2C-T-7

2C-T-7 is the most poorly known substance in this wiki, and saying so is the first act of harm reduction concerning it. None of what ordinarily grounds a page exists for it: no controlled human administration study, no pharmacokinetic data, no published non-fatal clinical case, not the slightest report of a death or of a clinical detection indexed after 2003. What the literature retains of it amounts to three deaths, occurring in 2000 and 2001, and two of them say the same thing: the quantity that kills by the nose is an ordinary quantity by the mouth. The rest is a laboratory file, that of a sulphur-containing phenethylamine, a partial agonist at the 5-HT2A receptor, described by Shulgin and sold in the early 2000s under the name Blue Mystic.

Pharmacology

The target is 5-HT2A, and it is demonstrated by antagonism rather than by affinity alone. In the mouse, the head twitch response induced by 2C-T-7 is blocked by M100907, a highly selective 5-HT2A antagonist. In the rhesus monkey, a Schild analysis gives pA2 values of 8.58 for M100907, 7.75 for ketanserin and 7.75 for ritanserin, values almost identical to those obtained with DOM, and the potency of the antagonists correlates with 5-HT2A affinity and not with 5-HT2C or alpha1 affinity. This is the most solid quantitative evidence in the file, and it comes from the monkey.

The cross-checked affinity at the human 5-HT2A is 5.3 nM, with partial agonist activity, higher than that of LSD and lower than that of serotonin on the two signalling pathways measured. The upper bound of 6.5 nM that circulates in aggregated tables, on the other hand, has no identifiable origin, the source it pointed to reporting no Ki at all, and all the other affinities in circulation, 5-HT2C, 5-HT1A, alpha1, alpha2, come from a tertiary database never cross-checked against a publication actually read.

Two negative results count for more than the positive ones. 2C-T-7 does not interact potently with the monoamine transporters, Ki above 4000 nM: it is neither a serotonin releaser nor a reuptake inhibitor. And it interacts with rat and mouse TAAR1, but not with the human one, which forbids transposing the animal data directly on this point.

The first of these two results kills a formula that has circulated widely, that of a pharmacodynamic kinship with MDMA. It comes from the abstract of the 2003 toxicology paper itself, but behaviour contradicts it: in the rat, 2C-T-7 substitutes for DOM and neither for MDMA nor for cocaine, and in the mouse it substitutes only for the hallucinogenic enantiomer of MDMA. The kinship is structural, it is neither entactogenic nor stimulant.

Metabolism is where harm reduction is decided. On cDNA-expressed human isoenzymes, MAO-A and MAO-B are the major enzymes in the deamination of the 2Cs, CYP2D6 contributing for 2C-T-7 only to a very small extent. 2C-T-7 is therefore a substrate of monoamine oxidase, and not a relevant inhibitor: confusing the two reverses the sense of the warning. As an inhibitor it is weak, and its individual value remains unknown after three search passes, the paper that measured it existing only as a PDF. What is known amounts to a class range, 10 to 125 µM on MAO-A and 1.7 to 180 µM on MAO-B, to be compared with the 0.39 µM of the only human blood concentration ever published.

Three deaths, and the only thing they establish

The number is stable, the breakdown is not. Two genuinely independent lineages of sources exist, the DEA documents and a piece of reporting from 2002, and they contradict each other on the date of the first death and on the number of cases by the nasal route. The medical toxicology review that compiles them does so under a title that says what it is, a survey of press reports: it does not count as a third confirmation.

What survives these disagreements is the central fact of this page. A 20-year-old man died after insufflating 35 mg. A 17-year-old boy died after insufflating 30 to 35. The third case combined an unknown quantity of 2C-T-7 with 200 mg of MDMA. Now 30 mg is the upper bound of Shulgin's oral range, confirmed by two full texts read, and these quantities represent three to seven times the upper bound of the common band of the nasal dose tables in circulation. Carrying a known oral dose over to the nasal route is the failure mode that killed here. The formula that lingers, according to which deaths occur from 30 mg upwards, is dangerous precisely through what it leaves out: it turns an ordinary oral dose into a supposedly lethal dose, or worse, the reverse.

The mechanism of these deaths is not established. What is described is a clinical picture, and it carries a clinical name that has to be known in order to make oneself understood in an emergency department: agitated delirium. Agitation worsening towards panic and then violence, copious and repeated vomiting, undressing suggestive of hyperthermia, rigidity, hypertension and tachycardia, heavy nosebleed after insufflation, convulsions, then cardiorespiratory arrest. Marked pulmonary oedema at autopsy in one case, cerebral haemorrhage in another. These signs come from three deaths, not from a clinical series: they describe the fatal outcome, not the spectrum of non-fatal poisonings, which has never been published.

