Herbal Medicine for Insomnia

Abstract

Insomnia is a common problem, and herbs can be quite helpful and are much safer than most drugs for insomnia. Moderately potent herbs that primarily work by enhancing sleep architecture or quality are reviewed in detail. These include Valeriana officinalis (valerian), Valeriana sitchensis (Pacific valerian) and related species, Humulus lupulus (hops), and Piscidia piscipula (Jamaica dogwood). Much milder nervines, requiring long-term use for full benefits - including Passiflora incarnata (passionflower), Melissa officinalis (lemonbalm), Nepeta cataria (catnip), Scutellaria lateriflora (skullcap), and Centella asiatica (gotu kola) - are discussed, and their place in improving insomnia is clarified. The much stronger and less often used sedative herbs Gelsemium sempervirens (gelsemium), Pulsatilla vulgaris (common pasque flower), P. patens (Eastern pasque flower), Anemone (Pulsatilla) occidentalis (western pasque flower), and A. tuberosa (desert anemone) are considered next. Finally, the delayed-onset sleep-maintaining herb Myristica fragrans (nutmeg) is put into clinical context.

Full text

Herbal Medicine for Insomnia
Eric Yarnell, ND, RH (AHG)
Abstract
Insomnia is a common problem, and herbs can be quite
helpful and are much safer than most drugs for insomnia.
Moderately potent herbs that primarily work by enhancing
sleep architecture or quality are reviewed in detail. These in-
clude Valeriana officinalis (valerian), Valeriana sitchensis
(Pacific valerian) and related species, Humulus lupulus (hops),
and Piscidia piscipula (Jamaica dogwood). Much milder
nervines, requiring long-term use for full benefits—including
Passiflora incarnata (passionflower), Melissa officinalis
(lemonbalm), Nepeta cataria (catnip), Scutellaria lateriflora
(skullcap), and Centella asiatica (gotu kola)—are discussed,
and their place in improving insomnia is clarified. The much
stronger and less often used sedative herbs Gelsemium sem-
pervirens (gelsemium), Pulsatilla vulgaris (common pasque
flower), P. patens (Eastern pasque flower), Anemone (Pulsa-
tilla)occidentalis (western pasque flower), and A. tuberosa
(desert anemone) are considered next. Finally, the delayed-
onset sleep-maintaining herb Myristica fragrans (nutmeg) is
put into clinical context.
Introduction
Insomnia is technically defined as difficulty falling asleep,
staying asleep, or nonrestorative sleep causing daytime im-
pairment or distress despite adequate opportunity and cir-
cumstance to sleep occurring at least three times per week for
at least 1 month.
1
This is important because there are distinct
herbs for patients with different types of insomnia. Note that
circadian rhythm disorders that often affect sleep, such as
jetlag, are not considered in this article.
Though there is much focus on reducing sleep latency
(speeding the time to fall asleep) among people affected by
insomnia and among makers of drugs for this problem, herbs
actually perform well primarily at enhancing the quality of
sleep (improving how restorative sleep is, in other words). The
growing support for this fact is critically important in advising
patients about what to expect from herbal treatment of in-
somnia, and because of how different this makes herbs from
sedative-hypnotic drugs.
The most common classes of drugs used to treat insomnia
are listed in Table 1. There is an urgent need for alternatives to
these drugs given their relatively poor efficacy, significant
safety concerns, and/or addictiveness, depending on the class
of drug under discussion.
Some classes of sleep medications, particularly the still
widely prescribed benzodiazepines, actually degrade the
quality of sleep.
2
People do fall asleep faster when taking these
drugs, but they do not go into deep, restorative sleep and end up
groggy and impaired in the daytime. For this reason, it is well
documented that benzodiazepines actually impair people’s
ability to drive and operate heavy machinery safely, and ulti-
mately do not improve sleep for most people.
3
This also in-
creases traffic accidents.
4
The opposite is true when it comes to
most herbs, as discussed below.
The addictiveness of benzodiazepines is also often over-
looked, particularly as longer acting agents are now in more
common use (shorter acting agents are more addictive).
