Lavender

Lavender is a commonly used essential oil in aromatherapy derived from the genera of plants Lavandula (of the family Labiatae), with species being used including latifolia, angustifolia, stoechas, and intermedia (sterile cross of latifolia and augustifolia).^[1] The most popular form appears to be augustifolia, and this species has also been referred to as both officinalis and vera in the past (with the three species names being seen as synonymous);^[1] the popularity of this species may be due to the robust flowers it bears, as it is claimed that the flowers produce a sweeter aroma relative to the foliage.

The species of augustifolia is sometimes referred to as English Lavender while the species of stoechas is referred to as French or Spanish Lavender; latifolia is sometimes informally known as Mediterranean Lavender, while intermedia has no such common name.^[1]

It is generally said that the chemical composition between species is similar and that all herbs have carminative properties, although there are some species specific claims such as as an abortifacient (latifolia), use in headaches (stoechas), and usage as a diuretic (angustifolia).^[1]

The essential oil portion of Lavender is a pale yellow, viscous liquid with a sweet fragrance, which is used commercially in balms, perfumes, and cosmetics since the 1920s.^[2] It holds a GRAS status (Generally recognized as safe) in the US under the FDA, and due to the 97.5% percentile of Lavender oil in cosmetics being approximately 0.74% (concentration according to the International Fragrance Assocaition or IFRA) it has been said that highest expected public exposure in heavy users of Lavender containing cosmetics may be 0.019mg/kg daily (assuming 100% absorption) and can be corrected to 0.003mg/kg assuming an approximate 15% absorption rate seen with the main two bioactives.^[2]

Lavender (following composition for Lavandula angustifolia) tends to contain:

• β-Linalool (35.01-38%)^[3][4]
• Linalylacetate (34-38.28%)^[3][4]
• Borneol/Lavandulol (3.4%)^[4]
• β-cis-Ocimene (2.8%)^[4]
• Caryophyllene (2.6)^[4]
• Lavandulylacetate (2.0%)^[4]
• β-trans-Ocimene (1.8%)^[4]
• 1,8-Cineole aka. Eucalyptol (1.7%)^[4]
• Terpinenol-4 (1.7%)^[4]
• Myrcene (1.2%)^[4]

There appears to be some species differences in regards to Camphor, with less than 2% in some species (augustifolia, dentata, and pinnata) and higher levels in others (stoechas and lanata).^[1] This seems to correlate with usage, as the low-Camphor Lavenders (relatively higher in sequesterpenes such as Caryophyllene and terpenes such as β-phellandrene) are used in cosmetics and high Camphor herbs used as repellant.^[1]

Silexan is an oil preparation from the flowers of Lavandula augustifolia^[5] that is used in the brand name product LASEA which is standardized for 20-45% linalool and 25-46% linalyl acetate.^[6] It is prescribed (or at least used) for Generalized Anxiety disorder in Germany without apparent benzodiazepene actions.^[7]

Oral ingestion of Lavender (80mg as Silexan) appears to result in an increase in serum Linalool with an apparent half-life of 4 hours following acute administration and 9 hours following 11 days of repeated oral ingestion.^[8] Oral ingestion of a daily doses of 160mg Silexan has been noted to raise plasma levels of linalool in the range of 2-9ng/mL, with average levels on the 5^th, 10^th, and 11^th day of dosing being fairly similar (2.02ng/mL, 3.30ng/mL, and 2.95ng/mL respectively);^[6] Linalyl acetate was below the level of detection (2ng/mL) in all cases.^[6]

In rats exposed to the aroma of lavender, detectable serum linalool is present within 7 minutes at the concentration of 3ng/mL linalool and 11ng/mL linalyl acetate (exact dose of aroma not disclosed, but aroma was used for the duration of one hour).^[9]

Both oral and aromatic exposure to Lavender has been linked to serum linalool concentrations in the nanomolar range

In a testing condition to enhance absorption (under occlusion in a 70:30 ethanol:water vehicle) it appears that the bioactive known as linalool can be topically absorbed but at a level of 14.4% of topical application over 24 hours of assessment^[10] and this rate of absorption appears to be similar for linalyl acetate.^[11] Absorption of the other terpenes camphor, 1,8-cineol, and carvacrol has also been noted in vitro, and ultraviolet radiation exposure appears to reduce the rate of absorption.^[12]

It has been noted that low molecular weight terpenes in general are absorption enhancers and appear to influence both lipophilic and hydrophilic compounds,^[13][14] although the usage of Lavender in augmenting absorption of other agents has not been investigated.

