Project Summary Anxiety, stress, and low levels of psychological well-being -- all byproducts of some aspects of modern living -- contribute substantially to the burden of poor health around the globe. One potentially low-cost, easy to administer, and non-addictive treatment option to address these outcomes may be provided by the benefits of a specific form of nature contact: "forest bathing". This therapeutic approach involves sitting in forested areas, and in some cases interacting with trees in guided ways. The specific ways in which individual components of multisensory inputs act together to instantiate the psychophysiological benefits of forest bathing are not well understood. The objective of this proposal is to investigate the contribution of the olfactory pathway to these benefits -- specifically the component of inhalation of volatile organic compounds (VOCs), including terpenes -- present in forest air. We will use an individual-level crossover design in which each session is conducted independently and on different days. Participants will be outfitted with a powered air purifying respirator (PAPR) to selectively modulate exposure to a natural suite of forest-derived volatile organic compounds (VOCs) while present in forest environments. Each participant will undergo two forest bathing sessions, one in which VOCs are not filtered (treatment condition), and one in which they are filtered (control condition). Sessions will be separated by a 5-day washout period for each participant, and order will be counterbalanced. We will estimate the average effect of treatment over 40 distinct treatment days against 40 distinct control/filtered days. Our power and sample size calculations (N = 40) were determined using previous nature exposure studies of similar cross-over design. We are adequately powered assuming the conventional targets of α = 0.05 and β = 0.80 with a 10% anticipated dropout rate, and including temperature, wind, and light variability during treatment days. The specific aim of this project is to 1) assess whether VOC inhalation regulates increases in the HF (ms[2]) component of HRV as the primary outcome (with decreases in blood pressure, heart rate, self-reported stress, and levels of inflammatory cytokines in serum included as secondary outcomes); and 1a) assess the degree of association of absorbed dose of seven forest-derived VOCs in serum (i.e., α-pinene, β-pinene, β-myrcene, ? 3- carene, d-limonene, β- carophyllene, α-humulene) with these outcomes. Our proposed research will further scientific understanding of the role that olfactory stimuli play in the multisensory processes that are responsible for the benefits of forest bathing. This work addresses several aspects of NCCIH Research Agenda with its specific focus on the development of methods that are key to the advancement of fundamental science as it relates to mental health and well-being. Our investigations will also contribute key evidence to the development of ...