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Herbs for Anxiety
Eric Yarnell, ND, RH (AHG)
Abstract
The many herbal options for patients with anxiety are dis-
cussed, focusing initially on Piper methysticum (kava) as one
of the most well-researched options in this setting. The un-
studied, but clinically as effective (and much more palatable),
Pedicularis spp. (lousewort) are also discussed. Other nervine
herbs including Lavandula angustifolia (true lavender),
L. latifolia (spike or Portuguese lavender), Lavandula xinter-
media (lavandin, Dutch lavender), L. stoechas (Spanish lav-
ender), Matricaria chamomilla (chamomile), and Passiflora
incarnata (passionflower) are reviewed (and a table of other
nervines is provided). Three formulas, including mixtures of
nervines, Ze 185, Euphytose, and Yı`Qı`Yaˇng Xı
¯n(Replenish
Qi and Nourish the Heart), are discussed. Miscellaneous
anxiolytics such as Crocus sativus (saffron), L-theanine from
Camellia sinensis (green tea), and the three calming adap-
togens Rhodiola rosea (roseroot), Centella asiatica (gotu
kola), and Withania somnifera (ashwagandha) are then de-
tailed. Herbal anxiolytics offer great promise to relieve
anxiety safely.
Keywords: anxiety, herbal medicine, Piper methysticum,
kava, kavapyrones
Introduction
Anxiety is a common response to stressful events. In the
short term, it is completely normal, but problems crop up when
stressors don’t go away (as is common in modern industrial
and postindustrial societies) or in people who have anxiety
disorders. While conventional medications exist to counteract
anxiety, they all have problems, including the troubling re-
ality of benzodiazepine addiction that has been and continues
to be little discussed. Herbal medicines that offer real alter-
natives for treating and preventing anxiety are considered
here, and their potential use for benzodiazepine addiction are
also discussed.
It should be noted that most, though not all, ofthe studies cited
in this paper relied upon the Hamilton Anxiety Rating Scale to
assess whether the agents studied helped anxious patients. Often
abbreviated the Ham-A, this scale has specifically been shown to
work poorly in studies of anxiolytic drugs, in part because it
cannot distinguish improvements in depression from those in
anxiety and because the adverse effects of the drugs specifically
worsen the somatic subsection of the questionnaire.
1
The latter
issue should be less of a problem with most herbal medicines,
given their much less significant adverse effects compared to
drugs, but these questions have not really been studied related to
herbs. The Diagnostic and Statistical Manual of Mental Dis-
order III and the two newer versions since (the book generally
recognized as the standard in psychiatry for diagnosis of mental
health problems) have definitions of generalized anxiety disor-
der that do not agree with one another and also conflict with
the Ham-A—another significant problem.
2
Other questionnaires
used to assess anxiety in other studies may suffer other problems.
These concerns should be kept in mind when considering the
efficacy of any treatment for anxiety.
Kava, the Much-Maligned King of Anxiolytics
Piper methysticum (kava) is a shrub in the Piperaceae family,
and probably the best-studied natural anxiolytic. Its origin is
unclear, but it is widespread throughout the Pacific Islands,
having been carried by the Polynesians as they migrated. The
root is the part used. It was and is a very important plant
throughout Polynesia, playing a prominent role in ceremony
and medicine.
3
Meta-analysis of clinical trials repeatedly confirms that kava
is superior to placebo at relieving anxiety, with minimal ad-
verse effects.
4
It is as effective and safer than multiple phar-
maceuticals used to treat anxiety, as reviewed in Table 1. A
meta-analysis of 10 human trials confirms that kava extracts
have no negative effect on cognitive function in humans, un-
like many other anxiolytic drugs.
5
Even studies in very heavy,
chronic ( >15 years) users of kava as a beverage found no
evidence of cognitive impairment.