What no one has measured

The list is longer than the list of what is known, and it is a result, not a gap in the search. The pharmacokinetics are empty in their entirety, by every route: bioavailability, Cmax, Tmax, half-life, clearance, nothing has ever been measured. Imaging is just as empty, in every species, and nor is there any data on pregnancy, breastfeeding, heart disease, epilepsy, age, or hepatic or renal impairment. The indexed corpus was gone through in full without finding a single non-fatal clinical case: this is not a failure of the query, it is the state of the field. Assaying this molecule in plasma is moreover technically difficult, the validation data of a reference method having been judged unacceptable for it, which partly explains the absence.

The only published human concentrations come from a single case, post mortem: cardiac blood 57 ng/mL, femoral blood 100 ng/mL, urine 1120 ng/mL, liver 854 ng/g. The gap between the two blood concentrations is a factor of two in the opposite direction to the classic expectation, post mortem redistribution has never been characterised for this molecule, and these figures do not constitute a reference range: they do not say at what concentration a living person is in danger.

There remains a neurotoxicity measured in cells, where 2C-T-7 is the most cytotoxic of the three 2C-Ts tested, with an EC50 below 75 µM. That is two orders of magnitude above the only known human blood concentration, no in vivo relevance follows from it, and the studies do not even agree among themselves on the mechanism.

Duration and tolerance

The duration of 2C-T-7 is established by no one, and that is the exact wording to retain. The figure of 8 to 15 hours that circulates everywhere has a single origin, Shulgin's self-experiments, repeated since by everyone. Against it, two distinct lineages give something shorter and agree roughly with each other: a medical toxicology review, citing a regulatory information sheet, gives for the oral route an onset of 1 to 2.5 h and a duration of 5 to 7 h, and a community table gives 6 to 10 h. The 8 to 15 h is therefore not the consensus with one dissenter, it is the isolated figure. None of the three rests on a measurement, and no single value should therefore be displayed.

By the nasal route, onset is 5 to 15 minutes and duration 2 to 4 hours. This 5 to 15 minute onset is the only figure in the whole file on which a peer-reviewed review and a community table agree exactly.

On tolerance, a single study, murine, but direct: tolerance develops to daily administration, as with DOI, and mice made tolerant to DOI show a cross-tolerance to 2C-T-7 that cannot be overcome by increasing the dose. This last point is the most useful in this line, because it describes the move someone would make spontaneously. No human tolerance data exist.

Harm reduction

The route of administration comes before the dose. This is the single best established point on this page, and it rests on three facts: the same quantity is ordinary by mouth and lethal by nose, the onset delay collapses from more than an hour to a quarter of an hour, and a heavy nosebleed appears in one of the cases in two independent sources, which suggests a direct local injury on top of the systemic effect. No peer-reviewed source gives a nasal dose range for 2C-T-7: the only ones that exist come from a community wiki which itself writes that they are not a recommendation.

Stimulants are the combination actually present in the record of the deaths. Two of the three deaths are attributed to concurrent MDMA use, including one case with 200 mg. A widely used combination table classes 2C-T-x plus stimulants and 2C-T-x plus cocaine as unsafe, a more severe category than the one applied to the generic 2Cs. This is the only family for which cases exist.

Nitrous oxide appears in one death, and nothing more. The 17-year-old boy had taken, besides the insufflated 2C-T-7, ecstasy, nitrous oxide and a product based on ephedrine and guaifenesin. No source attributes anything to it, and no risk of pharmacological interaction is established between this gas and this family: it is a co-exposure in one death, never an interaction, and to cite it otherwise would be to manufacture a danger.

MAOIs: a precaution, not an established fact, and the distinction is an honest one to hold. The mechanism is plausible. Since MAO is the main elimination route, an exogenous inhibitor closes it, and a medical toxicology review explicitly carries the warning in the form of an increase in serum concentrations and therefore in the risk of toxicity. This is an overdose through blocked clearance, not in the first place a serotonin syndrome, since this molecule does not touch the transporters. But the only published direct test is negative: researchers co-incubated the 2C-Ts with an MAO-A inhibitor and an MAO-B inhibitor to see whether the blockade worsened toxicity, and found no significant effect, whereas in the same model it does worsen that of mescaline, 2C-B and 2C-N. They themselves put forward an explanation that limits the reach of their result, namely that the metabolites could be as toxic as the parent molecule: a cell cytotoxicity model could hardly see what it was looking for, and it does not refute plasma accumulation. The warning is therefore given as a precaution, and it covers the three families of inhibitors since both isoforms take part. Among the substances of this wiki, this concerns Syrian rue and AMT, the only two established monoamine oxidase inhibitors in the set. What does not exist must be said just as plainly: no human case links 2C-T-7 with an MAOI, and the four sources describing the deaths, read in full, do not utter the word.

