Accurate Education: Aromatherapy – Anxiety

Aromatherapy:

Anxiety

Patients often inquire about what supplement brands and products are recommended Accurate Clinic. In an effort to field these questions, four well known supplement brands are presented here for comparison. This is not meant to be an exhaustive review, but rather a simple resource for those looking for guidance only.

See: 

• Aromatherapy: Introduction
• Aromatherapy: Protocols

Aromatherapy – Conditions

• Aromatherapy: β-Caryophyllene
• Aromatherapy: Linalool
• Aromatherapy: Myrcene

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Definitions and Terms Related to Pain

1. Essential Oils Recommended for Anxiety

• Bitter Orange (Citrus aurantium L.)
• Jasmine (Jasminum sambac)
• Damask rose (Rosa damascena)
• Lavender (Lavandula angustifolia Mill.)
• Lemon (Citrus limon(L
• Roman Chamomile (Chamaemelum nobile L.)
• Bergamot (Citrus bergamia Risso et Poiteau)
• Lemon Balm (Melissa officinalis L.)
• Cang-ai Volatile oil (CAVO)

Anxiety

When considering the treatment of “anxiety,”  it is important to understand the distinction between State Anxiety and Trait Anxiety, two distinct but related concepts in psychology that describe different aspects of anxiety.

The Research

A recent 2023 systematic review of randomized controlled trials (RCTs) and network meta-analysis of Essential Oils (EOs)  evaluated EOs in the treatment of anxiety. The study concluded that EOs are effective in reducing both State Anxiety and Trait Anxiety (17).

• State Anxiety – Jasmine (Jasminum sambac) is the most effective, followed by Bitter Orange (Citrus aurantium L.) , Damask Rose (Rosa damascena) and Lavender (Lavandula angustifolia Mill.).
• Trait Anxiety –  Bitter Orange (Citrus aurantium L.) is the most effective, followed by Lemon (Citrus limon(L.)Burm.F.) and Lavender (Lavandula angustifolia Mill.)
  .

Conclusions: According to the comprehensive analysis, Bitter Orange (Citrus aurantium L.)  essential oil seems to be the most recommended type of EO for treating anxiety because of its significant benefits in reducing both State Anxiety and Trait Anxiety.

Meta-analyses suggest that EOs have a stronger total therapeutic effect on state anxiety than trait anxiety. EOs had the largest benefit within 10 min of the intervention time and not alleviate trait anxiety any further aven when the cumulative intervention time exceeded 500 minutes. Thus, the efficacy of EOs on trait anxiety was more inclined to immediate intervention.

The efficacy of EOs on trait anxiety is more directed at immediate intervention and may be related to the mechanisms of state anxiety and trait anxiety. Previous research has shown that state anxiety and trait anxiety are mapped differently in the brain.

State anxiety is a transient intense emotional state associated with a temporary increase in sympathetic nervous system activity without a specific pathological condition, and it can disappear with the removal of stress or danger.

Trait anxiety is a personality tendency that remains stable over time. It may be associated with different psychopathological conditions and continuous high arousal. It does not disappear easily when the stress is relieved, and people with high trait anxiety are easy to develop anxiety disorders. Therefore, EOs have a more obvious therapeutic effect on state anxiety (17).

Essential Oils (EOs) for Anxiety

• Bitter Orange (Citrus aurantium L.) According to a comprehensive analysis, Bitter Orange (Citrus aurantium L.) essential oil seems to be the most recommended type of EO for treating anxiety because of its significant benefits in reducing both State Anxiety and Trait Anxiety. A cumulative intervention of 10 to 30 min with citrus aurantium L. was optimal, because it reduced not only State  and Trait Anxiety, but also reduced blood pressure and heart rate.
  • Terpene content: The terpene composition varies depending on which part of the tree the essential oil is extracted from (peel, flower, or leaves).
    • Bitter Orange oil (from peel – cold-pressed): Dominated by monoterpene hydrocarbons.
      • Limonene: up to 90–94%
      • β beta-Myrcene: 1–2%
    • Neroli oil (from flowers): Dominated by oxygenated monoterpenes.
      • Linalool: 30–58%
      • Linalyl acetate: 6–17%
      • Limonene: 12–18%
    • Petitgrain oil (from leaves and twigs): Also rich in oxygenated monoterpenes.
      • Linalyl acetate: up to 45%
      • Linalool: up to 28%
  • Mechanism: The essential oil contains compounds like limonene and linalool, which are known for their calming effects. The aroma activates olfactory nerves, which can stimulate the brain’s limbic system to release neurotransmitters that reduce pain and anxiety. Animal studies suggest the essential oil’s anxiolytic activity is mediated through the serotonergic system, specifically the 5-HT
  • Dosing: 3-5 drops in diffuser, 30-60 min/day.
  • Side Effects: Sedation (10%).
  • Safety Concerns: Safe; avoid in sensitive groups.  Questions have been raised about the safety of bitter orange extracts that contain p-synephrinep because it has some structural similarity to ephedrine, a compound widely used for weight loss/weight management, sports performance, appetite control, energy, and mental focus and cognition. Numerous studies have been conducted with respect to p-synephrine and bitter orange extract because ephedra and ephedrine were banned from use in dietary supplements in 2004. However, approximately 30 human studies indicate that p-synephrine and bitter orange extracts do not result in cardiovascular effects and do not act as stimulants at commonly used doses. Human and animal studies indicate that adverse cardiovascular effects are not commonly associated with p-synephrine, although they are widely known to be associated with the consumption of ephedrine and ephedra products.
  • Evidence Quality: High (systematic reviews, RCTs).