Limited evidence exists to suggest efficacy following topical administration, with one study in dogs applying lavender oil (0.18mL) behind the ears four times (each dose separated by 3.5 hours) noted a reduction in heart rate and possible calming effects as assessed by ambulatory ECG monitor.^[15]

Bioactives may be absorbed topically, although the absorption is not absolute

Concentrations of Lavender at 0.125% appear to not significantly affect skin cell viability, but all higher tested concentrations in vitro (0.25-2.00%) with a fairly remarkable drop of cell viability from 80-100% at 0.125% to less than 30% at 0.25%.^[16] These results suggest high concentrations of Lavender oil, possibly due to the linalool component, exerts cytotoxicity on skin cells.

One 9-year study assessing the usage of Lavender oil patches has reported that 13.9% of subjects report contact dermatitis upon using topical Lavender oil.^[17] Some authors^[16] suspect that this may be linked to linalool and possibly to contact dermatitis assocaited with deodourants, as linalool and limonene are the two most commonly used industrial fragrances^[18] in up to 97% of deodourants in once study.^[19]

Lavender has been known to spontaneously form terpenes upon exposure to the air via autooxidation of terpenes, and the conversion of linalool to two linalool hydroperoxides and linalool oxide (similar byproducts seen with linalyl acetate^[20]) into topical allergens^[21][22] proceeds upon air exposure due to a lack of antioxidative components in Lavender oil to attenuate the rate of this reaction.^[23] Linalool and Linalyl acetate themselves are weak or not allergenic, as they do not have the properties of being electrophilic or a free radical (these properties are integral to allergens, which pass the skin and form complexes with proteins to then trigger an immune response).^[23]

Although lower concentration of Lavender appear to be safe, topical application of the essential oil does not appear to be free from side-effects

Oral ingestion of Lavender oil at 160mg (as the brand name product Silexan) in otherwise healthy persons over 11 days had no significant effect on CYP1A2, CYP2C9, CYP2D6, and CYP3A4 as assessed by drug pharmacokinetics relative to placebo, while the influence on CYP2C19 appeared to be affected but was not deemed to be clinically relevant.^[6]

The main inhibitory neurotransmitter in the central nervous system is GABA, and the receptor this molecule acts upon known as GABA receptors;^[24][25] GABA receptors have a particular binding pocket known as a benzodiazepeine binding pocket (molecular target of benzodiazepeine drugs, commonly used in sleep and anxiety disorders with a possible addictive value over long term use).^[26]

The essential oil of Lavender has been shown to have affinity for GABA_A receptors, inhibiting TBPS binding at the channel site with an IC₅₀ of 40mcg/mL and complete binding inhibition at 1mg/mL. Although Lavender failed to displace the test drug (Rohypnol) from the benzodiazepine binding site, a 50:50 mixture of Lavender and Lemon Balm appeared to reduce the IC₅₀ failure from undetectable to less than 1mcg/mL.^[27]

In assessing the electrophysiology of Lavander in vitro, Lavender was able to concentration dependently reduce GABA_A dependent currents with statistical significance at 100mcg/mL and almost abolished spontaneous inhibitory post-synaptic currents;^[27] this event is not seen with pure GABA_A antagonists such as picrotoxin, as is thought to underlie why epileptic effects are not observed with Lavender.^[27] These observations are also thought to underlie the anti-agitation effects of Lavander and Lemon Balm.^[28][27]

Shows affinity for GABA_A receptors with no per se affinity for the benzodiazepine binding site, but is profoundly synergistic with Lemon Balm essential oil for affinity to the benzodiazepein binding site

In a behavioural conditioning test against the reference drug Diazepam (a benzodiazepeine), Lavender injections at 3-30mg/kg failed to induce a conditioning effect similar to benzodiazepine drugs^[7] and human studies using Lavender for anxiety fail to note either sedation or dependency.^[29]

Appears to be devoid of benzodiazepine action and dependency

A study in rats given isolated linalool failed to find any influence on corticosterone or catecholamines following ingestion of 125mg/kg acutely.^[30]

There is no apparent affinity for NMDA or AMPA glutaminergic receptors (as assessed by displacement of agonists).^[27]