5
Benzodiazepines are not first-line agents and should only be
used short-term (6 months or less) according to all major
guidelines on their use.
6
The patients have to wean slowly off
these drugs to prevent withdrawal symptoms.
Newer nonbenzodiazepine sedative drugs such as zolpidem
have less tendency to reduce time spent in deep sleep, but mostly
increase time spent in light sleep, which contributes to their
fairly minimal clinical benefit according to meta-analyses.
7,8
Some but not all studies also implicate zolpidem-type drugs in
increasing risk of traffic accidents and major injuries.
9,10
Misuse
(overdose, taking them at times other than before bed, and in
combination with alcohol or other sedatives) of zolpidem-type
drugs is rampant and has led to the rise of so-called sleep
driving, which is now a significant cause of impaired driving.
11
Though sleep driving is probably a rare adverse effect, the
sheer number of people taking these drugs means that there is a
significant problem with sleep driving. The problems with
benzodiazepines and zolpidem-type drugs are so significant
that some European countries have begun widespread public
campaigns against their use.
12
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AUGUST 2015 173

Moderate Potency Hypnotic Herbs
The roots of Valeriana officinalis (valerian), Valeriana
sitchensis (Pacific valerian), and possibly other species are
well-known mainstays in the herbal materia medica for treat-
ing people with insomnia. Valerian is native to Europe, while
Pacific valerian is from northeastern Russia and northwestern
North America. A meta-analysis of clinical trials on various
extracts of valerian found that it has minimal to no effect on
reducing sleep latency, but it consistently and significantly
improves sleep quality.
13
In head-to-head comparisons with
benzodiazepines, it is just as effective and significantly safer.
14
Studies going back to the 1990s and after show that valerian
reduces light (stage 1) sleep and lengthens deep (stage 3) or
slow-wave sleep in humans.
15,16
One small trial in older
women did not find an effect of valerian on sleep architec-
ture compared to placebo.
17
Valerian is safe and effective in
children.
18
The mechanisms of action of valerian are complex. It has
been stated, “The sedative and sleep inducing effect [of vale-
rian] cannot be attributed to one single substance and probably
not to one single mode of action.”
19
There is evidence of
multiple interactions between valerian’s compounds, g-amino
butyric acid (GABA), and the GABA
A
receptor (see Fig. 1).
20
Recall that GABA
A
receptors are predominantly found in the
central nervous system, while GABA
B
receptors are predom-
inantly found in skeletal muscle. Direct activation of GABA
A
receptors by valerian has been shown in vitro and in vivo,
particularly by the compound valerenic acid (see Fig. 2).
21
The
binding sites of various valerian compounds have not been
definitively determined; however, most, but not all, appear to
bind to sites distinct from those of GABA, benzodiazepines,
barbiturates, or ethanol.
22
Valerenic acid specifically appears
to bind to the loreclezole binding site.
23
Valerenic acid and
related sesquiterpenoids in valerian appear to cross the blood–
brain barrier to access GABA
A
receptors through a nontrans-
cellular transport system.
24
V. edulis spp. procera (Mexican
valerian) root extract, which did not contain valerenic acid, was
nonetheless shown to improve sleep architecture in patients
with insomnia, though V. officinalis was somewhat superior.
25
In rats, valerian also reduces the activity of the catabolic enzyme
GABA transaminase. Note that Glycyrrhiza glabra (licorice)
Table 1. Classes of Major Anti-Insomnia Drugs
Drug category Major examples
Effects on
sleep latency Effects on sleep quality Addictiveness
Benzodiazepines Temazepam,
clonazepam, lorazepam
Decrease it Degrade it (inhibit stage 3,
stage 4, and REM sleep)
High (schedule
IV drugs)
Nonbenzodiazepine
hypnotics (Z-drugs)
Zolpidem, zopiclone,
eszopiclone
Decrease it
slightly
Minimal effects on deep and
REM sleep, lengthen stage 2
sleep
Low (schedule
IV drugs)
H1-antagonists Diphenhydramine Decrease it Minimal effects None
Tricyclic antidepressants,
general (low dose)
Amitriptyline, doxepin Decrease it Suppress REM sleep
a
None
Tricyclic antidepressants,
special
Trazodone (low dose),
mirtazapine (low dose)
Decrease it No effect on REM None (mirtazapine)
to moderate
(trazodone)
Orexin antagonists Suvorexant Decrease it Minimal effects Low (schedule IV drug)
a
Rebound excessive dreaming with sudden discontinuation has been observed.
