Lavander Review
Lavander Review
Review article
A R T I C L E I N F O A B S T R A C T
Keywords:                                                     Introduction: Aromatherapy and decoctions of lavender have been traditionally used for their anxiolytic
Anxiety                                                       harboring-soothing effects without proper evidence. This study aims to systematically identify and appraise
Herbal medicine                                               systematic reviews on the anxiolytic effects of Lavandula angustifolia (lavender).
Lavender
                                                              Methods: The study protocol was published in PROSPERO (CRD42021279573). ISI Web of Science, Scopus,
Medicinal plant
Pharmacognosy
                                                              PubMed, Embase, Cochrane Library, CINAHL, Google Scholar, and PROSPERO were searched up to August 2022
Systematic review                                             without any limitation for systematic reviews studying the anxiolytic effects of lavender in humans. The report
                                                              from each study as whether or not lavender was anxiolytic was considered the primary outcome. The AMSTAR II
                                                              was utilized for the quality assessment.
                                                              Results: Thirty systematic reviews met the inclusion criteria, fifteen of which conducted meta-analyses. All studies
                                                              were published after 2010 and reported promising effects through different methods of lavender admin
                                                              istration—namely: inhalation, massage, and oral routes—on anxiety relief. Oral doses of 80 mg and 160 mg were
                                                              both effective, the higher dose being more efficient. The studies were conducted on various subjects, including
                                                              preoperative patients, cardiovascular patients, hemodialysis patients, cancer patients, dental patients, and
                                                              women in pre-labor. When assessed by AMSTAR II, four studies were of high quality, one had medium quality,
                                                              and the rest were of low or critically low quality. No major adverse event was reported.
                                                              Conclusions: Lavender has shown promising potential for anxiety in various settings. Lavender was effective when
                                                              inhaled, used as a massage oil, or taken orally. The oral route was the preferred long-term option and inhalation
                                                              was recommended for the short term.
1. Introduction                                                                                     physiological perturbations (Park and Kim, 2020; Schuyler, 2016). This
                                                                                                    disorder, which is thought to be the most common psychiatric disorder
    According to the Diagnostic and Statistical Manual of Mental Dis                               and has been on the rise in recent decades, often remains undertreated,
orders, 5th Edition: DSM-5, anxiety disorders share immoderate feelings                             leading to feelings of restlessness, early fatigue, impaired concentration,
of fear and anxiety features – as psychological disturbances - and related                          and an increased risk of cardiovascular disease (Lépine, 2002; Tully
    Abbreviations: DSM-5, Diagnostic and Statistical Manual of Mental Disorders, 5th Edition; L. angustifolia, Lavandula angustifolia; SR, systematic review; MA, meta-
analysis; PROSPERO, International prospective register of systematic reviews; AMSTAR, a measurement tool to assess the methodological quality of systematic
reviews; RCT, randomized controlled trial; GAD, generalized anxiety disorder; ICU, intensive care unit; SMD, standardized mean difference.
  * Correspondence to: Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Street, Tehran 13337, Iran.
    E-mail addresses: a-shamabadi@alumnus.tums.ac.ir (A. Shamabadi), s.akhond@neda.net (S. Akhondzadeh).
  1
    https://orcid.org/0000–0002-5211–2827
  2
    https://orcid.org/0000–0002-1041–6080
  3
    https://orcid.org/0000–0001-6182–4853
  4
    https://orcid.org/0000–0003-3226–9963
  5
    https://orcid.org/0000–0003-3509–7415
  6
    https://orcid.org/0000–0002-2277–5101
https://doi.org/10.1016/j.hermed.2023.100672
Received 20 March 2022; Received in revised form 17 August 2022; Accepted 24 May 2023
Available online 26 May 2023
2210-8033/© 2023 Elsevier GmbH. All rights reserved.
A. Shamabadi et al.                                                                                                       Journal of Herbal Medicine 40 (2023) 100672
et al., 2016). Anxiety can impose significant morbidity and mortality               relevant SRs that were missed. SA had three related SRs in his personal
through functional impairment, decreased quality of life, alcohol and               archive. In addition, the references of the included studies and Google
substance abuse, depression, cardiovascular disability, and suicide                 were manually reviewed and searched, respectively, to find possible
(Bachmann, 2018; Schuyler, 2016; Tully et al., 2016).                               misses. Title searching in Google Scholar was also done manually,
    Owing to the potential effectiveness, tolerability and possible non-            focusing on the first 200 citations.
interaction, and low cost, many patients with various diseases seek
traditional and herbal medicine interventions to control and treat dis
orders. This tendency is higher in patients with psychiatric disorders              2.2. Selection
than in patients without a medical history of psychiatry (Mamtani and
Cimino, 2002).                                                                           First, duplicate citations were removed using EndNote 20. Then,
    Lavandula is an evergreen perennial shrub of the family Lamiaceae               references were screened, and studies were selected by AS and AA
that originates from the Mediterranean region (Jianu et al., 2013; Pru             independently and in parallel. In any case of discrepancy, the senior
sinowska and Śmigielski, 2014). Lavender has received a great deal of              author was consulted.
attention from researchers in herbal medicine, and many in-vitro, ani                   Having the following criteria was essential for the eligibility of the
mal, and clinical studies have been conducted on its intervention. Jianu            studies: (i) be an SR or MA; (ii) published as full papers in peer-reviewed
et al. (2013) examined the antimicrobial properties of lavender essential           journals; (iii) used the words Lavandula or lavender in the title, abstract,
oil. They found a significant bactericidal effect against bacteria such as          or keywords; and (iv) investigated the anti-anxiety effects of lavender in
Shigella flexneri, Staphylococcus aureus, and Escherichia coli (Jianu et al.,       humans.
2013). In another study, Hajhashemi et al. studied the                                   The existence of the following criteria led to the exclusion of studies:
anti-inflammatory and analgesic properties of the leaf extracts and                 (i) on in-vitro or animal samples; (ii) of any type other than SR and MA;
essential oil of L. angustifolia. They found that some essential oil com           (iii) no transparent reporting of the study method; (iv) no distinction
ponents can have anti-inflammatory and analgesic effects (Hajhashemi                between clinical and pre-clinical studies; and (v) inclusion of fewer than
et al., 2003). A clinical trial conducted on 80 patients with depression            three studies with the characteristics required for this study. Indeed, the
disorder treated with citalopram, showed that infusion of 5 g of dried              non-specificity of the studies for lavender did not lead to exclusion.
shoots of L. angustifolia had positive therapeutic effects on these patients             There was no language limit for inclusion.
and reduced mean depression score (Nikfarjam et al., 2013). A study on                   If needed, the corresponding authors of the included studies were
patients who wanted to remove their wisdom teeth under local anes                  contacted for further information.
thesia also showed that inhaling lavender essential oil could reduce
peri-operative anxiety (Karan, 2019).
    As mentioned earlier, many studies have been conducted to evaluate              2.3. Data extraction
the effectiveness of lavender on various disorders, one of the most
important and notable of which is anxiety. These studies have compiled                  AS, AH, and AA independently and in parallel extracted the included
data for several systematic reviews (SRs) with or without meta-analysis             study data using Review Manager 5.4. Only the included studies were
(MA), assessing the generalizability of the results. These studies had              used to extract data—not their references. The senior author’s opinion
been conducted with different methods and qualities affecting their                 was sought in the absence of a consensus among the extractors.
validity. No study has so far collected and reviewed the evidence                       The following data were extracted and reported from each study:
generated by these SRs and evaluated their quality. Therefore, this study           name of the first author, year of publication, country of study, number of
aims to systematically review SRs with or without MAs investigating the             studies included, number of patients studied, follow-up of patients, risk
anxiolytic effects of lavender in humans and to evaluate the methodo               of bias assessment tool, limitations reported from studies included,
logical quality of the studies conducted.                                           lavender dose as intervention, analysis of results in case of MA, treat
                                                                                    ment outcome assessment, side effects, the conclusion of effectiveness,
2. Materials and methods                                                            and scores of the second version of a measurement tool to assess the
                                                                                    methodological quality of systematic reviews (AMSTAR II). The
2.1. Search                                                                         conclusion of lavender effectiveness in anxiety reported in each study
                                                                                    was the primary outcome of this study. In the end, the sources of funding
    The protocol for this SR was registered and published in the inter             for the studies included were reviewed by the senior author.
national prospective register of systematic reviews (PROSPERO) under
CRD42021279573. ISI Web of Science Core Collection, Scopus, PubMed,
Embase, Cochrane Library, and CINAHL databases were searched by the                 2.4. Quality assessment
first author on September 18, 2021, to obtain the study data. No limi
tations were considered regarding the time of publication, language,                    Using the AMSTAR II tool, which is developed for and is highly
document type, and publication status. According to the aim of this                 reliable in evaluating the methodological quality of SRs and MAs (Shea
study, which was to find and evaluate the SRs and MAs (#1) investi                 et al., 2017); AS, AH, and AA independently and in parallel evaluated
gating the anxiolytic effects (#2) of lavender (#3), the following phrases          the quality of the included studies.
established the search strategy:                                                        The AMSTAR version used for quality assessment is attached (Ap
    #1 - "systematic review" OR "meta-analysis".                                    pendix A). This version consists of 16 items examining various aspects of
    #2 - lavender OR Lavandula.                                                     the study quality. There are five two-point and eleven one-point items,
    #3 - anxi* (the wild-card term).                                                meaning that a study can have an overall score between zero and 21. Of
    The intersection of these three phrases was searched as the final               the 16 items in this tool, seven are critical. Details of the score and
search strategy in all the mentioned databases.                                     criticality of each item were specified at the evaluation site. In the
    After completing the review text, to cover and include the studies              evaluation, if up to one non-critical item is not observed in a study, it
published in the period of about one year, a research was performed on              will be reported as a high-quality study. Finding several non-critical
August 1, 2022, with the exact same protocol as the previous one                    items not observed will be reported as moderate quality study. Low-
(including no limitation in time of publication). The numbers and re               quality studies did not consider a critical item and critically low-
ports in the results section are from this last search.                             quality studies did not consider more than one critical item (Shea
    PROSPERO was manually searched on August 1, 2022, to include                    et al., 2017).
