2C-B

2C-B (4-bromo-2,5-dimethoxyphenethylamine) is a synthetic substituted phenethylamine psychedelic first synthesized by Alexander Shulgin in 1974 and subsequently characterized in the 1991 compendium PiHKAL as one of the six most important psychoactive phenethylamines in the 2,5-dimethoxy series. The compound is a structural analog of mescaline bearing a bromine substituent at the 4-position of the phenyl ring, a modification that confers substantially increased potency at serotonin 5-HT2A and 5-HT2C receptors relative to the unsubstituted parent compound. Pharmacologically, 2C-B acts as a partial agonist at the serotonin 5-HT2A, 5-HT2B, and 5-HT2C receptors, with reported binding affinity (Ki) at the 5-HT2A receptor ranging from 0.66 to 32 nM across published radioligand displacement assays and functional efficacy (Emax) ranging from 4 to 101 percent of the serotonin maximum depending on the signal transduction pathway measured. The discrepancy in reported efficacy reflects genuine pathway-dependent pharmacology: in phospholipase C-inositol phosphate accumulation assays, 2C-B demonstrates moderate partial agonism, whereas in Xenopus oocyte electrophysiology systems, the compound behaves primarily as an antagonist at the 5-HT2A receptor with minimal intrinsic activity, suggesting that the psychoactive effects may involve biased agonism, additional receptor targets, or downstream signaling selectivity not captured by conventional second-messenger assays.

The pharmacokinetics of 2C-B following oral administration are characterized by rapid absorption (onset 30 to 90 minutes), a short elimination half-life of approximately 1.2 to 2.5 hours in oral fluid, and a total duration of subjective effects of 3 to 6 hours. Metabolism proceeds predominantly through oxidative deamination catalyzed by monoamine oxidase A and B (MAO-A and MAO-B), producing the principal metabolites 4-bromo-2,5-dimethoxyphenylacetic acid and 2-(4-bromo-2,5-dimethoxyphenyl)ethanol, with secondary O-demethylation pathways generating species-variable hydroxylated metabolites. In human hepatocytes, a characteristic demethylated-deaminated metabolite, 2-(4-bromo-2-hydroxy-5-methoxyphenyl)ethanol, distinguishes human metabolism from that of rodent species and has implications for forensic identification.

Clinical pharmacology data for 2C-B in controlled settings remain limited but are expanding. The Papaseit et al. (2018) observational study in 16 experienced volunteers self-administering 10 to 20 mg orally documented moderate cardiovascular stimulation (systolic blood pressure increase of approximately 19 mmHg, heart rate increase of approximately 13 bpm), psychedelic alterations of moderate intensity, and minimal cortisol elevation relative to classical psychedelics. The Mallaroni et al. (2023) double-blind, placebo-controlled crossover trial at Maastricht University comparing 20 mg 2C-B with 15 mg psilocybin demonstrated that 2C-B produces qualitatively similar psychedelic alterations of consciousness but with significantly less dysphoria, less ego dissolution, and shorter duration than psilocybin at the tested doses. A 2026 double-blind, placebo-controlled crossover study at the University of Basel (Vizeli, Liechti, and colleagues) comparing 10, 20, and 30 mg 2C-B with 125 mg MDMA and 25 mg psilocybin in 24 healthy participants reported dose-dependent subjective effects, with 30 mg 2C-B producing comparable overall drug effects to MDMA, lower anxiety than psilocybin, and more moderate cardiovascular stimulation than MDMA.

2C-B was commercially marketed in Germany and the Netherlands as a sexual enhancer under the brand names Erox and Performax during the 1980s and early 1990s, prior to its classification as a controlled substance. It was placed in Schedule I of the United States Controlled Substances Act effective June 1995, and in Schedule II of the United Nations Convention on Psychotropic Substances in March 2001. The compound has no approved medical indication in any jurisdiction. This monograph reviews the chemistry, synthesis, and structure-activity relationships of 2C-B; the receptor pharmacology and signaling pathway selectivity; the pharmacokinetic and metabolic profile across species; the preclinical and emerging clinical evidence base; sourcing and quality verification considerations for research applications; reconstitution and handling; stack-interaction considerations; adverse-event and safety signal assessment; and a comparative evaluation of five structurally or pharmacologically related psychedelic phenethylamines against 2C-B on five competency standards.