Some classes of sleep medications,
particularly the still widely
prescribed benzodiazepines, actually
degrade the quality of sleep.
Figure 1. GABAergic effects of herbs.
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has been shown to enhance the anxiolytic effects of valerian by
unknown but presumably pharmacokinetic mechanisms.
26
Valerian’s constituents have been shown to have activity
unrelated to GABA. For instance, multiple compounds activate
the 5HT
5a
serotonin receptor.
27
This receptor is concentrated in
the suprachiasmatic nucleus of the hypothalamus area that
plays a role in regulating the sleep–wake cycle. Lignans in the
root are partial agonists of the adenosine A1 receptor, which is
associated with reductions in anxiety and wakefulness.
28
Valerian is generally very safe. Unlike benzodiazepines,
valerian actually improves people’s daytime alertness and
driving ability.
29
It is not habit-forming. Clinically, it is noted
that it, like most other herbs for sleep improvement, can very
occasionally cause stimulation instead of relaxation. It is not
clear in whom this occurs or why, but it is not common and not
a reason to avoid this herb compared to any other. A typical
dose of tincture is 2–3 ml at bedtime. A typical dose of capsules
is 500–1,000 mg at bedtime. There is at least epidemiologic
research showing valerian is safe in pregnancy.
30,31
There is no evidence of any negative pharmacokinetic in-
teractions between valerian and any drug.
32
Valerian specifi-
cally does not interact with alcohol at doses that definitively
interact with benzodiazepines.
33
Humulus lupulus (hops) strobiles (female flowers) are an-
other midpotency herbal medicine for improving sleep quality.
This vine is a circumboreal plant (native all around the
Northern Hemisphere) and has separate male and female
plants. Most clinical trials showing hops helpful for insomnia
patients have used it in combination with valerian, with at least
one of these studies suggesting a definite synergistic effect
from their combination.
34,35
One study of an extract with soy
and Juniperus oxycedrus (cade) oils and just 100 mg of hops
did not find it superior to placebo for insomnia.
36
Ingestion of
333 ml nonalcoholic beer (containing around 1 g of hops) at
dinnertime, compared to no beer, reduced sleep latency and
improved sleep quality in healthy nurses doing shift work in
one small trial.
37
The compounds responsible for hops effects on sleep have
not been determined. One study in mice suggested that hops
acted in part by activating melatonin receptors.
38
A study in
quail supported this idea somewhat, showing that low doses of
hops (similar to concentrations found in nonalcoholic beer)
seemed to enhance circadian rhythms, including reduced ac-
tivity at night.
39
Binding of hops extract compounds to 5-HT
6
,
5-HT
7
, melatonin-1, and melatonin-2 receptors was seen in
another in vitro study.
40
Various hops constituents may also
activate the GABA
A
receptor.
41
Hops is also well-known as a
phytoestrogen and inflammation modulator, but this will not be
discussed in any depth here except to point out that this herb is
most ideal in perimenopausal patients with chronic inflam-
matory conditions and insomnia.
Hops is generally very safe. Overdose may lead to unwanted
estrogenic adverse effects, but this takes work to achieve. It is
intensely bitter, which tends to limit dosing. Alcoholic beer
intake by lactating women decreases the amount of milk their
babies drink, possibly due to the hops content, though this is
unknown.
42
Nonalcoholic beer increased the antioxidant con-
tent of breast milk.
43
Piscidia piscipula (Jamaica dogwood) bark has a similar
level of potency as a sleep aid as valerian, or perhaps moder-
ately stronger. There is little research on this helpful medicine,
and so its use is largely based on history and experience.