                                                                                2
A. Shamabadi et al.                                                                                                         Journal of Herbal Medicine 40 (2023) 100672
    Characteristics of the included studies were summarized in a table              3.1. Searching and selecting
and discussed narratively. The number of randomized controlled trials
(RCT) and non-RCT studies included in each review was reported                          The study selection flow chart is shown in Fig. 1. In total, 195 records
separately. In some instances that studies of essential oils or in                 were obtained through database searching and other sources, which
terventions other than lavender were also included in the reviews, or               were all from the personal archives of SA, of which 105 were duplicate
studies of outcomes other than anxiety (assessed by a validated anxiety             citations. Subsequently, 90 citations underwent initial screening, the full
scale) were analyzed (such as pain, vital signs, saliva cortisol, etc.), we         text of 61 of which needed to be assessed for eligibility and inclusion in
only reported the relevant studies and their corresponding participants             this review. After assessing full texts, another 24 references were
in the summarized table. In addition, if the SRs included a risk of bias            excluded, and finally, 30 studies were included in this study. The reasons
assessment in their results, the mean score (calculated by summing up               for excluding the 31 studies and the characteristics of the 30 studies are
the risk of bias scores of all RCTs (only RCTs that addressed lavender              listed in Appendix B and Table 1, respectively. All RCTs included in the
were included) and dividing it by their number) was calculated and                  thirty systematic reviews are listed in Appendix C.
reported in the characteristics table.
    For the studies that had performed MA, the pooled effect data size              3.2. Anti-anxiety effects of lavender
were obtained and summarized in the table. The fraction of primary
studies that favored lavender intervention was reported for those re                   Out of the 30 SRs that were found concerning the effects of lavender
views that did not conduct quantitative analysis. A summary of the                  on anxiety, MA was conducted in 15 of them. All papers were published
conclusion of each study was also reported in the table.                            after 2010. Study characteristics and results are summarized in Tables 1
    Studies were categorized based on the administration routes                     and 2. Below, the studies are categorized and discussed narratively,
addressed, and the efficacy of each route for reducing anxiety was dis             based on the route of administration.
cussed. In addition to the overall effect of lavender on anxiety, any
assessment of effect disparity within genders or different age groups and
any analysis of optimal treatment dosage were reported.
                                                                   Studies included
                                                                in qualitative synthesis
                Included
(n = 30)
                                                                                3
A. Shamabadi et al.                                                                                                                 Journal of Herbal Medicine 40 (2023) 100672
Table 1
The characteristics of included studies.
  First Author,       RCT No./ NRT     Target population/ NO. of         Intervention (number of        Control        Outcome                ROB assessment      Average
  Year,               No.              participants                      trials)                                                              tool                trial ROB*
  Country
  Abdelhakim,         4/0              Cardiac surgery patients/ 250     Inhalation (4)                 Placebo or     STAI                   Cochrane ROB        5.0/7
    2019,                                                                                               standard                              assessment tool
    Egypt                                                                                               care
  AlMohammed,         23 non-          Cardiovascular disease            NR                             NR             NR                     No quality          -
    2022,             differentiated   patients/ NR                                                                                           assessment
    Saudi Arabia
  Amin,               6 non-           Coronary angiography              Inhalation (6)                 Placebo or     NR                     No quality          -
    2022a,            differentiated   patients/ NR                                                     standard                              assessment
    Iran                                                                                                care
  Amin,               12 non-          Cardiovascular disease            Inhalation (12)                Placebo,       STAI, DASS, BAI        No quality          -
    2022b,            differentiated   patients/ 878                                                    standard                              assessment
    Iran                                                                                                care, or
                                                                                                        active
                                                                                                        intervention
  Bouya,              3/0              Hemodialysis patients/ 200        Inhalation (3)                 No             HADS, STAI             Jadad               3.3/5
    2018,                                                                                               intervention
    Iran
  Cai,                6/2              Dental patient/ 1450              Inhalation (6/2)               Placebo or     STAI, MDAS, VAS        Cochrane ROB        2.6/7
    2019,                                                                                               active                                assessment tool
    China                                                                                               intervention
  Donelli,            64/25            Anxiety patients, anxiety         Inhalation and diffusion       Placebo,       STAI, Zung SAS,        Cochrane ROB        9 LR, 9
    2019,                              inducing (video, pre-             (43), massage (10), cap (8),   standard       HAMA, HADS, SIMA,      assessment tool     Unclear,
    Italy                              procedure)/ 9123                  drink (1), Inhalation and      care, or       DASS-21, VAS,                              46 HR
                                                                         massage in different arms      active         POMS, MDAS, BAI,
                                                                         (1), Shirodhara (1)            intervention   SPHERE
  Ghiasi,             5/0              women during first stage of       Inhalation (2), massage (2),   Placebo or     STAI, VAS              Cochrane ROB        2.4/6
   2019,                               labor/ 476                        variable (1)                   standard                              assessment tool
   Iran                                                                                                 care
  Gong,               12/0             Per-procedure, cancer, burn,      Inhalation (9), massage (2),   NR             STAI                   Jadad               3.3/7
   2020,                               healthy/ 1001                     Inhalation and massage in
   China                                                                 different arms (1)
  Guo,                12/0             Pre-surgery patients/ 1132        Inhalation (11), massage       Placebo or     STAI, VAS, DASS-21     Cochrane ROB        3.6/7
   2020,                                                                 (1)                            standard                              assessment tool
   China                                                                                                care
  Her,                2/3              Cardiac, postpartum, GI,          Inhalation (2/1), massage      Standard       STAI, BAI              Joanna Briggs       11/12
   2021,                               chemotherapy, and cancer          (0/2)                          care                                  Institute of
   Korea                               patients/ 294                                                                                          Critical
                                                                                                                                              Appraisal
                                                                                                                                              checklist
  Huang,              7/0              Pre-procedure/ 618                Inhalation (6), massage (1)    Placebo or     STAI                   Cochrane ROB        3.8/7
    2021,                                                                                               standard                              assessment tool
    China                                                                                               care
  Kang,               19/0             Healthy, anxiety patients, pre-   Inhalation (13), massage       Placebo or     STAI, HADS, BAI,       Cochrane ROB        4.9/7
    2019,                              procedure, ICU/ 1962              (4), cap (2)                   standard       HAMA, VAS,             assessment tool
    Korea                                                                                               care
  Kavradim,           6/0              Hypertension, coronary heart      Inhalation (6)                 Placebo or     STAI, BAI              Cochrane ROB        2.4/5
    2021,                              disease, acute coronary                                          standard                              assessment tool,
    turkey                             syndrome and heart failure (pre                                  care                                  version 2
                                       or post treatment)/ 425
  Kim,                30/0             subthreshold anxiety, SAD,        Inhalation (21), massage       Placebo or     STAI, HADS,            Cochrane ROB        4.0/5
    2021,                              healthy, cardiac, dental,         (5), cap (4)                   standard       DASS-21, VAS, BAI,     assessment tool,
    Korea                              hemodialysis, pregnant,                                          care           Zung SAS, HAMA,        version 2
                                       postpartum, pre-procedure, and                                                  MDAS,
                                       pre-surgery patients/ 3906x
  Lee,                10/0             Healthy, induced anxiety,         Inhalation (5), massage (3),   Placebo        HADS, SPHERE,          NR                  NR
    2011,                              dementia, pre-procedure,          cap (1), variable (1)                         STAI, HAMA, SF-36
    Hong Kong                          cancer patients/ 24857
  Li,                 9/0              Cancer patients/ 817              Inhalation (5), massage (3),   standard       STAI, HADS,            Cochrane ROB        3.5/7
    2022,                                                                both (1)                       care, or       VAS, OAI-23, BAI,      assessment tool
    China                                                                                               active         POMS,
                                                                                                        intervention
  Mardani,            5/3              Cancer patients/ 533              Inhalation (3/3), massage      NR             STAI, HADS, VAS,       Cochrane ROB        NR
   2022,                                                                 (2/0)                                         GAD-7                  assessment tool
   Iran
  Moller,             3/0              Subthreshold anxiety/ 697         Cap (3)                        Placebo or     HAMA                   Cochrane ROB        6.6/7
   2019,                                                                                                active                                assessment tool
