Zhang N, Chen J, Dong W, Yao L. The effect of copaiba oil odor on anxiety relief in adults under mental workload: a randomized controlled trial. Evid-Based Complement Alternat Med. March 2, 2022;2022:3874745. Doi: 10.1155/2022/3874745.
Volatile, aromatic plant essential oils (EOs) are used in aromatherapy to relieve stress and anxiety and promote a sense of well-being. EO compounds, with small molecular weights and high permeability enter into circulation through inhalation or the skin when used as a topical application. Studies have reported decreased blood pressure (BP), heart rate (HR), and blood oxygen saturation (SpO2) after inhalation of certain EOs. It has also been have found EOs with anxiolytic effects can reduce plasma corticosterone in animals and salivary cortisol in humans; both are commonly used markers of anxiety. Copaiba (Copaifera langsdorffii, Fabaceae) balsam is an aromatic resin used in folk medicine throughout Amazonia. Copaiba oil (CPO), extracted by hydro-distillation, has anti-inflammatory, skin-healing, and anti-parasitic properties. In patients with hand arthritis, massage with a 3% CPO cream significantly reduced time to complete dexterity tasks and reduced pain vs. control. β-caryophyllene, making up ~ 50% of CPO, has known anxiolytic effects. In vivo, peritoneal administration of CPO demonstrated an acute anxiolytic effect. However, there are no previous clinical reports of effects of CPO inhalation on anxiety. The authors conducted a randomized controlled trial (RCT) to measure the efficacy of CPO in relieving markers of stress and anxiety in adults.
The study was conducted at Shanghai Jian-Tong University (SJ-TU; Shanghai, People’s Republic of China). Recruited via social websites, participants answered an online questionnaire to ascertain eligibility. Criteria were age 18-40 years, no nasal diseases, no conditions affecting the sense of smell, no history of allergy to EOs, and no use of psychotropic drugs within the prior three months. Pregnant women and those planning a pregnancy were excluded. A total of 22 (17 women) were randomized to CPO (n = 11; doTERRA Commercial Co. Ltd, Shanghai) or odorless jojoba (Simmondsia chinensis, Simmondsiaceae; n = 11; Aromatic Place Research and Development Center, SJ-TU) oil (JO) as placebo. CPO composition, ascertained via gas chromatography/mass spectrometry, was 55.93% caryophyllene, 10.41% α-copaene, 6.81% trans-α-bergamotene, and 5.46% humulene.
In a space (1.7 × 1.7 × 1.85 m) set aside for the RCT, a table, chair, and monitor were set up. A diffuser that directly atomized EOs on a timed basis was placed on the floor in a corner behind the chair. Before test sessions, each participant was fitted with an Electroencephalogram (EEG) cap and allowed to sit quietly for 10 minutes. HR, BP, and SpO2 were measured. EEG was recorded for five minutes with eyes closed. Next, anxiety-provoking test tasks included a 300-second n-back memory/matching test, administered first in training and again in the test session, and a five-minute mental arithmetic task were given. Participants then completed the State-Trait Anxiety Inventory (STAI) and EEGs were recorded again for five minutes. The aroma diffuser was turned on at the start of the CPO odor intervention phase and EEGs were recorded for another five minutes before then-back and arithmetic task was administered. At the end of the intervention phase, EEG was recorded for five minutes, physiological parameters were re-measured, and the STAI was completed. Participants used five-point Likert scales to rate the comfort of the “odor environment” and intensity of the odor perceived. Blinding was “not… possible” due to the sensory nature of ART. This common problem was compounded in this RCT by continuous use of the same space for participants in both groups, apparently in random order, likely resulting in inhalation of residual compounds, at different levels, of both agents by some or most participants.
After n-back training, there were no significant between-group differences in STAI scores. Scores in both groups decreased after test tasks, but STAI state anxiety (S-AI) scores in CPO were significantly lower vs. JO (P < 0.05). After the mental arithmetic task, total STAI, S-AI, and trait anxiety (T-AI) scores were significantly lower in CPO vs. post-training, whereas only T-AI decreased significantly in JO (P < 0.05 for all). Neither CPO nor JO significantly affected BP. During n-back and mental arithmetic tasks, mean HR in CPO decreased significantly vs. JO (P < 0.05). SpO2 in CPO showed a slight upward trend during test tasks. Salivary cortisol in CPO decreased significantly during test tasks vs. post-training and vs. JO (P < 0.05 for both), trending upward in JO. EEG results showed significant reduction in beta power in the F3 region in the CPO group during the first five minutes of odor release vs. post-training. CPO treatment had a nonsignificant decrease in beta power in F4 during the same interval and a nonsignificant decreasing trend in alpha power in F3, F4, C3, and C4 regions. The CPO group rated the odor environment somewhat more favorably than JO, and as significantly more intense (P < 0.05).
The authors conclude CPO aromatherapy could help alleviate anxiety. Studies using a larger sample size and environments with controllable odor concentrations will be helpful to further explore the anxiolytic function of CPO. The authors declared no conflicts of interest.
—Mariann Garner-Wizard
Peer Reviewer Comments
The design of the study could not tackle confounding, and in this case, there are two clear examples of confounding. The first is between pharmacological effects due to the chemical composition of CPO, and its olfactory effects. Since there was no indication of the atmospheric concentration of CPO or of its rate of emission, it is impossible to ascertain whether the inhaled quantities were enough, after penetration in the blood, to cause a pharmacological effect at brain level, or whether they were low and granted just an olfactory effect. In this second case, we have the second example of confounding — between the olfactory stimulation of CPO and the olfactory stimulation of any VOC or perfumed molecule. While the authors mentioned the use of an incense diffuser, they do not clarify the specifics, for instance what kind of nebulizer and the power of the electrical motor. Knowing the type of nebulizer can be relevant since pneumatic nebulizers are more noisy than ultrasound ones, and their activation could have been noted by the participants during the test. Knowing the power of the nebulizer could have provided an idea of the amount of EO dispersed in the atmosphere, and hence arrive at an evaluation of the concentration in the air.