Limited animal research supports its effectiveness as a mod-
erate hypnotic.
44
This tree is also not that widespread and the
use of its bark limits the sustainability of the medicine.
Luckily, only small doses are used, but it should be considered
a second-line therapy when other treatments fail. Jamaica
dogwood should be avoided in pregnancy and lactation due to
lack of information about its safety in these settings. It is
otherwise safe at doses of tincture of 1–2 ml at bedtime.
A combination of valerian 300 mg, hops 30 mg, and Passi-
flora incarnata 80 mg was compared to zolpidem 10 mg at
bedtime in 78 patients with chronic insomnia in a randomized,
double-blind trial.
45
In this brief two-week trial, the two
treatments were equally effective at reducing sleep latency and
improving sleep quality. Daytime drowsiness was not different
between the groups and there were no serious adverse events.
This strongly suggests that herbal sleep aides are a legitimate
alternative to zolpidem and related drugs, though more robust
research is necessary to be certain. Another larger trial in-
volving 184 adults with insomnia found a combination of va-
lerian 187 mg and hops 42 mg as effective as diphenhydramine
50 mg compared to placebo for relieving insomnia over 1
month’s time.
46
Mild Potency Nervine Herbs
There are many herbs with a mild effect on sleep that are
generally called nervines. We have previously written in depth
about these herbs as a treatment for anxiety, but they are also
highly relevant for people with insomnia.
47
Only the effects of
these herbs on sleep will be reviewed here, as well as basics of
Figure 2. Valerenic acid.
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their use, as so much else has been written about them. Note
that all of these herbs are basically extremely safe, including in
pregnancy and lactation. They require long-term use for opti-
mal efficacy and are not typically effective at shortening sleep
latency. Finally, see Figure 1 for the effects of various of these
herbs on the GABA system in the brain.
Passiflora incarnata (passionflower) is a vine native to the
southeastern United States. Its leaves are used as medicine,
though its flower is considered among one of the most beautiful
in the world. A tea in relatively low doses (one cup per night)
for just one week improved sleep quality in healthy adults with
mild intermittent disturbed sleep.
48
It is particularly helpful in
patients with mild anxiety, showing benefits similar to those of
the benzodiazepine oxazepam.
49
In vitro it has been shown to
affect GABA
A
and GABA
B
channels and to affect GABA
uptake into neurons.
50
The usual dose of tincture or glycerite is
3–5 ml at bedtime, or 1,000–2,000 mg in capsules at bedtime.
In one case study, a combination of passionflower and va-
lerian was associated with rapid onset of hand tremor, dizzi-
ness, throbbing, and muscle fatigue in a patient who was
concomitantly taking lorazepam.
51
No other cases of such in-
teractions could be found in the literature.
Melissa officinalis (lemon balm) is from the Mediterranean
region, but is now widely cultivated in temperate areas. One
double-blind trial in overall healthy adults with mild insomnia
found a combination of valerian and lemon balm effective
compared to placebo.
52
A prior trial found this combination as
effective as benzodiazepines for insomnia.
53
These two herbs
together appear to mainly improve sleep quality.
54
Topical
application of lemon balm to the temples has also been sug-
gested by the late, great Rudolf Fritz Weiss, MD, for insom-
nia.
55
In vitro it inhibits GABA transaminase.
56
See Table 2 for
other herbs reported to inhibit GABA transaminase in pre-
clinical studies. Typical doses are essentially the same as for
passionflower. It is also commonly used as a tea at a dose of
5 g/cup, steeped for 15–30 minutes, strained, and drunk before
bed. Tea should be avoided in patients having sleep difficulties
due to nocturia. Note that Nepeta cataria (catnip) is very
similar to lemon balm and has a stronger lemon taste. Clini-
cally, it seems even more potent than lemon balm in all its
aspects.
Scutellaria lateriflora (skullcap) is a common plant of wet-
lands across much of North America; the leaves and flowers are
used as medicine. No clinical trials appear to have been con-
ducted on skullcap in people with insomnia. It has been shown
to have a mild anxiolytic effect in healthy, mildly anxious
adults.
