RCT · 2026

Brain imaging comparison of 2C-B and psilocybin in 22 healthy volunteers


Original title
Spatiotemporal mapping of brain organisation following the administration of 2C-B and psilocybin.
Authors
Mallaroni P, Singleton SP, Mason NL, et al.
Journal
Molecular psychiatry, 2026
Molecules
Psilocybin, 2C-B
Conditions
Healthy volunteers
Participants
22
Evidence grade
Moderate
Source
Read the original paper

The question

How does the lesser-studied psychedelic 2C-B change patterns of brain activity, and how do those changes compare with psilocybin?

What they did

Twenty-two healthy volunteers each received three conditions on separate occasions: 20 mg of 2C-B, 15 mg of psilocybin, and a placebo. Neither participants nor researchers knew which was given on a given day (double-blind crossover design). Brain activity at rest was recorded with a high-strength 7 tesla MRI scanner, and the researchers measured several features of how brain networks connect and vary over time. They also compared the pattern of brain effects with maps of serotonin and monoamine receptor and transporter distribution from PET imaging.

What they found

Compared with placebo, both 2C-B and psilocybin reduced connectivity within individual brain networks while broadly increasing connectivity between networks and between deeper brain structures and the cortex. Compared with psilocybin, 2C-B produced less pronounced reductions in the moment-to-moment variability of between-network connectivity, but raised connectivity in higher-order (transmodal) brain regions. Both drugs increased overall connectivity in spatially different patterns, yet produced similar increases in a measure of spontaneous brain complexity. The spatial pattern of effects lined up with known differences in the two drugs’ binding to serotonin receptors and monoamine transporters beyond the 5-HT2A receptor, and self-reported psychedelic effects tracked with changes along the transmodal axis of brain organization.

The fine print

This was a small study of 22 healthy volunteers, so the findings may not generalize to people with mental health conditions. Only one dose of each drug was tested, and blinding is difficult to maintain with psychedelics because their effects are noticeable. The outcomes are brain-imaging measures, not symptom or treatment outcomes, so nothing here shows clinical benefit. This summary is based on the abstract only.

What it means

2C-B and psilocybin both shift the brain toward more communication between networks, but they are not identical, and those differences appear to reflect their different pharmacology. This is early mechanistic work in healthy people, not evidence that either drug treats any condition.

Evidence grade: Moderate. A randomized, double-blind, placebo-controlled crossover trial, but with only 22 healthy volunteers and brain-imaging measures rather than clinical outcomes.

This summary is based on the study’s published abstract.

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