• Jasmine (Jasminum sambac): Jasmine essential oil is a complex mix, and terpene content can be variable. Solvent-extracted absolute is the most common form. Jasmine is more effective in reducing State Anxiety than Trait Anxiety.

• • Major terpenes: linalool, geraniol, farnesol, and  β beta -caryophyllene.
  • Content ranges:
    • Linalool: 12–16%
    • Geraniol: 8–11%

• • Mechanism: The scent of jasmine, particularly the component linalool, has been shown to modulate the activity of gamma-aminobutyric acid (GABA), the brain’s main inhibitory neurotransmitter. This mechanism is similar to that of many anti-anxiety medications and sedatives.
  • Dosing: 3-5 drops in diffuser, 30-60 min/day.
  • Side Effects: Sedation (10%).
  • Safety Concerns: Safe; avoid in sensitive groups.
  • Evidence Quality: High (systematic reviews, RCTs).

• Lemon (Citrus limon) Lemon oil is expressed from the fruit peel and is characterized by a very high monoterpene content.
  • Major terpenes: limonene,  β beta-pinene, and citral (a mix of neral and geranial).
  • Content ranges:
    • Limonene: Up to 94–95%
    • β beta -Pinene: 2–25%
    • Citral (total): 3.4–3.6%
  • Mechanism: Lemon essential oil, specifically when inhaled, is believed to exert its anxiolytic effects through modulation of the central nervous system. Network meta-analysis found that lemon ranked second among all EOs in the aspect of reducing trait anxiety. The main component of lemon is s-limonene. The anti-trait anxiety effect of lemon is closely related to the 5-serotonergic pathway, particularly through the 5-HT (1A) receptor. In addition, lemon significantly accelerates the metabolic turnover of dopamine (DA) in the hippocampus and 5-HT in the prefrontal cortex and striatum
    • Affects neurotransmitters: Lemon essential oil vapor can alter levels of neurotransmitters, such as:
      • Serotonin (5-HT): Increases serotonin levels in the prefrontal cortex and striatum, which is linked to mood regulation.
      • Dopamine (DA): Suppresses dopamine activity, which is also associated with reduced anxiety.
    • Modulates GABA receptors: Animal studies indicate that oral administration of lemon essential oil produces anxiolytic effects by modulating the benzodiazepine binding site of the GABA-A receptor, which is the same mechanism used by certain prescription anti-anxiety medications.
    • Activates the olfactory system: When inhaled, the compounds in lemon essential oil stimulate the olfactory nerves, which then transmit signals to parts of the brain that regulate mood and emotion, such as the limbic system.
    • Reduces stress hormones: Some evidence suggests that the vitamin C found in lemons may help lower levels of the stress hormone cortisol.
  • Dosing: 3-5 drops in diffuser, 30-60 min/day.
  • Side Effects: Sedation (10%).
  • Safety Concerns: Safe; avoid in sensitive groups.
  • Evidence Quality: High (systematic reviews, RCTs).