6
The biomolecular mechanisms of action of kava, and partic-
ularly its kavalactone (also known as kavapyrone) compounds
including (1)-kavain, (1)-yangonin, (1)-desmethoxyyangonin,
(1)-methysticin, and (1)-dihydromethysticin, have been in-
vestigated in numerous studies. Kava’s relationship with g-
aminobutyric acid type A (GABA
A
) channels has been most
extensively studied, resulting in a complex and nuanced picture.
GABA is the main inhibitory neurotransmitter in humans, and its
anxiolytic effects are mediated to a substantial degree by
GABA
A
receptors. Kava does not act at the same site on the
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GABA
A
channel or in the same ways as benzodiazepines,
ethanol, barbiturates, or general anesthetics.
7
Several in vitro
analyses suggest that kavalactones increase GABA
A
receptor
density and increase binding of GABA to its own binding
site, rather than affecting GABA
A
receptors directly.
8,9
These
affects are particularly prominent in the amygdala.
Concern about kava possibly causing liver damage exploded
in the 1990s, though there were reports of chronic traditional
kava beverage consumption raising serum aminotransferase
levels prior to this.
4,10
These studies found these elevations to
be minimal, and no reports have found that clinical disease
subsequently developed, such as hepatitis, cirrhosis, or liver
failure.
11,12
Several cases of hepatitis and liver failure, some
fatal, began to be reported in the 1990s, but as with most case
studies, the ability to establish a causal relationship was difficult
in most.
13
Many patients involved in these cases were actively
abusing alcohol, had prior liver disease including hepatitis C, or
were taking other potentially hepatotoxic drugs or substances,
thus confusing the picture. Despite the shaky evidence, many
countries banned kava. Based on an analysis of 93 case studies
of supposed kava hepatotoxicity reported through 2006, the
World Health Organization concluded only eight were “proba-
bly” due to kava.
14
Ultimately, these bans have been lifted in
most places, as evidence became overwhelming that kava is not
inherently hepatotoxic, that the cases represented idiosyncratic
harm at most, and that any adverse liver-related outcome was
extremely rare.
15,16
Kava may not be intrinsically hepatotoxic
but, out of an abundance of caution, should be avoided in
combination with known hepatotoxins (e.g., excessive alcohol,
acetaminophen, metronidazole) or in patients with severe liver
disease until more information is available.
Kava has many other clinical uses, although none are as well
attested as its indication for anxiety. One trial found that it
offset rebound anxiety for patients who were withdrawing
from benzodiazepines.
17
Insomnia, including when stress- or
anxiety-related, has been shown to be improved by kava.
18–20
Reduction in cravings for a wide range of drugs of abuse and
alcohol was demonstrated in a preliminary clinical trial.
21
Traditionally, it was regarded as specific for chronic pelvic
pain; while this has not been assessed in clinical trials, it has
proven helpful for this indication in the author’s clinical ex-
perience.
22
It can also help relieve phobias empirically.
Kava has a very strong taste that most find disagreeable; it
also causes a numbing of the mouth. Therefore, it is almost
always used in capsules or as a tincture as opposed to a tea,
though it is most traditionally used as a tea for medicinal
purposes. The usual dose of a crude kava extract in capsules is
400–800 mg two to three times a day; the last dose is generally
given at bedtime. For extracts standardized to kavalactone
content, 70 mg three times daily of kavalactones is a typical
dose (or 210 mg all at once at bedtime for insomnia). The dose
of a tincture (generally 1:2 to 1:3 weight:volume ratio, 60%
ethanol) is 1–2 mL two to three times a day, often mixed in a
little water.
