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Home/Research/Placebo/Neuroimaging & Brain Measures

Placebo for Neuroimaging & Brain Measures

19 papers and 145 clinical trials exploring placebo as a treatment for neuroimaging & brain measures.

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
IndicationApproximately 264 million people globally suffer from depression, with PTSD affecting around 8 million adults in the United States each year.

Neuroimaging & Brain Measures

Recent advances in neuroimaging have shed light on the neurobiological mechanisms underlying the effects of psychedelics, particularly in the treatment of mental health disorders such as depression and PTSD. Studies involving compounds like psilocybin and MDMA have demonstrated significant changes in brain activity associated with therapeutic outcomes.

Full Neuroimaging & Brain Measures profile

Academic Research

19 papers
Open Accessindividual

EXPRESS: Global Increases in Brain Glucose Metabolism Following Acute N,N-Dimethyltryptamine and Harmine Administration in Healthy Volunteers: A randomised [F]FDG-PET Study

This re-analysis of a randomised crossover study (n=14) in healthy men found that buccal DMT plus harmine (pharmahuasca) increased brain glucose metabolism compared with placebo, with widespread rises across the cortex, especially in higher-order networks. The increase was linked to harmine levels, but not to DMT levels or to how intense the experience felt.

Published
June 1, 2026
Journal
Journal of Cerebral Blood Flow and Metabolism
Authors
Egger, K., Bozsak, R., Aicher, H. D. D., Sari, H., Poetzsch, S. N., Rominger, A., Martin-Soelch, C., Smallridge, J. W., Dornbierer, D., Quednow, B. B., Scheidegger, M., Cumming, P.
Open Accessindividual

LSD Relaxes Structural Constraints on Brain Dynamics: A Connectome Harmonic MEG Study

This re-analysis of a brain imaging study (n=17) used magnetoencephalography (MEG) in people given LSD or placebo and found that LSD loosened the usual link between brain structure and low-frequency activity, while gamma activity changed in a more selective way. Changes in default-mode network regions were linked to stronger feelings of ego dissolution.

Published
May 29, 2026
Journal
Biorxiv
Authors
Subramani, V., Pascarella, A., Brunel, J., Harel, Y., Muthukumaraswamy, S., Carhart-Harris, R., Jerbi, K., Lioi, G., Farrugia, N.
Open Accessindividual

Time-resolved Neural and Experience Dynamics of Medium- and High-dose N,N-Dimethyltryptamine

This repeated-measures dose-dependent study (n=19) investigates DMT's subjective and neural dynamics under naturalistic conditions. Participants received 20mg or 40mg doses of freebase DMT in a blinded, counterbalanced design, with EEG data and time-resolved subjective measures collected. The 40mg dose produced more intense visual hallucinations and emotional responses. Neural analyses revealed alpha power and permutation entropy were most associated with subjective experiences, whereas lempel-ziv complexity was less predictive, challenging prior assumptions about its role in psychedelic states.

Published
December 30, 2025
Journal
Journal of Cognitive Neuroscience
Authors
Lewis-Healey, E., Pallavicini, C., Cavanna, F., D'Amelio, T., de la Fuente, L. A., Copa, D., Muller, S., Bruno, N., Tagliazucchi, E., Bekinschtein, T.
Open Accessindividual

N,N-dimethyltryptamine effects on connectome harmonics, subjective experience and comparative psychedelic experiences

This neuroscience secondary (n=25) of two earlier studies used connectome harmonic decomposition to analyse how DMT affects brain function across the structural connectome (white matter pathways), finding that DMT reshapes the connectome harmonic repertoire and increases repertoire entropy similarly to other psychedelics (psilocybin, LSD, ketamine), and importantly demonstrating for the first time that energy spectrum differences and repertoire entropy measures correlate with subjective experience intensity in a time-resolved manner, revealing close coupling between connectome harmonics and conscious experience under psychedelics.

Published
September 12, 2025
Journal
Neuropsychopharmacology
Authors
Vohryzek, J., Luppi, A. I., Atasoy, S., Deco, G., Carhart-Harris, R. L., Timmermann, C., Kringelbach, M. L.
Open Accessindividual

Reduced Brain Responsiveness to Emotional Stimuli With Escitalopram But Not Psilocybin Therapy for Depression

This secondary analysis of an RCT (n=59) investigates the impact of psilocybin-assisted therapy (PAT) and escitalopram (SSRI) on responsiveness to emotional stimuli in patients with moderate-to-severe major depressive disorder over a 6-week trial period. Responses to emotional faces were reduced in the SSRI group, not the psilocybin group at the follow-up.

