Botanicals for Mental Wellbeing

Research Guide

Note
This is not an exhaustive review of the entire body of research for each botanical, but a sample of some
of the research that does exist or is pertinent to material referenced in the lesson. For easy reference,
botanicals are listed in alphabetical order.

Chamomile (Matricaria recutita)

1. Amsterdam, et al. (2009, August). A randomized, double-blind, placebo-controlled trial of oral

Matricaria recutita (Chamomile) extract therapy for generalized anxiety disorder. J Clin
Psychopharmacol 29(4):378-82.

Summary: This randomized, double-blind trial compared use of chamomile extract to placebo in 57
patients for the treatment of mild-to-moderate generalized anxiety disorder (GAD). The Hamilton
Anxiety Rating was used to assess clinical improvement. Researchers concluded that study
participants receiving the chamomile extract had significantly decreased anxiety symptoms as
compared to placebo in mild-to-moderate GAD. This is a promising study, but is limited by its small
sample size.

2. Mao, J. J., Xie, S. X., Keefe, J. R., Soeller, I., Li, Q. S., & Amsterdam, J. D. (2016). Long-term
chamomile (Matricaria chamomilla L.) treatment for generalized anxiety disorder: a randomized
clinical trial. Phytomedicine, 23(14), 1735-1742. doi:10.1016/j.phymed.2016.10.012

Summary: 91 patients with moderate to severe generalized anxiety disorder (GAD) were studied
in an out-patient setting in this randomized, double-blind, placebo-controlled trial. Over a study
period of 12 weeks, patients were randomized to receive chamomile extract 500 mg three times
per day vs. placebo. Results of the study concluded that patients taking chamomile had significant
reduction of GAD symptoms as compared to placebo. Rate of adverse events were low for both
groups. These findings need to be confirmed in larger studies.

Ginkgo (Ginkgo biloba)

1. Weinmann, S., et al. (2010, March 17). Effects of Ginkgo biloba in dementia: a systematic review and
meta-analysis. BMC Geriatr. 10:14.

Summary: This study looked at nine different research trials (2372 total patients) examining the
efficacy of extracts of Ginkgo biloba in treating symptoms of dementia, including Alzheimer’s
disease. The authors found a statistically significant effect of Ginkgo biloba extracts in improving
cognition when compared to placebo. Quality of life was improved in patients with Alzheimer’s
using Ginkgo biloba extracts, but not in other groups of dementia patients.

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Botanicals for Mental Wellbeing
Research Guide

2. Mazza, M., et al. (2006, September). Ginkgo biloba and donepezil: a comparison in the treatment of
Alzheimer’s dementia in a randomized placebo-controlled double-blind study. Eur J Neurol. 13(9):
981-5.

Summary: Researchers designed a randomized, controlled trial of 76 patients with mild-to-moderate

dementia. Study participants were randomized to receive either 160 mg daily of Ginkgo biloba, 5 mg
donepezil, or a placebo over a period of 24 weeks. Severity of dementia was analyzed using the
Mini-Mental Status Examination and the Syndrom-Kurztest to see how study participants changed
from baseline. An improvement in attention, memory, and cognitive performance was seen in the
Ginkgo biloba group that was comparable to donepezil.

Ginseng (Panax ginseng)

1. Scaglione, F., et al. (1996). Efficacy and safety of the standardised ginseng extract G115 for
potentiating vaccination against the influenza syndrome and protection against the common
cold. Drugs Exp Clin Res. 22:65-72.

Summary: Conducted in Milan, Italy, this randomized, placebo-controlled study looked at the effects
of ginseng and its ability to prevent cold and flu symptoms. A total of 227 participants were
enrolled, 114 of whom received 100 mg/day of a ginseng extract vs. 113 who received placebo over
a period of four weeks. All of the study participants then received the influenza vaccine. Researchers
noted a significant increase in the antibody response to the flu vaccine in those who received the
ginseng extract, in addition to a lower number of coughs and lower incidence of flu when compared
to placebo. The main adverse event reported was insomnia.

