Relaxing sedative antistress anticonvulsive and spasmolytic properties

CNS effect

Thirty years ago a Bulgarian research team had already reported on certain central neurotropic effects of the EO of lavender and found this oil to be relaxing, calming and stress relieving (Tasev et al., 1969). In another paper the authors showed that linalool possesses central depressive effects similar to those of lavender oil, namely anticonvulsive, inhibitory to the spontaneous motor activity even if this had been stimulated by caffeine, or amphetamine pretreatment: at higher doses it was disturbing to the motor co-ordination and prolonged the narcotic effect of hexobarbital, ethyl alcohol and chloral hydrate. But, in toxic doses, linalool shows a narcotic effect. Even more effective than this prominent alcohol is terpinen-4-ol, a minor constituent of the EO of lavender (Atanassova-Shopova et al., 1970; 1973; Imaseki et al, 1962).

Mood-influencing effect and sedation

The EO of lavender, frequently used in aromatherapy, positively affected mood, EEG patterns of alertness and mathematical computations. This result of a test was assessed with 40 adults where the so-called lavender group subsequently had increased jS-power in the EEG, suggesting increased drowsiness, and reported on a less depressed mood and of feeling more relaxed;

furthermore they performed some (simple) mathematical computations faster and more accurately upon aromatherapeutical treatment (Diego et al., 1998). These results are in agreement with the findings of Kerl (1997) who tested the efficiency of children's memory in an elementary school. Especially anxious and timid pupils, who had bad scores on account of their inability to recite a paragraph learnt by heart, increased their marks after inhalation of lavender oil, which was presented on common olfactory strips to the children. Pupils who were originally self-assured and/or lethargic showed no increase, rather even a decrease, in their marks. Therefore, the anxiety-relieving potential of this EO was shown. A similar goal was achieved by an investigation by Ludvigson et al. (1989) where the effects of the odours of lavender and cloves on cognitive skills of college students were studied. Lavender adversely influenced arithmetic reasoning. Discussions raised by the results included implications for the claim that lavender is physiologically relaxing, the surprising absence of an effect of odour change on memory and possible interactions of odour and personality factors.

Another study with the aim to link the effects of odorants with the emotional process through autonomic nervous system responses was performed and found that among the tested odorants the inhalation of lavender oil elicited mostly 'happiness'. More than 60 subjects showed similar autonomic responses which can be transcribed into basic emotions (Vernet-Maury et al., 1999). Similar results were obtained in an experimental study which was performed on 122 patients to evaluate the use of aromatherapy. Those patients who received an aromatherapeutical treatment with lavender oil reported a significantly greater improvement in their mood and perceived levels of anxiety compared to controls (Dunn et al., 1995). Changes in electroencephalogram measurements to different odours revealed that the EO of lavender significantly increased the regression coefficient of the power spectra of frequency fluctuation of a-waves. Thus, showing that this form of an experiment can be used for the evaluation of psycho-physiological responses (Lee et al., 1994).

Inhalation studies using lavender in animals

Evidence for the sedative properties of the EO of lavender after inhalation is also provided by Buchbauer and his team. In animal experiments, this oil significantly decreased the motility of 'normal' test mice as well as of animals rendered hyperactive or in other words 'stressed' by a intraperitoneal caffeine injection before the test (Buchbauer et al., 1991). The experiments were performed on young mice, housed under normal conditions, not under any stressful conditions for the 'normal' approach, therefore physiological patterns of behaviour would be expected. For the period under investigation using essential oil inhalation, specially designed plastic cages were used with adequate air volume provision and a light barrier installed. This light barrier would be interrupted when the animals crossed it and was a reflection of their locomotor activity. This in turn is directly related to their degree of sedation or the opposite, that is, agitation. The animals were allowed 1 h for adaptation and then the EO was applied in glass tubes and the vapour diffused out in a continuous air-supply for an hour. The activity of the animals was monitored over an hour and data taken of their actual activity at 15 min, 30 min and at 1 h. The results were compared with a group of control mice exposed to the same conditions in another cage at the same time. The hyperactivated or 'stressed' mice were even more sedated by lavender vapour than those under 'normal' physiological conditions (Table 12.1).

Furthermore, the main constituents of this oil, namely linalool and linalyl acetate, elicited a similar, although weaker effect. The sedative effect was clearly visible in the behaviour of the mice, which rested in a corner, did not show signs of social activity like grooming, sniffing each other, exploring the environment and generally exhibited a reduced motility.

