PuSH - Publication Server of Helmholtz Zentrum München: 694. Investigating the potential of psilocybin for compulsive eating in a rat model of binge eating.

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Fabila, N.* ; Manaph, N.P.A.* ; Rudkowsky, V.* ; Sketriené, D.* ; Li, Y.* ; Anversa, R.G.* ; Walker, L.C.* ; Reichelt, A.C.* ; Foldi, C.J.* ; Menden, M.P. ; Brown, R.M.*

694. Investigating the potential of psilocybin for compulsive eating in a rat model of binge eating.

Int. J. Neuropsychopharmacol. 28, ii55 - ii56 (2025)

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BackgroundBinge eating disorder (BED) is the most prevalent eating disorder, often associated with metabolic syndrome and other mental health comorbidities. Despite its impact, current treatment options remain limited. BED is associated with compulsive intake of foods typically high in fat and sugar, as well as neuroplastic changes in brain regions such as the nucleus accumbens, dorsal striatum, and prefrontal cortex. Psilocybin, a psychedelic compound, has been shown to promote neuroplasticity and may offer a novel intervention for compulsive eating.Aims & ObjectivesThis study aimed to assess whether psilocybin reduces compulsive eating in a preclinical rodent model of BED. We hypothesised that psilocybin would reduce compulsive-like eating in our rat model.Method44 female rats were divided into four groups: Control + Saline, Control + Psilocybin, Binge + Saline, and Binge + Psilocybin. Binge groups received intermittent access to a high-fat/high-sugar (HFHS) diet 3x p/week for 1 hour for 10 weeks. Control rats received standard chow only. Compulsive eating was assessed using a conditioned suppression paradigm which involved assessment of eating of HFHS at baseline and then after 4 conditioning sessions. Psilocybin (2 mg/kg, i.p.) or saline was administered prior to the start of baseline acclimation sessions and again immediately after the 4th conditioning session (approx. 24 hours before test). Baseline sessions (30min) occurred over 12 days where rats were placed in fear-conditioning chambers with access to food (HFHS for binge groups, chow for controls). All rats then underwent conditioning (4 x 30min daily session) where a light cue was paired with a 0.5 mA foot shock. On test day, the latency to start eating in the presence of the cue was assessed as a measured of compulsive-like behaviour towards HFHS.ResultsPsilocybin at the dose tested did not impact latency to start eating or food intake on test day, but potentially affected freezing behaviour (analysis is ongoing).Discussion & ConclusionsWhile psilocybin did not significantly reduce compulsive eating at the tested dose, its potential effects on fear conditioning may reflect modulation of learning and memory circuits. Ongoing molecular analyses will further explore the possible underlying neurobiological mechanisms.

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