A long trip into the universe: Psychedelics and space travel

The authors synthesise existing literature and theorise several pathways by which psychedelics might be relevant to long‑duration spaceflight while repeatedly acknowledging the limited empirical basis for these claims. They summarise mechanistic evidence—largely from non‑human studies and emerging clinical work—indicating that classical psychedelics act primarily via serotonergic receptors (notably 5‑HT2A and 5‑HT1A) to enhance neuroplasticity (dendritic spine formation, axon branching, increased synaptic density) and may therefore help repair or adapt neural circuits that could be compromised by spaceflight. The paper links these neuroplastic effects to potential mitigation of space‑related declines in motor function and cognitive reserve, suggesting that enhanced plasticity could facilitate adaptation to novel and stressful extraterrestrial environments. B. and colleagues also discuss immune and inflammatory modulation by psychedelics, proposing that some immunomodulatory effects reported in preclinical studies could be relevant to the pro‑inflammatory changes and immune suppression observed during prolonged sojourns. The authors propose that psychedelics might exert indirect benefits via the gut‑brain axis: they review how spaceflight alters gut microbiome diversity and composition, note the microbiome’s role in neurotransmitter metabolism, and suggest (with caution) that psychedelics could influence wellbeing in part through microbiome‑mediated pathways. They emphasise, however, that evidence for microbiome‑mediated effects of psychedelics is limited in the current literature. On psychosocial outcomes, the paper argues that the phenomenology of psychedelic states—greater cognitive flexibility, enhanced creativity, empathy, meaning attribution and mystical or noetic experiences—could support interpersonal functioning, group cohesion and existential coping on long missions. The authors draw a parallel between astronaut reports of awe and transcendence when viewing Earth from orbit and the kinds of spiritual or mystical experiences induced by psychedelics, suggesting potential utility in processing isolation, separation from Earth, and end‑of‑life concerns that might arise in inaccessible mission contexts. The authors acknowledge substantial safety and operational concerns. Although clinical trials to date have reported relatively few adverse events with psilocybin and related compounds, psychedelics can produce intense subjective effects (dissociation, paranoia, hallucinations, confusion) that could be hazardous in confined, high‑risk environments. The paper calls for controlled hazard analyses and clinical studies in relevant settings (including the International Space Station) before any operational use. Proposed risk‑mitigation strategies include telemedicine and AI monitoring, sub‑psychedelic dosing schedules (microdosing), pharmacogenetic screening for susceptibility to adverse effects, development of reversal or neutralising agents and non‑psychedelic analogues that retain neuroplastic benefits, and the training of astronauts in established safety protocols from psychedelic‑assisted psychotherapy. The authors also advise careful consideration of dosing, scheduling and prioritising wellbeing applications rather than using psychedelics as treatments for severe psychiatric illness in space. Throughout, B. and colleagues stress that psychedelic science is in an early stage: much of the evidence for neuroplasticity and immunomodulation comes from preclinical or terrestrial clinical studies, and there are no empirical studies of psychedelic use in space. They recommend a cautious research agenda that tests safety and mechanisms in controlled, analog and orbital environments, explores cultivation or biomanufacture of psychedelic biomass within bioregenerative life‑support systems, and evaluates whether neuroplastic benefits can be decoupled from the full subjective ‘‘trip’’ prior to operational deployment.