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Set and setting in microdosing: an oft-overlooked principle

  • Theoretical and Methodological Perspective
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Abstract

Rationale

The use of psychedelics for medical and recreational purposes is rising. Contextual factors such as expectancy, intention, and sensory and social environment (set and setting) are widely recognized as moderating the effects of these substances. Nevertheless, clinical trials of microdosing — the ingestion of small, sub-hallucinogenic doses of psychedelics — rarely report their set and setting. This fact suggests that such factors are not considered important in the context of microdosing.

Objective

This paper challenges this assumption and makes the case for the crucial relevance of set and setting in microdosing practice. Building on set and setting theory and placebo theory, we explain why set and setting are of crucial importance in the case of microdosing.

Results

This reasoning helps elucidate the role of set and setting in determining the outcomes of microdosing and helps explain some of the contradictory results that have emerged in microdosing research in recent years.

Conclusion

Set and setting are important constructs to be considered especially in the context of microdosing psychedelics. By reporting set and setting, the results of microdosing research can be made more reliable and consistent.

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Notes

  1. A clear and rigorous definition of microdosing has yet to be established. Continuing on previous works by the authors, we use the term “sub-hallucinogenic” as our operational definition to sidestep the implication (hinted by the oft-used term “sub-perceptual”) that the individual has not perceived that they ingested a drug.

 References

  • Anderson T, Petranker R, Christopher A, Rosenbaum D, Weissman C, Dinh-Williams L-A, Hui K, Hapke E (2019a) Psychedelic microdosing benefits and challenges: an empirical codebook. Harm Reduct J 16(1):43. https://doi.org/10.1186/s12954-019-0308-4

    Article  PubMed  PubMed Central  Google Scholar 

  • Anderson T, Petranker R, Rosenbaum D, Weissman CR, Dinh-Williams L-A, Hui K, Hapke E, Farb NAS (2019b) Microdosing psychedelics: personality, mental health, and creativity differences in microdosers. Psychopharmacology 236(2):731–740. https://doi.org/10.1007/s00213-018-5106-2

    Article  CAS  PubMed  Google Scholar 

  • Austin P (2018) A quick guide to microdosing psychedelics: everything you want to know about this cutting-edge method of psychedelic use

  • Bershad AK, Schepers ST, Bremmer MP, Lee R, de Wit H (2019) Acute subjective and behavioral effects of microdoses of LSD in healthy human volunteers. Biol Psychiat. https://doi.org/10.1016/j.biopsych.2019.05.019

    Article  PubMed  Google Scholar 

  • Bershad AK, Preller KH, Lee R, Keedy S, Wren-Jarvis J, Bremmer MP, de Wit H (2020) Preliminary report on the effects of a low dose of LSD on resting-state amygdala functional connectivity. Biol Psychiatry: Cognitive Neurosci Neuroimaging 5(4):461–467

    Google Scholar 

  • Beyer SV (2010) Singing to the plants: a guide to mestizo shamanism in the upper Amazon (Reprint edition). University of New Mexico Press.

  • Bicket MC, Samus QM, McNabney M, Onyike CU, Mayer LS, Brandt J, Rabins P, Lyketsos C, Rosenblatt A (2010) The physical environment influences neuropsychiatric symptoms and other outcomes in assisted living residents. Int J Geriatr Psychiatry 25(10):1044–1054. https://doi.org/10.1002/gps.2460

    Article  PubMed  PubMed Central  Google Scholar 

  • Cameron LP, Nazarian A, Olson DE (2020) Psychedelic microdosing: prevalence and subjective effects. J Psychoactive Drugs 52(2):113–122

    Article  PubMed  PubMed Central  Google Scholar 

  • Carhart-Harris RL, Friston KJ (2019) REBUS and the anarchic brain: toward a unified model of the brain action of psychedelics. Pharmacol Rev 71(3):316–344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carhart-Harris R, Kaelen M, Whalley M, Bolstridge M, Feilding A, Nutt D (2014) LSD enhances suggestibility in healthy volunteers. Psychopharmacology 232(4):785–794. https://doi.org/10.1007/s00213-014-3714-z

    Article  CAS  PubMed  Google Scholar 

  • Carhart-Harris RL, Roseman L, Haijen E, Erritzoe D, Watts R, Branchi I, Kaelen M (2018) Psychedelics and the essential importance of context. J Psychopharmacol :0269881118754710. https://doi.org/10.1177/0269881118754710