In regards to dopaminergic receptors, injections of 10-1000mg/kg Lavender oil daily for 5 days appeared to dose-dependently increased DRD2 and DRD3 mRNA content in the olfactory bulb of rats with no influence on DRD1a, DRD4, and DRD5 mRNA while only DRD3 receptor protein content increased.^[31] 1000mg/kg (but not 10-100mg/kg) was associated with increased balance as assessed by a rotarod test, and these effects on mRNA were not seen in the striatum and no influence on tyrosine hydrolyase content was noted.^[31] It is thought these results may mediate Lavender-induced behavioural alterations as the DRD3 receptor is implicated in such.^[32]

Lavender is one of few essential oils used in aromatherapy with evidence for general anxiety reducing effects, alongside rose oil having some evidence.^[33] In animals exposed to the aroma of lavender (Lavandula officinalis) prior to either a stressor or no stress (water immersion test) was able to confer anxiolytic properties independent of whether stress was present, as assessed by an elevated maze plus test.^[34] When looking at NGFR and Arc mRNA levels, their decrease during stress was attenuated with Lavender aroma but during the nonstressed period they were slightly attenuated (of which the authors thought that Lavender may be inducing a stress response).^[34]

When isolating linalool, oral ingestion of this compound at 125mg/kg does not appear to have anxiolytic properties,^[30] although it appears linalyl acetate may be a prerequisite with anxiolysis only resulting from synergism of these two molecules.^[35]

One study in sheep noted that while exposure of lavender oil (via respiratory mask) to calm sleep reduced nervousness and agitation, that in a subset of sheep deemed as nervous exposure to lavender augmented the nervousness.^[36] The authors hypothesized that genetic differences in anxiety may mediate these effects, but did not conduct mechanistic studies.^[36]

Lavender, in research animals, appears to be associated with anxiety reducing properties independent of the presence of a stressor

An oil preparation known as Silexan (active component of the brand name LASEA) appears to be approved in Germany for the purposes of restlessness with anxious mood.^[6]

One multicenter study using Silexan (80 mg) against an active control of Lorazepam (0.5 mg) in persons with generalized anxiety disorder over 6 weeks noted that anxiety (as assessed by Hamilton Anxiety Rating Scale) was reduced to a comparable level with the benzodiazepine reference drug (46% relative to baselin) and with Silexan (45%).^[29] This study did not have a placebo control and similar potency was noted on other measurements (SF-36, SAS, and PSWQ-PW), and no sedation was noted with Lavender ingestion.^[29] Anxiolytic effects have been noted in another trial with Silexan, where the lavender oil reduced anxiety and improved sleep to a greater degree than placebo and was associated with more responders (76.9% versus 49.1%).^[37]

A study in 47 persons with somatization disorder, PTSD, or neurasthenia using Silexan at 80mg daily for 6 weeks noted significant reductions (relative to baseline) in depressed mood (57.4% of sample), sleep disorders (51.1%), restlessness (61.7%), and anxiety (44.7%) and significant improvements in cognitive functioning as assessed by the SF-36 mental health assessment (all subscales except body pain and general health).^[38]

Oral supplemenation of 80mg of Lavender oil daily appears to have general anxiolytic properties

In students experiencing anxiety with test taking, Lavender aroma has been associated with reduced self-reported anxiety^[39] and in a practical setting (Dental office lobby) there has been a reported reduction in anxiety associated with the aroma of Lavender, although only transiently.^[40]

Aromatherapy with Lavender has once been demostrated to reduce anxiety in the setting of trauma, where persons admitted to ICU and given aromatherapy reported reduced anxiety and a better mood; the effects were transient and did not appear to build up over time.^[41]

When looking at all evidence for Lavender, there appear to be consistent anxiolytic effects associated with supplementation although the robustness of the evidence for aromatherapy is less than desirable (due to inadequate sample sizes and blinding associated with aromatherapy).^[42]

The aroma of Lavender is also associated with anxiolytic properties, but has less robust evidence than oral supplementation. Two studies suggest that there is no build up or long lasting effect, and that the anxiolysis of the aroma lasts for as long as the aroma is present

In rats given isolation linalool, 125mg/kg did not appear to cause alterations in activity while preliminary dose testing noted that 300mg/kg linalool caused unconciousness in all rats tested and 175mg/kg appeared to hinder locomotion somewhat.^[30]

