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Lavender Oil for Anxiety and Depression

Review of the literature on the safety and efficacy of lavender


By Jeremy Appleton, ND
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Abstract
Lavender flower and its extracts have been used, both internally and by olfaction, for centuries as
a treatment for anxiety and depression. Modern analytical research has identified the main active
constituents of the oil; in vitro and animal studies have begun to elucidate mechanisms of action;
and controlled clinical trials in humans now document lavender’s efficacy, safety, and dose. This
paper reviews these developments, with summary details from selected studies, and provides a
preliminary comparison of lavender’s efficacy and safety to its main botanical and
pharmaceutical alternatives.

Introduction
Anxiety is a common complaint and may range from every day stress to clinically relevant symptoms
requiring medical intervention. Patients with generalized anxiety disorder (GAD) can experience
excessive anxiety and worry associated with the stresses of everyday life. Most cases of GAD begin in
childhood and can lead—without treatment—to a chronic condition, with fluctuating symptoms, often
exacerbated by stressful life events.1 Disturbed sleep has been observed to be among the most frequent
accompanying disorders of generalized anxiety.2 Individuals with anxiety disorder not otherwise specified
(AD NOS) also present with clinically significant symptoms, but they tend to report less worry, negative
affect, depression, and comorbidity than those with GAD.3

The most commonly prescribed agents in the medical treatment of anxiety are benzodiazepines and
selective serotonin reuptake inhibitors (SSRIs).4 The well-known side effects of benzodiazepines include
drowsiness, fatigue, confusion and disorientation, dizziness, decreased concentration, impaired memory,
dry mouth, and blurred vision. Benzodiazepines can impair the ability to drive or operate machinery and
may thus interfere with essential activities of daily living. They lower the tolerance to alcohol and are
widely reported to cause physical and psychological dependence and withdrawal symptoms. 5SSRIs, on
the other hand, may cause sedation and fatigue, gastrointestinal disturbances, agitation or
insomnia.6,7 The risks and inconveniences associated with available anxiolytic pharmaceutical
medications may be one of the reasons anxiety disorder is considered an undertreated condition. 8

Herbal preparations have long been a mainstay for treating anxiety and depression. Some botanical
agents, most notably kava (Piper methysticum), have demonstrated efficacy for clinically diagnosed
anxiety disorders.9-13Others, such as St. John’s wort (Hypericum perforatum), are clinically efficacious for
depression in most,14-25 though not all26,27 clinical studies. Kava, however, has been withdrawn by many
manufacturers due to concerns over potential hepatotoxicity,28-32 even though these effects may have
been primarily due to drug interactions, misuse, and poor quality extracts of this otherwise well-tolerated
phytomedicine; St. John’s wort’s popularity has suffered because it was found to stimulate cytochrome
P450 34, an enzyme that metabolizes at least half of the known pharmaceuticals sold today. 33 A safe,
non-sedating, non–habit forming herbal anxiolytic with proven efficacy for GAD and depression is,
therefore, of interest to clinicians.

Throughout history, lavender has been cultivated for its flowers and oils and used both cosmetically and
medicinally. A member of the Labiatae family, lavender is primarily used either dried or as an essential oil.
Historical use includes documented activity as an antibacterial, antifungal, carminative, sedative, and
antidepressant.34 Lavandula angustifolia, Mill. is the most common species of lavender utilized for health
purposes.35 Lavender is native to the Mediterranean, the Arabian Peninsula, Russia, and Africa.

Lavender has a high concentration of volatile oils, which impart its distinctive and pleasing fragrance. The
relaxing experience of lavender fragrance led to its deliberate, therapeutic use in aromatherapy to relieve
mild anxiety. Lavender has been also used internally for mood imbalances such as anxiety, insomnia, and
gastrointestinal distress, including “nervous stomach.” 36