  • Carver CS, White TL (1994) Behavioral inhibition, behavioral activation, and affective responses to impending reward and punishment: the BIS/BAS scales. J Pers Soc Psychol 67:319–333

    Article  Google Scholar 

  • Dimascio A, Klerman GL (1960) Experimental human psychopharmacology: the role of non-drug factors. In Sarwer-Foner GJ (ed) The dynamics of psychiatric drug therapy (1st ed., pp. 56–97). Charles C. Thomas

  • Dimascio A, Rinkel M (1963) Personality and drugs, “specific” or “non-specific” influence on drug action. In Rinkel M (ed), Specific and non-specific factors in psychopharmacology. Philosophical Library

  • Dobkin de Rios M (1975) Man, culture and hallucinogens: an overview. In: Rubin V (ed) Cannabis and culture. Mouton Publishers, pp 401–416

    Chapter  Google Scholar 

  • Dressler HM, Bright SJ, Polito V (2021) Exploring the relationship between microdosing, personality and emotional insight: a prospective study. J Psychedelic Stud 5(1):9–16. https://doi.org/10.1556/2054.2021.00157

    Article  Google Scholar 

  • Fadiman J (2011) The psychedelic explorer’s guide: safe, therapeutic, and sacred journeys. Park Street Press.

  • Fadiman J, Korb S (2019) Might microdosing psychedelics be safe and beneficial? An initial exploration. J Psychoactive Drugs 51(2):118–122

    Article  PubMed  Google Scholar 

  • Family N, Maillet EL, Williams LT, Krediet E, Carhart-Harris RL, Williams TM, Nichols CD, Goble DJ, Raz S (2020) Safety, tolerability, pharmacokinetics, and pharmacodynamics of low dose lysergic acid diethylamide (LSD) in healthy older volunteers. Psychopharmacology 237(3):841–853

    Article  CAS  PubMed  Google Scholar 

  • Feldman PE (1963) Non-drug parameters of psychopharmacology: the role of the physician. In: Rinkel M (ed) Specific and non-specific factors in psychopharmacology. Philosophical Library, pp 149–158

    Google Scholar 

  • Fields HL (2018) How expectations influence pain. Pain 159:S3–S10

    Article  PubMed  Google Scholar 

  • Garcia-Romeu A, Barrett FS, Carbonaro TM, Johnson MW, Griffiths RR (2021) Optimal dosing for psilocybin pharmacotherapy: considering weight-adjusted and fixed dosing approaches. J Psychopharmacol 35(4):353–361. https://doi.org/10.1177/0269881121991822

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gukasyan N, Nayak SM (2021) Psychedelics, placebo effects, and set and setting: insights from common factors theory of psychotherapy. Transcult Psychiatr :1363461520983684

  • Haden M, Emerson B, Tupper KW (2016) A public-health-based vision for the management and regulation of psychedelics. J Psychoactive Drugs 48(4):243–252. https://doi.org/10.1080/02791072.2016.1202459

    Article  PubMed  Google Scholar 

  • Haijen ECHM, Kaelen M, Roseman L, Timmermann C, Kettner H, Russ S, Nutt D, Daws RE, Hampshire ADG, Lorenz R, Carhart-Harris RL (2018). Predicting responses to psychedelics: a prospective study. Front Pharmacolo, 9https://doi.org/10.3389/fphar.2018.00897

  • Hartogsohn I (2016) Set and setting, psychedelics and the placebo response: an extra-pharmacological perspective on psychopharmacology. J Psychopharmacol 30(12):1259–1267. https://doi.org/10.1177/0269881116677852

    Article  CAS  PubMed  Google Scholar 

  • Hartogsohn I (2017) Constructing drug effects: a history of set and setting. Drug Sci Policy Law 3:2050324516683325. https://doi.org/10.1177/2050324516683325

    Article  Google Scholar 

  • Hartogsohn I (2018) The meaning-enhancing properties of psychedelics and their mediator role in psychedelic therapy, spirituality, and creativity. Front Neurosci 12:1–5

    Article  Google Scholar 

  • Hartogsohn I (2020) American trip: set, setting, and the psychedelic experience in the twentieth century. The MIT Press

    Book  Google Scholar 

  • Hartogsohn, I. (2022, January 13). Set and settings in psychedelic clinical trials and moving forward. Psychedelics as therapeutics: gaps, challenges and opportunities, Onlne. https://www.youtube.com/watch?v=DASxonJzvFg

