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Aleph-1 is the compound that started Alexander Shulgin's Aleph series, and it is a single-atom idea: take TMA-2, the 2,4,5-trimethoxy amphetamine, and swap the oxygen of the 4-methoxy group for a sulfur. The methylthio group is more lipophilic than a methoxy, the 5-HT2A receptor likes that, and potency jumps. Nichols and Shulgin published the synthesis in 1976 and predicted it would be about thirty times mescaline; Shulgin's own human record, later collected as entry four of PIHKAL, put the active range at roughly 5 to 15 mg with effects lasting six to eight hours. Modern pharmacology has since caught up with the guess. In a 2023 head-twitch study it bound the human 5-HT2A receptor with a Ki of 77.8 nM and behaved as a partial agonist there with an EC50 near 10 nM, and it induced the mouse head-twitch response with an ED50 of 0.80 mg/kg, four times the potency of TMA-2 and five times that of 2C-T, its phenethylamine counterpart. That is essentially the whole scientific file. There are no clinical studies, no toxicology, no overdose literature and no human data beyond a small number of self-reports from the 1970s.
- A clean demonstration that swapping a 4-methoxy oxygen for sulfur raises 5-HT2A potency several fold
- Well-defined receptor data as of 2023: 5-HT2A Ki near 78 nM with partial agonism in the low nanomolar range
- Useful reference point for the structure-activity relationships of 4-thio-substituted phenylalkylamines
- Historically important as the compound that opened Shulgin's Aleph series
- No clinical trials, no toxicology studies and no controlled human data of any kind
- Activates 5-HT2B receptors at low nanomolar concentrations, the receptor associated with heart valve fibrosis under repeated exposure
- Long duration relative to the dose window, so a miscalculation cannot be waited out quickly
- Active at a few milligrams, which makes accurate weighing a real hazard rather than a formality
- Controlled in most jurisdictions; in the United States it is not scheduled by name but falls under Schedule I treatment as a positional isomer of scheduled 2C-T compounds
- The name is not an acronym. Shulgin named it after aleph, the first letter of the Hebrew alphabet, because it opened a whole series of sulfur-substituted analogues.
- Receptor binding data for Aleph-1 was not published until 2023, roughly 47 years after its synthesis first appeared in the literature.
Mechanism
A receptor of the substituted amphetamine class, with the 2,5-dimethoxy pattern and a 4-position substituent that phenethylamine pharmacology has long associated with high potency. Measured binding gives Ki values of about 78 nM at human 5-HT2A and 355 nM at 5-HT2C, with partial agonism at 5-HT2A in calcium flux assays (EC50 near 10 nM, roughly 80 percent of 's maximum) and at 5-HT2B (EC50 near 19 nM). Efficacy estimates vary between assay systems, and some functional work reads it as a considerably stronger agonist than the calcium-flux figures suggest. Its alpha-methyl group is what separates it from 2C-T; adding that methyl raises head-twitch potency about fivefold in mice and roughly tenfold in humans.
Safetyrisks and cautions, not medical advice
There is no toxicology on Aleph-1. No clinical trials, no overdose literature, no controlled human data beyond a handful of self-reports from the 1970s, so any statement about a safety margin would be invented. What is measurable is the receptor profile, and one part argues against repeated use: it is an agonist at 5-HT2B with an EC50 near 19 nM, the receptor whose chronic activation produced the valvular heart disease that removed fenfluramine and pergolide from the market. Activity at a few milligrams is below what an ordinary scale weighs accurately, and a six to eight hour duration means a misjudged dose cannot be waited out.
History
Synthesised and first described in the literature by David Nichols and Alexander Shulgin in the Journal of Pharmaceutical Sciences in 1976, which reported the chemistry and predicted potency roughly thirty times that of mescaline. Shulgin had tested it in humans by the mid-1970s and reported the effects in 1978; the full account appears as entry four of PIHKAL in 1991, where Shulgin named it for the first letter of the Hebrew alphabet and used it to open a series of sulfur-substituted analogues. It then sat almost untouched for decades. Receptor binding and functional data for the compound were only published in 2023, as part of a Halberstadt and Liechti collaboration mapping the structure-activity relationships of 4-thio-substituted phenylalkylamines.
Subjective profileweighing the evidence above
One of the sharpest single-atom demonstrations in psychedelic chemistry, and one of the least studied molecules anyone actually takes. Potent at a few milligrams, active for most of a day, with a 5-HT2B agonist profile that argues hard against repeated use and a safety literature that is effectively empty.
Resources
This entry is here for reference.
Research
- 1.Sulfur analogs of psychotomimetic amines.
- 2.Use of the head-twitch response to investigate the structure-activity relationships of 4-thio-substituted 2,5-dimethoxyphenylalkylamines.
2 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
How is Aleph-1 different from DOM?
DOM carries a 4-methyl group; Aleph-1 carries a 4-methylthio group in the same position. Both are potent 5-HT2A agonists in the low milligram range, but they are separate molecules with separate potency and duration profiles, and Aleph-1 is by far the less studied of the two.
Is Aleph-1 the same thing as 2C-T?
No, though they are closely related. 2C-T is the phenethylamine; Aleph-1 adds an alpha-methyl group, making it the amphetamine homologue. That single methyl raises potency about fivefold in the mouse head-twitch assay and roughly tenfold in reported human dose ranges.
What is actually known about its safety?
Very little, and that is the honest answer rather than a hedge. There are no toxicology studies, no clinical data and no published overdose reports. What is known is that it activates 5-HT2B receptors at low nanomolar concentrations, which is the pharmacology behind valvular heart damage from repeated exposure to other 5-HT2B agonists.
Adverse effects
- No clinical trials, no toxicology studies and no controlled human data of any kind
- Activates 5-HT2B receptors at low nanomolar concentrations, the receptor associated with heart valve fibrosis under repeated exposure
- Long duration relative to the dose window, so a miscalculation cannot be waited out quickly
- Active at a few milligrams, which makes accurate weighing a real hazard rather than a formality
- Controlled in most jurisdictions; in the United States it is not scheduled by name but falls under Schedule I treatment as a positional isomer of scheduled 2C-T compounds