Pedicularis bracteosa (bracted lousewort) in the Oroban-
chaceae family is a potential alternative to kava that grows in
the mountains in western North America. Since it is so much
more local than the Pacific Islands, it is potentially much more
ecologically sustainable for people living in North America. It
has a much better taste than kava, and its actions are otherwise
clinically very similar or even more potent. This is entirely based
on clinical experience; there are no studies of the mechanism
or clinical efficacy of bracted lousewort. P. racemosa (sickletop
lousewort), P. groenlandica (elephant head), and P. contorta
(coiled lousewort) have also all been tried clinically and found
effective. All of these species are hemiparasitic and so cannot be
Table 1. Kava Compared to Pharmaceuticals
Comparison drug Trial results Reference
Opipramol Equally effective over eight weeks in double-blind, randomized trial Boerner 2003
a
Buspirone Equally effective over eight weeks in double-blind, randomized trial Boerner 2003
a
Oxazepam Oxazepam deteriorated cognitive functioning, including ability to drive,
while kava did not, in three head-to-head comparative trials
Sarris 2013
b
; Münte 1993
c
;
Heinze 1994
d
Superior to kava for anxiety in double-blind, randomized trial lasting one
week; oxazepam caused drowsiness while kava did not
Sarris 2012
e
D,L-kavain equally effective as oxazepam in head-to-head, double-blind,
randomized trial for anxiety
Lindenberg 1990
f
Diazepam Kava improved cognitive function while diazepam and placebo did not
in six-hour comparative trial
Gessner 1994
g
a
Boerner RJ, Sommer H, Berger W, et al. Kava-kava extract LI 150 is as effective as opipramol and buspirone in generalised anxiety disorder—an 8-week randomized, double-blind
multi-centre clinical trial in 129 out-patients. Phytomedicine 2003;10:38–49;
b
Sarris J, Laporte E, Scholey A, et al. Does a medicinal dose of kava impair driving? A randomized,
placebo-controlled, double-blind study. Traffic Inj Prev 2013;14:13–17;
c
Münte TF, Heinze JH, Matzke M, Steitz J. Effects of oxazepam and an extract of kava roots (Piper
methysticum) on event-related potentials in a word recognition task. Pharmacoelectroencephalography 1993;27:46–53;
d
Heinze HJ, Münthe TF, Steitz J, Matzke M.
Pharmacopsychological effects of oxazepam and kava-extract in a visual search paradigm assessed with event-related potentials. Pharmacopsychiatry 1994;27:224–230;
e
Sarris J,
Scholey A, Schweitzer I, et al. The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: A randomized, placebo-controlled, double-blind
study. Hum Psychopharmacol 2012;27:262–269;
f
Linderberg VD, Pitule-Schödel H. D,L-kavain in comparison with oxazepam in anxiety states. Fortschr Med 1990;108:49–54 [in
German];
g
Gessner B, Cnota P, Steinbach T. Extract of the kava-kava rhizome in comparison with diazepam and placebo. Z Phytother 1994;15:30–37 [in German].
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harvested within a few feet of any poisonous plants, lest they
contain toxic constituents from them (and they commonly grow
near Veratrum viride or false hellebore, Arnica spp., and Senecio
spp., all of which can be quite poisonous). Ideally, it is harvested
near Valeriana sitchensis (Sitka valerian), amplifying the ther-
apeutic qualities of louseworts, as observed clinically. The usual
dose of tincture, the only form these herbs are available in at
present (1:2 to 1:3 weight:volume, 30% ethanol) is 1–3 mL three
times a day.
A Plethora of Nervines
A category of herbs known as nervines are among the most
important traditional treatments for anxiety, previously dis-
cussed in this journal in more depth.
23
These herbs have in
common a tendency to be calming of the nervous system and
smooth-muscle spasmolytics, and thus are also helpful for in-
somnia, hypertension associated with increased vascular tone,
seizure disorders (though usually they are not potent enough to
be sufficient for their treatment), and neuropathic pain. Here,
the focus will be on their anxiolytic properties.