Other EOs have been tested in these experiments as well, showing in many cases that the hyperactivity caused by a caffeine pretreatment could easily be overcome by the inhalation of

Table 12.1 Effect of lavender and other EOs and fragrance compounds on motility in mice after 1 h of inhalation

Compound Effect on motility Effect on motility after caffeine

Table 12.1 Effect of lavender and other EOs and fragrance compounds on motility in mice after 1 h of inhalation

Compound Effect on motility Effect on motility after caffeine

Lavender oil






Linalyl acetate



Neroli oil


+ 1.9

Rose oil



Valerian root oil










+ 2.1


Methyl salicylate

+ 16.6


certain single fragrance compounds as well as of certain EOs. These included neroli oil, rosemary oil, sandalwood oil and also some common EO components: citronellal, benzaldehyde, linalool, linalyl acetate, a-terpineol and phenylacetate (Buchbauer et al, 1991; 1993; Jager et al, 1992).

The correlation of the motility of the animals to the linalool concentration in serum has also been proven (Buchbauer et al., 1991) as has the absorption of linalool from percutaneous application of lavender oil as a massage oil (Jager et al, 1992), thus furnishing evidence of the aromatherapeutical use of lavender, for example, in the form of herbal pillows, employed in folk medicine since ancient times in order to facilitate falling asleep or to minimise stressful situations. The experiments to determine percutaneous absorption from lavender massage was conducted on a male subject, the EO of lavender being diluted with peanut oil (2 per cent v/v) and one and a half grams of this mixture was spread over an area of the stomach and massaged gently into the skin for 10 min, after which the residue was removed (Jager et al., 1992). Blood samples were taken from the cubital vein at intervals for 90 min and later analysed. The maximal levels of both linalool and linalyl acetate were found in the blood after 20 min and there was virtually none left after 90 min. The experiment indicated that lavender components were very rapidly absorbed into the blood, but these experiments did not prove conclusively that this occurred from skin absorption, as the volatile oil could well have been absorbed by direct inhalation. Experiments, using complete occlusion of the nasal and oral passages under positive oxygen input using specially sealed masks have now added factual evidence to these experiments indicating that skin absorption did in fact occur.

A possible dependence of the calming effect on the lipophilicity of the applied odorant was also discussed (Buchbauer et al., 1993b). Qualitative analyses of the cortex of the test animals, treated with various odorants before sacrifice, showed that these could be found in this part of the brain, thus proving that the fragrance compounds must have passed the blood—brain barrier by means of a humoral transport (Buchbauer et al, 1993a).

One fragrance compound, 1,8-cineole was studied more intensively after inhalation using functional imaging in the brain (Nasel et al., 1994), its concentration in the blood after prolonged inhalation (Stimpfl et al., 1995) and its pharmacokinetics in humans (Jager et al., 1996). There are also studies on carvone after inhalation and massage (Fuchs et al, 1997) which indicate among other things that enantiomeric forms have a different metabolism and that they retain their enantiomeric quality after absorption into the blood (Jager et al., 2000).

Studies of chiral fragrances on the human autonomic nervous system parametres and self-evaluation have also been of interest (Heuberger et al, 2000) as has the influence of essential oils on human attentiveness (Ilmberger et al., 2001). Recent studies of sandalwood essential oil and a-santalol applied to man by inhalation and percutaneous absorption have shown contradictory effects: inhalation produced a stimulating effect, while the latter produced a relaxant effect, which may be due to the effect of the massage (Hongratanaworakit et al, 2000a,b). All these studies indicate a complex behaviour of essential oils and components and strongly caution against predicting similar effects of all essential oils or components on the basis of limited studies.

Interestingly, the relaxing effect of lavender could not only be observed in humans or in test animals, but also when applied to the treatment of stress and travel sickness of pigs (20 animals) which were transported by road for 2 h each day over a 2-day period. When lavender straw was used as bedding or mixed with wheat straw the incidence and severity of travel sickness was significantly decreased, as measured by concentrations of cortisol in the pigs saliva (Bradshaw et al, 1998).

A Japanese patent describes the method for evaluating the antistress effect of fragrances, by determination of cortisol in the saliva. The occurrence of this adrenocortical hormone in saliva is claimed to be related to the anti-stress effect of fragrances (Tanisawa et al., 1999). Another patent deals with hypnotics, foods and feeds containing the EO of lavender (Yano, 1998). A third patent proclaims the 'stress relaxation fragrances, their compositions and cosmetics containing them' which includes linalyl acetate or phenyl ethyl alcohol (Ishitoya et al, 1997).

In a review, Pahlow (1988) cited various forms of applications of lavender, for example, in a bath which is used to overcome the stress of the day and to gain a sort of calmness by means of relaxation and anticonvulsion; pillows filled with lavender flowers are also very common, and even, but to a lesser extent, the so-called sedative teas and sleep-promoting teas which have to be prepared as an infusion using dried lavender flowers.

