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.
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.
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.5 SSRIs, 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.9-13 Others, 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 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
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.55The following are selected examples of clinical trials on lavender aromatherapy:
- 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.
| || Dose||Length of|
|80 mg/d||10 weeks||AD NOS||26.8||-16|
|80 mg/d||6 weeks||GAD||25||-11.3|
|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|
|100 mg (70%|
|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 nausea73 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.
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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