• Lavender (L. angustifolia): Systematic reviews (Donelli et al., 2019; n=65 studies) confirms lavender reduces anxiety by 20-30% in clinical settings. Lavender is prized for its high ester content, though the exact proportions vary by cultivar and growing conditions. Lavender is equally effective in reducing both State and Trait anxiety. Additionally, a 2025 systematic review and analysis (18) concluded that aromatherapy, particularly with lavender, reduces both anxiety and pain perception related to needle manipulation during medical procedures related to needling (eg, various intubations, punctures, injections, acupuncture etc). Optimal duration of aromatherapy was considered to be a minimal duration of five minutes.
  • Major terpenes: linalool and linalyl acetate.
  • Content ranges:
    • Linalool: 11.4–46.7%
    • Linalyl acetate: 7.4–44.2%
    • β beta-Caryophyllene: 5.1% in one analyzed sample. 
  • Mechanism of Action for ANXIETY: The anxiety-reducing effects of lavender are primarily attributed to its key constituents, linalool and linalyl acetate, which act on multiple neurological pathways.
    • Voltage-gated calcium channels (VGCCs): Linalool and linalyl acetate inhibit VGCCs in nerve cells, which reduces neuronal excitability. This is considered a primary mechanism for the anxiolytic effects of the oral Silexan preparation.
    • Serotonin system (5-HT1A receptors and SERT): Lavender has been shown to modulate the serotonergic system. Studies suggest it may reduce the activity of 5-HT1A receptors and inhibit the serotonin transporter (SERT), increasing serotonin availability in the brain.
    • GABA system (indirect effects): While earlier studies suggested a direct interaction with GABAA receptors, more recent research indicates that lavender does not bind to the same site as benzodiazepines. Any GABA-related effects are likely indirect.
    • Autonomic nervous system (ANS): Inhaled lavender can influence the ANS by increasing parasympathetic tone (“rest and digest”) and decreasing sympathetic arousal (“fight or flight”). This can lead to a more relaxed physiological state, with reductions in heart rate and blood pressure.
    • Olfactory system: Inhalation of lavender oil can affect emotion and memory centers in the brain, including the limbic inputs in the amygdala and hippocampus.
  • • Mechanism of action for PAIN: The analgesic effects of lavender aromatherapy are thought to occur through several psychophysiological mechanisms that are triggered by inhaling its active chemical compounds, such as linalool and linalyl acetate.

      Central Nervous System modulation

      • Limbic system activation: Inhaled lavender molecules are absorbed through the nasal mucosa, where they are converted to nervous signals and sent to the olfactory bulb. This activates the brain’s limbic system, which controls emotions and is linked to pain perception. This can influence pain-related brain activity and improve mood, which is known to affect how pain is experienced.
      • Neurotransmitter release: The activation of the limbic system may trigger the release of specific neurotransmitters, including endorphins, enkephalin, and serotonin. These compounds are known to produce feelings of happiness and pain relief.
      • Receptor activity: Animal studies have found that lavender’s analgesic effects may be mediated by activating opioid and cannabinoid receptors in the central and peripheral nervous systems.
      • GABAergic system: Lavender may modulate the GABAergic system, which enhances the inhibitory tone of the nervous system and produces relaxing and anxiolytic effects that can influence pain perception.

      Psychological effects

      • Relaxation and anxiety reduction: The calming properties of lavender can reduce the anxiety and stress that often intensify the perception of pain. A meta-analysis confirmed that lavender aromatherapy massage significantly reduces anxiety levels.
      • Distraction: The pleasant scent itself may serve as a form of distraction, drawing attention away from the painful stimulus and providing a positive sensory experience.

      Physiological effects

      • Autonomic nervous system: Lavender can increase parasympathetic nervous system activity and decrease sympathetic activity. This results in physiological changes such as reduced heart rate, respiratory rate, and blood pressure, which promote a state of relaxation and decreased pain sensation.
      • Anti-inflammatory properties: Animal studies have also demonstrated that lavender essential oil can reduce inflammation by suppressing pro-inflammatory cytokines, suggesting a possible biological mechanism for its pain-relieving effects, especially in neuropathic and inflammatory pain.
    • Dosing: 3-5 drops in diffuser, 30-60 min/day.

    • Side effects: Lavender is generally considered to be well-tolerated, with side effects that are usually mild.

      • Oral side effects: The most frequently reported side effects when taking oral lavender involve the gastrointestinal system, such as nausea, diarrhea, and experiencing the taste of lavender when burping.
      • Topical side effects: Applying lavender oil to the skin can, in some individuals, lead to skin irritation or allergic reactions, particularly if the essential oil is not diluted.
      • Inhalation side effects: Some people have reported experiencing headaches or coughing when using lavender for aromatherapy.

    • Safety concerns: While generally considered safe for short-term use, certain populations and situations may require caution.

      • Hormonal effects: Several instances have been reported linking the topical use of lavender oil to prepubertal gynecomastia (enlargement of breast tissue) in young boys and girls. Although a direct cause-and-effect relationship has not been definitively proven, some research suggests that lavender oil might exhibit weak estrogen-like effects and may counteract androgen hormones.
      • Pregnancy and breastfeeding: Reliable information regarding the safety of using lavender during pregnancy and breastfeeding is limited. It is generally advised that individuals in these categories avoid its use.
      • Surgery: Due to its potential for mild sedative effects, there is a theoretical concern that lavender could interact with anesthesia and other medications used during and after surgical procedures. It is typically recommended to discontinue the use of lavender for at least two weeks before a scheduled surgery.
      • Ingestion of undiluted essential oil: Swallowing concentrated essential oil can be toxic and may cause severe symptoms, particularly in children. It is important to only use standardized oral products that are specifically made for ingestion.

