There is an increased societal trend to engage in microdosing, in which small sub-hallucinogenic amounts of psychedelics are consumed on a regular basis. Following subjective reports that microdosing enhances the experience of nature and art, in the present study we set out to study the effects of psilocybin microdosing on feelings of awe and art perception. In this preregistered combined field- and lab-based study, participants took part in a microdosing workshop after which they volunteered to self-administer a psilocybin microdose or a placebo for three consecutive weeks, while the condition was kept blind to the participants and researchers. Following a 2-week break, the condition assignment was reversed. During each block, participants visited the lab twice to measure the effects of psilocybin microdosing vs. placebo. We used standardized measures of awe, in which participants reported their experiences in response to short videos or when viewing abstract artworks from different painters. Our confirmatory analyses showed that participants felt more awe in response to videos representing funny animals and moving objects in the microdosing compared to the placebo condition. However, about two-third of our participants were breaking blind to their experimental condition. Our exploratory findings suggest that expectancy-effects may be a driving factor underlying the subjective benefits of microdosing.

Department of Experimental Neurobiology National Institute of Mental Health Klecany Czech Republic

Department of Psychology University of Amsterdam Nieuwe Achtergracht 129B 1018WT Amsterdam The Netherlands

Forensic Laboratory of Biologically Active Substances Department of Chemistry of Natural Compounds University of Chemistry and Technology Prague Prague Czech Republic

Institute of Psychology Leiden University Wassenaarseweg 52 2333 AK Leiden The Netherlands

Zobrazit více v PubMed

Anderson T, Petranker R, Rosenbaum D, Weissman CR, Dinh-Williams LA, Hui K, Farb NA. Microdosing psychedelics: personality, mental health, and creativity differences in microdosers. Psychopharmacology. 2019;236(2):731–740. doi: 10.1007/s00213-018-5106-2. PubMed DOI

Bai Y, Maruskin LA, Chen S, Gordon AM, Stellar JE, McNeil GD, ..., Keltner D (2017) Awe, the diminished self, and collective engagement: universals and cultural variations in the small self. J Pers Soc Psychol 113(2):185-209. 10.1037/pspa0000087

Belfi AM, Vessel EA, Brielmann A, Isik AI, Chatterjee A, Leder H, ..., Starr GG (2019) Dynamics of aesthetic experience are reflected in the default-mode network. Neuroimage 188:584-597. 10.1016/j.neuroimage.2018.12.017

Bershad AK, Schepers ST, Bremmer MP, Lee R, & de Wit H (2019) Acute subjective and behavioral effects of microdoses of lysergic acid diethylamide in healthy human volunteers. Biol Psychiatry. 10.1016/j.biopsych.2019.05.019

Bershad AK, Preller KH, Lee R, Keedy S, Wren-Jarvis J, Bremmer MP, de Wit H. Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity. Biol Psychiatry Cogn Neurosci Neuroimaging. 2020;5(4):461–467. doi: 10.1016/j.bpsc.2019.12.007. PubMed DOI PMC

Bogenschutz MP, Forcehimes AA, Pommy JA, Wilcox CE, Barbosa PCR, Strassman RJ. Psilocybin-assisted treatment for alcohol dependence: a proof-of-concept study. J Psychopharmacol. 2015;29(3):289–299. doi: 10.1177/0269881114565144. PubMed DOI

Cameron LP, Benson CJ, DeFelice BC, Fiehn O, Olson DE. Chronic, intermittent microdoses of the psychedelic N, N-dimethyltryptamine (DMT) produce positive effects on mood and anxiety in rodents. ACS Chem Neurosci. 2019;10(7):3261–3270. doi: 10.1021/acschemneuro.8b00692. PubMed DOI PMC

Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, ..., Nutt DJ (2012) Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A 109(6):2138-2143. 10.1073/pnas.1119598109

Carhart-Harris RL, Leech R, Hellyer PJ, Shanahan M, Feilding A, Tagliazucchi E, ..., Nutt D (2014) The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs. Front Hum Neurosci 8. 10.3389/fnhum.2014.00020

Carhart-Harris RL, Muthukumaraswamy S, Roseman L, Kaelen M, Droog W, Murphy K, ..., Nutt DJ (2016) Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proc Natl Acad Sci U S Am 113(17):4853-4858. 10.1073/pnas.1518377113

European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2019) European drug report: trends and developments, 2019

Fadiman J, Korb S. Might microdosing psychedelics be safe and beneficial? An initial exploration. J Psychoactive Drugs. 2019;51(2):118–122. doi: 10.1080/02791072.2019.1593561. PubMed DOI

Family N, Maillet EL, Williams LTJ, Krediet E, Carhart-Harris RL, Williams TM, ..., Raz S (2020) Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers. Psychopharmacology (Berl) 237(3):841-853. 10.1007/s00213-019-05417-7