Many nervines are in the Lamiaceae family, and some of the
best studied of this class, are Lavandula angustifolia (true
lavender), L. latifolia (spike or Portuguese lavender), the hybrid
of L. angustifolia and L. latifolia known as Lavandula xin-
termedia (lavandin, Dutch lavender), and L. stoechas (Spanish
lavender). Treating these herbs as though they were all the same
medicine is the height of folly, however, as they are clearly
different between species and also form what are known as
chemotypes within the same species. Chemotypes can easily
interbreed but, based on a complex interplay of genetic and
environmental elements, will produce very different terpenoid
mixes and thus make very different volatile oils (whether ex-
tracted by steam distillation or supercritical carbon dioxide),
which can then have very different clinical actions.
True lavender is generally required to contain 25–45% li-
nalyl acetate, 25–38% linalool, and 3–30% lavandulyl acetate
to be labeled as such. Spike lavender has <25% linalyl acetate
and instead predominantly camphor and 1,8-cineole. Lavandin
is generally intermediate between these two. Spanish lavender
contains a very high content of camphor (15–30%) and
fenchone (12–28%). That being said, for example, a true lav-
ender grown in eastern Algeria was shown to contain primarily
1,8-cineole (29.4%) and camphor (24.6%), though it is possi-
ble this is because they had an undetected hybrid growing and
not actual L. angustifolia.
24
The failure of most research on
members of the Lamiaceae family, most or all of which have
chemotypes, either to assess or document the chemotype used
greatly hampers generalizability of studies and reveals a flaw
with people ignorant of the details of medicinal plants at-
tempting to carry out research on them.
A proprietary preparation known as Silexan is the most
studied form of lavender. It is a true lavender product con-
taining steam-distilled volatile oil standardized to 20–45%
linalool and 25–46% linalyl acetate, with a usual dose of 80–
160 mg once daily. A meta-analysis of three randomized, double-
blind trials found that Silexan was superior to placebo at reducing
anxiety and improving sleep without morning sleepiness or other
sedative adverse effects.
25
There is evidence from a head-to-head
trial that Silexan is just as or more effective than paroxetine, with
significantly fewer adverse effects in patients with generalized
anxiety disorer.
26
In another head-to-head trial, it was just as
effective as and safer than lorazepam for reducing anxiety.
27
Lavender has shown no cytochrome P450-related interactions
in humans and is generally very safe. A report of reversible
gynecomastia in three boys exposed to uncharacterized lav-
ender and Melaleuca alternifolia (tea tree) oil body-care
products are not credible; no other reports of such effects have
appeared before or since this report.
28
This extremely safe
nervine should be considered for patients with mild to mod-
erate anxiety.
Another common nervine of European origin that has been
shown repeatedly to be anxiolytic is Matricaria chamomilla
(chamomile) of the Asteraceae family. The capitulum (which is
actually a cluster of many flowers) is the part used as medicine.
The first double-blind trial of this herb involved 57 subjects with
generalized anxiety disorder who were randomized to either a
chamomile extract standardized to 1.2% apigenin (an anxiolytic
flavonoid) 500 mg t.i.d. or placebo for eight weeks.
29
There was
a modest but significant improvement in anxiety with chamo-
mile extract compared to placebo, with no difference in adverse
effects between the treatments. A later analysis of data from this
trial also concluded that chamomile extract had significant an-
tidepressant activity compared to placebo.
30
A larger open trial
confirmed that this extract had anxiolytic effects in 179 pa-
tients.
31
A subset of these patients (n593) agreed to continue in
a double-blind, randomized, placebo controlled trial lasting 26
weeks.
32
While chamomile was not superior to placebo for
preventing anxiety relapse, patients in the chamomile group had
consistently and significantly lower anxiety scores compared to
placebo. Again, there were low rates in adverse effects with
chamomile, with no significant difference compared to placebo.
This extremely safe nervine should also be considered for pa-
tients with mild to moderate anxiety.
Passiflora incarnata (passionflower) is a vine native to the
southeastern United States and is a member of the Passi-
floraceae family (Fig. 1). No other members of this genus ap-
pear to be medicinal, though their fruits are delicious. The
leaves of passionflower are used as a nervine in traditional
herbalism. One double-blind trial compared a tincture of pas-
sionflower to oxazepam tablets in 36 anxious adults, each
group receiving a placebo as well (either liquid or tablet as
appropriate).