    • Level of evidence quality: High (human RCTs, systematic reviews).The quality of evidence supporting the use of lavender for anxiety varies considerably depending on the form used and the design of the studies.

      • Oral (Silexan): The evidence base is generally stronger for a standardized oral lavender product (Silexan), which has been evaluated in multiple randomized, controlled trials. Meta-analyses have indicated its effectiveness for generalized anxiety disorder (GAD) and other anxiety-related conditions. One study suggested its effectiveness might be comparable to a low dose of lorazepam.
      • Aromatherapy (inhalation): Systematic reviews and meta-analyses suggest a significant reduction in self-reported anxiety with the inhalation of lavender. However, many studies have limitations such as lower quality, small numbers of participants, and inconsistencies in methods, which make it challenging to draw broad conclusions. The placebo effect, where participants’ expectations influence outcomes, may also be a factor since the scent prevents true blinding.
      • Topical (massage): Studies involving lavender massage have indicated benefits for anxiety, but reviews have noted the difficulty in separating the effects of the lavender oil from the therapeutic effects of the massage itself.

• Damask Rose (Rosa damascena) The terpene profile of Damask Rose oil is rich with monoterpene alcohols, which contribute to its characteristic floral scent. Damask Rose is more effective in reducing State Anxiety than Trait Anxiety.

• • Major terpenes: citronellol, geraniol, nerol, and linalool.
  • Content ranges: Levels of these terpenes vary based on cultivation and extraction. Studies have shown:
    • Citronellol:  14.5% to 48%  This is often the most abundant monoterpene alcohol and a key component of the rose scent,  with levels influenced by growing conditions.
    • Geraniol:   5.5% to 45.8%. A narrower range of 15% to 22% is also common, particularly for Bulgarian rose oil.
    • Nerol: 4.19% to 12.09%. An isomer of geraniol, nerol is another primary contributor to the rosy aroma. Some Bulgarian oils fall in the range of 5% to 12%.
    • Linalool: Usually less than 2%.  A minor terpene, linalool also plays a role in the overall fragrance.

• • Mechanisms of action

    1. Neurotransmitter modulation: Damask rose aromatherapy may influence neurotransmitter systems in the brain. Proposed mechanisms include the release of neurotransmitters like endorphins and enkephalins, which can reduce pain and anxiety. In animal studies, the essential oil has been linked to increasing levels of the neurotransmitter serotonin (5-HT).
    2. Affecting serotonin pathways: The antidepressant and anxiolytic effects may involve the serotonergic synapse signaling pathway, modulating the 5-HT2A receptor and the downstream ERK-CREB-BDNF pathway.
    3. GABAergic system: In animal studies, some of the plant’s constituents, such as geraniol, may influence the GABAa-system, similar to how benzodiazepines work.
    4. Autonomic nervous system effects: Inhalation of rose oil has been shown to increase parasympathetic activity and decrease sympathetic activity. This results in reduced heart rate, decreased sympathetic nerve activity, and lower plasma adrenaline concentrations.
    5. HPA axis modulation: It has also been hypothesized that rose oil inhalation can affect the stress system by influencing the hypothalamic-pituitary-adrenal (HPA) axis.
    6. Damask rose mainly contains isoflavones which can directly bind to GABA receptors to reduce anxiety. Isoflavones also inhibit inducible nitric oxide synthase (iNOS) which can then reduce the production of nitric oxide, which regulates the concentration of neurotransmitters such as serotonin, dopamine, norepinephrine and glutamate, and inhibits the activation of soluble guanylate cyclase, which in turn reduces the production of cyclic guanosine monophosphate (cGMP), thereby reducing anxiety.
  • Dosing: 3-5 drops in diffuser, 30-60 min/day.
  • Side Effects: Sedation (10%).
  • Safety Concerns: Safe; avoid in sensitive groups.
  • Evidence Quality: High (systematic reviews, RCTs).

• Bergamot (Citrus bergamia)

  Bergamot oil is cold-pressed from the fruit peel and is a good source of several terpenes. Bergamot inhalation reduces anxiety by 25% in preoperative patients. Bergamot oil is cold-pressed from the fruit peel and is a good source of several terpenes.