Lavender Constituents
Lavender essential oil is obtained from steam distillation processing of the flowering tops of L.
angustifolia. Modern analytical methods, such as capillary gas chromatography, have demonstrated that
lavender oil contains more than 160 constituents, many of which interact synergistically to contribute to its
healing effects. The main active constituents of lavender oil are linalool, linalyl acetate, terpinen-4-ol, and
camphor. The quantity of the linalyl acetate is determined by the method of steam distillation as it
degrades upon distillation to yield linalool. The highest content of linalyl acetate is obtained when fresh
lavender flowers are steam distilled right after harvest. Other constituents found in lavender include: cis-
ocimene; terpinen-4-ol, ß-caryophyllene; lavandulyl acetate; 1,8-cineole; and small amounts of limonene,
geraniol, lavandulol, ß-pinene, camphene, geranyl acetate, and neryl acetate.37,38

Relative amounts of bioactive constituents can vary significantly from one lavender oil to another. The
European Pharmacopoeia includes limits or ranges for the content of the predominant components.
Specifically, oils with high concentrations of esters and low concentrations of cineol and other minor
components are generally considered to be of higher quality because these parameters indicate that a
gentle and careful production process was applied and that high quality raw materials were used. A high
quality lavender extract would not only comply with this monograph but would ideally exceed those
specifications with a higher content of linalyl acetate (ideally 33–45%) and lavandulyl acetate (≥1.5%),
and a lower limit for the content of cineol (≤2 %).39

Mechanisms of action
In vitro and in vivo studies have demonstrated multiple possible mechanisms of action of lavender oil, as
well as its individual constituents, which may partly account for its relaxing effects when taken orally.
Lavender oil has potentiated expression of GABA-A receptors in cell culture;40 it has shown spasmolytic
activity on guinea pig ileum;41 linalool, a main active ingredient of lavender oil, has been shown in animals
to inhibit glutamate binding in the brain;42 linalool has also inhibited acetylcholine release and influenced
ionic conductance in neurons;43 linalyl acetate is described to exert a relaxing effect.44 Lavender oil has
reduced dose-dependently spontaneous motility and caffeine-induced hyperactivity of mice.45

Lavender oil aromatherapy has been shown to


be effective in the management of anxiety and
depression and small and medium-sized
controlled and uncontrolled clinical trials.
Clinical Efficacy of Lavender
Lavender Aromatherapy
Much prior research on lavender has focused on the administration of lavender via an olfactory route. The
anxiolytic activity of lavender olfaction has been demonstrated in several small and medium-sized clinical
trials.46-53 The efficacy of aromatherapy of lavender is thought to be due to the psychological effects of the
fragrance combined with physiological effects of volatile oils in the limbic system. 54 These calming effects
of lavender oil and single constituents may be the origin of the traditional use of lavender. Lavender oil
olfaction has been shown to decrease anxiety, as measured by the Hamilton rating scale,51 and can
increase mood scores.5 The following are selected examples of clinical trials on lavender aromatherapy:
5

 Dunn and colleagues demonstrated anxiolytic activity of lavender oil aromatherapy in patients in
intensive care units. Subjects received at least 1 session of aromatherapy with 1% lavender
essential oil. Significant anxiolytic effects were noted in the 1st treatment, though 2nd and 3rd
treatments did not appear to be as effective.47
 Alaoui-Ismaili and colleagues found that the aroma of lavender is considered by subjects to be very
pleasant and is correlated with changes in the autonomic nervous system. 56
 Tysoe and colleagues conducted a study of lavender oil in burner use on staff mood and stress in a
hospital setting. A significant number of respondents (85%) believed that lavender aroma improved
the work environment following the use of the lavender oil burners. 57
 Diego and colleagues demonstrated that people receiving lavender oil (10%) olfaction for 3 minutes
felt significantly more relaxed and had decreased anxiety scores, improved mood and increased
scores of alpha power on EEG (an indicator of alertness), and increased speed of mathematical
calculations.58
 Lewith and colleagues investigated the effects of lavender aromatherapy on depressed mood and
anxiety in female patients being treated with chronic hemodialysis. 59 The effects of aromatherapy
were measured using the Hamilton rating scale for depression (HAMD) and the Hamilton rating
scale for anxiety (HAMA). Lavender aroma significantly decreased the mean scores of HAMA,
suggesting an effective, noninvasive means for the treatment of anxiety in hemodialysis patients.
 Lavender aromatherapy, with or without massage, may also reduce the perception of pain and the
need for conventional analgesics in adults and children, though more rigorously controlled trials are
needed.60

Oral Lavender Supplementation: Anxiety


Lavender oil has also been shown to be effective via the oral route. Several clinical studies have
demonstrated the benefit of lavender extracts in comparison to reference or placebo in decreasing
symptoms of anxiety and depression.

