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Cited by 192Psychedelics and Drug StudiesPain Management and Placebo EffectParanormal Experiences and Beliefs

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Self-blinding citizen science to explore psychedelic microdosing

Open access
Szigeti, Balázs, Kartner, Laura, Blemings, Allan, Rosas, Fernando, Feilding, Amanda, Nutt, David J, Carhart-Harris, Robin L, Erritzoe, David·2021·eLife
DOI 10.7554/elife.62878PMC PMC7925122
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Abstract

Microdosing is the practice of regularly using low doses of psychedelic drugs. Anecdotal reports suggest that microdosing enhances well-being and cognition; however, such accounts are potentially biased by the placebo effect. This study used a 'self-blinding' citizen science initiative, where participants were given online instructions on how to incorporate placebo control into their microdosing routine without clinical supervision. The study was completed by 191 participants, making it the largest placebo-controlled trial on psychedelics to-date. All psychological outcomes improved significantly from baseline to after the 4 weeks long dose period for the microdose group; however, the placebo group also improved and no significant between-groups differences were observed. Acute (emotional state, drug intensity, mood, energy, and creativity) and post-acute (anxiety) scales showed small, but significant microdose vs. placebo differences; however, these results can be explained by participants breaking blind. The findings suggest that anecdotal benefits of microdosing can be explained by the placebo effect.