Serotonin: zero cases for this molecule, and yet no clinical silence. The indexed literature does not contain a single serotonin syndrome attributed to 2C-T-7, and the direct mechanism is weak, the transporters being beyond 4000 nM. But the reference clinical review retains serotonergic toxicity among the possible presentations of a 2C poisoning, and it would be false to write that the clinical side is mute on this. A reservation to be aware of: the pharmacological support it invoked, a reuptake inhibition by the 2Cs, has been contradicted by a later binding measurement. Caution in serotonergic combination remains real, the established risk is not.

The seizure threshold, and this is the most actionable cross-cutting fact. Convulsions appear in two of the three deaths, and the clinical review writes that convulsions and delirium have been reported with 2C-T-7. This molecule is one of the ten, out of the fourteen in the corpus, whose epileptogenic threshold is in question, and it is the crossing that makes the danger rather than the count: to lay it over a neighbour whose signal rests, like its own, on counted human cases, 2C-I for example, is to stack the same load twice, whereas elsewhere in this set the second support is only an animal signal, an isolated case or an unquantified clinical mention, DPT being the typical case. The four remaining substances in the set do not carry it. Outside the corpus, tramadol is classed unsafe with the 2C-T-x for precisely this reason, and lithium is the only medicine to which a death in this set has been attributed.

Vomiting under a sedative is the best established lethal chain, and it is mechanical. Copious vomiting belongs to the picture of the 2C-T-7 deaths. The sedatives in this corpus are nitrous oxide, DXM and diphenhydramine. Never leave a person who is vomiting under a psychedelic alone or lying on their back. In the picture described above, they cannot place themselves in that position: what protects them is the recovery position and a sober third party to hold them in it.

DPT is the only measured interaction between two substances of this corpus. In the rat and in the monkey, DPT and 2C-T-7 additively potentiate the discriminative stimulus of DOM. This is animal discrimination data, it says nothing about a toxicity, and it appears here because it is the only existing measurement and because its lack of clinical translation must be stated rather than filled in.

Product identity kills in this family. The 2Cs are white powders of very different potency and duration, and a product sold as 2C-B that in fact contained 2C-P, a molecule with an estimated half-life of 19 hours, sent a 19-year-old man to hospital. More seriously, a product announced as 2C-I and identified on analysis as 2C-E caused one death and about ten poisonings in Blaine, Minnesota, in 2011, the substitution of molecule adding to a transposition of route towards insufflation. This tally is given with its reservation, and the reservation must be given everywhere the case is told: the sources do not count the same way, one giving ten people hospitalised in addition to the dead man, the other ten in all. This is the only death in this corpus caused by a confusion of names, and it is one more reason not to harden its figure. No colorimetric reagent separates one 2C from another 2C. Two name traps, finally, for anyone redoing this research: 2C-T-7-FLY is a distinct compound, and a Japanese paper spells the compound 4C-T-7, a typo that makes it invisible to any search.

In the emergency department, no one will be identified. Across nine commercial immunoassays, the cross-reactivity of the 2C and 2C-T series is below 0.4%, and urinary concentrations of up to 50,000 ng/mL are not enough to return a positive result. A negative screen therefore rules nothing out. Saying what was taken and keeping the bag materially changes the care given, because it is the only way to make it known.

What an emergency department will do is worth knowing for the person accompanying them. There is no antidote. Management is symptomatic, with airway maintenance, cardiac monitoring and a calm environment, and immediate action is required in case of agitated delirium, hyperthermia or convulsions: rapid sedation, fluid resuscitation, cooling. Benzodiazepines serve to treat agitation, hypertension, tachycardia and hyperthermia. One sentence from the clinical review deserves to be retained as it stands: antipyretics have no place in the treatment of a drug-induced hyperthermia, because they act by lowering the hypothalamic set point of a febrile patient. Neuroleptics are discussed and retained, with the only drawback named being the possible worsening of panic and of the visual symptomatology. A reservation to keep: this review discusses neither the conflict with the seizure threshold nor the one with thermoregulation, although convulsions and hyperthermia belong to the picture it describes itself. This is an absence observed in the text, and no other source consulted settles it.