Orally administered lavender capsules (100 mL and 200 mL) were tested in 97 healthy subjects in a
randomized double-blind, placebo-controlled clinical trial.61 Film clips were used to elicit anxiety. Measures
included anxiety, State Trait Anxiety Inventory (STAI), mood, positive and negative affect scale (PANAS),
heart rate (HR), galvanic skin response (GSR), and heart rate variation (HRV). After baseline
measurements, capsules were administered. Participants viewed a neutral film clip, then an anxiety-
provoking and light-hearted recovery film clip. For the 200 mL lavender dose during the neutral film clip,
there was a trend toward reduced state anxiety, GSR, and HR and increased HRV. In the anxiety-eliciting
film, lavender was mildly beneficial in females but only on HRV measures. In males, sympathetic arousal
increased during the anxiety film (GSR). HRV significantly increased at 200 mL during all 3 film clips in
females, suggesting decreased anxiety. The authors concluded that lavender has anxiolytic effects in
humans under conditions of low anxiety, but they were unable to draw conclusions about high anxiety or
clinical anxiety disorders.

Kasper and colleagues investigated the efficacy of lavender oil (WS ® 1265) for AD NOS in comparison to
placebo in a primary care setting.62 This study was the first double-blind, randomized, placebo-controlled
trial to document the anxiolytic efficacy of orally administered lavender essential oil for anxiety disorder. In
27 general and psychiatric practices, 221 adults reporting unspecified anxiety were randomized to receive
80 mg per day of lavender oil or placebo for 10 weeks with office visits every 2 weeks. A baseline HAMA
total score of ?18 and a total score > 5 for the Pittsburgh Sleep Quality Index (PSQI) were required. The
primary outcome measures were HAMA and PSQI total score decrease between baseline and week 10.
Secondary efficacy measures included the Clinical Global Impressions scale, the Zung Self-rating Anxiety
Scale, and the SF-36 (Quality of Life) Health Survey Questionnaire. Subjects taking WS® 1265 showed a
total score decrease by 16.0 ± 8.3 points (mean± SD, 59.3%) for the HAMA and by 5.5 ± 4.4 points
(44.7%) for the PSQI compared to 9.5 ± 9.1 (35.4%) and 3.8 ± 4.1 points (30.9%) in the placebo group
(P<0.01 one-sided, intention to treat). WS® 1265 was superior to placebo regarding the percentage of
responders (76.9 vs. 49.1%, P<0.001) and remitters (60.6 vs. 42.6%, P=0.009). Adverse effects were
uncommon and included dyspepsia (4.7% in the treatment group vs 1.8% in the placebo group) and
eructation (3.7% in the treatment group and none in the placebo group). Lavender had a significant
beneficial influence on quality and duration of sleep and improved general mental and physical health
without causing any unwanted sedative or other drug-like effects. Researchers concluded that the
lavender oil “is both efficacious and safe” for AD NOS and predicted that it could emerge as “a gentle
therapeutic alternative in the treatment of anxiety.”