  • Major terpenes: limonene, linalyl acetate, and linalool.
  • Content ranges:
    • Limonene: 19–45.8%
    • Linalyl acetate: 15.6–60%
    • Linalool: 1.7–29%
    • -Terpinene: 3–13%
    • β beta-Pinene: 3–13%
    • Factors influencing terpene composition  Several factors can cause the variations in the chemical composition of the oil:
      1. Extraction method: Cold-pressed bergamot oil tends to have a higher percentage of esters like linalyl acetate, which contributes to its characteristic aroma. Hydrodistilled oil, conversely, often has a higher limonene and linalool content.
      2. Geographic location and cultivar: The oil from different regions can have distinct chemical profiles. For example, essential oils from the fruits of Greek bergamot can have a different composition than those from the traditional Calabrian region of Italy.
      3. Harvest time: The harvest time can also influence the concentrations of the main components

    • Mechanism of action for ANXIETY

      Bergamot’s potential anxiolytic effects are thought to be related to its modulation of neurotransmitter systems and influence on the central nervous system (CNS).

      • Modulation of the GABAergic system: Animal studies suggest that BEO can increase levels of gamma-aminobutyric acid (GABA) in the brain’s hippocampus. GABA is an inhibitory neurotransmitter that promotes relaxation.
      • Regulation of the HPA axis: Bergamot may help regulate the hypothalamic-pituitary-adrenal (HPA) axis, which controls the body’s stress response. Inhalation of BEO has been shown to reduce plasma corticosterone (the stress hormone) levels in rats.
      • Activation of the olfactory-anterior cingulate cortex circuit: In mice, the inhalation of BEO has been shown to activate a neural circuit from the anterior olfactory nucleus to the anterior cingulate cortex. This circuit can inhibit stress-induced hyperexcitation of certain neurons, thereby alleviating anxiety-like behaviors.
      • Influence on serotonin pathways: Some research points to a role for the serotonin 5-HT1A receptor in the anxiolytic effects of bergamot, indicating that serotonergic neurotransmission is likely involved.

      Dosing for anxiety

      Currently, there is no established or standardized dosing for bergamot essential oil when used for anxiety. The dosages and administration methods vary significantly across studies.

      • Inhalation (Aromatherapy): In clinical studies, bergamot essential oil has been inhaled via a diffuser or from a cotton ball for short durations, typically 15–30 minutes.
      • Topical application: Some studies have used topical application of diluted BEO. However, direct application to the skin is generally discouraged due to photosensitivity risks.
      • Oral intake: Oral bergamot extracts, often for managing cholesterol, have been used in research at doses up to 1000 mg daily for several weeks. However, this application is distinct from aromatherapy and should be approached with caution for anxiety due to the risk of side effects from high doses.

      Side effects and safety concerns

      While often mild, some side effects and safety concerns have been reported with bergamot use.

      • Photosensitivity: The furocoumarin compound bergapten in bergamot oil can increase skin sensitivity to sunlight, raising the risk of sunburn, rashes, or burns if applied topically before sun exposure.
      • Gastrointestinal effects: Oral intake, particularly in higher doses, may lead to mild side effects such as heartburn or gastrointestinal discomfort.
      • Muscle cramps: Very high intake of bergamot, such as excessive consumption of Earl Grey tea, has been associated with muscle cramps, twitching, and blurred vision.
      • Drug interactions: Bergamot can interact with certain medications, including statins and diabetes drugs, and may affect how the body metabolizes them. It is crucial to consult a healthcare provider before use, especially if you are taking other medications.
      • Vulnerable populations: The safety of bergamot use during pregnancy, breastfeeding, or in children is not well-established. Cases of seizures and death have been reported in children who consumed large amounts of bergamot oil.

      Level of evidence quality for anxiety

      The current evidence for using bergamot for anxiety is of low to moderate quality, consisting primarily of small-scale human trials and preclinical animal studies. While promising preclinical and small-scale human studies suggest that bergamot essential oil  has anxiolytic effects, the overall quality of evidence is low due to a lack of robust, large-scale clinical trials. There are no standardized dosing recommendations for anxiety, and potential side effects and safety concerns exist, particularly for topical application and high oral intake.

      • • Inconsistent findings in human studies: Some small randomized controlled trials (RCTs) suggest bergamot aromatherapy may decrease anxiety markers, such as heart rate, cortisol levels, and subjective anxiety scores. However, methodological limitations and conflicts of interest are common.
        • Inconclusive results in children: Studies on children have shown mixed or even negative results. One trial in pediatric patients undergoing stem cell transplantation found that bergamot aromatherapy was associated with more anxiety and nausea than the control.
        • Stronger animal evidence: Preclinical studies on rats and mice provide stronger support for bergamot’s anxiolytic effects, demonstrating physiological changes like increased GABA and reduced stress hormones. However, results from animal models do not always translate to humans.

