Acute dose-dependent effects of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) compared with 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin in a double-blind, placebo-controlled study in healthy participants

Apr 28, 2026Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

Immediate dose-related effects of 2C-B compared with MDMA and psilocybin in healthy adults

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Abstract

At a 30 mg dose, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) induced subjective effects comparable to MDMA, lasting an average of 4.9 hours.

2C-B produced dose-dependent subjective effects, with the 30 mg dose exerting effects similar to MDMA but lower than those of psilocybin.
Only psilocybin caused significant 'bad drug effects' and anxiety compared to placebo.
The 30 mg dose of 2C-B resulted in psychedelic-type alterations of consciousness and increased emotional empathy, akin to MDMA's effects.
MDMA showed the highest cardiovascular stimulation, followed by psilocybin and then 2C-B.
Only MDMA significantly increased plasma oxytocin and neurophysin I concentrations.
2C-B exhibited dose-proportional pharmacokinetics with a plasma elimination half-life of approximately 1.3 hours.

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Based on its in vitro profile and preliminary evidence, 4-bromo-2,5-dimethoxyphenethylamine (2C-B) may have psychoactive properties that are similar to 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin, which are investigated for the treatment of posttraumatic stress disorder and depressive disorders. We compared acute effects of 2C-B (10, 20, and 30 mg), 125 mg MDMA, and 25 mg psilocybin in 24 healthy participants (12 women, 12 men) using a double-blind, randomized, placebo-controlled, crossover design. Outcome measures included acute subjective effects, autonomic effects, adverse effects, effects on emotional and cognitive empathy, plasma oxytocin and neurophysin I concentrations, and pharmacokinetics up to 9 h. 2C-B produced dose-dependent subjective effects, with the 30 mg dose exerting comparable "any drug effects" to MDMA but lower "any drug effects" than psilocybin. Only psilocybin induced "bad drug effects" and "anxiety" compared with placebo. The 30 mg dose of 2C-B induced psychedelic-type alterations of state of consciousness and increased emotional empathy similarly to MDMA. The average subjective effect duration of 30 mg 2C-B was 4.9 h and similar to MDMA (4.8 h) and shorter than psilocybin (6.1 h). MDMA produced the highest cardiovascular stimulation, followed by psilocybin and 2C-B. Only MDMA increased plasma oxytocin and neurophysin I concentrations. 2C-B exhibited dose-proportional pharmacokinetics, with a plasma elimination half-life of ~1.3 h. The 30 mg dose of 2C-B induced entactogenic and psychedelic effects similarly to MDMA and psilocybin, respectively. MDMA is more cardiostimulant than psilocybin and 2C-B. At the tested dose-level, psilocybin is more distressing than MDMA and 2C-B. These results may assist with dose-finding for future 2C-B research and provide a direct comparison with standard doses of the prototypical compounds MDMA and psilocybin. Trial registration: ClinicalTrials.gov identifier: NCT05523401.

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Acute dose-dependent effects of 4-bromo-2,5-dimethoxyphenethylamine (2C-B) compared with 3,4-methylenedioxymethamphetamine (MDMA) and psilocybin in a double-blind, placebo-controlled study in healthy participants

Abstract

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