57
It is an herb with a very strong tradition as a mild
improver of sleep quality however, and should be considered
right alongside the other herbs discussed here. It has a bitter
quality and so may be most appropriate for patients who also
have atonic digestive tracts. Doses are the same as for pas-
sionflower.
Centella asiatica (gotu kola) is a tropical native in which the
entire plant (roots and aerial parts) is used as medicine. It is a
multifaceted, widely applicable plant useful as a calming
adaptogen, immunomodulator, and antifibrotic. While again
not specifically studied in modern times for insomnia, it has
shown promise as an anxiolytic in preliminary clinical trials.
58
It should be considered in immunosuppressed or anxious pa-
tients with or without sclerotic conditions also struggling with
insomnia. Doses are the same as for passionflower, though it
loses much of its potency when dried and is not very effective
in capsules.
Sedative Herbs
For patients who primarily have difficulty falling asleep,
there are stronger herbs that are more sedating and can actually
reduce sleep latency. These herbs are more likely to cause
daytime sleepiness if taken during the daytime, but generally
lessen it when taken at bedtime due to improved sleep quality.
There is no evidence that these herbs interfere with deep sleep.
These herbs are not recommended either for use without the
Table 2. Preclinical Studies of Inhibition of GABA Transaminase by Herbs
Herb Part used Model Reference
Piper tuerckheimii (cordoncillo) Root In vitro a
Adiantum wilsonii (Wilson’s maidenhair fern) Rhizome In vitro a
Erigeron breviscapus (d
eng zh
an c
ao, shortscape fleabane) Whole plant In vitro b
Gastrodia elata (ti
an má, gastrodia)* Rhizome In vitro c, d
Acorus gramineus (Japanese sweet root) Rhizome Mice e
Angelica dahurica (Chinese angelica) Root In vitro f
*Endangered species, do not use.
a
Awad R, Ahmed F, Bourbonnais-Spear N, et al. Ethnopharmacology of Q’eqchi’Maya antiepileptic and anxiolytic plants: Effects on the GABAergic system. J Ethnopharmacol
2009;125:257–264;
b
Tao YH, Jiang DY, Xu HB, Yang XL. Inhibitory effect of Erigeron breviscapus extract and its flavonoid components on GABA shunt enzymes. Phytomedicine
2008;15:92–97;
c
Choi JH, Lee DU. A new citryl glycoside from Gastrodia elata and its inhibitory activity on GABA transaminase. Chem Pharm Bull (Tokyo) 2006;54:1720–1721;
d
Ha JH,
Shin SM, Lee SK, et al. In vitro effects of hydroxybenzaldehydes from Gastrodia elata and their analogues on GABAergic neurotransmission, and a structure-activity correlation. Planta
Med 2001;67 :877–880;
e
Koo BS, Park KS, Ha JH, et al. Inhibitory effects of the fragrance inhalation of essential oil from Acorus gramineus on central nervous system. Biol Pharm Bull
2003;26:978–982;
f
Choi SY, Ahn EM, Song MC, et al. In vitro GABA-transaminase inhibitory compounds from the root of Angelica dahurica. Phytother Res 2005;19:839–845.
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assistance of a practitioner skilled in their use, or for practi-
tioners until they have had a chance to train with someone who
has experience with them.
Gelsemium sempervirens (gelsemium, yellow jessamine) is
a vine that is native to the eastern part of North America,
extending as far south as Guatemala. The root is the potent
medicine and should only ever be used under direct supervision
of a practitioner experienced with its use. Just 10 drops of fully
concentrated (1:2–1:3 weight:volume) fresh root tincture is a
good starting dose for severe difficulties falling asleep. This
can be increased by 5 drops per night each night that it is
ineffective, up to the point that 1 ml (30 drops) is reached, mild
adverse effects occur (in which case the dose should be de-
creased), or sleep is readily achieved. It is also a moderately
potent smooth and skeletal muscle relaxant based on clinical
experience with it, and so when cramping of these structures is
associated with difficulty sleeping, gelsemium should be
considered. In overdose it begins to cause ataxia, diplopia,
prostration, dilated pupils, ptosis, and impaired speech. In se-
vere overdose, death from respiratory depression can occur,
though this is extremely rare.