Sedative properties of enantiomers of linalool

In other experiments, the sedative properties of linalool were examined using the optically active alcohols, (R)-( —)-, and (£)-( +)-linalool and its racemate. The subjects were healthy young volunteers, who were first required to evaluate thirteen impression items as a sensory evaluation before and after work. Mental work and physical activity was also included as well as listening to a recording. The effect of the racemic mixture of both alcohols showed a tendency towards a greater decrease of the jS-wave, identical to the outcome observed for (R)-( —)-linalool, the genuine enantiomer of the EO of L. angustifolia. The effect of (£)-( +)-linalool, obtained from coriander oil, showed the reverse (Sugawara et al., 1998).

Potentiation of GABAa receptors

Recently, an important paper from another Japanese research team was published: Aoshima et al. (1999) discussed the potentiation of GABAa receptors expressed in Xenopus oocytes by perfumes and phytoncides. Essential oils, including various lavender oils and lavender perfumes as well — and such phytoncides as leaf alcohol, hinokitol, pinene, eugenol, citronellol and citronellal, potentiated the response in the presence of GABA at low concentrations (10 and 30 ^M), possibly because they bound to the potentiation-site in GABAA receptors and increased the affinity of GABA to the receptors. Since it is known that the potentiation of GABAA receptors by benzodiazepine, barbiturate, steroids and anesthetics induces an anxiolytic, anticonvulsant and sedative activity, the results obtained by Aoshima et al., suggest the possibility that the intake of perfume or phytoncid by various ways modulates the neural transmission in the brain through ionotropic GABAA receptors.

Sleep promoter

The relief of stress and the relaxant property of lavender oil — a problem especially found in hospitals, hospices and homes for the aged, was emphasised again by Lis-Balchin (1997) as well as by Delaveau et al. (1989). In order to test the hypotheses that lavender oil has a sedative effect and that the resultant sleep promotes therapeutic activity, a pilot study was arranged with acutely ill elderly people as well as later on with long-term patients. The results showed a positive trend towards sleep improvement using lavender (Hudson, 1996). However, a somewhat contradictory statement was published by Uehleke (1996) who said that the EO of lavender elicits no sedative properties but exerts some 'harmonising' effects. A difference between stimulation of the olfactory system and pharmacodynamic effects after absorption through the skin is discussed.

To investigate the effects of lavender oil for insomnia, the hours of sleep were initially measured for 2 weeks, then measured again for another 2-week period after medication withdrawal, and then measured for a final 2 weeks during which lavender oil was diffused into the ward. The amount of time spent asleep was significantly reduced after withdrawal of medication, but returned to the same level with lavender oil as that under medication (Hardy et al., 1995).

Swiss mice, who had diluted lavender oil (1/60 in olive oil) orally administered, showed sedative effects, which were observed using various tests (hole broad test, four plates test, plus maze test, potentiation of barbiturate sleeping time). A significant interaction occurred with pentobarbital, because the sleeping time was increased and the time actually asleep was shortened (Guillemain et al., 1989).

Psychopharmacological effects

Relationships could be established between personality traits and the effect of odour on task performance using several odours, such as lavender (Knasko, 1992). A Japanese patent application claims the usage of several monoterpenes as brain stimulants and/or enhancers of brain activity. These compounds can be incorporated into food, such as chewing gums (Nakamatsu, 1995).

A psychopharmacological in vivo evaluation of one of the main components of lavender oil, namely linalool, proved its dose-dependent, marked sedative effect on the CNS, including hypnotic, anticonvulsant and hypothermic properties. The psychopharmacological effect could be caused by an inhibitory activity of this mono-terpene alcohol on glutamate binding in the cortex of the test animals, for example, rats (Elisabetsky et al., 1995b). The sedative properties of linalool could also be proved by Elisabetsky et al. (1995a). These effects revealed the usefulness of the traditional folk medicinal use of several plant species by the indigenous peoples in different continents. The effects of odorant inhalation on pentobarbital-induced sleeping time in rats were studied by Komori et al. (1997).

Spasmolytic and sedative effects on rats and fish

Various terpene alcohols possess spasmolytic and sedative properties as shown in animal experiments using mice and also on the rat duodenum (Imaseki and Kitabatake, 1962). Among these alcohols linalool had also been tested. The calming properties of at least some of these alcohols like linalool, could be shown by the inhibition of the fight aggressiveness of fishes, even if in this special case this alcohol exerted the weakest effect (Binet, 1972; Binet et al., 1972). This experimental design had already been used years ago by Laboratoires Meram (1966) who tested a series of terpene alcohols, linalool included. The results were similar to those mentioned above and additionally a potentiation of the barbiturate narcosis of the rats was found.