33
Though oxazepam had a more rapid onset of
action, the two medications were equally effective at reducing
anxiety. Passionflower caused significantly fewer adverse ef-
fects, in contrast to a deterioration in job performance seen in
the oxazepam group. This is very commonly seen with ben-
zodiazepines, as they prevent deep sleep and thus cause day-
time sleepiness. This problem is almost never encountered
with nervines, as they actually enhance sleep quality, as has
been confirmed for passionflower.
34
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Numerous trials have looked at passionflower as an alternative
to benzodiazepines to quell anxiety prior to dental or surgical
procedures. In one double-blindtrial, a passionflower extract in a
single dose of 500 mg 90 minutes before surgery significantly
reduced anxiety compared to placebo in 60 adults.
35
A similar
double-blind trial found that 700 mg of an aqueous extract of
passionflower 30 minutes before administration of spinal anes-
thesia was superior to placebo at alleviating anxiety.
36
In a
similar double-blind trial of patients going into surgery, pas-
sionflower crude leaf powder 1 g and melatonin 6mg were
compared.
37
Both medications significantly reduced anxiety
compared to baseline, while neither reduced pain. Melatonin
caused significantly more sedation than passionflower, while
passionflower caused significantly more cognitive dysfunction
than melatonin after surgery. A single-blind trial randomized
63 adults undergoing periodontal treatment to either a liquid
extract of passionflower 20 drops the night before and morning
after treatment, placebo, or no treatment.
38
Anxiety was sig-
nificantly lower in the passionflower group compared to both
control groups. A double-blind trial in 40 adults undergoing
wisdom-tooth extraction randomized them to take either an
uncharacterized passionflower capsule 260 mg or midazolam
15 mg 30 minutes before surgery.
39
Anxiety reduction was the
same between the groups, while only those in the midazolam
group reported not remembering the procedure.
It is recommended that passionflower tincture or glycerite be
used at a dose of 3–5 mL three times per day regularly, starting
as soon as possible before an anxiety-producing event or on-
going for chronic anxiety. Usually the last dose is given at
bedtime. If used in capsules, a dose of 1–2 g three times daily is
recommended of crude leaf (unextracted). Passionflower is
extremely safe with no known drug interactions.
Table 2 lists a number of other nervine herbs that could be
useful for anxiety. A detailed discussion of all these herbs is
beyond the scope of this article, and readers should reference
our prior work for more information.
Nervine Formulas
Very often in practice, multiple anxiolytics are combined in a
formula to individualize treatment to patients and to leverage
potential synergy between distinct mechanisms of action in
different herbs. At least one Chinese and two Western herbal
formulas have been studied forpatients with anxiety and will be
reviewed here to show the potential of this approach. However,
it is worth pointing out that none of these individualized for-
mulas have been studied and that there are negative studies on
herbal formulas given to groups of anxious patients.
40
One proprietary Swiss formula known as Ze 185 containing
Petasites hybridus (butterbur) root 90 mg (with all pyrrolidi-
zine alkaloids chemically removed), Valeriana officinalis
(valerian) root 90 mg, passionflower leaf 90 mg, and Melissa
officinalis (lemonbalm) leaf 60 mg per capsule has been stud-
ied in patients with anxiety syndromes. One double-blind
randomized trial compared this formula (at a dose of one tablet
t.i.d.) to one without the butterbur (same amounts and dose,
just without this herb) and placebo in patients with somatoform
disorders.
41
The full formula and the one without butterbur were
significantly superior to placebo at relieving anxiety and de-
pression. The full formula was also significantly better than the
formula without butterbur at improving these parameters.
There were minimal adverse effects, and none were serious. A
more recent double-blind trial in healthy adults found that the full
Ze 185 formula could reduce anxiety reactions to laboratory-
induced acute stress.