2. Barton, D. L., Liu, H., Dakhil, S. R., Linquist, B., Sloan, J. A., Nichols, C. R., . . . Loprinzi, C. L. (2013).
Wisconsin Ginseng (Panax quinquefolius) to Improve Cancer-Related Fatigue: A Randomized,
Double-Blind Trial, N07C2. JNCI Journal of the National Cancer Institute, 105(16), 1230-1238.
doi:10.1093/jnci/djt181

Summary: Researchers looked at the effects of using Wisconsin Ginseng in the treatment of
cancer-related fatigue (CRF) in this double-blind, randomized, placebo-controlled trial. 364
participants with all types of cancer (with exception of brain cancer and CNS lymphoma) from 40
different institutions to receive 2000 mg powdered root standardized to 3% ginsenosides vs.
placebo over a period of 8 weeks. Other causes of fatigue had been ruled out and study
participants’ fatigue was rated using the Multidimensional Fatigue Symptom Inventory–Short Form
(MFSI-SF) as the primary endpoint. A statistically significant difference was seen at 8 weeks for the
ginseng group vs. the placebo group in fatigue symptoms. This benefit was greater in patients
receiving active cancer treatment vs those who had completed treatment.

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Botanicals for Mental Wellbeing
Research Guide

Hops (Humulus lupulus)

1. Morin, C.M., et al. (2005, November). Valerian-hops combination and diphenhydramine for treating
insomnia: a randomized, placebo-controlled trial. Sleep. 28(11).

Summary: A total of 184 participants with mild insomnia were studied across nine sleep disorder
centers throughout the United States. Study participants were randomized to receive a combination
of valerian and hops extracts at bedtime vs. diphenhydramine vs. placebo over a period of 28 days.
Measurement of sleep parameters were daily diaries and polysomnography, in addition to clinical
outcome ratings from patients and physicians, including quality of life measures. Study findings
revealed the valerian-hops combination and diphenhydramine showed modest improvement in
insomnia when compared with placebo. The valerian-hops combination appeared safe, was
associated with improved quality of life, and did not produce rebound insomnia when it was
discontinued at the conclusion of the study.

2. Koetter, U., Schrader, E., Käufeler, R., & Brattström, A. (2007). A randomized, double blind,
placebo‐controlled, prospective clinical study to demonstrate clinical efficacy of a fixed valerian
hops extract combination (Ze 91019) in patients suffering from non‐organic sleep disorder.
Phytotherapy Research, 21(9), 847-851. doi:10.1002/ptr.2167

Summary: Researchers sought to study the effects of valerian and valerian + hops combination in
non-organic sleep disorders. This small study randomized 30 participants to receive 500 mg
valerian extract, 500 mg valerian extract + 120 mg hops extract (referred to as Ze 91019) vs.
placebo over a period of 4 weeks. Objective sleep measures utilized the validated method of a
hypnogram and monitoring sleep latency, which was the study’s primary endpoint. Results of the
study revealed the valerian + hops combination was significantly superior to the placebo in
reducing sleep latency. The single valerian extract, however, failed to be superior vs. placebo. This
was a very small study and ideally larger-scale studies of hops need to be performed.

Kava (Piper methysticum)

1. Pittler, M.H. & Ernst, E. (2002). Kava extract for treating anxiety. Cochrane Database Syst Rev.
(2):CD003383.

Summary: This Cochrane Review was performed on seven randomized, double-blind trials studying
the effect of mono-preparations (meaning kava was the only botanical used and not part of an
herbal combination) of kava extract on the treatment of anxiety. All seven of the reviewed trials
found kava superior to placebo in the treatment of anxiety. Three of these studies used the
Hamilton Anxiety Score, a validated scoring system to measure anxiety, and showed a significant
treatment with the use of kava. Adverse effects reported as mild, transient, and infrequent. The

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Botanicals for Mental Wellbeing
Research Guide

study authors concluded “the evidence presented implies that kava extract is superior compared
with placebo and relatively safe as a treatment option for anxiety.”

2. Sarris, et al. (2013, October). Kava in the treatment of generalized anxiety disorder: a double-blind,
randomized, placebo-controlled study. J Clin Psychopharmacol. 33(5):643-8.

Summary: A six-week, double-blind, randomized controlled trial was performed using 75 patients
who had a diagnosis of generalized anxiety disorder (GAD). Anxiety was measured using the
Hamilton Anxiety Rating Scale. Results showed a significant decrease in anxiety among those taking
the kava extract vs. placebo. The botanical was well-tolerated without adversely affecting the liver.

3. Smith K, & Leiras, C. (2018). The effectiveness and safety of Kava Kava for treating anxiety
symptoms: A systematic review and analysis of randomized clinical trials. Complementary
Therapies in Clinical Practice, 33, 107-117. doi:10.1016/j.ctcp.2018.09.003

Summary: This 2018 systematic review and meta-analysis looked at 7 kava vs. placebo-controlled
trials of a total of 427 participants using the Hamilton Anxiety Rating Scale as the primary
endpoint for most of the trials. Researchers concluded that kava appears to be a short-term
treatment for anxiety with the ability to improve symptoms, but not is not appropriate for
prolonged anti-anxiety use. Although it wasn’t seen in this particular review, study authors noted
that liver toxicity possible if Kava is taken for longer than 8 weeks.