Linalool appears to cause dose-dependent sedation in rats even in isolation

In regards to body temporature, it has been noted that the aroma of Lavender is associated with reduced body temperature in rats within 30 minutes of exposure during the light period (waking) with no significant effect during the dark period and that these effects were dependent on the prescence of an active suprachiasmatic nuclei (removal of which abolished the effects).^[43] A reduction of body temperature has been noted in humans following inhalation of the aroma, and was measured during waking hours.^[44] These observations may be related to a known link between the olfactory buld and the suprachiasmatic nuclei and circadian rhythm.^[45]

Body temperature appears to be a biomarker of stimulation and/or sedation, and may be reduced (in accordance with sedation) following exposure to the aroma

Acute inhalation of Lavender aroma has been noted to increase the frequency of self-reported drowsiness^[44] and one study using Lavender aromatherapy in persons undergoing hospitalization for coronary heart disease (for 3 days of hospitalization, their rooms were filled with Lavender for 9 hours during sleep) noted that Lavender was associated with improvements in self-reported sleep, where the rating score (SMHSQ) improved 31% (no change for control).^[46] Odorant exposure to sleep has been noted previously to modulate breathing, with lavender (not influence arousal but being associated with less waking periods when the aroma is present during sleep) able to alter breathing patterns^[47] and has been associated with increasing short-wave sleep in otherwise healthy persons.^[48] This improved sleep has been noted as a side-effect of studies in infantile colic.^[49]

These beneficial effects on sleep quality have been noted with insomniac women with a rating of greater than 5 on the Pittsburgh Sleep Quality Index (PSQI, chinese modification) where inhalation of Lavender aroma for 20 minutes daily twice a week for 12 weeks (0.25cc in an ultrasonic ionizer aromatherapy diffuser) relative to control (a class teaching proper sleep techniques, no aromatherapy nor placebo) noted a reduction in heart rate and heart rate variability as well as improvements in sleep quality.^[50] This has been replicated in younger women, where women reporting sleeplessness from stress (college students) reported improvements from 4 weekly aromatherapy sessions with Lavender oil^[51] and in a mixed gender cohort (small sample of 10) with general insomnia.^[52]

There are multiple trials to support the idea that aromatherapy with Lavender can aid in sleep quality, particularly in persons with disturbed sleep either from stress or insomnia; the quality of any individual trial, however, is somewhat lackluster. Benefit has been noted either with aromatherapy throughout the day or a few times a week, or with the scent of aroma being in the air during sleep

Chronic daily ingestion of 80mg Lavender oil (oral supplement) that was capable of reducing anxiety in persons with generalized anxiety disorder was not associated with the side-effect of sedation.^[29]

Lavander is thought to be anti-agitative (anger reducing), and possible synergistic in this regard with Lemon Balm. Both of these essential oils have general inhibitory effects on neuronal signalling, with both Lavender^[27] and Lemon Balm^[28] are able to reversibly reduce signalling via GABA_A receptors and reduce the frequency of spontanous excitatory and inhibitory synaptic signalling.

One study (duplicated in Medline^[53][54]) using Vogel and Geller conflict tests in mice noted that Lavender caused dose-dependent reductions in conflict (thought to be due to GABA_A interactions, as 0.5mg/kg Diazepam also caused anti-conflict effects); Juniper, Frankensence (Boswella thurifera), Cypress, Geranium (Pelargonium adoratissimum), and Jasmine were without effect.^[54]

Lavender, in animal models of conflict, shows anti-aggressive properties and there appears to be some mechanistic studies looking into how this works

Lavender aroma, in otherwise healthy humans delivering 1mL of Lavender oil via respiratory mask (rate of 2L/min), has noted a decrease in respiratory and heart rate relative to placebo aroma (sweet almond oil) and increases in the self-reported mood states of 'good', 'active', 'fresh', and 'relaxed' as well as 'drowsy' with no significant effect on 'bad', 'stress', 'romantic', 'frustrated', 'uncomfortable', 'calm', or 'disgust'.^[44] One other study to note frustration noted that the self-report of 'anger-frustration' appeared to be reduced following bath aromatherapy (placing a 20% essential oil of Lavender into bath water) while energy and arousal were unaffected.^[55]