Published
May 7, 2025
Journal
American Journal of Psychiatry
Authors
Wall, M. B., Demetriou, L., Giribaldi, B., Roseman, L., Ertl, N., Erritzoe, D., Nutt, D. J., Carhart-Harris, R. L.
Open Accessindividual

Network control energy reductions under DMT relate to serotonin receptors, signal diversity, and subjective experience

This re-analysis (n=14) applies a receptor-informed network control theory framework to investigate the effects of DMT on the brain's control energy landscape. It reveals that DMT, like LSD and psilocybin, reduces global control energy, with these trajectories correlating with EEG signal diversity and subjective intensity ratings. Furthermore, the regional effects of DMT correlate with serotonin 2a receptor density, demonstrating a potential proof-of-concept for predicting pharmacological intervention effects on brain dynamics using control models.

Published
April 18, 2025
Journal
Communications Biology
Authors
Singleton, S. P., Timmermann, C., Luppi, A. I., Eckernäs, E., Roseman, L., Carhart-Harris, R. L., Kuceyeski, A.

Clinical Trials

145 trials
Not yet recruitingPhase II

Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers

This Phase II, randomised, double-blind, placebo-controlled crossover trial (n=92) will evaluate the analgesic potential of a single intravenous infusion of (2R,6R)-hydroxynorketamine (HNK) in healthy adults aged 18 to 60 years. The study will assess whether 0.5 mg/kg HNK reduces acute experimental pain during quantitative sensory testing (QST) and will also examine pain-related and emotion-related brain responses. Participants will receive HNK or matched placebo as a single intravenous infusion over approximately 40 minutes, with visits repeated 1 to 3 weeks apart in the treatment group. A no-treatment control arm is included to help estimate natural changes and placebo effects. Pain ratings, blood draws, and functional MRI assessments will be repeated before and after infusion, including follow-up measures immediately after treatment, at 4 to 5 hours, and one day later. The trial will also compare placebo with the no-treatment group to gauge placebo analgesia.

Started
June 15, 2026
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT07504601
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

Elucidating the Relevance of the Psychedelic Experience to Psilocybin's Anti-Anhedonic Effects

This Phase I, randomised, open-label, crossover trial (n=85) will assess whether psilocybin’s anti-anhedonic effects in people with major depressive disorder and anhedonia are linked to the psychedelic experience. Participants will receive two oral 25 mg doses of psilocybin across two sessions, with 1 mg oral risperidone given 30 minutes before psilocybin in one session to blunt acute psychedelic effects. The study includes two experimental sequences: psilocybin first followed by psilocybin plus risperidone, or the reverse order. Participants will undergo three MRI sessions: baseline before treatment, then one day after each psilocybin session. The trial will compare clinical, behavioural and imaging responses using fMRI tasks related to aesthetic processing, reward, sexual arousal and cognitive flexibility, alongside self-report measures of well-being, depression, anhedonia and altered states of consciousness, with follow-up extending to about 12 weeks after enrolment.

Started
November 1, 2025
Type
interventional
Blinding
none
Randomized
Yes
Registry ID
NCT07490353
Not yet recruitingPhase I/II

The Acute Effects of Psilocybin on Cognition, Memory, and Brain Function

This double-blind, placebo-controlled, crossover trial (n=48) will study the effects of psilocybin (15 mg) on memory, cognition, and brain function in healthy adults.

Started
September 1, 2025
Type
interventional
Blinding
quadruple
Randomized
Yes
Registry ID
NCT07079852
CompletedPhase I

A Study Assessing Brain Activity, Safety, Tolerability, and Pharmacokinetics Following Multiple Doses of MLS101 (Psilocybin) in Healthy Volunteers

This Phase I randomised, single-blind trial (n=20) will study the effects of multiple low doses of psilocybin (MLS101) on brain activity, safety, tolerability, and pharmacokinetics in healthy adult volunteers.

Started
July 1, 2025
Type
interventional
Blinding
single
Randomized
Yes
Registry ID
NCT07050368
CompletedPhase I

Comparative Acute Effects of R-MDMA and S-MDMA in Healthy Participants (R-S-)

This randomised, triple-blind, placebo-controlled Phase I crossover trial (n=24) will compare the acute effects of two enantiomers of MDMA—R-MDMA (300 mg) and S-MDMA (100 mg)—in healthy adult participants.

Started
May 1, 2025
Type
interventional
Blinding
triple
Randomized
Yes
Registry ID
NCT06905652

Explore further

Search all Placebo papers Search all Neuroimaging & Brain Measures trials Full Placebo profile Full Neuroimaging & Brain Measures profile