Woelk and Schlaefke conducted a multicenter, double-blind, randomized Phase III study of lavender oil
(Silexan, WS® 1265, Dr. Willmar Schwabe, Karlsruhe, Germany) in comparison to low-dose lorazepam for
patients with GAD.63 The Hamilton Anxiety Rating Scale (HAMA-total score) was used as the primary
objective measurement to monitor changes in the level of tension and relaxation beginning at baseline
through week 6 of the trial. Additional data were collected using the Self-rating Anxiety Scale, Penn State
Worry Questionnaire, SF-36 Health Survey Questionnaire, and specific sections of the Clinical Global
Impressions of severity disorder. A total of 77 female (76.6%) and male (23.4%) subjects 18–65 years of
age were randomized into groups. Participants were eligible for the study if they met the inclusion criteria
of a HAMA-total score of greater than 18, as well as a score equal to or greater than 2 on both anxious
mood and tension items. Secondary objective outcome data were obtained from responder and remission
rate comparisons made between the 2 treatment groups. In order for a participant to qualify as having a
significant response to treatment they were required to have a reduction of at least 50% in the HAMA-
total score during the 6-week trial. Remission was defined as a HAMA-total score of less than 10 points at
the end of the 6-week study. The results demonstrated that WS® 1265 was comparable to the
conventional approach in its ability to promote relaxation.* The HAMA-total score decreased by 45% in
the WS® 1265 group and decreased by 46% in the conventional group. At the conclusion of the 6-week
intervention, 40% of the WS® 1265 group and 27% of the conventional treatment group were determined
to be in remission. The WS® 1265 group had a response rate of 52.5% compared to only 40.5% taking the
conventional option. Adverse effects in the WS® 1265 group were uncommon and included nausea
(5.2%), eructation (3.9%), and dyspepsia (2.6%).

Oral Lavender Supplementation: Depression


In a 4-week randomized, double-blind study, researchers compared the efficacy of a tincture of L.
angustifolia with imipramine in the treatment of mild to moderate depression.64 Forty-five adult outpatients
who met the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) for major
depression based on the structured clinical interview for DSM-IV participated in the trial. Patients had a
baseline Hamilton Rating Scale for Depression (HAMD) score of at least 18. In this study, patients were
randomly assigned to receive lavender tincture (1:5 in 50% alcohol ) 60 drops per day plus placebo tablet
(Group A), imipramine tablet 100 mg per day plus placebo drops (Group B), or imipramine tablet 100
mg/per day plus lavender tincture 60 drops per day (Group C) for 4 weeks. Lavender tincture at this
concentration was found to be less effective than imipramine in the treatment of mild to moderate
depression (P=0.001). In the imipramine group, anticholinergic effects such as dry mouth and urinary
retention were observed, whereas headache was observed more in the lavender tincture group. The
combination of imipramine and lavender tincture was more effective than imipramine alone (P<0.0001).
Researchers concluded that lavender tincture may be of therapeutic benefit in the management of mild to
moderate depression, but only as adjuvant therapy.

In an open-label Phase II trial, Stange and colleagues administered 80 mg per day of lavender oil
(Silexan, WS® 1265, Dr. Willmar Schwabe Pharmaceuticals, Karlsruhe, Germany) to 50 patients with
neurasthenia, post-traumatic stress disorder, or somatization disorder for 3 months.65 Using the State
Trait Anxiety Inventory, von Zerssen’s Depression Scale, and a sleep diary for assessment, researchers
found that state and trait anxiety as well as depression were reduced and efficiency of sleep was
improved significantly. Controlled clinical trials are needed to confirm whether oral lavender oil is an
effective treatment for depression.

Comparison to Kava, Benzodiazepines, and Antidepressants


To date, lavender has been compared to benzodiazepines,66 paroxetine (an SSRI antidepressant), and
imipramine (a tricyclic antidepressant). It has also been compared to kava. 67 Kava was perhaps the best
studied botanical anxiolytic and was the leading product in this category until concerns about liver toxicity
prompted many companies to discontinue offering it. In a 6-week study, kava was found to produce a
mean reduction of the HAMA score of 10 points, whereas the mean reduction of that score from lavender
(WS® 1265) has ranged from 11.3 points (6-week study)63 to 16 points (10-week study),62 suggesting
comparable to superior efficacy. Pharmaceutical anxiolytics (primarily benzodiazepines) typically produce
HAMA reductions in the range of 11 to 15.3, suggesting comparable to superior efficacy of WS® 1265
without the attendant side effects.62,63,68,69

The Hamilton Anxiety Scale is used in most clinical trials of anxiolytic agents for GAD. In the study by
Kasper and colleagues,62 a diagnosis of AD NOS was used instead, but the HAMA scale was still
employed and baseline HAMA scores were similar across all trials (ie, > 18). At first glance it might
appear that patients with AD NOS responded better to lavender than patients with GAD. However, the
study of lavender for GAD was of shorter duration (6 weeks) than the study of lavender for AD NOS. In
the longer study, the mean HAMA score change at the 6-week mark was nearly identical to that seen at
the end of the 6-week study of patients with GAD. Therefore, the additional month of therapy at the same
dose is likely to have had additional effects.

