Running title: “Sleep in Psychedelic Therapy?” 1 A Role for Enhanced Functions of Sleep in Psychedelic Therapy? 1 2 3 Tom Froese 1, 2 * , Iwin Leenen 3 , and Tomas Palenicek 4 4 5 6 1 Institute for Applied Mathematics and Systems Research (IIMAS), National Autonomous 7 University of Mexico (UNAM), Mexico City, Mexico 8 9 2 Center for the Sciences of Complexity (C3), UNAM, Mexico City, Mexico 10 11 3 National Institute for Educational Assessment (INEE), Mexico City, Mexico 12 13 4 National Institute of Mental Health, Klecany, Czech Republic 14 15 Correspondence: Tom Froese (t.froese@gmail.com) 16 17 Keywords: rat models; psilocybin; memory consolidation; psychedelic assisted therapy; 18 altered states of consciousness; sleep 19 20 21 ABSTRACT 22 23 After a hiatus of several decades there has been a resurgence of studies into the therapeutic 24 potential of serotonergic psychedelics. When administered in controlled settings, they have 25 been reported to induce a wide variety of long-lasting positive psychological changes. 26 However, the mechanisms by which psychedelics impart these long-lasting benefits remain 27 poorly understood. Here we highlight one possibility that has remained underexplored: a 28 beneficial interaction with the self-optimizing functions of sleep. 29 30 31 BACKGROUND 32 33 There is a resurgence of studies into the therapeutic potential of serotonergic psychedelics, 34 especially of N, N-diethyllysergamide (LSD) and psilocybin (Kupferschmidt, 2014). 35 Although these substances acutely alter perception, mood, and cognition, they are generally 36 considered physiologically and psychologically safe and, unlike many other mind-altering 37 drugs, they do not lead to dependence (van Amsterdam et al., 2011; Nichols, 2016). When 38 administered in controlled settings, they have been reported to induce long-lasting positive 39 changes: improvements in wellbeing and mood in healthy subjects and in patients suffering 40 from severe depression and anxiety, attenuation of addictions, and reduction in unwanted 41 behavioral patterns (for reviews, see Dos Santos et al., 2016; Garcia-Romeu et al., 2016; 42 Carhart-Harris and Goodwin, 2017). 43 44 However, the mechanisms by which psychedelics impart these long-lasting benefits remain 45 poorly understood, and more theoretical work is urgently required in order to guide future 46 empirical research in the most fruitful directions. Here we would like to highlight one 47