42
Another proprietary formula known as Euphytose contains
valerian extract 50 mg, passionflower extract 40 mg, Crataegus
spp. (hawthorn) extract 10 mg, and Ballota nigra (white hore-
hound) extract 10 mg per tablet. An older study investigated a
prior formulation that also contained the mild stimulants Cola
nitida (kola nut) and Paullinia cupana (guarana´), which really
do not make sense to include in a formula with such mild ner-
vines (they might be needed if more intense sedative herbs were
being used). In this trial, 182 patients with anxiety and adjust-
ment disorder were randomized to Euphytose with stimulants
or placebo in a double-blind manner.
43
After seven days of
Figure 1. Passiflora incarnata. Drawing by Meredith Hale and
reprinted with permission.
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treatment with two tablets t.i.d., Euphytose with stimulants
started to lower anxiety significantly compared to placebo, a
benefit that was maintained to the end of the 28-day study.
The Chinese herbal formula Yı`Qı`Yı`ng Xı
¯n (Replenish Qi
and Nourish the Heart; see Table 3 for ingredients) has been
investigated as a treatment for anxiety. In a randomized trial
(blinding not described), 202 patients with generalized anxiety
disorder took either Replenish Qi and Nourish the Heart powder
10 g b.i.d. or paroxetine 20–60 mg daily for six months; all sub-
jects underwent cognitive–behavioral therapy.
44
Both groups had
a significant reduction in anxiety compared to baseline; there was
no difference between them in efficacy. Anxiety recurred sig-
nificantly more often in the paroxetine group than in the herbal
formula group after medication discontinuation. Adverse effects
were rare and minor in both groups.
Miscellaneous Anxiolytics
Crocus sativus (saffron) in the Iridaceae family has very long
styles (and prominent stigmas at their tips), which are part of
Table 2. Additional Anxiolytic Nervine Herbs
Herb Part used Typical tincture
a
dose Clinical trial (if available)
Eschscholzia californica
(California poppy)
Whole flowering plant,
including roots
3–5 mL t.i.d. Hanus 2004 (combined with
Crataegus and magnesium)
c
Crataegus spp. (hawthorn)
b
Leaf and flower 5–10 mL t.i.d. Hanus 2004 (combined with
Eschscholzia and magnesium)
c
Melissa officinalis (lemon balm)
b
Leaf 3–5 mL t.i.d. Cases 2011
d
; Kennedy 2006
(combined with Valeriana)
e
Tilia spp. (linden) Flower 3–5 mL t.i.d. None identified
Leonurus cardiaca (motherwort) Flowering tops 1–2 mL t.i.d. Ovanesov 2006
f
Avena spp. (oats) Fresh milky oats 1–5 mL t.i.d. None identified
Scutellaria lateriflora (skullcap) Flowering tops 3–5 mL t.i.d. Wolfson 2003
g
Hypericum perforatum (St. John’s wort) Flowering tops 2–5 mL t.i.d. Bitran 2011
h
Valeriana spp. (valerian) Root 1–2 mL t.i.d. Andreatini 2002
i
; Kennedy
2006 (combined with
Melissa)
e
Verbena spp. (verbena) Flowering tops 1–3 mL t.i.d. None identified
Agastache rugosa (licorice mint) Flowering tops 1–3 mL t.i.d. None identified
Ziziphus jujuba (jujube) Fruit 1–3 mL t.i.d. None identified
Rosmarinus officinalis (rosemary) Volatile oil 3–5 drops inhaled q.d. McCaffrey 2009 (combined
with lavender volatile oil)
j
a
Glycerite is also effective for all the plants listed, in the author’s experience, except Eschscholzia californica.
b
See also main text for discussion of clinical trials of other combination herbal formulas that include this herb.
c
Hanus M, Lafon J, Mathieu M. Double-blind, randomised, placebo-controlled study to evaluate the efficacy and safety of a fixed combination containing two plant extracts
(Crataegus oxyacantha and Eschscholzia californica) and magnesium in mild-to-moderate anxiety disorders. Curr Med Res Opin 2004;20:63–71;
d
Cases J, Ibarra A, Feuillere N, et al.
