After a hiatus of several decades, there has been a resurgence of studies into the therapeutic potential of serotonergic psychedelics. When administered in controlled settings, they have been reported to induce a wide variety of long-lasting positive psychological changes. However, the mechanisms by which psychedelics impart these long-lasting benefits remain poorly understood. Here, we highlight one possibility that has remained underexplored: a beneficial interaction with the self-optimizing functions of sleep.

References

Alonso, J. F., Romero, S., Mañanas, M. A., Riba, J. ( 2015 ). Serotonergic psychedelics temporarily modify information transfer in humans . International Journal of Neuropsychopharmacology, 18(8), 1 – 9 . doi:10.1093/ijnp/pyv039

Google Scholar Crossref

Barbanoj, M. J., Riba, J., Clos, S., Giménez, S., Grasa, E., Romero, S. ( 2008 ). Daytime Ayahuasca administration modulates REM and slow-wave sleep in healthy volunteers . Psychopharmacology, 196, 315 – 326 .

Google Scholar Crossref | Medline | ISI

Carhart-Harris, R. L., Goodwin, G. M. ( 2017 ). The therapeutic potential of psychedelic drugs: Past, present, and future . Neuropsychopharmacology, 42, 2105 – 2113 .

Google Scholar Crossref | Medline

Carhart-Harris, R. L., Kaelen, M., Bolstridge, M., Williams, T. M., Williams, L. T., Underwood, . . . Nutt, D. J. ( 2016 ). The paradoxical psychological effects of lysergic acid diethylamide (LSD) . Psychological Medicine, 46, 1379 – 1390 .

Google Scholar Crossref | Medline | ISI

Carhart-Harris, R. L., Leech, R., Hellyer, P. J., Shanahan, M., Feilding, A., Tagliazucchi, E., . . . Nutt, D. ( 2014 ). The entropic brain: A theory of conscious states informed by neuroimaging research with psychedelic drugs . Frontiers in Human Neuroscience, 8, Article 20. doi:10.3389/fnhum.2014.00020

Google Scholar Crossref

Carhart-Harris, R. L., Nutt, D. ( 2014 ). Was it a vision or a waking dream? Frontiers in Psychology, 5, 255 . doi:10.3389/fpsyg.2014.00255

Google Scholar Crossref | Medline | ISI

Carhart-Harris, R. L., Roseman, L., Bolstridge, M., Demetriou, L., Pannekoek, J. N., Wall, M. B., . . . Nutt, D. J. ( 2017 ). Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms . Scientific Reports, 7, Article 13187. doi:10.1038/s41598-017-13282-7

Google Scholar Crossref

Colasanti, B., Khazan, N. ( 1975 ). Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat . Psychopharmacologia, 43, 201 – 205 .

Google Scholar Crossref | Medline

Dos Santos, R. G., Osório, F. L., Crippa, J. A. S., Riba, J., Zuardi, A. W., Hallak, J. E. C. ( 2016 ). Antidepressive, anxiolytic, and antiaddictive effects of ayahuasca, psilocybin and lysergic acid diethylamide (LSD): A systematic review of clinical trials published in the last 25 years . Therapeutic Advances in Psychopharmacology, 6, 193 – 213 .

Google Scholar SAGE Journals | ISI

Freeman, W. J. ( 1999 ). How brains make up their minds. London, England : Weidenfeld & Nicolson .

Google Scholar

Garcia-Romeu, A., Kersgaard, B., Addy, P. H. ( 2016 ). Clinical applications of hallucinogens: A review . Experimental and Clinical Psychopharmacology, 24, 229 – 268 .

Google Scholar Crossref | Medline | ISI

Gelman, A., Carlin, J. B., Stern, H. S., Rubin, D. B. ( 2004 ). Bayesian data analysis ( 2nd ed. ). Boca Raton, FL : Chapman & Hall .

Google Scholar

Hobson, J. A. ( 2001 ). The dream drugstore: Chemically altered states of consciousness. Cambridge : The MIT Press .

Google Scholar

Kass, R. E., Raftery, A. E. ( 1995 ). Bayes factors . Journal of the American Statistical Association, 90, 773 – 795 .

Google Scholar Crossref | ISI

Kay, D. C., Martin, W. R. ( 1978 ). LSD and tryptamine effects on sleep/wakefulness and electrocortigogram patterns in intact cats . Psychopharmacology, 58, 223 – 228 .

Google Scholar Crossref | Medline

Kometer, M., Pokorny, T., Seifritz, E., Vollenweider, F. X. ( 2015 ). Psilocybin-induced spiritual experiences and insightfulness are associated with synchronization of neuronal oscillations . Psychopharmacology, 232, 3663 – 3676 .

Google Scholar Crossref | Medline | ISI

Kupferschmidt, K. ( 2014 ). High hopes . Science, 345, 18 – 23 .

Google Scholar Crossref | Medline | ISI

Landmann, N., Kuhn, M., Maier, J.-G., Spiegelhalder, K., Baglioni, C., Frase, L., . . . Nissen, C. ( 2015 ). REM sleep and memory reorganization: Potential relevance for psychiatry and psychotherapy . Neurobiology of Learning and Memory, 122, 28 – 40 .

Google Scholar Crossref | Medline

Meisel, C., Olbrich, E., Shriki, O., Achermann, P. ( 2013 ). Fading signatures of critical brain dynamics during sustained wakefulness in humans . The Journal of Neuroscience, 33, 17363 – 17372 .

Google Scholar Crossref | Medline

Monti, J. M., Jantos, H. ( 2006 ). Effects of the serotonin 5-HT2A/2C receptor agonist DOI and of the selective 5-HT2A or 5-HT2C receptor antagonists EMD 281014 and SB-243213, respectively, on sleep and waking in the rat . European Journal of Pharmacology, 553, 163 – 170 .

