{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:45:51Z","timestamp":1785735951959,"version":"3.56.0"},"reference-count":128,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Psychedelic-assisted therapy has shown rapid and durable benefits across multiple psychiatric conditions, yet the mechanisms underlying these effects remain incompletely understood. Full-dose psychedelic sessions simultaneously engage serotonergic neurochemistry, high-intensity subjective experience, and autonomic-interoceptive physiology, making it difficult to determine which components are necessary or sufficient for therapeutic change. This perspective proposes that three partially separable research approaches, a single low dose of a psychedelic, high-ventilation breathwork, and vagus nerve stimulation (VNS), offer complementary mechanistic probes for disentangling these pathways. A single, sub-psychedelic dose provides a model of low-intensity 5-HT2A engagement that isolates pharmacological and early plasticity-related effects while minimizing experiential and autonomic confounds. Breathwork induces robust experiential and autonomic shifts through CO\n                    <jats:sub>2<\/jats:sub>\n                    -driven physiological perturbation and interoceptive amplification, enabling investigation of experiential and autonomic contributions in the absence of serotonergic pharmacology. VNS, in turn, modulates vagal-autonomic and interoceptive circuits without inducing altered states of consciousness, offering a controlled method for probing autonomic influences on affective and cognitive processes. Examining these perturbations within shared experimental frameworks may clarify how neurochemical plasticity, experiential meaning-making, and autonomic recalibration interact to support psychological change. This mechanistic precision can guide the development of interventions that are safer, more scalable, and more individually tailored than current full-dose psychedelic protocols.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2026.1892474","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T05:29:54Z","timestamp":1785734994000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecules, meaning, and physiology: disentangling the active ingredients of psychedelic therapeutics"],"prefix":"10.3389","volume":"20","author":[{"given":"Kim P. 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