IUPAC: 2-(4-bromo-2,5-dimethoxyphenyl)ethan-1-amine · C₁₀H₁₄BrNO₂ · MW 260.13 g/mol · CAS 66142-81-2 (HCl 51354-35-7)
4-Bromo-2,5-dimethoxyphenethylamine. First synthesised by Alexander Shulgin (1974), documented in PIHKAL. The prototype of the "2C" ring-substituted phenethylamine psychedelics — a primary amine, two carbons to the ring, 2,5-dimethoxy pattern with a 4-bromo handle. Street/context names: Nexus, Bees, Venus, and (as an adulterated pink-powder mixture) tusi / "tucibí" / "pink cocaine".
*34 nM at the antagonist-labeled ([³H]ketanserin) state; sub-nanomolar (0.66–1 nM) at the high-affinity agonist ([¹²⁵I]DOI) state. See binding table.
2C-B is a ring-substituted phenethylamine psychedelic. Its psychedelic action is partial agonism at the 5-HT2A receptor, activating Gq/11 → PLCβ → IP₃/DAG signaling in layer V cortical pyramidal neurons — the shared final common pathway of the classic serotonergic psychedelics. Unlike transporter drugs (cocaine at DAT, MDMA at SERT), 2C-B engages a GPCR directly and does not meaningfully release monoamines.
The pharmacophore is austere: a protonatable primary amine, an ethyl tether, a 2,5-dimethoxy aromatic pattern and a 4-bromo substituent. The 2- and 5-methoxy oxygens hydrogen-bond to the serine cluster of TM5/TM3 (S5.46 / S3.36), the amine forms the canonical salt bridge to Asp3.32, and the lipophilic 4-bromo buries into a hydrophobic subpocket toward TM6 — the single change that lifts 2C-B's 5-HT2A affinity roughly two orders of magnitude over the unsubstituted 2C-H parent.
The protonated amine salt-bridges to Asp155 (D3.32); the 2,5-dimethoxy oxygens engage Ser159/Ser242; the 4-Br fills a hydrophobic pocket. This anchors 2C-B in the deep orthosteric site and biases the receptor toward the active, transducer-coupled conformation.
2C-B binds the high-affinity, G-protein-coupled active state (labeled by the agonist [¹²⁵I]DOI) with Ki ≈ 0.66–1 nM, but the antagonist-labeled ([³H]ketanserin) state at ~34 nM — a ~30–50× agonist-state selectivity, the fingerprint of a true agonist.
2C-B is a partial agonist: at human 5-HT2C it drives only ~74% of serotonin's maximal Ca²⁺ response (Emax). It occupies the pocket with very high affinity yet stabilizes the active state incompletely — high potency, submaximal ceiling.
2C-B also binds 5-HT2C (rat Ki ~36 nM; human functional EC₅₀ ~4.1 µM). 5-HT2C activity shapes anxiogenic tone, satiety and the ceiling on euphoria, and is part of why higher doses turn edgy rather than simply "more".
Unlike the DOx amphetamine psychedelics (DOB, DOI) and unlike amphetamine itself, 2C-B has no α-methyl group. Its side chain is therefore an ordinary substrate for monoamine oxidase — giving a shorter, "softer" course than α-methylated analogs.
The gap between "barely there" and "full psychedelic" is only ~10–15 mg. A partial agonist with very high affinity saturates receptor occupancy over a narrow concentration band, producing a notoriously steep dose–response curve.
Efficacy vs LSD. LSD's diethylamide moiety folds a hydrophobic "lid" (the extracellular loop 2 / TM region) over the orthosteric pocket, slowing dissociation to hours and yielding near-full 5-HT2A efficacy with pronounced β-arrestin recruitment. 2C-B has no such lid: it binds tightly but releases quickly and activates the receptor to a submaximal ceiling. Experientially this reads as a shorter, more body-forward, more controllable and often more sensual/entactogen-tinged trip than the long, cognitively immersive LSD state — a difference rooted in residence time and partial efficacy, not in the target.
Formal human PK for 2C-B is poorly characterised — there are no rigorous published bioavailability, volume-of-distribution or terminal half-life figures, and we do not invent them here. The dose, onset and duration values below are the consensus of PIHKAL, forensic case data and harm-reduction reporting, not controlled pharmacokinetic studies. What is well established is the metabolic route, mapped in human hepatocyte / recombinant-CYP work (Carmo et al., 2005; Theobald & Maurer, 2007) and rodent studies (Kanamori et al., 2002).
Metabolism cascade: two parallel routes. Oxidative deamination by monoamine oxidase removes the amine to give the inactive 4-bromo-2,5-dimethoxyphenylacetic acid ("2C-B acid"); in parallel, cytochrome-P450 O-demethylation (chiefly CYP2D6, with CYP3A4/2C9/1A2 contributions) opens a phenol that is conjugated (glucuronide/sulfate) and cleared renally.