Google Scholar Crossref | Medline

Muthukumaraswamy, S. D., Carhart-Harris, R. L., Moran, R. J., Brookes, M. J., Williams, T. M., Errtizoe, D., . . . Nutt, D. J. ( 2013 ). Broadband cortical desynchronization underlies the human psychedelic state . The Journal of Neuroscience, 33, 15171 – 15183 .

Google Scholar Crossref | Medline | ISI

Nichols, D. E. ( 2016 ). Psychedelics . Pharmacological Reviews, 68, 264 – 355 .

Google Scholar Crossref | Medline | ISI

Rahman, A., Languille, S., Lamberty, Y., Babiloni, C., Perret, M., Bordet, R., . . . Aujard, F. ( 2013 ). Sleep deprivation impairs spatial retrieval but not spatial learning in the non-human primate grey mouse lemur . PLoS ONE, 8(5), e64493 . doi:10.1371/journal.pone.0064493

Google Scholar Crossref | Medline | ISI

Rambousek, L., Palenicek, T., Vales, K., Stuchlik, A. ( 2014 ). The effect of psilocin on memory acquisition, retrieval, and consolidation in the rat . Frontiers in Behavioral Neuroscience, 8, 180 . doi:10.3389/fnbeh.2014.00180

Google Scholar Crossref | Medline

Rasch, B., Born, J. ( 2013 ). About sleep’s role in memory . Physiological Reviews, 93, 681 – 766 .

Google Scholar Crossref | Medline | ISI

Ravassard, P., Hamieh, A. M., Malleret, G., Salin, P.-A. ( 2015 ). Paradoxical sleep: A vigilance state to gate long-term brain plasticity? Neurobiology of Learning and Memory, 122, 4 – 10 .

Google Scholar Crossref | Medline

Riba, J., Anderer, P., Jané, F., Saletu, B., Barbanoj, M. J. ( 2004 ). Effects of the South American psychoactive beverage Ayahuasca on regional brain eletrical activity in humans: A functional neuroimaging study using low-resolution electromagnetic tomography . Neuropsychobiology, 50, 89 – 101 .

Google Scholar Crossref | Medline | ISI

Sampedro, F., de la Fuente Revenga, M., Valle, M., Roberto, N., Domínguez-Clavé, E., Elices, M., . . . Riba, J. ( 2017 ). Assessing the psychedelic “after-glow” in Ayahuasca users: Post-acute neurometabolic and functional connectivity changes are associated with enhanced mindfulness capacities . International Journal of Neuropsychopharmacology, 20, 698 – 711 .

Google Scholar Crossref | Medline

Schartner, M. M., Carhart-Harris, R. L., Barrett, A. B., Seth, A. K., Muthukumaraswamy, S. D. ( 2017 ). Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin . Scientific Reports, 7, Article 46421. doi:10.1038/srep46421

Google Scholar Crossref | Medline

Siegel, J. M. ( 2001 ). The REM sleep-memory consolidation hypothesis . Science, 294, 1058 – 1063 .

Google Scholar Crossref | Medline | ISI

Smith, C., Rose, G. M. ( 1996 ). Evidence for a paradoxical sleep window for place learning in the Morris water maze . Physiology & Behavior, 59, 93 – 97 .

Google Scholar Crossref | Medline

Tagliazucchi, E., Roseman, L., Kaelen, M., Orban, C., Muthukumaraswamy, S. D., Murphy, K., . . . Carhart-Harris, R. ( 2016 ). Increased global functional connectivity correlates with LSD-induced ego dissolution . Current Biology, 26, 1 – 8 .

Google Scholar Crossref | Medline

Tylš, F., Páleníček, T., Horáček, J. ( 2014 ). Psilocybin—Summary of knowledge and new perspectives . European Neuropsychopharmacology, 24, 342 – 356 .

Google Scholar Crossref | Medline | ISI

van Amsterdam, J., Opperhuizen, A., van den Brink, W. ( 2011 ). Harm potential of magic mushroom use: A review . Regulatory Toxicology and Pharmacology, 59, 423 – 429 .

Google Scholar Crossref | Medline | ISI

Vollenweider, F. X., Kometer, M. ( 2010 ). The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders . Nature Reviews Neuroscience, 11, 642 – 651 .

Google Scholar Crossref | Medline | ISI

Watson, R. A., Buckley, C. L., Mills, R. ( 2011 ). Optimization in “self-modeling” complex adaptive systems . Complexity, 16, 17 – 26 .

Google Scholar Crossref

Winkelman, M. ( 2010 ). Shamanism: A biopsychosocial paradigm of consciousness and healing. Santa Barbara, CA : Praeger .

Google Scholar

Wolbers, T., Wiener, J. M. ( 2014 ). Challenges for identifying the neural mechanisms that support spatial navigation: The impact of spatial scale . Frontiers in Human Neuroscience, 8, 571 . doi:10.3389/fnhum.2014.00571

Google Scholar Crossref | Medline | ISI

Woodward, A., Froese, T., Ikegami, T. ( 2015 ). Neural coordination can be enhanced by occasional interruption of normal firing patterns: A self-optimizing spiking neural network model . Neural Networks, 62, 39 – 46 .

Google Scholar Crossref | Medline

Youngblood, B. D., Zhou, J., Smagin, G. N., Ryan, D. H., Harris, R. B. S. ( 1997 ). Sleep deprivation by the “flower pot” technique and spatial reference memory . Physiology & Behavior, 61, 249 – 256 .

Google Scholar Crossref | Medline