   Germany                                                                                              intervention
  Moradifar,          20 non-          Surgery patients/ 3974            Inhalation (19), massage       Placebo,       STAI, HADS, VAS,       NR                  NR
   2021a,             differentiated                                     (1)                            standard       DASS-21, MDAS
   Iran                                                                                                 care, or
                                                                                                        active
                                                                                                        intervention
                                                                                                                                                      (continued on next page)
                                                                                          4
A. Shamabadi et al.                                                                                                                      Journal of Herbal Medicine 40 (2023) 100672
Table 1 (continued )
  First Author,        RCT No./ NRT     Target population/ NO. of        Intervention (number of           Control        Outcome                  ROB assessment      Average
  Year,                No.              participants                     trials)                                                                   tool                trial ROB*
  Country
  Moradifar,           8 non-           Cardiac patients/ 664            Inhalation (8)                    Placebo or     STAI, DASS-21            NR                  NR
    2021b,             differentiated                                                                      standard
    Iran                                                                                                   care
  Perry,               15/0             Healthy, cancer patients, pre-   Inhalation (8), massage (2),      Mostly         STAI, MDAS, VAS,         Jadad               1.4/5
    2012,                               procedure, ICU patients, GAD     oil drip (1), oil bath (1), cap   placebo,       Cox & McKay’s
    United                              or sub subthreshold anxiety/     (3)                               lorazepam      Stress/arousal
    Kingdom                             1565                                                               for one of     adjective checklist,
                                                                                                           Silexan        HAMA, UMACL,
                                                                                                           trials         UWIST
  Purohit,             4/0              Dental outpatients/ 1146         Inhalation (4)                    Placebo,       STAI, MDAS               Cochrane ROB        4.5/7
    2021,                                                                                                  paroxetine                              assessment tool
    India
  Sarris,              3/0              GAD/ 814                         Cap (3)                           NR    NR                                NR                  NR
    2022,
    Australia
  Sayed,               40/0             Cardiac, induced anxiety,        Inhalation (22), massage          NR             Anxiety on different     Cochrane ROB        NR
    2020,                               subthreshold anxiety, GAD,       (3), cap (7)                                     scales (not specified)   assessment tool
    Egypt                               healthy, ICU, hemodialysis,
                                        pregnant, postpartum, pre-
                                        procedure/ 2131
  Tabatabaeichehr,     5/0              Labor anxiety/ 1417              Inhalation (3), massage (2)       Placebo or     VAS, STAI                Cochrane ROB        2.4/6
    2020,                                                                                                  standard                                assessment tool
    Iran                                                                                                   care
  Trkulja,             6/0              Patients with subthreshold       Cap (4)                           Mostly         HAMA                     NR                  5 LR, 1 HR
    2020,                               anxiety, GAD/ 1502                                                 placebo,
    Croatia                                                                                                lorazepam,
                                                                                                           and other
                                                                                                           aroma
  Von Känel,          5/0              Patients with subthreshold       Cap (5)                           Placebo,       HAMA, SF-36              Cochrane ROB        NR
    2020,                               anxiety, GAD/ 1172                                                 lorazepam                               assessment tool
    Switzerland
  Yap,                 5/0              Anxiety patients/ 1463           Cap (5)                           Placebo or     HAMA                     Cochrane ROB        5.0/7
    2019,                                                                                                  active                                  assessment tool
    Malaysia                                                                                               intervention
  Yeung,               5/0              Anxiety patients/ 1325           Cap (5)                           Placebo        HAMA                     NR                  NR
    2018,
    USA
NR: not reported; RCT: randomized clinical trial; NRT: non randomized trial; ROB: risk of bias; HADS: hospital anxiety and depression score; HAMA: Hamilton anxiety
rating score; SPHERE: somatic and psychological health report; STAI: the state-trait anxiety inventory; SF-36: the short form 36; MDAS: modified dental anxiety scale;
VAS: visual analog scale; PSS: perceived stress scale; UMACL: UWIST mood adjective checklist; BAI: beck anxiety inventory; DASS-21: depression anxiety stress scale-
21; Zung SAS: Zung self-rating anxiety scale; POMS: Profile of Mood States; SIMA: The Single-Item Math Anxiety scale; OAI-23: Ostomy Adjustment Inventory-23; GAD-
7: General Anxiety Disorder-7; ROB: risk of bias; LR: low risk; HR: high risk; GI: gastrointestinal.
  *
    The average trial ROB for each systematic review was calculated by summing up all the “low risk” scores for all RCTs (only RCTs that addressed lavender against
anxiety were included) and dividing it by the number of RCTs. The denominator in each fraction is the number of bias domains used in each systematic review to assess
RCTs.
3.2.1. Administration routes                                                                  et al., 2020; Tabatabaeichehr and Mortazavi, 2020), one as medium
                                                                                              (Ghiasi et al., 2019), and the rest four were of high quality (Donelli et al.,
3.2.1.1. Inhalation aromatherapy. Twenty-three studies compared                               2019; Huang et al., 2021; Kang et al., 2019; Turan Kavradim et al.,
inhalation aromatherapy to a comparator which mainly consisted of                             2021). In most studies, lavender was used as a monotherapy and was not
placebo or standard care (Abdelhakim et al., 2020; Amin et al., 2022a;                        administered in combination with other conventional anxiolytic drugs.
Amin et al., 2022b; Bouya et al., 2018; Cai et al., 2021; Donelli et al.,                     However, many reviews contained trials where lavender was inhaled as
2019; Ghiasi et al., 2019; Gong et al., 2020; Guo et al., 2020; Her and                       a blend of several essential oils.
Cho, 2021; Huang et al., 2021; Kang et al., 2019; Kim et al., 2021; Lee                           As demonstrated in Table 2, 11 studies assessed inhalation aroma
et al., 2011; Li et al., 2022; Mardani et al., 2022; Moradifar et al., 2021a;                 therapy without conducting a quantitative analysis (Amin et al., 2022a;
Moradifar et al., 2021b; Perry et al., 2012; Purohit et al., 2021; Sayed                      Amin et al., 2022b; Bouya et al., 2018; Cai et al., 2021; Ghiasi et al.,
et al., 2020; Tabatabaeichehr and Mortazavi, 2020; Turan Kavradim                             2019; Lee et al., 2011; Moradifar et al., 2021a; Moradifar et al., 2021b;
et al., 2021). The target population varied considerably among studies                        Perry et al., 2012; Sarris et al., 2022; Tabatabaeichehr and Mortazavi,
and included patients with generalized anxiety disorder (GAD) or                              2020). Most of the primary trials included in the reviews showed the
sub-syndrome anxiety, healthy patients with trial-induced anxiety,                            superiority of lavender inhalation over comparators. The smallest frac
cancer patients, intensive care unit (ICU) patients, pregnant women,                          tion was presented in a study by Perry et al., where only four out of eight
patients undergoing various procedures such as surgery, dental pro                           included studies favored lavender. None of these studies were of high
cedures, hemodialysis, and chemotherapy. The quality assessment                               quality.
revealed that five studies were characterized as critically low (Amin                             In respect of the studies that performed MA, eight studies reported
et al., 2022a,b; Lee et al., 2011; Moradifar et al., 2021a,b), 13 as low                      the effect size as standardized mean difference (SMD), which ranged
(Abdelhakim et al., 2020; Bouya et al., 2018; Cai et al., 2021; Gong et al.,                  from 0.57 to 1.23, significantly in favor of the lavender intervention
2020; Guo et al., 2020; Her and Cho, 2021; Kim et al., 2021; Li et al.,                       (Donelli et al., 2019; Guo et al., 2020; Her and Cho, 2021; Kang et al.,
2022; Mardani et al., 2022; Perry et al., 2012; Purohit et al., 2021; Sayed                   2019; Kim et al., 2021; Li et al., 2022; Sayed et al., 2020; Turan
                                                                                          5
A. Shamabadi et al.                                                                                                                     Journal of Herbal Medicine 40 (2023) 100672
Table 2
Results summary of included studies.
  First Author,       Fraction of studies         Meta-analysis          Adverse events            Conclusion                                Limitations
  Year,               favoring lavender
  Country             intervention
  Abdelhakim,         -                           Anxiety (including 1   None                      Aromatherapy especially lavender          Blindness, small sample size, no
   2019,                                          non-lavender trial):                             reduces cardiac surgery anxiety, pain     standard dosage
   Egypt                                          MD − 3.21 [− 6.08                                and HR.
                                                  to − 0.35], I2: 90 %
  AlMohammed,         Aromatherapy (21/23)        -                      NR                        Lavender significantly improved           NR
    2022,                                                                                          anxiety
    Saudi Arabia
  Amin,               Inhalation (10/12)          -                      NR                        Lavender significantly ameliorates the    NR
    2022b,                                                                                         anxiety signs in some cardiovascular
    Iran                                                                                           diseases
  Amin-a,             Inhalation (6/6)            -                      NR                        Aromatherapy with lavender                Lack of chemical composition and
    2022,                                                                                          significantly decreases                   phytochemical analysis
    Iran                                                                                           anxiety in coronary angiography
                                                                                                   patients.