Why MAO dependence matters twice. First, because deamination is a major clearance route, 2C-B's effects are meaningfully prolonged and intensified by any MAO inhibitor — harmala alkaloids (ayahuasca/"pharmahuasca"), moclobemide, phenelzine, tranylcypromine, selegiline, even the MAOI antibiotic linezolid. This is a genuine danger, not a way to "boost" the trip: it removes the body's main brake and layers serotonergic + adrenergic load on top of a serotonergic drug. Second, CYP2D6 O-demethylation means CYP2D6 poor metabolisers (~7–10% of Europeans) and anyone on strong CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion) will shift more clearance onto the MAO route and see altered exposure.
5-HT2A partial agonism on layer V cortical pyramidal neurons is the entry point; from there the experience is built by where those neurons project. 2C-B sits, subjectively, between the classic psychedelics and the entactogens — visually and sensorially rich at low-to-moderate doses, more fully psychedelic and more overwhelming as the steep curve is climbed.
Gq-driven excitation of layer V pyramidal cells in visual and association cortex increases glutamatergic drive and disrupts normal top-down predictive filtering — the substrate of colour enhancement, geometric/patterned visuals, altered depth and time, and loosened associative cognition. This is the same 5-HT2A mechanism as LSD/psilocin, expressed through a shorter, partial-agonist pulse.
At lower doses 2C-B is characteristically physical — tactile enhancement, warmth, mild stimulation and a sociable, sensual quality that has earned it an "MDMA-lite meets LSD-lite" reputation. Mechanistically this fringe reflects its partial efficacy and mixed 5-HT2 profile rather than the massive monoamine release that defines true entactogens like MDMA.
Peripheral and central 5-HT2 activation produces the "body load" — mild-to-moderate nausea, muscle tension, vasoconstriction, pupil dilation and stimulation. It is usually manageable at common doses but scales sharply, and above ~30 mg can become genuinely unpleasant (anxiety, tachycardia, thermal dysregulation) rather than simply "stronger".
Because occupancy of a high-affinity partial agonist saturates over a narrow band, 2C-B behaves almost like distinct drugs across its range: ~10 mg is light and sensual, ~20 mg is clearly psychedelic, ~30 mg+ is intense and often overwhelming. Small absolute errors (a few milligrams) move you between these regimes — the core reason accurate weighing matters more here than for most substances.
Tolerance to 5-HT2A psychedelics develops rapidly and is cross-tolerant with LSD/psilocybin; the practical floor between meaningful sessions is on the order of a week or two. There is no evidence of a compulsive-use / dependence liability comparable to stimulants or opioids.
Evidence-based, non-moralistic. 2C-B's specific risks are dose control, mistaken identity, and dangerous serotonergic combinations — all manageable with accurate information, a scale, and a test kit.
The most information-rich number on this page is not a single Ki but the gap between two of them: ~34 nM against the antagonist-labeled ([³H]ketanserin) receptor versus ~0.66–1 nM against the agonist-labeled ([¹²⁵I]DOI) receptor. Same molecule, same pocket — the ~30–50× difference is entirely about which conformational ensemble the receptor is in when 2C-B binds.
Read this the way FlexAID∆S reads a complex — through the entropy term of ΔG = ΔH − TΔS. An unliganded GPCR is a broad, high-Shannon-entropy ensemble flickering between inactive and active-like states. When 2C-B docks — amine to Asp3.32, dimethoxy oxygens to the Ser3.36/Ser5.46 cluster, 4-bromo into the TM6 hydrophobic subpocket — it selects and rigidifies the active-state sub-ensemble: the toggle-switch Trp6.48 rotamer set, the TM6 register, the ordered extracellular cap. That collapse of conformational entropy is a real −TΔS penalty, and it is precisely why the agonist-state affinity is enormous: the enthalpic contacts (halogen contact, salt bridge, H-bonds) are large enough to pay for ordering the receptor, so the drug preferentially recognises the pre-organised active state.
Partial agonism falls straight out of the same accounting. LSD folds its diethylamide "lid" over the pocket and clamps the active state almost completely — a deep entropy collapse, slow koff, near-full efficacy. 2C-B has no lid: it binds with high affinity but leaves the active-state ensemble incompletely ordered, so a residual pool of conformational entropy persists in the bound complex. Higher residual receptor entropy at the bound state → a lower activation ceiling → the submaximal Emax we measure functionally (~74% at 5-HT2C) and feel as a shorter, lower-ceiling, more controllable trip than LSD. Efficacy, here, is literally how much conformational entropy the ligand is able to remove.
| Target | Affinity | Rel. | Mechanism |
|---|---|---|---|
|
5-HT2A
Serotonin 2A · human · [³H]ketanserin
|
Ki = 34 nM
antagonist-state label
|
Partial agonist | |
|
5-HT2A *
Serotonin 2A · human · [¹²⁵I]DOI
|
Ki = 0.66–1 nM
agonist high-affinity state
|
Active state | |
|
5-HT2C
Serotonin 2C · human · Ca²⁺ func.
|
EC₅₀ = 4.1 µM
Emax 74% of 5-HT
|
Partial agonist | |
|
5-HT2C
Serotonin 2C · rat · [³H]mesulergine
|
Ki = 36 nM
binding (190 nM in A9 cells)
|
Agonist | |
|
5-HT2A
Serotonin 2A · rat · cross-species
|
Ki = 0.88–16 nM
DOI 0.88 · ketanserin 16
|
Agonist |