Pilot trial of Melissa officinalis L leaf extract in the treatment of volunteers suffering from mild-to-moderate anxiety disorders and sleep disturbances. Med J Nutrition Metab
2011;4:211–218;
e
Kennedy DO, Little W, Haskell CF, Scholey AB. Anxiolytic effects of a combination of Melissa officinalis and Valeriana officinalis during laboratory induced stress.
Phytother Res 2006;20:96–102;
f
Ovanesov KB, Ovanesova IM, Arushanian EB. Effects of melatonin and motherwort tincture on the emotional state and visual functions in anxious
subjects. Eksp Klin Farmakol 2006;69:17–19 [in Russian];
g
Wolfson P, Hoffmann DL. An investigation into the efficacy of Scutellaria lateriflora in healthy volunteer s. Altern Ther
Health Med 2003;9:74–78;
h
Bitran S, Farabaugh AH, Ameral VE, et al. Do early changes in the HAM-D-17 anxiety/somatization factor items affect the treatment outcome among
depressed outpatients? Comparison of two controlled trials of St John’s wort (Hypericum perforatum) versus a SSRI. Int Clin Psychopharmacol 2011;26:206–212;
i
Andreatini R,
Sartori VA, Seabra MLV, Leite JR. Effect of valepotriates (valerian extract) in generalized anxiety disorder: A randomized placebo-controlled pilot study. Phytother Res.
2002;16:650–654;
j
McCaffrey R, Thomas DJ, Kinzelman AO. The effects of lavender and rosemary essential oils on test-taking anxiety among graduate nursing students. Holist
Nurs Pract 2009;23:88–93.
Table 3. Replenish Qi and Nourish
the Heart Formula
Panax quinquefolius (American ginseng, xīyáng sh
en) root 30 g
Panax ginseng (red ginseng, hóng sh
en) steamed root 30 g
Scutellaria baicalensis (Baikal skullcap, huáng qín) root 30 g
Asparagus cochinchinensis (asparagus, ti
an mén d
ong) root 30 g
Ophiopogon japonicus (dwarf lilyturf, mài mén d
ong) tuber 30 g
Schisandra chinensis (schisandra, wuˇwèi zıˇ) fruit 30 g
Salvia miltiorrhiza (red sage, d
an sh
en) root 30 g
Panax notoginseng (sanqi ginseng, s
an qī) root 30 g
Acorus calamus (sweet flag, shuıˇch
ang pú) rhizome 30 g
Polygala tenuifolia (thin leaf milkwort, yuaˇn zhì) root-bark 30 g
Gardenia jasminoides (gardenia, sh
an zhīzıˇ) fruit 30 g
Glycine max (fermented soybean, dàn dòu chıˇ) fruit 30 g
Amber (fossilized resin, huˇpò) 30 g
Ziziphus jujuba (jujube, su
an zaˇo rén) seed 30 g
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the female reproductive system in plants. These structures are
used commonly as the spice saffron. It is often said to be the
most expensive in the world, as obtaining the structures is
difficult because harvest requires much human labor. A great
deal of research has been done on the effects of saffron extracts
on mood disorders, including anxiety.
In one double-blind trial of 66 adults with major depressive
disorder and anxious distress, subjects were randomized to
30 mg saffron extract or citalopram 40 mg daily for six
weeks.
45
Both treatments significantly reduced anxiety and
depression compared to baseline, with no significant difference
between them. Both were associated with low rates of mild
adverse effects. A double-blind trial in 60 anxious, depressed
adults found that 50 mg b.i.d. of saffron extract was signifi-
cantly more effective than placebo at improving both anxiety
and depression.
46
A third double-blind trial in 128 healthy
adults with low mood, stress, and anxiety but not meeting the
formal definition of depression randomized them to take saf-
fron extract at a dose of 22 or 28 mg per day or placebo for four
weeks.