Lemon balm (Melissa officinalis)

1. Akhondzadeh, et al. (2003). Melissa officinalis extract in the treatment of patients with mild to
moderate Alzheimer’s disease: a double blind, randomised, placebo controlled trial. J Neurol
Neurosurg Psychiatry 74:863-6.

Summary: 45 patients with mild-moderate Alzheimer’s disease were randomized to receive a fixed
dose of Melissa officinalis extract vs. placebo. Changes regarding cognition and mood were analyzed
using the validated ADAS-cog and CDR-SB scores. After four months of treatment, patients receiving
the Melissa officinalis extract showed improvement from baseline scores regarding cognition. It was
also noted that there was improved agitation in the Melissa officinalis group as compared to
placebo. While promising, this was a very small study and further research needs to be done
regarding the use of Melissa officinalis and its effects on cognition and agitation in Alzheimer’s
patients.

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Botanicals for Mental Wellbeing
Research Guide

2. Ranjbar, M., Firoozabadi, A., Salehi, A., Ghorbanifar, Z., Zarshenas, M. M., Sadeghniiat-Haghighi, K.,
& Rezaeizadeh, H. (2018). Effects of Herbal combination (Melissa officinalis L. and Nepeta
menthoides Boiss. & Buhse) on insomnia severity, anxiety and depression in insomniacs:
Randomized placebo controlled trial. Integrative Medicine Research, 7(4), 328-332.
doi:10.1016/j.imr.2018.08.001

Summary: Researchers for this study aimed to look at the effects of using a combination herbal
preparation of Melissa officinalis (Lemon Balm) and Nepeta menthoides (Persian Lavender) on not only
insomnia but also anxiety and depression. A total of 54 participants completed this randomized,
placebo-controlled trial for a period of 4 weeks, receiving either three 500 mg tablets (100 mg Melissa
officinalis + 400 mg Nepeta menthoides) each night vs. placebo. The primary endpoints of insomnia,
depression, and anxiety were based on the Insomnia Severity score (ISI), Persian‐language version of the
Beck Depression Inventory‐Second edition (BDI), and Persian version of Beck Anxiety Inventory (BAI),
respectively. Results revealed the combination of Melissa officinalis and Nepeta menthoides significantly
improved the depression and anxiety of insomniacs by the reduction of BDI and BAI scores vs. placebo.
Also, severity of insomnia was improved as reflected by decreasing ISI score. No serious adverse events
were reported. Limitations of this study include small sample size, short duration of treatment, and lack
of follow-up after the trial.

Passionflower (Passiflora incarnata)

1. Akhondzadeh, et al. (2001, October). Passionflower in the treatment of opiates withdrawal: a

double blind randomized controlled trial. J Clin Pharm Ther.26(5): 369-73.

Summary: Clonidine is a pharmaceutical widely used in the treatment of physical symptoms of

opiate withdrawal, such as increased blood pressure, but typically does not work well to alleviate
the emotional symptoms of withdrawal, including anxiety, irritability/agitation, drug cravings, or
depression. This study aimed to use a combination of passionflower extract and clonidine vs.
clonidine with placebo in the outpatient detoxification from opiate withdrawal in 65 study
participants over 14 days. Severity of opiate withdrawal syndromes was measured using the Short
Opiate Withdrawal Scale (SOWS). Results of the study concluded that both treatment combinations
helped with the physical symptoms of opiate withdrawal, but the clonidine/passionflower extract
improved the emotional symptoms of opiate withdrawal while the clonidine-only treatment group
did not see any improvement.

2. Akhondzadeh, S., et al. (2001, October). Passionflower in the treatment of generalized anxiety: a
pilot double-blind randomized controlled trial with oxazepam. J Clin Pharm Ther. 26(5):363-7.

Summary: This small pilot study looked at the use of a passionflower extract vs. a standard
pharmaceutical, oxazepam, in the treatment of generalized anxiety disorder (GAD). Thirty-six study
participants were randomized to receive either 45 drops/day plus a placebo tablet or 30 mg/day

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Botanicals for Mental Wellbeing
Research Guide

oxazepam plus placebo drops over a four-week period. The results showed that passionflower
extract was effective in the treatment for GAD and was associated with lower levels of impairment
when compared to oxazepam.

Rhodiola (Rhodiola rosea)

1. Darbinyan, V., et al. (2007). Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild
to moderate depression. Nord J Psychiatry. 61(5):343-348.