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Figures

Figure 1. Timeline and outcomes. Top horizontal arrow shows the experimental timeline and the three timepoints associated with accumulative outcomes (blue frame). 1/3 of the participants were randomly assigned to one of the three groups, where the groups differ in the number of placebo/microdose weeks during the dose-regime: 4/0 for PL, 2/2 for HH, and 0/4 for the MD group. Note that even for microdose weeks, placebo capsules are mixed into the schedule, for example, weeks 1 and 3 for the HH group are microdose weeks. Acute measures (green frames) were taken on Thursdays, while the potential microdose was still active. Post-acute measures (purple frame) were administered on Sundays, when no capsule was taken, these outcomes test the weekly effects of microdosing. For a list of measures administered at each timepoint, see Table 1.
Figure 1. Timeline and outcomes. Top horizontal arrow shows the experimental timeline and the three timepoints associated with accumulative outcomes (blue frame). 1/3 of the participants were randomly assigned to one of the three groups, where the groups differ in the number of placebo/microdose weeks during the dose-regime: 4/0 for PL, 2/2 for HH, and 0/4 for the MD group. Note that even for microdose weeks, placebo capsules are mixed into the schedule, for example, weeks 1 and 3 for the HH group are microdose weeks. Acute measures (green frames) were taken on Thursdays, while the potential microdose was still active. Post-acute measures (purple frame) were administered on Sundays, when no capsule was taken, these outcomes test the weekly effects of microdosing. For a list of measures administered at each timepoint, see Table 1.CC BY · PubMed Central
Figure 2. Overview of the self-blinding setup. First, capsules are prepared: microdoses are put into opaque gel capsules, while empty capsules are used as placebos. Next, weekly sets of capsules are assembled according to the dose schedule (A; no capsules taken on Wed., Sat., and Sun.). Then, capsules are placed inside zip bags with a printed day label (Monday, Tuesday, etc.; zip bags and day labels not shown on figure). Next, each weekly set and a unique QR code are placed inside envelopes. Eight such weekly envelopes are prepared, four of which correspond to microdose weeks (MD) and four that corresponds to placebo weeks (PL). The eight envelopes are used in a semi-random drawing process (orange arrow, B), which involves another set of QR codes and random number generation, see Appendix 1—figure 1 for details. The drawing selects four envelopes, corresponding to the 4 weeks of the dose period, while the remaining four are discarded (green arrow). The drawing is constrained such that only the three combinations of PL/MD weeks are possible, as shown in C, each with a probability of 1/3. Panel D shows the content of each envelope. Participants open the corresponding envelope each week and take the matching capsule every day. Scanning the QR links to the study’s IT system and enables to decode which capsule was taken when.
Figure 2. Overview of the self-blinding setup. First, capsules are prepared: microdoses are put into opaque gel capsules, while empty capsules are used as placebos. Next, weekly sets of capsules are assembled according to the dose schedule (A; no capsules taken on Wed., Sat., and Sun.). Then, capsules are placed inside zip bags with a printed day label (Monday, Tuesday, etc.; zip bags and day labels not shown on figure). Next, each weekly set and a unique QR code are placed inside envelopes. Eight such weekly envelopes are prepared, four of which correspond to microdose weeks (MD) and four that corresponds to placebo weeks (PL). The eight envelopes are used in a semi-random drawing process (orange arrow, B), which involves another set of QR codes and random number generation, see Appendix 1—figure 1 for details. The drawing selects four envelopes, corresponding to the 4 weeks of the dose period, while the remaining four are discarded (green arrow). The drawing is constrained such that only the three combinations of PL/MD weeks are possible, as shown in C, each with a probability of 1/3. Panel D shows the content of each envelope. Participants open the corresponding envelope each week and take the matching capsule every day. Scanning the QR links to the study’s IT system and enables to decode which capsule was taken when.CC BY · PubMed Central
Figure 3. Flow diagram showing participation and completion rates through the study. The completion of the 4 weeks follow-up timepoint was optional.
Figure 3. Flow diagram showing participation and completion rates through the study. The completion of the 4 weeks follow-up timepoint was optional.CC BY · PubMed Central
Figure 4. Each panel shows the adjusted mean estimate of the change from baseline and the 95% CI for the accumulative outcomes. Top horizontal bars represent the over time comparisons for each group (from baseline to post-regime [week 5] and from baseline to follow-up). Symbols on top of bars show the significance for the PL/HH/MD groups, respectively (e.g. change from baseline to post-regime in well-being was significant for the MD group, but not significant for the other two groups, see legend). There was no significant between-groups difference at any timepoint for any scale. Sample size was 240/191/159 at the pre-, post-regime and 4 weeks follow-up timepoints, respectively. See Supplementary files 4, 5, and 6 for the unadjusted descriptive statistics, adjusted mean differences (and their significance) associated with both over time and between group comparisons and model parameters, respectively.
Figure 4. Each panel shows the adjusted mean estimate of the change from baseline and the 95% CI for the accumulative outcomes. Top horizontal bars represent the over time comparisons for each group (from baseline to post-regime [week 5] and from baseline to follow-up). Symbols on top of bars show the significance for the PL/HH/MD groups, respectively (e.g. change from baseline to post-regime in well-being was significant for the MD group, but not significant for the other two groups, see legend). There was no significant between-groups difference at any timepoint for any scale. Sample size was 240/191/159 at the pre-, post-regime and 4 weeks follow-up timepoints, respectively. See Supplementary files 4, 5, and 6 for the unadjusted descriptive statistics, adjusted mean differences (and their significance) associated with both over time and between group comparisons and model parameters, respectively.CC BY · PubMed Central
Figure 5. Acute and post-acute outcomes stratified by guess and condition. On each panel, the four bars represent the adjusted mean estimates and the associated 95% CI of the four strata corresponding to the four combinations of guess (PL/MD) and condition (PL/MD). For the psychological measures (all, but CPS) the sample size was 857 (participants contributed four scores corresponding to the four acute/post-acute assessment timepoints during the dose period), while for cognitive performance it was 684, see bottom of each panel for the condition, guess, and the proportion of scores in the given strata. Top horizontal lines represent comparisons between strata derived from the models. The two short lines on top are the comparisons between PL and MD conditions with fixed guess, while the two longer lines below are the comparisons between PL and MD guesses with fixed drug condition, see Supplementary file 8 for numerical results. Note that for all self-reported outcomes, change in guess is almost always significant, while a change in condition is never significant. In the case of cognitive performance, neither change in guess nor change in condition is significant.
Figure 5. Acute and post-acute outcomes stratified by guess and condition. On each panel, the four bars represent the adjusted mean estimates and the associated 95% CI of the four strata corresponding to the four combinations of guess (PL/MD) and condition (PL/MD). For the psychological measures (all, but CPS) the sample size was 857 (participants contributed four scores corresponding to the four acute/post-acute assessment timepoints during the dose period), while for cognitive performance it was 684, see bottom of each panel for the condition, guess, and the proportion of scores in the given strata. Top horizontal lines represent comparisons between strata derived from the models. The two short lines on top are the comparisons between PL and MD conditions with fixed guess, while the two longer lines below are the comparisons between PL and MD guesses with fixed drug condition, see Supplementary file 8 for numerical results. Note that for all self-reported outcomes, change in guess is almost always significant, while a change in condition is never significant. In the case of cognitive performance, neither change in guess nor change in condition is significant.CC BY · PubMed Central
Appendix 1—figure 1. Semi-random drawing process during the self-blinding setup, which corresponds to panel B of Figure 2 in the main text. After the eight envelopes are prepared, pairs of microdose and placebo envelopes are placed inside big envelopes together with the corresponding ‘big envelope QR’ (a set of four QRS in the red frame) and then sealed. Once each big envelope is assembled, they are shuffled, and one is randomly selected. ‘1’ and ‘3’ are written on the two small envelopes inside (that contain the capsules and the weekly QR code, see Figure 2 of the main text) to designate that these will be used for weeks 1 and 3 (Panel A). Next, the other big envelope needs to be selected with the help of the big envelope QRs. Each big envelope QR has four QR codes: envelope id and 1,2,3. First, a random number is generated between 1 and 3 (dice roll) and the corresponding QR is scanned (Panel B). Scanning displays a message ‘You need to find big envelope with ID XXXX’. Then, a random big envelope is opened and the ‘Envelope ID’ field is scanned from the big envelope QR inside. Scanning displays ‘This big envelope’s ID is YYYY’. This process is continued until big envelope XXXX is found. ‘2’ and ‘4’ are written on the two small envelopes inside to designate that these will be used for weeks 2 and 4.
Appendix 1—figure 1. Semi-random drawing process during the self-blinding setup, which corresponds to panel B of Figure 2 in the main text. After the eight envelopes are prepared, pairs of microdose and placebo envelopes are placed inside big envelopes together with the corresponding ‘big envelope QR’ (a set of four QRS in the red frame) and then sealed. Once each big envelope is assembled, they are shuffled, and one is randomly selected. ‘1’ and ‘3’ are written on the two small envelopes inside (that contain the capsules and the weekly QR code, see Figure 2 of the main text) to designate that these will be used for weeks 1 and 3 (Panel A). Next, the other big envelope needs to be selected with the help of the big envelope QRs. Each big envelope QR has four QR codes: envelope id and 1,2,3. First, a random number is generated between 1 and 3 (dice roll) and the corresponding QR is scanned (Panel B). Scanning displays a message ‘You need to find big envelope with ID XXXX’. Then, a random big envelope is opened and the ‘Envelope ID’ field is scanned from the big envelope QR inside. Scanning displays ‘This big envelope’s ID is YYYY’. This process is continued until big envelope XXXX is found. ‘2’ and ‘4’ are written on the two small envelopes inside to designate that these will be used for weeks 2 and 4.CC BY · PubMed Central
Appendix 1—figure 2. Attitude toward psychedelics in the sample at baseline. At the top of each panel is the item answered and below the bar graphs show the percentage of participant responses (n = 240).
Appendix 1—figure 2. Attitude toward psychedelics in the sample at baseline. At the top of each panel is the item answered and below the bar graphs show the percentage of participant responses (n = 240).CC BY · PubMed Central
Appendix 1—figure 3. Characteristics of the microdoses used by participants. Top panel shows the distribution of doses for both LSD/LSD analogues (n = 180, 12.8 ± 5.5 μg) and psilocybin containing mushrooms (n = 56, 0.19 ± 0.12 g), bottom table provides additional information on the microdose preparation.
Appendix 1—figure 3. Characteristics of the microdoses used by participants. Top panel shows the distribution of doses for both LSD/LSD analogues (n = 180, 12.8 ± 5.5 μg) and psilocybin containing mushrooms (n = 56, 0.19 ± 0.12 g), bottom table provides additional information on the microdose preparation.CC BY · PubMed Central