Forstmann M, Yudkin DA, Prosser AMB, Heller SM, Crockett MJ. Transformative experience and social connectedness mediate the mood-enhancing effects of psychedelic use in naturalistic settings. Proc Natl Acad Sci U S A. 2020;117(5):2338–2346. doi: 10.1073/pnas.1918477117. PubMed DOI PMC

Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance. Psychopharmacology. 2006;187(3):268–283. doi: 10.1007/s00213-006-0457-5. PubMed DOI

Hendricks PS. Awe: a putative mechanism underlying the effects of classic psychedelic-assisted psychotherapy. Int Rev Psychiatry. 2018;30(4):331–342. doi: 10.1080/09540261.2018.1474185. PubMed DOI

Holze F, Liechti ME, Hutten N, Mason NL, Dolder PC, Theunissen EL, ..., Kuypers KPC (2021) Pharmacokinetics and pharmacodynamics of lysergic acid diethylamide microdoses in healthy participants. Clin Pharmacol Ther 109(3):658-666. 10.1002/cpt.2057

Horsley RR, Palenicek T, Kolin J, Vales K. Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats. Behav Pharmacol. 2018;29(6):530–536. doi: 10.1097/Fbp.0000000000000394. PubMed DOI

Hutten N, Mason NL, Dolder PC, & Kuypers KPC (2019) Self-rated effectiveness of microdosing with psychedelics for mental and physical health problems among microdosers. Front Psychiatry 10. 10.3389/fpsyt.2019.00672

Hutten N, Mason NL, Dolder PC, Theunissen EL, Holze F, Liechti ME, ..., Kuypers KPC (2020) Mood and cognition after administration of low LSD doses in healthy volunteers: a placebo controlled dose-effect finding study. Eur Neuropsychopharmacol 41:81-91. 10.1016/j.euroneuro.2020.10.002

Johnson MW, Hendricks PS, Barrett FS, Griffiths RR. Classic psychedelics: an integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacol Ther. 2019;197:83–102. doi: 10.1016/j.pharmthera.2018.11.010. PubMed DOI

Johnstad PG. Powerful substances in tiny amounts: an interview study of psychedelic microdosing. Nordic Stud Alcohol Drugs. 2018;35(1):39–51. doi: 10.1177/1455072517753339. DOI

Keltner D, Haidt J. Approaching awe, a moral, spiritual, and aesthetic emotion. Cogn Emot. 2003;17(2):297–314. doi: 10.1080/02699930302297. PubMed DOI

Krebs TS, Johansen PO. Lysergic acid diethylamide (LSD) for alcoholism: meta-analysis of randomized controlled trials. J Psychopharmacol. 2012;26(7):994–1002. doi: 10.1177/0269881112439253. PubMed DOI

Kuypers KPC. The therapeutic potential of microdosing psychedelics in depression. Ther Adv Psychopharmacol. 2020;10:2045125320950567. doi: 10.1177/2045125320950567. PubMed DOI PMC

Kuypers KPC, Ng L, Erritzoe D, Knudsen GM, Nichols CD, Nichols DE, ..., Nutt D (2019) Microdosing psychedelics: more questions than answers? An overview and suggestions for future research. J Psychopharmacol 33(9):1039-1057. 10.1177/0269881119857204

Kyzar EJ, Nichols CD, Gainetdinov RR, Nichols DE, Kalueff AV. Psychedelic drugs in biomedicine. Trends Pharmacol Sci. 2017;38(11):992–1005. doi: 10.1016/j.tips.2017.08.003. PubMed DOI

Lifshitz M, van Elk M, Luhrmann TM. Absorption and spiritual experience: a review of evidence and potential mechanisms. Conscious Cogn. 2019;73:102760. doi: 10.1016/j.concog.2019.05.008. PubMed DOI

Passie T, Seifert J, Schneider U, Emrich HM. The pharmacology of psilocybin. Addict Biol. 2002;7(4):357–364. doi: 10.1080/1355621021000005937. PubMed DOI

Petranker R, Anderson T, Farb N. Psychedelic research and the need for transparency: polishing Alice’s looking glass. Front Psychol. 2020;11:1681. doi: 10.3389/fpsyg.2020.01681. PubMed DOI PMC

Petranker R, Anderson T, Maier L, Barratt M, Ferris J, Winstock AR (2020b) Microdosing psychedelics: subjective benefits and challenges, substance testing behavior, and the relevance of intention. J Psychopharmacol. 10.1177/0269881120953994

Piff PK, Dietze P, Feinberg M, Stancato DM, Keltner D. Awe, the small self, and prosocial behavior. J Pers Soc Psychol. 2015;108(6):883–899. doi: 10.1037/pspi0000018. PubMed DOI