  Bouya,              Inhalation (2/3)            -                      NR                        Beneficial effects                        No standard dosage
    2018,
    Iran
  Cai,                Inhalation (6/6),           -                      None                      Aromatherapy is effective and             High heterogeneity,
    2019,             inhalation NRTs (2/2)                                                        comparable to music intervention.         High ROB
    China
  Donelli,            -                           Silexan 80 on          Headache,                 All administration methods were           Low quality studies, Heterogeneity
    2019,                                         HAMA:                  palpitation, infection,   effective in the treatment of anxiety.
    Italy                                         MD − 2.90 [− 4.40      GI disorders              no effects on BP
                                                  to − 0.36], I2: 74 %   All non-serious
                                                  Silexan 80 on Zung
                                                  SAS:
                                                  MD − 2.62 [− 4.84
                                                  to − 0.39], I2: 17 %
                                                  Inhalation on STAI-
                                                  S score:
                                                  MD − 5.99 [− 9.39
                                                  to − 2.59], I2: 95 %
                                                  Inhalation on STAI-
                                                  T score:
                                                  MD − 8.14
                                                  [− 14.44 to
                                                  − 1.84], I2: 91 %
                                                  All lavender
                                                  Inhalation:
                                                  SMD − 0.73
                                                  [− 1.00 to − 0.46],
                                                  I2: 85 %
                                                  Massage:
                                                  SMD − 0.66
                                                  [− 0.97 to − 0.35],
                                                  I2: 61 %
  Ghiasi,             Inhalation (2/2), massage   -                      None                      Positive effects                          Small sample sizes, methodological
   2019,              (2/2), variable (1/1)                                                                                                  limitations, heterogeneity
   Iran
  Gong,               -                           Lavender sub group:    None                      Aromatherapy alleviate anxiety            A third had high risk of bias, doses
   2020,                                          MD: − 7.17 [− 8.06                               especially temporary anxiety.             were not mentioned, adverse effect
   China                                          to − 6.28], I2: 76 %                             Inhalation was better than massage.       were not reported
  Guo,                -                           Lavender Subgroup:     None                      Aromatherapy reduces preoperative         All cases were elective surgeries,
   2020,                                          SMD: − 0.50                                      anxiety in adults                         most in middle east (cultural
   China                                          [− 0.73 to − 0.27],                                                                        difference), no standard dosage, high
                                                  I2: 63 %                                                                                   ROB, language limitation
  Her,                -                           Anxiety:               NR                        Aromatherapy had a significant effect     Time and language limitations,
    2021,                                         G − 0.93 [− 1.47 to                              on anxiety
    Korea                                         − 0.38], I2: 82 %
  Huang,              -                           Lavender sub group:    None                      Aromatherapy as an effective              ROB, high heterogeneity
    2021,                                         MD − 4.43 [− 8.24                                treatment for preoperative anxiety
    China                                         to − 0.63], I2: 89 %
  Kang,               -                           Relieving anxiety:     None                      Safe anxiolytic effect; both mentally     High heterogeneity
    2019,                                         G − 0.65 [− 0.84 to                              and physically
    Korea                                         − 0.46], I2:73%
                                                  Inhalation
                                                  subgroup:
                                                  G − 0.71 [− 0.97 to
                                                  − 0.45], I2:76 %
                                                  Massage subgroup:
                                                  G − 0.61 [− 1.06 to
                                                  − 0.15], I2:75 %
                                                                                                                                                           (continued on next page)
                                                                                       6
A. Shamabadi et al.                                                                                                                       Journal of Herbal Medicine 40 (2023) 100672
Table 2 (continued )
  First Author,        Fraction of studies          Meta-analysis          Adverse events            Conclusion                                Limitations
  Year,                favoring lavender
  Country              intervention
                                                    Silexan subgroup:
                                                    G − 0.54 [− 0.84 to
                                                    − 0.23], I2:54 %
  Kavradim,            -                            Anxiety:               NR                        Aromatherapy reduced anxiety,             Limited number of included studies,
    2021,                                           G 1.23 [0.68–1.78],                              systolic blood pressure, heart rate and   only English language, no standard
    turkey                                          I2: 84 %                                         breath rate                               dosage
  Kim,                 -                            Anxiety:               None                      inhalation and massage application of     ROB, lack of blinding, only English
    2021,                                           SMD − 0.72                                       lavender leads to a significant
    Korea                                           [− 0.90 to − 0.55],                              decrease in anxiety levels
                                                    I2: 84 %
                                                    Inhalation
                                                    subgroup:
                                                    G − 0.83 [− 1.03 to
                                                    − 0.62]
                                                    Massage subgroup:
                                                    G − 0.60 [− 1.02 to
                                                    − 0.18]
                                                    Silexan subgroup:
                                                    G − 0.41
                                                    [− 0.84–0.03]
  Lee,                 Inhalation (4/5), massage    -                      None                      Positive and safe effects                 Different durations, methodological
    2011,              (1/3), cap (1/1), Variable                                                                                              limitations
    Hong Kong          (0/1)
  Li,                  -                            Anxiety (lavender      NR                        Aromatherapy is an effective              Only English, Heterogeneity,
    2022,                                           subgroup):                                       therapeutic option in alleviating         blinding difficulty
    China                                           SMD − 1.12                                       anxiety of cancer patients
                                                    [− 1.94 to − 0.31],
                                                    I2: 92 %
  Mardani,             Inhalation (3/3),            -                      None                      The use of lavender for mitigating        ROB, high heterogeneity
   2022,               inhalation NRTs (2/3),                                                        cancer anxiety has been suggested.
   Iran                massage (1/2)
  Moller,              -                            Silexan:               Eructation, dyspepsia,    Significant anxiolytic effects            Limited number of included studies,
   2019,                                            MD − 3.83, [− 6.37     allergic skin reactions                                             funding by manufacturers
   Germany                                          to − 1.28], I2: 74.7
                                                    %
  Moradifar,           Aromatherapy (18/19),        -                      NR                        Lavender essential oil has the            NR
    2021a,             massage (1/1)                                                                 potential to reduce anxiety in patients
    Iran                                                                                             undergoing various types of surgery
  Moradifar,           Aromatherapy (6/8)           -                      NR                        Lavender is able to significantly         NR
    2021b,                                                                                           decrease anxiety in patients with
    Iran                                                                                             CABG surgery
  Perry,               Inhalation (4/8), massage    -                      Gastrointestinal          Promising but inconclusive effects        Methodological limitations,
    2012,              (0/2), cap (3/3), oil bath                          problems                                                            publication bias
    United             (0/1), oil drip (0/1)
    Kingdom
  Purohit,             -                            Dental anxiety         None                      Effective at decreasing patient dental    Limited number of the included
    2021,                                           level: I2: 1%                                    anxiety                                   studies
    India                                           MD − 3.36 [ − 3.77
                                                    to − 2.95], I2: 1 %
  Sarris,              Cap (3/3)                    -                      None                      Lavender is provisionally                 NR
    2022,                                                                                            recommended for GAD
    Australia
  Sayed,               -                            First week             NR                        Lavender aromatherapy and massage         Low quality and small sample size,
    2020,                                           Aromatherapy:                                    were the most effective short-term        lack of blinding, inadequate
    Egypt                                           SMD − 0.57                                       options. Silexan 80 mg was clinically     withdrawal report
                                                    [− 1.14 to − 0.01]                               beneficial for long-term.