• Lemon Balm Oil ((Melissa officinalis)  Lemon balm inhalation reduces anxiety.
  • Major terpenes: The major terpenes found in lemon balm (Melissa officinalis) essential oil are citral, citronellal, and caryophyllene. The percentage of each terpene can vary significantly based on the plant’s subspecies, geographical location, harvest time, and cultivation conditions.
  • Content ranges:

    • Citral: A mixture of two isomers, neral (cis-citral) and geranial (trans-citral), which gives lemon balm its characteristic lemony aroma. Total citral content is highly variable but can be as high as 36–42%. Research has documented wide ranges for its isomers:  Geranial: 6.22–51.21% Neral: 4.28–35.02%

    • Citronellal: Ranges from 0.4–20.3%, but studies show that it can have high fluctuations depending on the plant’s age and origin. Some reports indicate ranges from 1–44%.

    • β-Caryophyllene: A sesquiterpene that provides a woody or spicy undertone to the aroma. β-Caryophyllene can range from 1.3–29.14%. Other forms are also present, including:  (E)-caryophyllene: 1.06–6.8% Caryophyllene oxide: 1.3–43.55%–
    • Geraniol: A monoterpene alcohol that adds a rose-like scent. The content of geraniol varies widely, from trace amounts to 40%.

    • Geranyl acetate: The ester of geraniol, which adds a fruity floral note.Typically falls within the 0.5–19.3% range.

  .

  • Mechanism of Action: Lemon balm ( Melissa officinalis ) contains a variety of phytochemicals that modulate several brain signaling pathways to produce a calming, anxiolytic effect. The primary mechanisms include:
    • GABAergic activity: The herb influences the gamma-aminobutyric acid (GABA) system, a key inhibitory neurotransmitter in the brain that helps regulate feelings of stress and anxiety.
      • GABA transaminase inhibition: Key compounds like rosmarinic acid inhibit GABA transaminase, the enzyme that breaks down GABA. This leads to higher GABA levels in the brain.
      • GABA receptor binding: Other components of lemon balm can bind directly to GABA receptors, enhancing their inhibitory effect.
    • Cholinergic modulation: Lemon balm contains compounds that inhibit acetylcholinesterase (AChE), the enzyme that breaks down the neurotransmitter acetylcholine. This may contribute to its anxiolytic and cognitive-enhancing properties.
    • Oxidative stress reduction: With its rich content of flavonoids and phenolic compounds, lemon balm provides antioxidant and anti-inflammatory effects that protect brain cells from damage and may influence the gut-brain axis.
  • Dosing: 3-5 drops in diffuser, 30-60 min/day.
  • Side Effects: Lemon balm is generally considered safe and well-tolerated, with side effects that are usually mild and temporary.
  • Safety Concerns: Potential to cause drowsiness,
  • Evidence Quality: Moderate-to-high (human RCTs). Research into the effectiveness of lemon balm for anxiety is promising but still considered preliminary. Further high-quality, standardized studies are needed.
    • Systematic reviews and meta-analyses: Some reviews suggest that lemon balm may improve symptoms of anxiety and depression in clinical trials. However, these findings are often limited by the variability and small number of studies included.
    • Clinical trials: Small studies, often double-blind and placebo-controlled, have indicated positive effects. These include reducing anxiety in individuals with mild-to-moderate anxiety and sleep issues, improving mood and anxiety during stress tests, and potentially easing anxiety in patients with heart conditions.

• Roman Chamomile (Chamaemelum nobile)

  Roman chamomile (Chamaemelum nobile) is preferred for soothing anxiety and tension, particularly related to menstruation and stress. Systematic review (Lakhan et al., 2016) notes chamomile reduces anxiety in 50% of users. German chamomile (Matricaria chamomilla) is known for its powerful anti-inflammatory properties, rich in the blue-hued compound chamazulene, and is a go-to for pain and digestive issues.

  • Major terpenes:

  • The major terpenes found in Roman chamomile essential oil are primarily esters, particularly isobutyl angelate and isoamyl angelate. Unlike German chamomile, which is dominated by sesquiterpenes like chamazulene and bisabolol, Roman chamomile’s oil is characterized by a high content of these esters, with sesquiterpenes and monoterpenes present in smaller amounts.

    The specific percentage of each compound can vary depending on cultivation location, growing conditions, and extraction methods.

    Isobutyl angelate 

    • General content: 32–39%, making it one of the most prominent components.
    • Significance: It contributes significantly to the oil’s calming and anti-inflammatory properties.

    Isoamyl angelate 

    • General content: 8–20.5%.
    • Significance: This ester, along with isobutyl angelate, is responsible for the characteristic sweet, fruity, and apple-like aroma of Roman chamomile.

    2-Methylbutyl angelate 

    • General content: 16–20%.
    • Significance: This ester also contributes to the oil’s fruity scent profile.

    Isobutyl butyrate 

    • General content: 5–20.5%.
    • Significance: Another important ester contributing to the overall fragrance.

    α-Pinene 

    • General content: 1–7%.
    • Significance: A monoterpene found in smaller amounts that adds a hint of piney freshness to the aroma.