An increase in midfrontal alpha power has been detected via EEG with lavender aroma, which correlated with improvements in self-reported mood (less depressed and anxious mood states and increased relaxation), ^[56] and relaxation has been noted elsewhere in humans alongside an increase in Theta 1 (3.5-5.5Hz) and a decrease in Beta1 (13.5-20Hz) which correlated with relaxed states.^[57] An increase in Theta power has been noted elsewhere with Lavender aroma in the whole brain with no significant influence on any Beta power.^[44]

One study, however, has noted a decrease in Alpha1 (8-11Hz) in the posterior temporal lobe associated with Lavender aroma^[58] which contrasts the results seen in another study (whole brain including posterior lobes); this study also noting a whole brain increase in Alpha2 power.^[44]

This relaxation has been noted in more practical settings, where one study using a dental office noted that filling the lobby with the aroma of lavender outperformed the aroma of orange, a music control, and a music-less and aroma-free control on the parameters of anxiety and mood state (less anxious and reporting a better overall mood).^[59]

Multiple EEG studies to support the self-reported increases in relaxation associated with Lavender aroma, with limited evidence to support an anti-aggressive effect

In 61 college-aged females with higher than average menstrual pain (6-10 on a VAS rating scale), an abdominal massage with 2 drops of Lavandula officinalis (Lavender) to one drop Clary Sage and one drop Rosa centifolia (Rose oil) was compared to placebo aromatherapy (almond oil, same method of appplication and volume of 5cc) and control (no aromatherapy). It was noted that aromatherapy was associated with an average reduction in pain from 7 (0-10 rating scale) down to 5 and then 3 on days 1 and 2, respectively; control failed to reduce pain, and placebo aromatherapy appears to work in some persons to a lesser extent than combination therapy (herb intervention still significantly greater than the placebo group).^[60] The authors noted that although heavier flows appears to be correlated with greater pain,^[61] that there were no significant difference between groups.^[60] A similar application method with a similar aromatherapy (Rose switched for Origanum majorana; Marjoram) noted that in persons with diagnosed primary dysmenorrhea given aromatherapy (placebo given synthestic scents; different molecules) that the herbal aromatherapy group experienced significantly greater pain relief associated with menstrual symptoms.^[62]

One study has been conducted with Lavender oil in isolation against placebo massage oil, where massage (2mL of essential oil applied to hands, and then followed by a 15 minute massage) following lavender oil was found to significantly reduce the pain associated with menstruation to a greater degree than placebo as assessed by VAS (rating scale).^[63] Lavender oil experienced a 38% reduction in pain while placebo experienced a 9.8% reduction, both statistically significant relative to baseline but lavender oil also significantly more relative to placebo.^[63]

The main bioactives thought to mediate these analgesic effects are linalyl acetate, linalool, and eucalyptol due to their concentrations in Lavender oil.^[62]

Some evidence to support the notion that the aroma of Lavender can reduce menstrual pain, but these studies are confounded with the inclusion of Clary Sage and another herb (Rose or Marjoram, depending on study)

The aroma of lavender is able to exert neuroprotective effects against scopolamine-induced cognitive degeneration in rats exposed to the inhalation, as assessed by a week of exposure causing an antiapoptotic effect (preserving cell count) and induction of anti-oxidant enzymes.^[64] and inhalation elsewhere in a scopolamine model has been linked to preserving cognitive function (reduced by the toxin).^[65]

Similar protective effects have been noted following oral ingestion of 50-200mg/kg lavender oil in response to focal cerebral ischemia, where 200mg/kg reduced the infarct size to a comparable degree as Edaravone at 3mg/kg (neurological deficit scores showed a similar trend, but was not statistically significant; no treatment normalized the scores).^[66]

Both inhalation as well as oral ingestion of Lavender are linked to general neuroprotective effects in response to damaging stimuli

Inhalation of lavender oil for 15 minutes in persons suffering from Migraine headaches (relative to the placebo control of liquid paraffin) noted that the severity of headaches was lesser in the lavender condition and the responders to lavender (relative to placebo) was greater.^[67]

There is no apparent effect on nicotinic acetylcholine receptors up to 1mg/mL using lavender oil,^[27] although one other study using isolated linalool at 2-80mcg/mL noted that in a mouse neuromuscular junction that linalool reduced the efficacy of the nerve impulse in acetylcholine release (pre-synaptically) and was thought to confer anti-cholinergic effects.^[68]