                                                    Massage:
                                                    SMD − 0.20
                                                    [− 1.28–0.88]
                                                    Silexan 80:
                                                    SMD − 0.26
                                                    [− 2.12–1.60]
                                                    First follow up
                                                    Aromatherapy:
                                                    SMD − 0.57
                                                    [− 0.97 to − 0.16]
                                                    Massage:
                                                    SMD − 0.20
                                                    [− 1.11–0.70]
                                                    Silexan 80:
                                                    SMD − 0.33
                                                    [− 1.11–0.44]
                                                    Silexan 160:
                                                    SMD − 0.18
                                                                                                                                                             (continued on next page)
                                                                                         7
A. Shamabadi et al.                                                                                                                       Journal of Herbal Medicine 40 (2023) 100672
Table 2 (continued )
  First Author,        Fraction of studies         Meta-analysis         Adverse events            Conclusion                                  Limitations
  Year,                favoring lavender
  Country              intervention
                                                   [− 1.57–1.21]
                                                   Follow up endpoints
                                                   Aromatherapy:
                                                   SMD 1.79
                                                   [0.46–3.12]
                                                   Massage:
                                                   SMD 0.15
                                                   [− 1.56–1.87]
                                                   Silexan 80:
                                                   SMD − 0.19
                                                   [− 1.40–1.02]
                                                   Silexan 160:
                                                   SMD − 0.20
                                                   [− 2.38–1.99]
  Tabatabaeichehr,     Inhalation (3/3), massage   -                     None                      Aromatherapy has a positive effect on       Small sample size, short intervention
    2020,              (2/2)                                                                       pain relief and lowers labor anxiety        and f/u
    Iran
  Trkulja,             Cap (5/6)                   -                     Gastrointestinal          Moderate evidence for short-term            NR
    2020,                                                                problems                  efficacy
    Croatia
  Von Känel,          -                           HAMA somatic          None                      Supporting role in anxiety disorders        Identical authors, similar effect sizes
    2020,                                          anxiety (Items                                  including somatic symptoms
    Switzerland                                    7–13):
                                                   SMD − 0.31
                                                   [− 0.52 to − 0.10],
                                                   I2: 68 %
                                                   SF-36 physical
                                                   health subscore:
                                                   SMD − 0.31
                                                   [− 0.44 to − 0.18],
                                                   I2: 0%
                                                   HAMA insomnia
                                                   (Items 4):
                                                   SMD − 0.30
                                                   [− 0.51 to − 0.10],
                                                   I2: 68%
                                                   SF-36 vitality
                                                   subscore (Fatigue):
                                                   SMD − 0.31
                                                   [− 0.52 to − 0.10],
                                                   I2: 25%
  Yap,                 -                           Silexan 80:           Nausea, eructation,       Significant effect of Silexan 160 mg        Only English, all in Germany,
    2019,                                          MD − 3.820            breath odor and           versus placebo,                             funding by manufacturers
    Malaysia                                       [− 5.261 to           diarrhea                  Silexan 80 mg and paroxetine
                                                   − 2.380]
                                                   Silexan 160:
                                                   MD − 4.963
                                                   [− 7.167 to
                                                   − 2.759]
  Yeung,               Cap (5/5)                   -                     NR                        Herbal medicines mitigate                   Publication bias, funding by
    2018,                                                                                          anxiety and depression                      manufacturers, no standard dosage
    USA
NR: not reported; NRT: non-randomized trial; RCT: randomized clinical trial; G: Hedges’ G; MD: mean difference; SMD: standardized mean difference
Kavradim et al., 2021). Interestingly, one study showed that lavender                       Mardani et al., 2022; Moradifar et al., 2021a; Perry et al., 2012; Sayed
inhalation only has significant short-term efficacy, as the calculated                      et al., 2020; Tabatabaeichehr and Mortazavi, 2020). Comparators
long-term effect size was insignificant (Sayed et al., 2020). The other                     mainly included standard care or placebo. The number of reviews with
four studies reported mean differences which ranged from 3.21 to 7.17                       critically low, low, medium, and high quality on the AMSTAR-II scale
(Abdelhakim et al., 2020; Gong et al., 2020; Huang et al., 2021; Purohit                    were two (Lee et al., 2011; Moradifar et al., 2021a), nine (Gong et al.,
et al., 2021); however, two of these reviews included a study irrelevant                    2020; Guo et al., 2020; Her and Cho, 2021; Kim et al., 2021; Li et al.,
to lavender inhalation in their analysis (Abdelhakim et al., 2020; Gong                     2022; Mardani et al., 2022; Perry et al., 2012; Sayed et al., 2020;
et al., 2020). Accordingly, all results significantly favored lavender                      Tabatabaeichehr and Mortazavi, 2020), one (Ghiasi et al., 2019), and
inhalation, regardless of the study qualities.                                              three (Donelli et al., 2019; Huang et al., 2021; Kang et al., 2019),
                                                                                            respectively. Most of the primary RCTs used lavender in a monotherapy
3.2.1.2. Massage aromatherapy. Massage therapy efficacy was evalu                          massage setting with only four exceptions which were included in
ated in 15 studies in a range of populations such as ICU patients, cancer,                  studies by Ghiasi et al., Her et al., Kim et al., and Lee et al.
coronary, and burn patients, pregnant women before and after delivery,                          Out of these studies, six were unable to conduct MA and reported
and pre-procedure patients (Donelli et al., 2019; Ghiasi et al., 2019;                      their results narratively (Ghiasi et al., 2019; Lee et al., 2011; Li et al.,
Gong et al., 2020; Guo et al., 2020; Her and Cho, 2021; Huang et al.,                       2022; Moradifar et al., 2021a; Perry et al., 2012; Tabatabaeichehr and
2021; Kang et al., 2019; Kim et al., 2021; Lee et al., 2011; Li et al., 2022;               Mortazavi, 2020). Ghiasi et al. (2019), Mardani et al. (2022), and
                                                                                       8
A. Shamabadi et al.                                                                                                       Journal of Herbal Medicine 40 (2023) 100672
Tabatabaeichehr and Mortazavi (2020) reported the effectiveness of                   Additionally, in a critically low-quality review, the methods of lavender
lavender massage aromatherapy. Additionally, the only massage trial                  interventions were not clearly stated, although they concluded that
included in Moradifar et al. (2021a) review favored this therapy. In                 lavender could significantly improve anxiety (AlMohammed et al.,
contrast, among the relevant trials included in the remaining two re                2022).
views, lavender massage was significantly superior to placebo in none
(Perry et al., 2012), or one (Lee et al., 2011) RCT.                                 3.2.2. Optimal dosage
    Two of the high-quality studies quantitatively reported SMDs of 0.61                 The number of essential oil drops used for inhalation varied greatly,
and 0.66, significantly favoring lavender massage (Donelli et al., 2019;             but most studies used 1–6 drops. The concentration of used solutions for
Kang et al., 2019). Moreover, a low-quality review reported a similar                inhalation or massage was rarely noted. No study compared different
SMD of 0.60 (Kim et al., 2021). On the contrary, one low quality re                 dosages of lavender in inhalation or massage setting. Regarding the oral
ported a non-significant effect size for the massage method (Sayed et al.,           route, 80 mg and 160 mg per day dosage have shown significant efficacy
2020). The other five reviews included too few studies on lavender                   (Sarris et al., 2022; Trkulja and Barić, 2020; Yap et al., 2019). By con
massage intervention to justify a separate subgroup analysis (Gong et al.,           ducting a network MA, one study showed the superiority of the 160 mg
2020; Guo et al., 2020; Her and Cho, 2021; Huang et al., 2021; Li et al.,            dosage (Yap et al., 2019). However, a network MA in another study
2022).                                                                               demonstrated that the dose of 80 mg per day was more effective for
                                                                                     long-term treatment (Sayed et al., 2020). In addition, this study rec
3.2.1.3. Oral administration. 12 studies included RCTs that investigated             ommended the inhalation method as the administration route of choice
effects of oral administration of lavender against anxiety (Donelli et al.,          for short-term treatments. Both of these studies were assessed as low
2019; Kang et al., 2019; Kim et al., 2021; Lee et al., 2011; Möller et al.,         quality.
2019; Perry et al., 2012; Sarris et al., 2022; Sayed et al., 2020; Trkulja
and Barić, 2020; von Känel et al., 2021; Yap et al., 2019; Yeung et al.,           3.2.3. Gender or age differences in efficacy
2018). Except in two studies, all of the investigations on oral lavender                 The higher prevalence of stress-related psychiatric disorders in
treatment were carried out in a monotherapy setting using Silexan, a                 women made us explore the relationship between lavender efficacy and
commercial capsule. The two studies were included by Sarris et al.                   the gender of the recipient. Only two studies addressed this issue (Huang
(2022) and Perry et al. (2012), where the used capsules contained lav               et al., 2021; von Känel et al., 2021). In the review by von Känel et al.
ender powder or a combination of lavender and sunflower oil, respec                 (2021)the administration of oral lavender capsules in patients with GAD
tively. The target population included healthy volunteers and patients               or anxiety was investigated. Treatment effects were not significantly
with GAD or sub-syndrome anxiety. Comparator groups received pla                    different between men and women in this study. In contrast, a subgroup
cebo or active treatments such as lorazepam. Overall quality was criti              analysis of three studies with exclusively female patients in the review
cally low in six (Lee et al., 2011; Möller et al., 2019; Sarris et al., 2022;       by Huang et al. (2021) did not reveal a significant effect size, although
Trkulja and Barić, 2020; von Känel et al., 2021; Yeung et al., 2018), low          the overall effect size of the studies was significant.
in four (Kim et al., 2021; Perry et al., 2012; Sayed et al., 2020; Yap et al.,           In addition, von Känel et al. (2021) found the effects of lavender on
2019), and high in two of the studies (Donelli et al., 2019; Kang et al.,            anxiety symptoms to be independent of age. No other study investigated
2019). The original RCTs that investigated oral lavender intervention                the possible impacts of age of the patient on the results of lavender
overlapped considerably between reviews.                                             treatment.
    Four studies did not implement MA to report their results (Lee et al.,
2011; Perry et al., 2012; Trkulja and Barić, 2020; Yeung et al., 2018).             3.3. Quality assessment
Due to the mentioned overlap, the results of these reviews were similar,
and all of them reported a significant efficacy for using Silexan in                    Table 3 shows each study with its score for the AMSTAR II items.
managing mild to moderate anxiety. Furthermore, in an extensive                      Based on this tool, only four SRs had high quality, and just one had
clinical guideline systematically investigating the treatment of psychi             medium quality. Most reviews had low (n = 10) and critically low
atric disorders using nutraceuticals and phytoceuticals, Sarris et al.               quality (n = 5).