Polito V, Stevenson RJ. A systematic study of microdosing psychedelics. PLoS ONE. 2019;14(2):e0211023. doi: 10.1371/journal.pone.0211023. PubMed DOI PMC

Preston JL, Shin F. Spiritual experiences evoke awe through the small self in both religious and non-religious individuals. J Exp Soc Psychol. 2017;70:212–221. doi: 10.1016/j.jesp.2016.11.006. DOI

Prochazkova L, Lippelt DP, Colzato LS, Kuchar M, Sjoerds Z, Hommel B. Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting. Psychopharmacology. 2018;235(12):3401–3413. doi: 10.1007/s00213-018-5049-7. PubMed DOI PMC

Rabkin JG, Markowitz JS, Stewart J, Mcgrath P, Harrison W, Quitkin FM, Klein DF. How blind is blind - assessment of patient and doctor medication guesses in a placebo-controlled trial of imipramine and phenelzine. Psychiatry Res. 1986;19(1):75–86. doi: 10.1016/0165-1781(86)90094-6. PubMed DOI

Rucker JJH, Iliff J, Nutt DJ. Psychiatry & the psychedelic drugs. Past, present & future. Neuropharmacology. 2018;142:200–218. doi: 10.1016/j.neuropharm.2017.12.040. PubMed DOI

Shiota MN, Keltner D, Mossman A. The nature of awe: elicitors, appraisals, and effects on self-concept. Cogn Emot. 2007;21(5):944–963. doi: 10.1080/0269993060923668. DOI

Silvia PJ, Nusbaum EC. On personality and piloerection: individual differences in aesthetic chills and other unusual aesthetic experiences. Psychol Aesthet Creat Arts. 2011;5(3):208–214. doi: 10.1037/a0021914. DOI

Sinclair RC, Hoffman C, Mark MM, Martin LL, Pickering TL. Construct accessibility and the misattribution of arousal: Schachter and Singer revisited. Psychol Sci. 1994;5(1):15–19. doi: 10.1111/j.1467-9280.1994.tb00607.x. DOI

Spee B, Ishizu T, Leder H, Mikuni J, Kawabata H, Pelowski M. Neuropsychopharmacological aesthetics: a theoretical consideration of pharmacological approaches to causative brain study in aesthetics and art. Prog Brain Res. 2018;237:343–372. doi: 10.1016/bs.pbr.2018.03.021. PubMed DOI

Studerus E, Gamma A, Kometer M, Vollenweider FX. Prediction of psilocybin response in healthy volunteers. PLoS ONE. 2012;7(2):e30800. doi: 10.1371/journal.pone.0030800. PubMed DOI PMC

Tellegen A, Atkinson G. Openness to absorbing and self-altering experiences (“absorption”), a trait related to hypnotic susceptibility. J Abnorm Psychol. 1974;83(3):268. doi: 10.1037/h0036681. PubMed DOI

van Elk M, Karinen A, Specker E, Stamkou E, & Baas M (2016) ‘Standing in awe’: the effects of awe on body perception and the relation with absorption. Collabra 2(1)

van Elk M, Gomez MAA, van der Zwaag W, van Schie HT, Sauter D. The neural correlates of the awe experience: reduced default mode network activity during feelings of awe. Hum Brain Mapp. 2019;40(12):3561–3574. doi: 10.1002/hbm.24616. PubMed DOI PMC

Van Laar MW, Gestel BV (2017) Nationale drug monitor. Trimbos-instituut

Vessel EA, Starr GG, Rubin N. The brain on art: intense aesthetic experience activates the default mode network. Front Hum Neurosci. 2012;6:1–17. doi: 10.3389/fnhum.2012.00066. PubMed DOI PMC

Wild TC, Kuiken D, & Schopflocher D (1995) The role of absorption in experiential involvement. J Personal Soc Psychol 69(3): 569–579. Retrieved from://WOS:A1995RR98400015

Winstock A, Barratt MJ, Maier LJ, Ferris J (2018) Global drug survey (GDS) 2018. Key findings report

Yaden DB, Kaufman SB, Hyde E, Chirico A, Gaggioli A, Zhang JW, Keltner D. The development of the Awe Experience Scale (AWE-S): a multifactorial measure for a complex emotion. J Posit Psychol. 2019;14(4):474–488. doi: 10.1080/17439760.2018.1484940. DOI

Yanakieva S, Polychroni N, Family N, Williams LTJ, Luke DP, Terhune DB. The effects of microdose LSD on time perception: a randomised, double-blind, placebo-controlled trial. Psychopharmacology. 2019;236(4):1159–1170. doi: 10.1007/s00213-018-5119-x. PubMed DOI PMC

Psilocybin-assisted neurofeedback for the improvement of executive functions: a randomized semi-naturalistic-lab feasibility study

Natural language signatures of psilocybin microdosing

Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study

Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study