47
Stress and anxiety symptoms were significantly better
in the 28 mg dose group compared to placebo; the 22 mg dose
group did not see different results from the placebo group. All
of this supports saffron extracts as very safe ways to address
anxiety, though the exact best extract or dose remains elusive.
Camellia sinensis (green tea) leaf and particularly its alka-
loid L-theanine (which is the opposite of caffeine, being a
relaxant) have also been studied as treatments for anxiety.
48
In
one double-blind trial involving 60 adults with schizophrenia
or schizoaffective disorder on ongoing antipsychotic medica-
tions, subjects were randomized to add either L-theanine
400 mg or placebo daily for eight weeks.
49
Anxiety symptoms
were significantly decreased in the L-theanine group compared
to placebo, as were hallucinations/delusions and general psy-
chotic symptoms. There were few adverse effects, and they
were all mild, with no significant difference between groups. A
similar trial using the green tea flavonoid epigallocatechin
gallate further suggests that it is L-theanine or something else
in green tea that is crucial to reducing anxiety.
50
Neither L-
theanine 200 mg nor alprazolam 1 mg were effective anxio-
lytics in a small sample of healthy adults subjected to an arti-
ficial form of anticipatory anxiety.
51
One open trial in 20
patients with major depressive disorder found 250 mg of L-
theanine daily helped reduce depression and anxiety, improve
sleep, and improve cognitive function.
52
Rhodiola rosea (roseroot, Crassulaceae family) is a cir-
cumboreal adaptogen herb with relaxing properties. This is
fairly unusual for an adaptogen, as most such herbs tend to be
at least mildly stimulating. An open trial in 10 adults with
generalized anxiety disorder found that 340 mg of roseroot
extract daily for 10 weeks significantly reduced anxiety com-
pared to baseline.
53
Adverse effects were mild and limited. A
small randomized trial compared 200 mg b.i.d. of a different
roseroot extract to placebo for 14 days in eight mildly anxious
adults and also found it significantly reduced anxiety.
54
Clearly, a double-blind, randomized trial is warranted for ro-
seroot in anxiety. Until then, it can be safely used, particularly
in patients under chronic stress. A typical dose of tincture
would be 1–3 mL t.i.d.
The two other major, historically relaxing adaptogen herbs,
Centella asiatica (gotu kola) in the Apiaceae family and
Withania somnifera (ashwagandha) in the Solanaceae family,
have also been shown to be anxiolytic in preliminary clinical
trials.
55–57
Both are extremely safe, including with long-term
use (and often they can take weeks or months to show truly
how effective they can be). Gotu kola is much more effective
fresh, which means that for most people in temperate climates
(since it is a tropical plant), the best way to take it is as a fresh-
plant tincture or glycerite at a dose of 3–5 mL t.i.d. It tastes
quite pleasant. Ashwagandha does fine with drying and can be
taken in capsules at doses of 1 g b.i.d. or in tincture at doses of
1–2 mL t.i.d. It has a strong taste many will find disagreeable.
Conclusion
Clearly, there are many herbs with great potential to help
patients with anxiety. Generally, it is recommended that one or
two nervines, one of which is either kava or lousewort, be
mixed with a calming adaptogen and one miscellaneous an-
xiolytic in a formula to optimize patient benefits. However,
some patients prefer a single herb, in which case options are
bountiful. Overall, effects tend to be best when patients use
these products for several months, though they can start to be
noticeably effective within two weeks (certainly in the case of
kava and lousewort). Further research is needed and warranted
on these fascinating and apparently safe therapeutic options for
anxious patients. n
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Eric Yarnell, ND, RH (AHG), is chief medical officer of Northwest Nat-
uropathic Urology, in Seattle, Washington, and is a faculty member at Bastyr
University in Kenmore, Washington.
To order reprints of this article, contact the publisher at (914) 740-2100.
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