(2022) found acceptable evidence for implementing oral lavender in
patients with GAD.                                                                   4. Discussion
    Most of the reviews that performed MA were based on the 80 mg
dosage of Silexan. Four studies summarized their results as SMDs, which              4.1. Summary of evidence
ranged from 0.20 to 0.54, supporting the Silexan treatment (Kang et al.,
2019; Kim et al., 2021; Sayed et al., 2020; von Känel et al., 2021),                    Through a systematic approach, 30 SRs and MAs evaluating anxio
though two of them did not find the effect to be significant (Kim et al.,            lytic effects of lavender in various groups of participants were found, all
2021; Sayed et al., 2020). The other three studies reported mean dif                of them suggesting lavender as a promising anti-anxiety agent. An SMD
ferences varying from 2.62 to 3.83 (Donelli et al., 2019; Möller et al.,            ranging from 0.57 to 1.23 was reported for inhalation as the most
2019; Yap et al., 2019). As stated, most of the included original trials             investigated route of administration, with 23 reviews addressing it.
were similar among the reviews.                                                      Massage therapy was mentioned in 15 reviews, demonstrating an SMD
                                                                                     of around 0.60. The oral route was also investigated in 12 studies, with
3.2.1.4. Other routes. Three reviews included routes of administration               SMDs ranging from 0.20 to 0.54, suggesting the efficacy of 80 mg and
other than the above mentioned methods (Ghiasi et al., 2019; Lee et al.,             160 mg Silexan capsules in mild to moderate anxiety.
2011; Perry et al., 2012). Perry et al. (2012) included two RCTs where
effects of lavender oil dripping and oil bath on anxiety scales were                 4.2. Other implications
assessed in healthy populations, though none of these methods proved
superior to placebo. Ghiasi et al. (2019) and Lee et al. (2011) each                    As mentioned earlier, studies of lavender, similar to other natural
included one of the two RCTs of the same author that have investigated               products that have polyvalent activities reported on them, have not been
the effects of various essential oils, including lavender, in pre-labor              limited to anxiety disorders. Lavender has other scientific implications,
women using different administration methods such as inhalation,                     and there are also many reports of the effects of lavender intervention on
massage, foot bath, birthing pool, and acupressure points. Only the                  other psychiatric disorders. An SR of seven RCTs concluded that lav
study in the review by Ghiasi et al. (2019), reported significant results.           ender had antidepressant effects in patients with a definitive diagnosis.
                                                                                     However, its prescription is not recommended for treating depression
                                                                                 9
                                                                                                                                                                                                              A. Shamabadi et al.
     Table 3
     The quality assessment of the included studies based on the AMSTAR II tool.
      First Author, year        Item 1     Item 2*       Item 3   Item 4*   Item 5   Item 6   Item 7*   Item 8   Item 9*   Item 10   Item 11*   Item 12   Item 13*   Item 14   Item 15*   Item 16   Quality
                                (0–1)      (0–2)         (0–1)    (0–2)     (0–1)    (0–1)    (0–2)     (0–2)    (0–2)     (0–1)     (0–1)      (0–1)     (0–1)      (0–1)     (0–1)      (0–1)
      Abdelhakim, 2019          1          1             1        1         1        1        2         2        2         0         1          0         0          1         0          1         L
      AlMohammed, 2022          1          0             0        1         1        0        0         1        0         0         -          -         0          0         -          1         CL
      Amin, 2022a               1          0             0        0         1        1        0         1        0         0         -          -         0          0         -          1         CL
      Amin, 2022b               1          0             0        0         0        0        0         1        0         0         -          -         0          0         -          1         CL
      Bouya, 2018               1          1             1        2         1        1        2         2        1         0         -          -         0          0         -          1         L
      Cai, 2019                 1          1             1        1         1        1        0         2        2         0         -          -         1          0         -          1         L
      Donelli, 2019             1          2             1        1         1        1        2         2        2         0         1          1         1          1         1          1         H
      Ghiasi, 2019              1          1             0        1         1        1        2         2        2         0         -          -         1          1         -          1         M
      Gong, 2020                1          1             1        1         0        0        2         2        2         0         1          1         0          1         1          1         L
      Guo, 2020                 1          1             1        1         1        1        2         2        2         0         1          1         0          1         1          1         L
      Her, 2021                 1          2             0        1         1        1        0         1        2         0         1          1         1          1         1          1         L
      Huang, 2021               1          1             1        2         1        1        2         2        2         0         1          1         1          1         1          1         H
      Kang, 2019                1          1             1        1         1        1        2         2        2         0         1          1         1          1         1          1         H
      Kavradim, 2021            1          1             1        2         1        1        2         2        2         0         1          1         1          1         1          1         H
10
      Kim, 2021                 1          2             0        1         1        1        0         1        2         0         1          1         1          1         1          1         L
      Lee, 2018                 0          1             1        1         1        0        0         2        2         0         -          -         0          0         -          1         CL
      Li, 2022                  1          2             0        1         1        1        0         1        2         0         1          1         1          1         1          1         L
      Mardani, 2022             1          1             0        1         1        1        0         1        2         0         -          -         1          0         -          1         L
      Moller, 2017              0          0             1        0         0        0        1         2        2         1         1          1         1          1         0          1         CL
      Moradifar, 2021a          1          1             0        0         1        1        0         1        1         0         -          -         1          0         -          1         CL
      Moradifar, 2021b          1          1             0        0         1        1        0         1        0         0         -          -         0          0         -          1         CL
      Perry, 2012               1          1             1        1         1        1        2         2        2         0         -          -         0          1         -          1         L
      Purohit, 2021             1          1             1        2         1        1        2         2        2         0         1          1         0          1         1          1         L
      Sarris (2022)             1          1             1        1         1        1        0         1        0         0         -          -         0          0         -          1         CL
      Sayed, 2020               1          1             1        1         1        1        1         1        2         0         1          0         1          1         0          1         L
      Tabatabaeichehr, 2020     1          1             1        1         1        1        1         1        2         0         -          -         0          0         -          1         L
      Trkulja, 2020             1          1             1        0         0        0        0         2        2         0         -          -         0          0         -          0         CL
      Von Kanel, 2020           1          1             1        0         0        0        0         2        2         0         1          0         0          0         0          1         CL
      Yap, 2019                 1          1             1        1         1        1        1         2        2         1         1          1         1          1         0          1         L
      Yeung, 2018               0          0             1        1         1        1        2         2        0         0         -          -         0          0         -          1         CL
yet (Shamabadi and Akhondzadeh, 2021). A study showed that                          comfort, they should first be thoroughly studied.
concomitant use of lavender essential oil and psychotropic drugs has                    In addition, it should be noted that many clinical trials consider
been more effective than psychotropic medications alone for treating                intervention as an effective one based on statistical analysis when the p-
dementia (Mascherona et al., 2021). Watson et al. (2019) performed an               value is less than 0.05. At the same time, the intervention may not be
RCT of L. angustifolia and lemon balm (Melissa officinalis) essential oils          clinically significant because minimal changes can lead to statistically
intervention to treat agitated behavior in older people with and without            significant results. Even a minor change in the total score of a scale
dementia. They showed that L. angustifolia effectively reduces agitation            might be statistically significant, but it is not necessarily clinically
in patients with dementia but has a low effect on patients without de              visible (Hengartner and Plöderl, 2018).
mentia (O’Connor et al., 2013). Another study revealed that inhaled
lavender improves the quality and quantity of sleep as well as the quality          5. Conclusions
of life in patients with diabetes mellitus type II (Lari et al., 2020).