In a comprehensive study, using nine commercial EOs, the spasmolytic activity on the rat isolated phrenic nerve diaphragm was investigated. In comparison with the activity on field-stimulated guinea pig ileum preparations, the EO of lavender significantly reduced the twitch response to nerve stimulation without any hints of a contracture which was the case, for example, with the EO's of fennel or dill (Lis-Balchin et al, 1997a). Recently, these authors showed that the mechanism of this spasmolytic activity was post-synaptic and not atropine-like. It was most likely to be mediated through cAMP and not through cGMP. The tonus decrease of skeletal muscle preparations of the phrenic nerve diaphragm of rats was also shown (Lis-Balchin et al, 1999).

Linalool is not only one of the main components of the EO of lavender but also of some other oils, such as Hyssop oil from Hyssopus officinalis L. var. decumbens (Lamiaceae). Together with 1,8-cineole and limonene its spasmolytic potential was shown by the inhibition of acetyl choline- and BaCl2-induced contractions of isolated guinea pig ileum by means of a concentration dependent, but non-competitive manner. The other two components showed only a weak, but spasmogenic action (Mazzanti et al, 1998).

Effects on the autonomic system

The effect of different odorants, among them lavender, on the emotional process was estimated in terms of autonomic nervous system activity. Parametres for the latter were: skin potential, skin resistance, skin blood flow and skin temperature, instantaneous respiratory frequency and heart rate. It seems that the autonomic response reflects the odour valence only through some parametres related to the main preferential channels. Thus a global autonomic pattern has to be considered (Alaoui et al., 1997). In another study the effects of two fragrance oils on human CNS were reported using neuro-physiological measurements. Lavender oil increased auditory reaction time and slowed critical flicker fusion frequency, irrespective of the subject's preference. Specific characteristic changes produced by the fragrance on quantitative EEG were noted. A decrease of 'fast' activity during lavender inhalation was observed as well. Thus, the effects of fragrance oils must be considered from the psychological as well as the physiological point of view (Yagyu, 1994). The physiological response to seven odours (among them lavender) was assessed by EEG recordings and topographical brain maps. Interestingly, subjects rated the odour of lavender oil as unpleasant. The odours that caused the greatest increase in theta waves, included the EO of lavender. Jasmine and lavender tended to induce theta wave increases sooner than birch tar. Widespread increase in theta waves occurred in most subjects during stimulation with the appropriate odour (Klemm et al., 1992).

In an interesting assay, the anxiety reduction potency of lavender odour was studied and the possibility of whether frequency fluctuation coefficients of alpha waves could be an indicator for this reduction was examined. As a result, anxiety decreased when the subject felt in a good mood and the anterior frequency fluctuation asymmetry also correlated with the anxiety level. The slope coefficient of frequency fluctuation of alpha waves was found to be a good indicator in estimating the state of anxiety (Yoshida et al, 1998).

In another experiment to investigate the effects of the odour of EOs, such as lavender oil, on human brain function, event-related potentials were recorded on the EEG in nine healthy adults, while they were working on a visual oddball task. As a result, differences between the conditions with and without the odour and between the EO's were observed in the distribution of current density in the anterior part and the deep areas of the brain (Kana et al., 1998). Schulz et al. (1997) mentioned among other psycho-phytopharmaceuticals lavender flowers as suitable to overcome many disorders, inconveniences of health, ailments, indispositions, states of restlessness, uneasiness and nervousness, then difficulties in falling asleep and also anxiety. Delta- and theta-waves showed an increase especially in a pharmaco-EEG two hours post-application, similar, but lesser effects were noted on the delta waves in comparison with a placebo and to diazepam.

Finally, the findings of Rovesti (1971; 1973; 1974) published in a series of papers, should be mentioned here as they are in agreement with a lot of results ascertained later by other scientists. Lavender oil as well as its constituent linalool, relieves anxiety and considerably lowers nervous excitability. Antidepressive and antispasmodic effects upon application of an essence of lavender have been noticed.

Effect on glutamate-binding sites

Another paper reports on the anticonvulsive effects of inhaling lavender oil vapour. Pentetrazol-and nicotine-induced convulsions as well as electroshock convulsions, but not strychnine-induced ones, in mice were blocked significantly and dose-dependently by inhalation of this oil. These effects may be based on an augmentation of GABA-ergic action (Yamada et al., 1994). Elisabetsky et al. (1999) investigated the pharmacokinetic basis of the anticonvulsant properties of linalool by examining its effects on behavioural and neurochemical aspects of glutamate expression. Specifically, linalool inhibits by means of a competitive antagonism the L-[3H] glutamate binding at CNS-membranes as well as it delaying NMDA- and blocks quinolinic acid induced convulsions. Finally, there was a report on mineral baths which have antiseptic, anti-spasmodic and tranquilizing properties as well as analgesic, bactericidal, phytocidal, tonic or other hygienic actions. The EOs can be collected from fresh flowers and from cultivated plants, such as lavender (Biskys et al, 1996).

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