Sources

• B. Dean et al. (2013), review of the synthetic phenethylamines, J Med Toxicol (full text read; best clinical source: kinetics by route, agitated delirium, management protocol, MAOI warning. Its table of deaths is explicitly a survey of press reports and does not count as a primary source).
• A.L. Halberstadt et al. (2023), structure-activity relationships of sulphur-containing 2,5-dimethoxyphenylalkylamines, Psychopharmacology (full text read; ED50 of the head twitch response, Ki values for the series, Shulgin's oral dose as cited, and confirmation that no duration appears in it).
• E. Gil-Martins et al. (2024), neurotoxicity of the 2Cs and of the corresponding NBOMes, J Xenobiotics (full text read; cytotoxicity, and the only published direct test of the worsening by MAO inhibition, negative).
• E. Pottie et al. (2023), biased agonism of phenylalkylamine 5-HT2A agonists, ACS Chem Neurosci (full text read; only individual functional values for 2C-T-7, no Ki).
• D.S. Theobald and H.H. Maurer (2007), MAO and CYP isoenzymes involved in the deamination of the 2Cs, Biochem Pharmacol (abstract read, full text inaccessible; central source of the MAO substrate status. The measured Michaelis-Menten parameters, which would make it possible to calibrate the MAOI warning instead of giving it wholesale, are published nowhere else).
• L. Wagmann et al. (2019), interactions of the 2Cs with the human monoamine oxidases, Drug Test Anal (abstract read, full text not read, three access routes exhausted; the individual value for 2C-T-7 remains unknown, and the authors conclude that a pharmacological contribution of MAO inhibition cannot be excluded).
• D. Luethi et al. (2018), receptor interaction profiles of the sulphur-containing 2Cs, Neuropharmacology (abstract read, full text inaccessible; 5-HT2 partial agonism, absence of interaction with the transporters, human TAAR1 no).
• B. Curtis et al. (2003), post mortem identification and quantification of 2C-T-7, J Anal Toxicol (abstract read, full text paywalled; sole source of the concentrations, and the detailed clinical history of this case remains inaccessible).
• W.E. Fantegrossi et al. (2005), hallucinogen-like actions of 2C-T-7 in mice and rats, Psychopharmacology (abstract read; the numerical binding values of this work are definitively inaccessible).
• N. Khorana et al. (2004), stimulus effects of three sulphur-containing psychoactive agents, Pharmacol Biochem Behav (substitution for DOM only, neither cocaine nor MDMA).
• J.X. Li, K.C. Rice, C.P. France (2009), apparent pA2 analysis in the rhesus monkey, JPET and J.X. Li, W. Koek, K.C. Rice, C.P. France (2010), JPET (additivity of DPT and 2C-T-7 on the DOM stimulus, in the rat and the monkey).
• K.S. Murnane et al. (2009), discriminative effects in mice trained to the MDMA enantiomers, JPET (substitution for R(-)-MDMA only).
• D.A. Smith et al. (2014), tolerance and cross-tolerance to the head twitch response, JPET (sole tolerance source, murine).
• S. Kerrigan et al. (2011), evaluation of commercial immunoassays on the psychedelic phenethylamines, J Anal Toxicol (non-detection on screening).
• V. Habrdova et al. (2005), quantification of synthetic phenethylamines in plasma by GC-MS, J Mass Spectrom (validation data unacceptable for 2C-T-7).
• A. Stoller et al. (2017), 2C-P taken for 2C-B, J Anal Toxicol (product identity risk; different molecule).
• F. Schifano et al. (2005), online and street market for 2C-T-7, J Psychopharmacol (analysis of a corpus of websites, not a clinical series).
• L.A. King (2014), new phenethylamines in Europe, Drug Test Anal (drawn from the European risk assessment, standing in for the report itself, which is inaccessible).
• DEA, temporary placement of 2C-T-7 in Schedule I, Federal Register 67-183, 2002 and permanent placement, Federal Register 69-53, 2004 (read in HTML; deaths, doses, routes).
• K. Platoni, 2C-T-7's Bad Trip, East Bay Express, 2002 (read in HTML; reporting, the most detailed source on the circumstances of the three deaths).
• Erowid, 2C-T-7 Vault (corpus of user reports, to be read on site; its licence forbids reproduction. Pages not read, 403 reproduced and archive inaccessible: no claim on this page rests on Erowid).
• PsychonautWiki, 2C-T-7 and TripSit, combinations (community resources, not peer reviewed; the only sources of nasal dose ranges and of combination categories, never to be presented as a dosage).
• A. Shulgin and A. Shulgin, PiHKAL, entry 43, 1991. Original not read. The oral dose of 10 to 30 mg is confirmed by two full texts that cite it; the duration of 8 to 15 h comes from this source and from no other, and has never been measured.
• DEA information sheet on 2,5-dimethoxy-4-(n)-propylthiophenethylamine, updated 16 February 2011. Not read, available as a PDF only. It is the original source of the kinetics by route, whose useful content passes through Dean et al. 2013, which was read.
• EMCDDA risk assessment report on 2C-I, 2C-T-2 and 2C-T-7. Not read, page returning 403 and report in PDF. The date of 4 April 2003 and the mention of experts judging the evidence insufficient, both of which circulate, are not verified and do not appear here.
• Asanuma et al. (2020), neurotoxicity of the 2Cs in monoaminergic cell lines, Forensic Toxicology. Not read, known only through the citation of it by Gil-Martins et al. 2024, which notes moreover that its results on oxidative stress contradict theirs.