In a meta-analysis of 21 double-blind, placebo-controlled trials in patients with GAD, Hidalgo and


colleagues determined average effect sizes for HAMA total score change versus baseline of 0.50 for
pregabalin, 0.45 for hydroxyzine, 0.42 for venlafaxine XR, 0.38 for benzodiazepines, 0.35 for selective
serotonin reuptake inhibitors (SSRIs) and 0.17 for buspirone.70 The effect size of lavender (WS® 1265)
was computed to be 0.75 in AD NOS. The significant reduction of anxiety-related symptoms in patients
treated with lavender was not only evident in the judgment of the investigators, but was also perceived by
the study participants subjectively according to the results of the self-rating questionnaire.

The effects of lavender extract (WS® 1265) and other anxiolytic agents on HAMA scores are compared in
Table 1 below. They are expressed as a mean HAMA score change.

TABLE 1
Length of HAMA score Mean HAMA
Dose Diagnosis
study at baseline score change
Lavender (WS®
80 mg/d 10 weeks AD NOS 26.8 -16
1265)62
Lavender (WS®
80 mg/d 6 weeks GAD 25 -11.3
1265)63
Lorazepam63 0.5 mg/d 6 weeks GAD 25 -11.6
Bromazepam71 3 mg TID 6 weeks GAD 28.07 -13
Oxazepam70 5 mg TID 6 weeks GAD 28.24 -11
Kava(WS® 100 mg (70%
6 weeks GAD 28.35 -10
1490) 70
kavalactones) TID
Escitalopram72 10-20 mg/d 24 weeks GAD 23.7 -15.3
Paroxetine71 20-50 mg/d 24 weeks GAD 23.4 -13.3
Duloxetine68 60-120 mg/d 9-10 weeks GAD -11.1
Based upon the available data, it appears that therapy with at least some lavender extracts is comparable or superior
in efficacy to many commonly prescribed anxiolytics, including benzodiazepines, SSRIs, and kava. The adverse
event profile for lavender is the least severe of these options by a wide margin. In particular, benzodiazepines are
well-known for their significant habit-forming potential, a drawback not found with lavender preparations.

Adverse Events, Safety and Dosage


The German Commission E Monographs list no contraindications, side effects, or drug interactions for
lavender flower. Internal use of the volatile oil of lavender oil has been reported to cause nausea 73 and
drowsiness after excessive intake.74 This effect may be dose- and/or quality-dependent, as the
occurrence of nausea was higher in the placebo group than in the treatment group (WS® 1265) in the
largest and longest controlled clinical trial of lavender oil supplementation. 62

In a brief report, Henley and colleagues described 3 cases of otherwise healthy boys with prepubertal
gynecomastia,75 all of whom had normal serum concentrations of endogenous steroids and none of whom
had been exposed to any known exogenous endocrine disruptors. The repeated topical application of 1 or
more over-the-counter personal care products that contained lavender oil or lavender oil and tea tree oil
was documented for all 3 patients. The authors performed in vitro tests that suggested weak estrogenic
and antiandrogenic activities of the oils that may have contributed to an imbalance in estrogen and
androgen pathway signaling.

The effective dose of lavender oil is suggested to be 20–80 mg per day.36 The best-designed clinical
studies with the most robust combination of efficacy and tolerability used 80 mg per day of a well-defined
lavender oil. No serious adverse events during either of the published studies on this extract were
reported.

Conclusion
Lavender oil aromatherapy has been shown to be effective in the management of anxiety and depression
and small and medium-sized controlled and uncontrolled clinical trials. The best validated use of lavender
as an anxiolytic agent is oral supplementation of 80 mg per day of a high-quality, well-defined lavender
essential oil that has a demonstrated efficacy comparable or superior to benzodiazepines and kava, with
a super safety profile.

Conflict of Interest Statement


Jeremy Appleton, ND, is an employee of Schwabe North America, a subsidiary of Dr. Willmar Schwabe
GmbH & Co, which manufactures and distributes WS® 1265, discussed in this article.

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