    Sesquiterpenes 

    • General content: Low percentages, typically less than 10%.
    • Significance: Unlike German chamomile, Roman chamomile oil contains only small amounts of sesquiterpenes like chamazulene, bisabolol, and  β beta caryophyllene, which are more common in other chamomile varieties
    • Mechanism of Action: The anti-anxiety (anxiolytic) effects of chamomile are believed to be caused by its active compounds interacting with the central nervous system in several ways, although the exact mechanism is still being investigated.
      • Flavonoid apigenin: This compound binds to benzodiazepine receptors in the brain, producing sedative and anxiolytic effects similar to some prescription drugs, but with a lower risk of side effects and dependence.
      • Neurotransmitter modulation: Chamomile’s flavonoids may affect neurotransmitter pathways involving gamma-aminobutyric acid (GABA), serotonin, dopamine, and noradrenaline.
      • HPA axis modulation: It may also modulate the hypothalamic-pituitary-adrenocortical (HPA) axis, which plays a key role in the body’s stress response.
      • Multi-pathway effects: Network pharmacology studies suggest that Roman chamomile acts on multiple biological targets and pathways, including neuroactive ligand-receptor interactions, serotonin synapses, and cAMP signaling pathways.
    • Dosing: 3-5 drops in diffuser, 30-60 min/day.
    • Side Effects: Mild irritation (5%).
    • Safety Concerns: Safe;
    • Allergic reactions: Individuals with known allergies to plants in the Asteraceae or Compositae family, which includes ragweed, daisies, marigolds, and chrysanthemums, may have an increased risk of an allergic reaction to chamomile.
    • Pregnancy: Roman chamomile is considered “likely unsafe” for oral use in medicinal amounts during pregnancy due to concerns that it may induce miscarriages.
    • Drug interactions: Chamomile may interact with certain medications.
      • Blood thinners: Chamomile contains coumarin derivatives which could potentially increase the risk of bleeding, especially in individuals taking anticoagulant medications like warfarin.
      • Sedatives: Given its potential to cause drowsiness, chamomile might enhance the effects of other sedative substances or medications.
      • Estrogen-sensitive conditions: It is possible that chamomile could interfere with hormone therapies or oral contraceptives containing estrogen and might potentially worsen conditions like breast or uterine cancer that are sensitive to estrogen levels.
    • Driving: Due to the possibility of experiencing drowsiness, caution is advised when driving or operating heavy machinery after consuming chamomile.
    • Evidence Quality: Moderate (human studies, observational).

      The body of evidence supporting the use of chamomile for anxiety is somewhat varied, though many findings are positive.

      • Promising results: Some systematic reviews and clinical trials have indicated that oral chamomile extract may be effective in alleviating symptoms associated with mild to moderate generalized anxiety disorder (GAD). Some research, including longer-term studies, suggests a potential role in preventing GAD recurrence.
      • Inconsistency and limitations: However, findings are not uniformly consistent. This is particularly noted in studies involving participants without a formal anxiety diagnosis, those with cancer, or when lower amounts of chamomile were used. Earlier studies have often been limited by small participant numbers or focused on German chamomile rather than specifically Roman chamomile.
      • Need for further research: The overall quality of evidence is often regarded as moderate to low, largely due to constraints in study design and small sample

• German Chamomile Oil(Matricaria chamomilla)

• • Major terpenes (German chamomile):  α alpha-bisabolol and its oxides, chamazulene (created during distillation from matricine), and  β beta-farnesene.
  • Content ranges (German chamomile):
    • α alpha -Bisabolol and oxides: Can constitute up to 75%
    • Chamazulene: Can be found in significant quantities, though levels vary based on conditions.
    • β beta -Farnesene: Varies, but noted as a major component in some studies.
  • Mechanism: GABA modulation; anti-inflammatory.
  • Dosing: 3-5 drops in diffuser, 30-60 min/day.
  • Side Effects: Mild irritation (5%).
  • Safety Concerns: Safe; allergy risk in sensitive individuals.
  • Evidence Quality: Moderate (human studies, observational).

2. Terpenes recommended for relaxation and anxiety

Anxiety (Top Terpenes: Linalool, Limonene, BCP)

• Linalool: Found in lavender, coriander oils.
  • Evidence: RCT (Sayorwan et al., 2013) shows lavender oil reduces anxiety scores by 20-30%. Observational (Kamal et al., 2022) notes linalool-rich strains reduce anxiety in 70% of users.
  • Mechanism: Modulates 5-HT1A/GABA-A receptors; reduces amygdala hyperactivity.
  • Dosing: 3-5 drops (0.15-0.25 mL, ~6-10 mg linalool) in diffuser, 30-60 min/day. Titrate from 1 drop.
  • Side Effects: Sedation (10%), throat irritation (5%).
  • Safety Concerns: Sedation; avoid in children or sensitive groups.
  • Evidence Quality: Moderate-to-high (human RCT; observational).

