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Home/Research/Placebo/Microdosing

Placebo for Microdosing

8 papers and 11 clinical trials exploring placebo as a treatment for microdosing.

CompoundComparator / Control

Placebo

Placebo is the most widely referenced comparator in psychedelic clinical research, appearing in over 500 trials. Understanding how placebos are designed, administered, and interpreted is essential to evaluating the evidence base for psychedelic-assisted therapies — and one of the field’s most contested methodological challenges.

Full Placebo profile
IndicationAround 300 million people worldwide are affected by a variety of mental health conditions that microdosing may address.

Microdosing

Microdosing involves the regular consumption of sub-hallucinogenic doses of psychedelics, primarily for cognitive enhancement and emotional wellbeing. Although popularised through anecdotal reports, rigorous scientific evidence on its effects is still limited, pointing to a critical need for further research in this emerging field.

Full Microdosing profile

Academic Research

8 papers
Open Accessindividual

It's all about the relationship: The caregiver experience of supporting a person with advanced cancer going through an LSD microdosing trial

This secondary analysis of an RCT (n=15 interviews) found that caregivers of people with advanced cancer were generally supportive of participation in an LSD microdosing plus meaning-centred psychotherapy trial, though some were initially hesitant. It highlighted the bidirectional nature of patient-caregiver well-being, with the intervention seen as offering hope, easing existential distress, and strengthening their relationship.

Published
February 26, 2026
Journal
Palliative & Supportive Care
Authors
Cottam, F., Wells, A., Clayden, C., Reynolds, L.
Open Accessindividual

Microdosing psychedelics and its effect on creativity: Lessons learned from three double-blind placebo controlled longitudinal trials

This combined analysis (n=175) of three double-blind placebo-controlled longitudinal experiments investigated the effects of microdosing psilocybin (0.74 -; 1.71mg) on creativity and found that it increased the originality of their ideas while generating novel applications for ordinary things (divergent thinking). However, it did not increase the number of novel ideas, or their ability to detect features that are common across multiple things (convergent thinking).

Published
November 2, 2025
Journal
Neuropsychopharmacology
Authors
Prochazkova, L., van Elk, M., Marschall, J., Rifkin, B. D., Fiacchino, D., Fejer, G., Hommel, B., Schoen, N.
Open Accessindividual

An investigation of acute Physiological and Psychological Moderators of Psychedelic-induced Personality Change among Healthy Volunteers

This re-analysis of a single-blind, fixed-order trial (n=28) investigates the effects of a single high-dose psilocybin (25 mg) on personality traits in psychedelic-naïve healthy volunteers. It finds significant reductions in neuroticism one month post-administration, moderated by subjective experience meaningfulness and ego dissolution, suggesting psilocybin catalyses lasting personality changes with therapeutic potential.

Published
January 1, 2025
Journal
Neuroscience Applied
Authors
Godfrey, K., Weiss, B., Zhang, X., Spriggs, M. J., Peill, J. M., Lyons, T., Carhart-Harris, R. L., Erritzoe, D.
Open Accessmeta

Is microdosing a placebo? A rapid review of low-dose LSD and psilocybin research

This review (2024) critically assesses the available evidence from dose-controlled studies investigating low doses of LSD and psilocybin. It proposes eight potential issues, such as small sample sizes, a limited number of controlled studies, and the possibility of selection bias, that challenge the claims that microdosing is predominantly a placebo effect. It suggests that it is currently inconclusive whether microdosing is merely a placebo.

Published
June 14, 2024
Journal
Journal of Psychopharmacology
Authors
Polito, V., Liknaitzky, P.
Open Accessmeta

Microdosing psychedelics: Current evidence from controlled studies

This systematic review (s=14) compiles double-blind, placebo-controlled studies on microdosing LSD (5-20μg) under laboratory conditions. It reports that acute low doses of LSD affect blood pressure, sleep, neural connectivity, mood, social cognition, and perceptions of pain and time, with noticeable effects at 10-20 μg but not at 5μg. While no serious adverse effects were noted, repeated microdosing did not significantly change mood or cognition.