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Citations

Cites

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Research works printed but not linked: 1

  1. Fadiman J, Krob S. 2017. Microdosing: the phenomenon, research results, and startling surprises. Lecture Presented at the Psychedelic Science 2017 Conference.

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Metadata

Authors
Szigeti, B., Kartner, L., Blemings, A., Rosas, F., Feilding, A., Nutt, D. J., Carhart-Harris, R. L., & Erritzoe, D.
Affiliations
  • Imperial College London (GB)
  • Centre for Psychedelic Research, Imperial College London, London, United Kingdom
  • Beckley Foundation (GB)
Corresponding author
Szigeti, Balázs
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2021-03-02
Volume
10
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.62878
PMC
PMC7925122
OpenAlex
W3134377893
Cited by
192
References
46
Citations by year
2026: 24 · 2025: 31 · 2024: 34 · 2023: 35 · 2022: 45 · 2021: 22
FWCI
23.19
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • Figshare (submittedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • National Institute for Health and Care Research (ACF-2013-21-501, CL-2017-21-004)
  • Academy of Medical Sciences (SGL019\1063)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Psychedelics and Drug Studies
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
  • Social Sciences › Psychology › Social Psychology › Paranormal Experiences and Beliefs
Keywords
psychedelic microdosing, placebo effect, citizen science, subjective well-being, mood, anxiety, creativity, emotional state
MeSH terms
Citizen Science, Adult, Affect, Cognition, Creativity, Dose-Response Relationship, Drug, Emotions, Female, Hallucinogens, Humans, Male, Placebo Effect

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