When looking at the acetylcholinesterase enzyme, Lavender oil appeared to inhibit the enzyme with an IC₅₀ of 0.82+/-0.60mg/mL (820µg/mL) in vitro while isolated linalool appeared inactive; Lavender significantly underperformed relative to the active control of Galantamine.^[69]

One study on aromatherapy in general (morning aroma of lemon oil and rosemary at 0.04mL and 0.08mL for 2 hours met with evening application of Lavender and orange at 0.08mL and 0.04mL for 90 minutes) on 28 elderly persons of which 17 had Alzheimer's noted that after 28 days of aromatherapy noted some significant improvement on GBSS rating subscales (spontaneity, feeling function, and psychotic manifestations) and improvement in abstract function for those with Alzheimer's; msot rating scales, overall, did not reach statistical significance but trended towards betterment.^[70] One other study using multiple exposures to Lavender oil (1 hour thrice a day following meals, where 2 drops of lavender were placed on clothing) in a pilot study noted that the aroma of Lavender was associated with a reduction in the Neuropsychiatric Inventory (NPI) rating scale by 42% (control experienced a 16% reduction); the Barthel Index and MMSE were both iunchanged after 4 weeks.^[71]

Currently weak evidence to support the notion that aromatherapy benefits Alzheimer's disease per se

Contrasting results exist on blood pressure, with one publication reporting that the aroma of Lavender for 3 minutes decreased respiratory and heart rate alongside blood pressure while another confirmed the reduction in breathing rate and subjective calmness while both heart rate and diastolic blood pressure increased; unfortunately neither study can be found online (published as thesis statements reported in the introduction of this study^[44]) It has been thought that these differences are reflective of a hedonic effect (whether the scent is 'liked' by the participant or not) with pleasant aromas being known to reflect as a decrease in blood pressure.^[72] A later study which only included persons who found Lavender pleasant noted a decrease in systolic and diastolic blood pressure as well as respiratory rate and body temperature.^[44]

Lavender oil, in LPS-stimulated THP-1 cells at 0.1% (0.2-0.8% cytotoxic), is able to preserve cell survival in the presence of LPS and significantly reduce subsequent IL-1β by 44% which appears to be downstream of preventing upregulation of TLR4 (via inhibiting NF-kB activation related to preventing HSP70 induction).^[73]

One study assessing the influence of Lavender aroma in otherwise healthy humans on immune function failed to find a significant influence on neutrophil function as assessed by serum biomarkers (CXCL8 release and CD16).^[4]

It has been reported in a few case studies that prepubertal gynecomastia (enlargement of breast adipose, usually in males) has been linked to Lavender and tea tree oil in three boys aged 3-10^[74] and Lavender oil has subsequently been described as an endocrine disrupting agent.^[75] It has been commented that none of these case studies showed alterations in serum hormones (aside from a single case with elevated testosterone^[76]).

In vitro, an MCF-7 assay using a standard of Lavandula augustifolia has shown estrogenic activity (luciferase activity and estrogenic gene products) at a maximal activity of 0.025% of medium with an efficacy of approximately half that of 1nM 17β-estradiol and half of this concentration (0.0125%) being 34% as effective as estrogen reference.^[74] This was inhibited by fulvestrant, an estrogen receptor antagonist

One rat study in immature female rats following topical application of 20 or 100mg/kg lavender oil (in 5mL/kg volume) failed to show signs of estrogenicity as assessed by uterine and ovary weight.^[2]

It has been noted that the subsequent in vitro assessments may not have been enough to draw conclusions from^[76] (same comment appears to be duplicated in Medline^[77])

In assessing the actions of lavender oil on the androgen receptor in MDA-kb2 cells, lavender itself failed to activate the receptor when no androgen was present while 0.005% concentration of lavender oil was able to inhibit 52% of DHT-dependent signalling (as well as Magnolia alternifolia or tea tree oil at 41%).^[74] The protein content of the receptor was not modified, and the observed effects appears to be selective to the androgen receptor (with no observed effects on glucocorticoid receptors) and the efficacy seemed comparable to 1µM flutamide.^[74]

Possible anti-androgenic effects, which need to be confirmed in a living system and are not yet tied into a known molecule present in Lavender (although obtained with a Sigma-Aldrich reference of lavender oil)

The aroma of lavender appears to protect from formaldehyde (aroma) induced testicular injury in a similar manner as rose oil, and as such may preserve testosterone levels in this scenario.^[78]

In persons suffering from recurrent aphthous ulceration (canker sores), application of lavender oil appears to exert a modest protective and healing effect relative to both baseline and placebo with increased healing rates and less inflammation and self-reported pain assessments; this was attributed to antiinflammatory and antibacterial effects.^[79]

Infantile colic is excessive crying in a baby (greater than 3 hours a day for 3 days a week) that is not caused by a known medical condition and is thought to be more related to emotional distress (a medical term used to refer to a fussy period experienced by infants).