Published
January 26, 2024
Journal
Biological Psychiatry
Authors
Murphy, R., Muthukumaraswamy, S., De Wit, H.
Open Accessindividual

The difference between ‘placebo group’ and ‘placebo control’: a case study in psychedelic microdosing

Using computational modelling the authors show that weak blinding combined with positive expectancy produces an "activated expectancy bias" that can inflate treatment estimates and generate false positives, and introduce the Correct Guess Rate Curve (CGRC) to estimate outcomes under perfect blinding. Re-analysis of a self‑blinding psychedelic microdose trial suggests observed microdose–placebo differences may reflect AEB (microdosing functioning as an active placebo), and they propose a blinding‑integrity tool compatible with the CGRC.

Published
July 26, 2023
Journal
Scientific Reports
Authors
Szigeti, B., Nutt, D. J., Carhart-Harris, R. L., Erritzoe, D.

Clinical Trials

11 trials
Not yet recruitingPhase I

Psilocybin Microdosing on Cognition, Mood and Quality of Life

This Phase I, randomised, double-blind, parallel trial (n=20) will study the effects of intermittent psilocybin microdosing on mood, cognition, subjective well‑being and brain structure/function in healthy adults with no history of psychedelic use aged 21–40. The primary aim is basic science: to evaluate whether 30 days of intermittent microdosed psilocybin produces measurable changes on psychological, cognitive and neuroimaging outcomes compared with placebo, in the presumed absence of overt psychedelic experiences. Participants will be randomised to receive either 2 mg powdered psilocybin (from Psilocybe cubensis) in capsules or matching 0 mg placebo capsules three times weekly for four weeks, with weekly assessments and re‑assessment after 30 days of steady dosing; primary outcome measures are assessed from enrolment to end of treatment (8 weeks). Outcomes include task‑based fMRI (Complex Working Memory Span task), structural and diffusion imaging (including NODDI), neuropsychological batteries (NIH Toolbox, Switching Stroop, Flanker, Penn Conditional Exclusion, Face‑Name Associative Memory, 9‑hole pegboard), personality and symptom scales (NEO‑FFI, Beck Depression and Anxiety Inventories, Harvard Flourishing), and ecological momentary assessments via MindLamp. Key eligibility features are no prior psychedelic use, ability to consent, effective contraception for women of childbearing potential, and exclusion for current mood/psychotic disorders, substance use disorders, significant medical/neurological illness or MRI contraindications.

Started
April 1, 2026
Type
interventional
Blinding
double
Randomized
Yes
Registry ID
NCT07449351
RecruitingPhase I

Drug Effects on Mood and Behavior – Expectancy (MESA-X)

Early Phase I, randomised, placebo-controlled single-session study (n=48) testing a low (13 µg) dose of LSD versus placebo under known versus uncertain drug-identity instructions (balanced placebo design).

Started
June 26, 2025
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT07061886
CompletedPhase I

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Multiple Doses of MLS101 in Healthy Participants

This randomised, quadruple-blind, placebo-controlled trial (n=24 planned; 16 actual reported) will evaluate the safety, tolerability, and pharmacokinetics of multiple doses of MLS101 (a low-dose psilocybin formulation) in healthy adult participants.

Started
November 8, 2024
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT06643637
CompletedPhase I

A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of MLS101 in Healthy Participants

This Phase I interventional, randomized, quadruple-blind, placebo-controlled study (planned n=80; ACTUAL 24) will assess safety, tolerability and pharmacokinetics of low-dose psilocybin (MLS101) in healthy adults using SAD and MAD cohorts.

Started
March 1, 2024
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT06326606
CompletedPhase II

Microdosing Psychedelics to Improve Mood

Randomized, triple-blind, placebo-controlled crossover Phase II study (n=50) testing weekly 2 mg oral psilocybin microdoses versus placebo in adults with major depressive disorder.

Started
April 4, 2022
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT05259943
WithdrawnPhase I

Mood and Cognitive Effects of Psilocybin in Healthy Participants (MELO)

Double-blind, randomised, placebo-controlled, within-subject study (n=20) testing six low/microdoses of oral psilocybin (0, 1, 2, 5, 8, 10 mg) in healthy volunteers to identify doses that improve mood, cognition and sleep without hallucinogenic effects.

Started
April 1, 2022
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT05252598

Explore further

Search all Placebo papers Search all Microdosing trials Full Placebo profile Full Microdosing profile