                                                                                        All of the 30 reviews included demonstrated the effectiveness of
4.3. Low methodological quality of the included studies                             lavender as an anxiolytic in various populations, including preoperative,
                                                                                    cardiovascular, hemodialysis, cancer, and dental patients and pre-labor
    Version II of AMSTAR is the most recent update for AMSTAR and                   women. Lavender aromatherapy seems to be a safe and tolerable
would be a critical point of view (Shea et al., 2017). In this review,              method, showing anti-anxiety properties when inhaled, administered
AMSTAR II showed that most studies did not have acceptable quality.                 orally, or used as a massage oil. The most common complication was
Considering the fact that AMSTAR II has a precise reviewing platform, it            mild gastrointestinal problems, and no other major adverse effect was
is a justifiable tool for judging the quality of SRs. Unfortunately, most of        reported. No gender or age preference was reported in any of the studies.
the studies found and included had low or critically low quality;                   Given the variability of dosages and conflicting results, no definitive
therefore, their results and conclusions should be treated with caution.            conclusion on optimal dosage was possible. The most reported effect size
                                                                                    was for the inhalation method, though evidence implied that inhalation
4.4. Significant limitations of core studies                                        is most effective for the short term while the oral route is preferable for
                                                                                    longer treatment durations. Due to the lack of dose standardization and
    Due to the breadth of this topic, which entails the exclusion of dis           low overall quality of the reviews, implementing further trials and re
cussion of all sub-topics, and the importance of paying attention to the            views with better qualities and standardized treatment methods is
limitations and drawbacks of previous studies, some of the most critical            recommended.
limitations of core studies included in the 20 SRs are shortly mentioned
and discussed.                                                                      Funding
    Herbal medicines were widely used in the past and were later
replaced by modern medicines (Yuan et al., 2016). They have attracted                   This study was supported by a grant from Tehran University of
interest again lately because of their potential to treat diseases with             Medical Sciences (TUMS) to Professor Shahin Akhondzadeh (grant
probable minor side effects (Li and Weng, 2017; Yuan et al., 2016).                 number 56403). TUMS had no role in the design, conduct, data collec
However, like current conventional medications, medicinal plants                    tion, data interpretation, manuscript preparation, review, final
should be approved via the long-established scientific approach. In the             approval, and the decision to submit the paper for publication.
first stage, a pre-clinical trial has to be performed. Subsequently, three
phases of clinical trials must be conducted (in each phase, the effects and         Author contribution
side effects are evaluated). Eventually, the medications become publicly
available, and their side effects will be re-evaluated (Eder and Herrling,             A.S.: Conceptualization, Methodology, Investigation, Data curation,
2015). In this regard, a committee of the European Medicines Agency is              Writing—original draft preparation, Writing—review and editing, Su
responsible for issuing information on the uses and safety of herbal                pervision, Project administration; A.H.: Data curation, Writing—origi
medicinal products (Knöss and Chinou, 2012).                                       nal draft preparation; A.A.: Data curation, Writing—original draft
    Lavandula may be known by a specific name in some countries, and                preparation, Writing—review and editing; H.G.: Writing—original draft
each region has a particular lavender with different micromorphological             preparation; M.G.: Writing—original draft preparation, Writing—re
and phytochemical characteristics (Kahkeshani et al., 2014). For this               view and editing; S.A.: Supervision, Project administration, Software,
reason, buying plants from open markets, as seen in some studies, re               Resources, Funding acquisition.
duces the likelihood of achieving reliable results. Although Lavandula is
endemic to the northern Mediterranean region, its different species and             Declaration of Competing Interest
subspecies are found in different countries (Edwards et al., 2015).
Consequently, clinical studies should investigate and mention the spe                  The authors declare that they have no known competing financial
cies and characteristics of the plant used.                                         interests or personal relationships that could have appeared to influence
    Not mentioning the part of the plant used and not performing an                 the work reported in this article.
accurate standardization are other remarkable limitations in the core
studies. It is necessary to prepare the ingredients and constituents in             Acknowledgments
specific proportions and use them in studies to achieve reliable and
reproducible results (Shamabadi and Akhondzadeh, 2021). Linalool and                    None.
linalyl acetate are the main ingredients in lavender essential oil. Other
important ingredients in lavender include 1,8-cineole, camphor, and
                                                                                    Appendices A–C. Supporting information
endo-borneol (Jianu et al., 2013). Although the beneficial and harmful
ingredients cannot be identified and studied in the first few studies on a
                                                                                       Supplementary data associated with this article can be found in the
medicinal plant, their identification will be easier with the proper
                                                                                    online version at doi:10.1016/j.hermed.2023.100672.
standardization and characterization.
    As mentioned, L. angustifolia has been used in studies and adminis
                                                                                    References
tered through various routes, including oral, inhaled, and topical, which
could result in different outcomes. Although the various prescribing                Abdelhakim, A.M., Hussein, A.S., Doheim, M.F., Sayed, A.K., 2020. The effect of
routes allow the physician to consider the patient’s limitations and                   inhalation aromatherapy in patients undergoing cardiac surgery: a systematic review
                                                                               11
A. Shamabadi et al.                                                                                                                                 Journal of Herbal Medicine 40 (2023) 100672
     and meta-analysis of randomized controlled trials. Complement Ther. Med. 48,                    Lépine, J.-P., 2002. The epidemiology of anxiety disorders: prevalence and societal costs.
     102256.                                                                                              J. Clin. Psychiatry 63, 4–8.
AlMohammed, H.I., Alanazi, N., Maghrabi, E.F., Alotaibi, M., 2022. Role of                           Li, D., Li, Y.X., Bai, X., Wang, M.J., Yan, J.Z., Cao, Y.J., 2022. The effects of
     aromatherapy as a natural complementary and alternative therapy in cardiovascular                    aromatherapy on anxiety and depression in people with cancer: a systematic review
     disease: a comprehensive systematic review. Evid. -Based Complement. Altern. Med.                    and meta-analysis. Front. Public Health 10, 13.
     2022, 13.                                                                                       Li, F.-S., Weng, J.-K., 2017. Demystifying traditional herbal medicine with modern
Amin, A., Amraei, M., Shahijan, M.K., Nadri, S., Moradifar, N., 2022a. The effects of                     approach. Nat. Plants 3 (8), 17109.
     aromatherapy on patients undergoing coronary angiography: a systematic review of                Mamtani, R., Cimino, A., 2002. A primer of complementary and alternative medicine and
     clinical trials. J. HerbMed Pharmacol. 11 (1), 1–9.                                                  its relevance in the treatment of mental health problems. Psychiatr. Q 73 (4),
Amin, A., Gavanrudi, M.R., Karami, K., Raziani, Y., Baharvand, P., 2022b. The role of                     367–381.
     aromatherapy with lavender in reducing the anxiety of patients with cardiovascular              Mardani, A., Maleki, M., Hanifi, N., Borghei, Y., Vaismoradi, M., 2022. A systematic
     diseases: a systematic review of clinical trials. J. HerbMed Pharmacol. 11 (2),                      review of the effect of lavender on cancer complications. Complement. Ther. Med.
     182–187.                                                                                             67.
Bachmann, S., 2018. Epidemiology of suicide and the psychiatric perspective. Int. J.                 Mascherona, I., Ferretti, M., Soldini, E., Biggiogero, M., Maggioli, C., Fontana, P.E., 2021.
     Environ. Res. Public Health 15, 7.                                                                   Essential oil therapy for the short-term treatment of behavioral and psychological
Bouya, S., Ahmadidarehsima, S., Badakhsh, M., Balouchi, A., Koochakzai, M., 2018.                         symptoms of dementia: a monocentric randomized pilot study. Aging Clin. Exp. Res.
     Effect of aromatherapy interventions on hemodialysis complications: a systematic                     33 (8), 2251–2259.
     review. Complement Ther. Clin. Pract. 32, 130–138.                                              Möller, H.J., Volz, H.P., Dienel, A., Schläfke, S., Kasper, S., 2019. Efficacy of silexan in
Cai, H., Xi, P., Zhong, L., Chen, J., Liang, X., 2021. Efficacy of aromatherapy on dental                 subthreshold anxiety: meta-analysis of randomised, placebo-controlled trials. Eur.
     anxiety: a systematic review of randomised and quasi-randomised controlled trials.                   Arch. Psychiatry Clin. Neurosci. 269 (2), 183–193.
     Oral. Dis. 27 (4), 829–847.                                                                     Moradifar, N., Amraei, M., Karami, K., Shahijan, M.K., Nadri, S., Amin, A., 2021a.
Donelli, D., Antonelli, M., Bellinazzi, C., Gensini, G.F., Firenzuoli, F., 2019. Effects of               Aromatherapy with lavender essential oil in patients with surgery-related anxiety: a
     lavender on anxiety: a systematic review and meta-analysis. Phytomedicine 65,                        systematic review. Res. J. Pharmacogn. 8 (4), 101–111.
     153099.                                                                                         Moradifar, N., Shahijan, M.K., Bakhtiari, N., Tavakoli, M., Amin, A., 2021b.
Eder, J., Herrling, P.L., 2015. Trends in modern drug discovery. N. Approaches Drug                       Aromatherapy in patients undergoing coronary artery bypass surgery: a systematic
     Discov. 3–22.                                                                                        review of clinical trials. Glob. J. Med. Pharm. Biomed. Update 16 (6), 7.
Edwards, S.E., Rocha, Id.C., Williamson, E.M. and Heinrich, M. 2015. Lavender. In                    Nikfarjam, M., Parvin, N., Assarzadegan, N., Asghari, S., 2013. The effects of Lavandula
     Phytopharmacy (eds S.E. Edwards, Id.C. Rocha, E.M. Williamson and M. Heinrich).                      angustifolia mill infusion on depression in patients using citalopram: a comparison
     pp. 237–241. (Wiley-Blackwell), https://doi.org/10.1002/9781118543436.ch66.                          study. Iran. Red. Crescent Med. J. 15 (8), 734.
Ghiasi, A., Bagheri, L., Haseli, A., 2019. A systematic review on the anxiolytic effect of           O’Connor, D.W., Eppingstall, B., Taffe, J., van der Ploeg, E.S., 2013. A randomized,
     aromatherapy during the first stage of labor. J. Caring Sci. 8 (1), 51–60.                           controlled cross-over trial of dermally-applied lavender (Lavandula angustifolia) oil
Gong, M., Dong, H., Tang, Y., Huang, W., Lu, F., 2020. Effects of aromatherapy on                         as a treatment of agitated behaviour in dementia. BMC Complement. Altern. Med. 13
     anxiety: a meta-analysis of randomized controlled trials. J. Affect Disord. 274,                     (1), 1–7.