Summary: Researchers performed a randomized, double-blind, placebo-controlled study regarding

the use of rhodiola extract (known as SHR-5) on participants with mild-moderate depression, using
DSM-IV criteria and the HAM-D depression score. Participants were randomized into one of three
groups: Group A (n=31) received 340mg/day SHR-5, Group B (n=29) received 680 mg/day of SHR-5,
and Group C (n=29) received a placebo over a period of six weeks. Results of the study revealed that
participants receiving the rhodiola extract SHR-5 in both Groups A and B had improved depression,
insomnia, and emotional stability when compared to placebo. No serious side effects were reported.

2. Mao, J.J. (2014). Rhodiola Rosea Therapy for Major Depressive Disorder: A Study Protocol for a
Randomized, Double-Blind, Placebo- Controlled Trial. Journal of Clinical Trials, 04(03).
doi:10.4172/2167-0870.1000170

Summary: In this study, researchers hypothesized that using Rhodiola rosea in the treatment of
depression would be as effective as the common pharmaceutical sertraline, but with less side
effects. 57 participants were randomized to receive either Rhodiola extract 340 mg, standardized to
a content of rosavin 3.07%/rhodioloside 1.95%, sertraline, or placebo over a period of 12 weeks.
Researchers used the Hamilton Depression Rating (HAM-D) as the primary endpoint; Beck
Depression Inventory (BDI), and Clinical Global Impression Change (CG1/C) scores to assess severity
of depression of study participants were also used. Results revealed that sertraline was more
effective in reducing HAM-D scores than rhodiola and placebo. However, Rhodiola was better
tolerated and had fewer side effects than the sertraline group. Researchers concluded “these
findings suggest that R. rosea, although less effective than sertraline, may possess a more favorable
risk to benefit ratio for individuals with mild to moderate depression.”

St. John’s wort (Hypericum perforatum)

1. Linde, K. & Berner, N.M. (2008, October 8). St. John’s wort for major depression. Cochrane Database
Syst Rev (4): CD000448.

Summary: The 2008 Cochrane Review analyzed 29 trials with 5489 patients comparing St. John’s
wort (hypericum extracts) to placebo (18 trials) as well as standard pharmaceuticals (17 trials). It

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Botanicals for Mental Wellbeing
Research Guide

was reported that patients given the hypericum extracts dropped out of trials due to adverse effects
less frequently than those receiving pharmaceutical antidepressants. Study authors concluded that
hypericum extracts are “a) superior to placebo in patients with major depression; b) are similarly
effective as standard antidepressants; c) and have fewer side effects than standard
antidepressants”.

2. Apaydin, et al. (2016, September 2). A systematic review of St. John’s wort for major depressive
disorder. Syst Rev. 5(1):148

Summary: This systematic review found comparable results to the Cochrane Review, concluding that
monotherapy with St. John’s wort is superior to placebo for mild-to-moderate depression and does
not significantly differ from standard antidepressant medications. The study noted a lack of research
on severe depression.

3. Schulz, V. (2006, February). Safety of St. John’s wort extract compared to synthetic antidepressants.
Phytomedicine.13(3); 199-204.

Summary: Post-marketing surveillance of 14,245 patients taking standardized St. John’s wort
extracts (SWE) showed adverse effects to be tenfold lower than those with standard
antidepressants. Adverse effects with SWE were noted to be mild and transient in most cases. Risks
to patients were noted not to be caused by SWE but by concurrent use of SWE with drugs with a
narrow therapeutic window such as anticoagulants, immunosuppressants, and antineoplastic
agents, among others. SWE should not be used with selective serotonin reuptake inhibitor (SSRI)
medications or other antidepressants.

Valerian (Valeriana officinalis)

1. Taibi, D.M., et al. (2007, June). A systematic review of valerian as a sleep aid: safe but not effective.
Sleep Med Rev. 11(3): 209-30.

Summary: A systematic review of 37 different trials involving the use of valerian for sleep in both
healthy individuals and those with insomnia. No significant differences were found in those using
valerian vs. placebo. The evidence did find valerian to be safe with rare reports of adverse effects.

2. Fernandez-San Martin, M.I., et al. (2010, June). Effectiveness of Valerian on insomnia: a meta-
analysis of randomized placebo-controlled trials. Sleep Med. 11(6): 505-11.

Summary: A systematic review of 18 randomized controlled trials (RCTs) involving the use of valerian
as a sleep aid compared to placebo. Results suggested that valerian is effective for a subjective
improvement in insomnia, but its effectiveness hasn’t been demonstrated with quantitative or
objective measures.

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