  • Helman, C. G. (2001). Chapter 1 — placebos and nocebos: the cultural construction of belief. In D. Peters (Ed.), Understanding the placebo effect in complementary medicine (pp. 3–16). Churchill Livingstone. http://www.sciencedirect.com/science/article/pii/B9780443060311500046

  • Hutten NRPW, Mason NL, Dolder PC, Kuypers KPC (2019) Motives and side-effects of microdosing with psychedelics among users. Int J Neuropsychopharmacol 22(7):426–434. https://doi.org/10.1093/ijnp/pyz029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hyde RW (1960). Psychological and social determinants of drug action. In G. J. Sarwer-Foner (Ed.), Dynamics of psychiatric drug therapy (1st ed., pp. 297–315). C.C. Thomas.

  • Kaertner LS, Steinborn MB, Kettner H, Spriggs MJ, Roseman L, Buchborn T, Balaet M, Timmermann C, Erritzoe D, Carhart-Harris RL (2021) Positive expectations predict improved mental-health outcomes linked to psychedelic microdosing. Sci Rep 11(1):1–11

    Article  Google Scholar 

  • Kettner HS, Rosas F, Timmermann C, Kärtner L, Carhart-Harris RL, Roseman L. (2021). Psychedelic communitas: intersubjective experience during psychedelic group sessions predicts enduring changes in psychological wellbeing and social connectedness. Front Pharmacol 12.https://doi.org/10.3389/fphar.2021.623985

  • Kilindi, I. (2013, July 12). High-dose mushrooms beyond the threshold. Breaking Convention: The 2nd multidisciplinary convention on psychedelic consciousness, University of Greenwich. https://www.youtube.com/watch?v=ejdKeghBhNs

  • Lasagna L (1963) The relation of drug induced changes to personality. In: Rinkel M (ed) Specific and non-specific factors in psychopharmacology. Philosophical Library, pp 114–129

    Google Scholar 

  • Lea T, Amada N, Jungaberle H (2019) Psychedelic microdosing: a subreddit analysis. J Psychoactive Drugs 0(0):1–12. https://doi.org/10.1080/02791072.2019.1683260

    Article  Google Scholar 

  • Leary T, Litwin G, Metzner R (1963) Reactions to psilocybin administered in a supportive environment. J Nerv Ment Dis 137:561–573

    Article  CAS  PubMed  Google Scholar 

  • Levine RA (2001) Culture and personality studies 1918–1960: myth and history. J Pers 69(6):803–818

    Article  CAS  PubMed  Google Scholar 

  • Lowe H, Toyang N, Steele B, Valentine H, Grant J, Ali A, Ngwa W, Gordon L (2021) The therapeutic potential of psilocybin. Molecules 26(10):2948

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCrae RR, Costa PT (1987) Validation of the five-factor model of personality across instruments and observers. J Pers Soc Psychol 52(1):81

    Article  CAS  PubMed  Google Scholar 

  • Monson CM, Wagner AC, Mithoefer AT, Liebman RE, Feduccia AA, Jerome L, Yazar-Klosinski B, Emerson A, Doblin R, Mithoefer MC (2020) MDMA-facilitated cognitive-behavioural conjoint therapy for posttraumatic stress disorder: an uncontrolled trial. Eur J Psychotraumatol 11(1):1840123

    Article  PubMed  PubMed Central  Google Scholar 

  • Noorani T. (2021). Containment matters: set and setting in contemporary psychedelic psychiatry. Philosophy, Psychiatry & Psychology.

  • Olson JA, Suissa-Rocheleau L, Lifshitz M, Raz A, Veissiere SP. (2020). Tripping on nothing: placebo psychedelics and contextual factors. Psychopharmacology, 1–12.

  • Ona G (2018) Inside bad trips: exploring extra-pharmacological factors. J Psychedelic Stud 2(1):53–60. https://doi.org/10.1556/2054.2018.001

    Article  Google Scholar 

  • Ona G, Bouso JC (2020) Potential safety, benefits, and influence of the placebo effect in microdosing psychedelic drugs: a systematic review. Neurosci Biobehav Rev 119:194–203

    Article  CAS  PubMed  Google Scholar 

  • Perkins D, Schubert V, Simonová H, Tófoli LF, Bouso JC, Horák M, Galvão-Coelho NL, Sarris J (2021) Influence of context and setting on the mental health and wellbeing outcomes of ayahuasca drinkers: results of a large international survey. Front Pharmacol, 12https://doi.org/10.3389/fphar.2021.623979