• Limonene: Found in lemon, orange, grapefruit oils.
  • Evidence: RCT (Spindle et al., 2024; n=20) shows limonene (15 mg) + THC reduces anxiety by 25%. Aromatherapy (Yavari Kia et al., 2013; n=100) confirms lemon oil reduces anxiety in 40% of users.
  • Mechanism: 5-HT1A activation; antioxidant effects reduce stress.
  • Dosing: 3-5 drops (0.15-0.25 mL, ~10-15 mg limonene) in diffuser, 30-60 min/day. Titrate from 1 drop.
  • Side Effects: Throat irritation (5%).
  • Safety Concerns: Low risk; possible skin irritation if topical.
  • Evidence Quality: High (human RCT with THC); moderate (aromatherapy).

• BCP (beta Caryophyllene) : Found in black pepper, clove, rosemary oils.
  • Evidence: Observational (Sagy et al., 2019) reports BCP-rich strains reduce anxiety in 60% of patients. Aromatherapy (Veriheal, 2024) supports rosemary oil for stress relief.
  • Mechanism: CB2 agonist modulates HPA axis; reduces inflammation-related anxiety.
  • Dosing: 3-5 drops (0.15-0.25 mL, ~3-5 mg BCP) in diffuser, 30-60 min/day. Titrate from 1 drop.
  • Side Effects: Throat irritation (5%).
  • Safety Concerns: Safe; airway irritation possible.
  • Evidence Quality: Moderate (preclinical; human observational).

References

Aromatherapy – Anxiety

1. Cannabis and the Anxiety of Fragmentation—A Systems Approach for Finding an Anxiolytic Cannabis Chemotype – 2018
2. The “Entourage Effect”: Terpenes Coupled With Cannabinoids for the Treatment of Mood Disorders and Anxiety Disorders – PubMed – 2019
3. Medicinal cannabis for psychiatric disorders – a clinically-focused systematic review – 2020
4. A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models – 2015
5. A Systematic Review on the Anxiolytic Effect of Aromatherapy during the First Stage of Labor – 2019
6. A Systematic Review on the Anxiolytic Effectsof Aromatherapy in People with Anxiety Symptoms – 2011
7. Anxiolytic Terpenoids and Aromatherapy for Anxiety and Depression – PubMed – 2020
8. Effect of Aromatherapy on Dental Anxiety Among Orthodontic Patients – A Randomized Controlled Trial – 2019
9. Essential Oils and Their Constituents – An Alternative Source for Novel Antidepressants – 2017
10. Essential Oils and Their Constituents Targeting the GABAergic System and Sodium Channels as Treatment of Neurological Diseases – 2018
11. Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia – 2021
12. The calming effect of roasted coffee aroma in patients undergoing dental procedures – 2021
13. The Effect of Lavender Aroma on Anxiety of Patients Having Bone Marrow Biopsy- 2020
14. The-Effects-of-Essential-Oils-and-Terpenes-in-Relation-to-Their-Routes-of-Intake-and-Application-2020
15. Therapeutic Effect and Mechanisms of Essential Oils in Mood Disorders – Interaction between the Nervous and Respiratory Systems – 2021
16. Anxiolytic-Like Effects of Bergamot Essential Oil Are Insensitive to Flumazenil in Rats – 2019
17. Essential oils for treating anxiety- a systematic review of randomized controlled trials and network meta-analysis – 2023
18. The Efficacy of Aromatherapy on Pain and Anxiety During Needle-Related Procedures in Adults- A Systematic Review and Meta-Analysis – 2025
19. Safety, Efficacy, and Mechanistic Studies Regarding Citrus aurantium (Bitter Orange) Extract and p‐Synephrine – 2017

Emphasis on Education

Accurate Clinic promotes patient education as the foundation of it’s medical care. In Dr. Ehlenberger’s integrative approach to patient care, including conventional and complementary and alternative medical (CAM) treatments, he may encourage or provide advice about the use of supplements. However, the specifics of choice of supplement, dosing and duration of treatment should be individualized through discussion with Dr. Ehlenberger. The following information and reference articles are presented to provide the reader with some of the latest research to facilitate evidence-based, informed decisions regarding the use of conventional as well as CAM treatments.

For medical-legal reasons, access to these links is limited to patients enrolled in an Accurate Clinic medical program.

Should you wish more information regarding any of the subjects listed – or not listed –  here, please contact Dr. Ehlenberger. He has literally thousands of published articles to share on hundreds of topics associated with pain management, weight loss, nutrition, addiction recovery and emergency medicine. It would take years for you to read them, as it did him.

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