     1028–1040.                                                                                      Park, S.C., Kim, Y.K., 2020. Anxiety disorders in the DSM-5: changes, controversies, and
Guo, P.P., Li, P., Zhang, X.H., Liu, N., Wang, J., Yang, S., Yu, L., Zhang, W., 2020. The                 future directions. Adv. Exp. Med. Biol. 1191, 187–196.
     effectiveness of aromatherapy on preoperative anxiety in adults: a systematic review            Perry, R., Terry, R., Watson, L.K., Ernst, E., 2012. Is lavender an anxiolytic drug? A
     and meta-analysis of randomized controlled trials. Int. J. Nurs. Stud. 111.                          systematic review of randomised clinical trials. Phytomedicine 19 (8–9), 825–835.
Hajhashemi, V., Ghannadi, A., Sharif, B., 2003. Anti-inflammatory and analgesic                      Prusinowska, R., Śmigielski, K.B., 2014. Composition, biological properties and
     properties of the leaf extracts and essential oil of Lavandula angustifolia Mill.                    therapeutic effects of lavender L). A review. Herba Pol. 60 (2), 56–66.
     J. Ethnopharmacol. 89 (1), 67–71.                                                               Purohit, A., Singh, A., Purohit, B., Shakti, P., Shah, N., 2021. Is aromatherapy associated
Hengartner, M.P., Plöderl, M., 2018. Statistically significant antidepressant-placebo                    with patient’s dental anxiety levels? A systematic review and meta-analysis. J. Dent.
     differences on subjective symptom-rating scales do not prove that the drugs work:                    Anesth. Pain. Med. 21 (4), 311–319.
     effect size and method bias matter! Front. Psychiatry 9, 517.                                   Sarris, J., Ravindran, A., Yatham, L.N., Marx, W., Rucklidge, J.J., McIntyre, R.S.,
Her, J., Cho, M.K., 2021. Effect of aromatherapy on sleep quality of adults and elderly                   Akhondzadeh, S., Benedetti, F., Caneo, C., Cramer, H., Cribb, L., de Manincor, M.,
     people: a systematic literature review and meta-analysis. Complement. Ther. Med.                     Dean, O., Deslandes, A.C., Freeman, M.P., Gangadhar, B., Harvey, B.H., Kasper, S.,
     60.                                                                                                  Lake, J., Lopresti, A., Lu, L., Metri, N.J., Mischoulon, D., Ng, C.H., Nishi, D.,
Huang, H.F., Wang, Q., Guan, X.F., Zhang, X., Kang, J.G., Zhang, Y.C., Zhang, Y.H.,                       Rahimi, R., Seedat, S., Sinclair, J., Su, K.P., Zhang, Z.J., Berk, M., 2022. Clinician
     Zhang, Q., Li, X.B., 2021. Effect of aromatherapy on preoperative anxiety in adult                   guidelines for the treatment of psychiatric disorders with nutraceuticals and
     patients: a meta-analysis of randomized controlled trials. Complement. Ther. Clin.                   phytoceuticals: the world federation of societies of biological psychiatry (WFSBP)
     Pract. 42.                                                                                           and Canadian network for mood and anxiety treatments (CANMAT) taskforce. World
Jianu, C., Pop, G., TGruia, A., Horhat, F.G., 2013. Chemical composition and                              J. Biol. Psychiatry 1–32.
     antimicrobial activity of essential oils of lavender (Lavandula angustifolia) and               Sayed, A.M., Morsy, S., Tawfik, G.M., Naveed, S., Minh-Duc, N.T., Hieu, T.H., Ali, Z.A.,
     lavandin (Lavandula x intermedia) grown in Western Romania. Int. J. Agric. Biol. 15,                 Shinkar, A., Doheim, M.F., Hashan, M.R., Huy, N.T., 2020. The best route of
     4.                                                                                                   administration of lavender for anxiety: a systematic review and network meta-
Kahkeshani, N., Khanavi, M., Hadjiakhoondi, A., 2014. Differentiation of Lavandula                        analysis. Gen. Hosp. Psychiatry 64, 33–40.
     angustifolia Mill. and Nepeta menthoides Boiss & Buhse using microscopic and                    Schuyler, D., 2016. Anxiety. Prim. Care Companion CNS Disord. 18, 5.
     phytochemical evaluations.                                                                      Shamabadi, A., Akhondzadeh, S., 2021. Efficacy and tolerability of Lavandula
Turan Kavradim, S., Yangöz, Ş.T., Ozer, Z., 2021. Effectiveness of aromatherapy                         angustifolia in treating patients with the diagnosis of depression: a systematic review
     inhalation on anxiety and haemodynamic variables for patients with cardiovascular                    of randomized controlled trials. J. Complement. Integr. Med.
     disease: A systematic review and meta-analysis. Int. J. Clin. Pract. 75, e14593.                Shea, B.J., Reeves, B.C., Wells, G., Thuku, M., Hamel, C., Moran, J., Moher, D.,
von Känel, R., Kasper, S., Bondolfi, G., Holsboer-Trachsler, E., Hättenschwiler, J.,                    Tugwell, P., Welch, V., Kristjansson, E., 2017. AMSTAR 2: a critical appraisal tool for
     Hatzinger, M., Imboden, C., Heitlinger, E., Seifritz, E., 2021. Therapeutic effects of               systematic reviews that include randomised or non-randomised studies of healthcare
     Silexan on somatic symptoms and physical health in patients with anxiety disorders:                  interventions, or both. bmj 358.
     a meta-analysis. Brain Behav. 11, 4.                                                            Tabatabaeichehr, M., Mortazavi, H., 2020. The effectiveness of aromatherapy in the
Kang, H.J., Nam, E.S., Lee, Y., Kim, M., 2019. How strong is the evidence for the                         management of labor pain and anxiety: a systematic review. Ethiop. J. Health Sci. 30
     anxiolytic efficacy of lavender?: Systematic review and meta-analysis of randomized                  (3), 449–458.
     controlled trials. Asian Nurs. Res. (Korean Soc. Nurs. Sci. ) 13 (5), 295–305.                  Trkulja, V., Barić, H., 2020. Current research on complementary and alternative
Karan, N.B., 2019. Influence of lavender oil inhalation on vital signs and anxiety: a                     medicine (CAM) in the treatment of anxiety disorders: an evidence-based review.
     randomized clinical trial. Physiol. Behav. 211, 112676.                                              Adv. Exp. Med. Biol. 415–449.
Kim, M., Nam, E.S., Lee, Y., Kang, H.J., 2021. Effects of Lavender on anxiety, depression,           Tully, P.J., Harrison, N.J., Cheung, P., Cosh, S., 2016. Anxiety and cardiovascular disease
     and physiological parameters: systematic review and meta-analysis. Asian Nurs. Res.                  risk: a review. Curr. Cardiol. Rep. 18 (12), 120.
     15 (5), 279–290.                                                                                Watson, K., Hatcher, D., Good, A., 2019. A randomised controlled trial of Lavender
Knöss, W., Chinou, I., 2012. Regulation of medicinal plants for public health–European                   (Lavandula angustifolia) and Lemon Balm (Melissa officinalis) essential oils for the
     community monographs on herbal substances. Planta Med. 78 (12), 1311–1316.                           treatment of agitated behaviour in older people with and without dementia.
Lari, Z.N., Hajimonfarednejad, M., Riasatian, M., Abolhassanzadeh, Z., Iraji, A.,                         Complement Ther. Med. 42, 366–373.
     Vojoud, M., Heydari, M., Shams, M., 2020. Efficacy of inhaled Lavandula                         Yap, W.S., Dolzhenko, A.V., Jalal, Z., Hadi, M.A., Khan, T.M., 2019. Efficacy and safety of
     angustifolia Mill. Essential oil on sleep quality, quality of life and metabolic control             lavender essential oil (Silexan) capsules among patients suffering from anxiety
     in patients with diabetes mellitus type II and insomnia. J. Ethnopharmacol. 251,                     disorders: a network meta-analysis. Sci. Rep. 9 (1), 1–11.
     112560.                                                                                         Yeung, K.S., Hernandez, M., Mao, J.J., Haviland, I., Gubili, J., 2018. Herbal medicine for
Lee, Y.L., Wu, Y., Tsang, H.W., Leung, A.Y., Cheung, W.M., 2011. A systematic review on                   depression and anxiety: a systematic review with assessment of potential psycho-
     the anxiolytic effects of aromatherapy in people with anxiety symptoms. J. Alter.                    oncologic relevance. Phytother. Res. 32 (5), 865–891.
     Complement Med. 17 (2), 101–108.                                                                Yuan, H., Ma, Q., Ye, L., Piao, G., 2016. The traditional medicine and modern medicine
                                                                                                          from natural products. Molecules 21, 5.
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