  • Petranker R, Anderson T, Farb N (2020a) Psychedelic research and the need for transparency—polishing Alice’s looking glass. PsyArXiv. https://doi.org/10.31234/osf.io/vgt3r

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

  • Petranker R, Kim J, Anderson T (2022) Microdosing as a response to the meaning crisis: a qualitative analysis. J Humanist Psychology :00221678221075076

  • Polito V, Liknaitzky P (2022) The emerging science of microdosing: a systematic review of research on low dose psychedelics (1955-2021) and recommendations for the field. Neurosci Biobehav Rev :104706https://doi.org/10.1016/j.neubiorev.2022.104706

  • Polito V, Stevenson RJ (2019) A systematic study of microdosing psychedelics. PLoS ONE 14(2):e0211023. https://doi.org/10.1371/journal.pone.0211023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pollan M (2018) How to change your mind: what the new science of psychedelics teaches us about consciousness, dying, addiction, depression, and transcendence. Penguin Press

  • Prochazkova L, Lippelt DP, Colzato LS, Kuchar M, Sjoerds Z, Hommel B (2018) Exploring the effect of microdosing psychedelics on creativity in an open-label natural setting. Psychopharmacology 235(12):3401–3413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prochazkova L, Elk van M, Marschall J, Rifkin BD, Fejer G, Schoen N, Fiacchino D, Kuchar M, Hommel B (2021) Microdosing psychedelics and its effect on creativity: lessons learned from three double-blind placebo controlled longitudinal trials. PsyArXiv. https://doi.org/10.31234/osf.io/emcxw

  • Rosegrant J (1976) The impact of set and setting on religious experience in nature. J Sci Study Relig 15(4):301–310. https://doi.org/10.2307/1385633

    Article  Google Scholar 

  • Sessa B (2012) The Psychedelic Renaissance: reassessing the role of psychedelic drugs in 21st century psychiatry and society. Muswell Hill Press

  • Stewart-Williams S (2004) The placebo puzzle: putting together the pieces. Health Psychol: Off J Division Health Psychol, American Psychol Assoc 23(2):198–206. https://doi.org/10.1037/0278-6133.23.2.198

    Article  Google Scholar 

  • Strickland JC, Garcia-Romeu A, Johnson MW (2020) Set and setting: a randomized study of different musical genres in supporting psychedelic therapy. ACS Pharmacology & Translational Science

  • Sunstein CR (2014) Nudging: a very short guide. J Consum Policy 37(4):583–588

    Article  Google Scholar 

  • Szigeti B, Kartner L, Blemings A, Rosas F, Feilding A, Nutt DJ, Carhart-Harris RL, Erritzoe D (2021) Self-blinding citizen science to explore psychedelic microdosing. Elife 10:e62878. https://doi.org/10.7554/eLife.62878

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamir M, Bigman YE (2018) Expectations influence how emotions shape behavior. Emotion 18(1):15

    Article  PubMed  Google Scholar 

  • Ulrich R (1984) View through a window may influence recovery from surgery. Science (New York) 224(4647):420–421

  • Waldman A (2018) A really good day: how microdosing made a mega difference in my mood, my marriage, and my life (Reprint edition). Anchor

  • Watts R, Luoma JB (2020) The use of the psychological flexibility model to support psychedelic assisted therapy. J Contextual Behav Sci 15:92–102. https://doi.org/10.1016/j.jcbs.2019.12.004

    Article  Google Scholar 

  • Wenzel M, von Versen C, Hirschmüller S, Kubiak T (2015) Curb your neuroticism—mindfulness mediates the link between neuroticism and subjective well-being. Personality Individ Differ 80:68–75

    Article  Google Scholar 

  • Williams F (2018) The nature fix: why nature makes us happier, healthier, and more creative (1 edition). W. W. Norton & Company

  • Zeifman RJ, Spriggs MJ, Kettner H, Lyons T, Rosas F, Mediano PAM, Erritzoe D, Carhart-Harris R (2022) From relaxed beliefs under psychedelics (REBUS) to revised beliefs after psychedelics (REBAS): preliminary development of the relaxed beliefs questionnaire (REB-Q). PsyArXiv. https://doi.org/10.31234/osf.io/w8j6t

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Hartogsohn, I., Petranker, R. Set and setting in microdosing: an oft-overlooked principle. Psychopharmacology 239, 3771–3777 (2022). https://doi.org/10.1007/s00213-022-06249-8

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