In a group of 40 infants (2-6 weeks of age) given an abdominal massage with lavender oil (1 drop or 1cc of a solution that is 4% Lavender to 96% almond oil, for 5-15 minutes) noted that infants in the lavender oil group experienced a reduction in crying rate while no such decrease was noted in control.^[80] Elsewhere, it has been noted that Lavender influences both the mother and infant during a bathing period when a drop is added to the water and improves infantile sleep.^[49]

Melissa officinalis (Lemon Balm) is a herb with a high rosmarinic acid content and is known for being relaxing and slightly sedative at the cost of attention; the essential oil (lemon oil) may be used for aromatherapy despite most evidence being on the oral ingestion portion.

Despite the fact that Lavender oil in isolation fails to displace agonists form the benzodiazepine binding site of GABA_A receptors up to 1mg/mL, a 50:50 mixture of Lavender and Lemon Balm appeared to reduce the IC₅₀ value from undetectable (greater than 1mg/mL) to less than 1mcg/mL, approximately a thousand-fold synergism as lemon balm alone is also inactive on the benzodiazepine receptor.^[27]

Appears to remarkably synergistic with Lemon Balm oil on benzodiazepine affinity, although the activation or antagonism of this receptor is not yet known (only affinity). If agonism is present, then the addition of lemon balm to lavender may reverse the lack of benzodiazepine like actions into a sedative component via this receptor subset

Bergamot oil has been claimed to be synergistic in regards to relaxation when paired with lavender oil,^[81] but the one study to note this failed to compare the combination therapy against lavender or bergamot oil in isolation and could not establish synergism.

Insufficient evidence to support synergism

One study using the Silexan oral preparation of lavender at 160mg in women on birth control (combination therapy of ethinyl estradiol with levonorgestrel) found that supplementation did not interfere with the kinetics of the birth control when they were taken together over the course of 21 days.^[82]

The LD₅₀ of lavender oil, as injections, appears to be 6.5g/kg in rats.^[79]

In regards to the genotoxicity of the oil in vitro, linalyl acetate was able to increase the frequency of micronuclei in lymphocytes (indicative of genotoxicity) in a concentration dependent manner; linalool was not genotoxic, and lavender oil only showed such effects at the highest tested concentration (100mcg/mL).^[83]

Contact dermatitis with Lavender oil has been noted in case studies^[84] and one nine year study assessing the tolerability of Lavender oil has reported that 13.9% of subjects report contact dermatitis upon usage.^[17]

Lavender oil is sometimes omitted during pregnancy and it is thought that the species of Lavandula stoechas has abortifacient properties.^[1]

Traditionally recommended to not use large amounts of lavender during pregnancy, but this topic has not been highly addressed

The essence of Lavender oil (0.96% concentration) applied via a sitz bath to women following childbirth noted the lavender oil group (relative to control, sitz bath without Lavender) was associated with less rescue analgesic usage and a pain relieving effect.^[85] Compared to a Betadine group, there were no significant differences in any parameter on a Redness, Edema, Ecchymosis, Discharge and Approximatio (REEDA) rating scale.^[85] A similar study adding Lavender oil to a bath (with a control group and a group given synthetic lavender) noted that Lavender oil was associated with a reduced average pain rating when used for 3-5 days, although this failed to reach statistical significance.^[86]

A review has been conducted assessing the interactions of Lavender oil and perineal (post childbirth) trauma and pain^[87] concluded that there was a significant lack of evidence and consensus on this topic although it appears safe if lower concentrations of lavender oil is used (as concentrations above 0.125% directly affect skin cell viability^[16] and that usage in a bath is an unreliable indicator of concentration as the oil can collect in a few globules rather than evenly disperse^[87])

Mixed evidence as to the efficacy in lavender baths for reducing post-birth pain