagner,
2005) none of the AEs were seen to be clearly related
to intake of the treatment, because other reasons were
more likely to be the cause, which suggests that
Rhodiola rosea L. (Vitano®) can continue to be consid-
ered to have an adequate safety and tolerability profile,
with a positive benefit-risk ratio.
Mood measures and sleep were assessed by self-
report, and this could be considered a limitation to the
study. Future research is needed to replicate the current
findings, and it would be desirable to supplement the
subjective nature of self-reports with more objective in-
dices. Clinical interviews could be used to assess mood,
and sleep could be assessed via wrist actigraphy or
EEG. The lack of placebo control is another limitation
of this study. It is unlikely that the findings were the re-
sult of placebo effects, as changes appeared gradual and
were specific to certain measures. As this was a non-
placebo RCT, however, we cannot determine a causal
relationship, and we cannot exclude that some of the
changes were because of time alone or other factors.
Overall the results demonstrated that Rhodiola rosea
L. (Vitano®) is effective in the treatment of mild anxiety
and stress. It improved confusion, anger, and total
mood, and was well tolerated.
Acknowledgements
This research was supported by a grant funded by Dr Willmar
Schwabe Gmbh & Co. KG. We thank Laura Gribble for her help in
data collection.
Conflict of Interest
The authors declare no conflict of interest.
Table 4. Results, means (SD), and p-value for the cognitive tests for the Control and Vitano® groups
Group G × T
Measure T1 T2 T3 T4 F-value F-value
Simple reaction
Time (ms)
Control 387.00 (64.42) 378.15 (50.51) 383.11 (58.32) 386.22 (51.72) 0.05 0.26
Vitano® 372.48 368.98 375.17 374.89
(34.11) (43.59) (37.54) (41.60)
Choice Reaction
Time (ms)
Control 506.60 (73.81) 488.73 (65.03) 486.95 (64.96) 507.91 (77.63) 1.18 2.93
Vitano® 491.18 (64.51) 481.58 (59.25) 481.92 (59.23) 475.58 (52.76)
SART (%ge correct)
Control 89.30 (13.06) 89.93 (17.82) 95.33 (5.39) 95.50 (5.29) 1.50 0.78
Vitano® 92.40 (8.56) 94.05 (6.13) 95.55 (4.06) 94.07 (7.64)
Symbol
Digit
Coding (%ge correct)
Control 94.78 (4.57) 93.97 (5.19) 95.30 (4.51) 93.94 (8.20) 1.15 0.70
Vitano® 92.91 (7.66) 94.02 (4.83) 94.59 (5.78) 95.79 (4.67)
*p=<0.05, **p=<0.01.
RHODIOLA ROSEA, MOOD AND COGNITION
Copyright © 2015 John Wiley & Sons, Ltd. Phytother. Res. (2015)
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