Pulsatilla vulgaris (common pasque flower), P. patens
(eastern pasque flower), Anemone (Pulsatilla)occidentalis
(western pasque flower), and A. tuberosa (desert anemone) are
all used as medicine. They come from Eurasia (the former two)
or North America (the latter two). The flowering tops in early
seed are used. Though commonly European herbalists rec-
ommend using only dried forms of these herbs for safety,
clinically these are practically without activity and are not
recommended. Fresh plant material is much more active and
with proper doses still safe. Touching or ingesting the fresh sap
can cause blistering, but this is readily avoided when har-
vesting and making medicine by wearing gloves and a mask
and not consuming the herb before it is mixed with ethanol.
Fresh pasque flower is an even more potent sedative, with
just 5 drops of fully concentrated tincture being the starting
bedtime dose. Like gelsemium, it is not safe for use except
under close supervision by a practitioner experienced with
pasque flower. This should be increased by just one drop per
night until 15 drops (0.5 ml) dose is reached, mild adverse
effects (similar to those of gelsemium) occur (which again
should trigger a dose reduction), or sleep is readily achieved.
Sadly, given its efficacy and safety at the doses recommended,
there is no research on crude pasque flower.
Myristica fragrans (Nutmeg)
Nutmeg is the seed of Myrtistica fragrans and other similar
species of tree, which are native to the Banda Islands. These
trees are dioecious, and the fruits appear only on the female
trees. The outer portion of the nutmeg when harvested is covered
with a red netted structure, which yields the spice mace. This is
removed and the remaining hard nut is referred to as nutmeg.
Fresh grated nutmeg (which requires a specialized spice
grinder to accomplish as it is so hard) is an unusual herb in that
it has a very long delayed onset of action in promoting sleep, on
the order of four hours in the average person. Thus, it is the
most specific herb to use for patients who wake up in the
middle of the night and can’t fall back asleep, when taken at
bedtime. It can also be taken at dinner time (provided this is
roughly four hours before bed) to have a sleep-inducing affect
at bedtime. This is based on its traditional use in Ayurvedic
medicine and modern clinical application, but has not been
rigorously tested. One trial of an Ayurvedic formula featuring
nutmeg did support its effectiveness as a sleep enhancer.
59
In
the traditional medicine of the Moluccas (Spice Islands), where
it is native, nutmeg was used for insomnia.
60
The usual dose of fresh nutmeg is 0.25–0.5 teaspoons. It is
traditionally taken with milk, though other fatty foods (such as
nut butter) can also be used, to enhance absorption. For dried
powder, at least twice the dose should be used. It can be slowly
increased on subsequent nights up to a maximum of 1–2 tea-
spoons. In overdose (probably 3–10 times the therapeutic dose),
nutmeg can cause neurological damage and hallucinations.
61
Conclusion
Herbal medicines offer many ways to improve sleep in
people with insomnia. They are most prominent as ways to
enhance sleep quality, which takes some time to work. Specific
agents should be chosen based on their efficacy in specific
situations and taking into account other issues going on with an
individual patient. The moderately potent sleep quality en-
hancers such as valerian, hops, and Jamaica dogwood can be
considered as initial agents in most cases of insomnia, even
when they feature difficulty falling or staying asleep. Com-
bining one of these with at least one of the gentler sleep
quality-enhancing nervine herbs (to obtain synergistic effects)
is also recommended. If there is no improvement after 2–3
months of using these agents at appropriate doses, different
herbs should be tried for another couple of months. Only at that
point should sedative herbs be tried. However, for more severe
sleep-onset problems, sedatives may be tried immediately.
Finally, for patients who have predominant early waking,
nutmeg at bedtime should be tried for 1–2 months, alone or
combined with sleep quality enhancers.
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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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