5-MeO-DiPT

The best established fact about 5-MeO-DiPT is epidemiological, not pharmacological: it describes a population of users, not an action. On the molecule itself the literature is thin to the point that this thinness is the result, no clinical trial, no imaging, no human pharmacokinetics, and a single published death. What little pharmacology exists in fact contradicts the picture people have of it, since this serotonin transporter inhibitor lowers extracellular serotonin in the intact animal. It is a synthetic tryptamine described by Shulgin in the 1970s, sold under the names foxy and foxy methoxy, active by mouth without needing an MAOI, and between 2000 and 2015 it became a sex drug used very predominantly by men who have sex with men in Japan and China.

Pharmacology

It is a full agonist, and not a partial one, at three serotonin receptors, with Emax values from 93.8 ± 6.7 to 99.7 ± 2.7 per cent. At human receptors in HEK293 cells: 5-HT2A, Ki 162 ± 32 nM and EC50 84 ± 20 nM; 5-HT1A, Ki 149.3 ± 7.6 nM and EC50 56 ± 20 nM; 5-HT2C, ten times weaker. These first two Ki values do not compare directly, they are obtained by displacement of two different agonist radioligands, and the ratio between these two receptors is precisely the point of disagreement about the molecule: two studies find a selectivity for 5-HT1A, one in rat brain, the other at cloned human receptors with molecular docking, and only one does not find it. Two against one, on different preparations, and this page does not settle it.

The serotonin transporter, for its part, is inhibited competitively and reversibly but moderately, and the three reuptake measurements in rat synaptosomes span a factor of three depending on the laboratory, IC50 of 646, 1800 and 2200 nM. At the human transporter, binding gives a Ki of 874 ± 71 nM and an IC50 of 239 ± 39 nM, and affinity is low micromolar elsewhere. Remember the order of magnitude, 0.6 to 2.2 µM, that is three to ten times weaker than its affinity for its own 5-HT2A. It is not a releaser: no reverse transport, and in vitro it prevents the releasing action of methamphetamine.

In vivo the effect goes the other way, and this is the most counter-intuitive fact on this page. In microdialysis in the mouse, at 10 and 20 mg/kg, 5-MeO-DiPT decreases striatal extracellular serotonin; in the mouse lacking the transporter it does nothing; but under a 5-HT1A antagonist it increases it strongly. The rise that reuptake blockade would produce is therefore masked and bounded by the activation of its own 5-HT1A autoreceptors, and the authors conclude that anything inhibiting 5-HT1A function would lead to greater effects on serotonin. In the rat, at other doses and in other regions, a second team finds a rise. The contradiction between species is not resolved. What is usable out of it: the analogy with an SSRI is a shortcut, and the brake that belies it has a name.

Metabolism goes through the cytochromes, not through monoamine oxidase. O-demethylation to 5-OH-DiPT is carried, among six enzymes tested on human liver microsomes, by CYP2D6 alone, which quinidine at 1 µM is enough to abolish almost completely: this route has no backup. N-deisopropylation uses five of them, three of which are major, CYP1A2, CYP2C8 and CYP3A4. An MAO route exists but remains minor, attested by 5-methoxy-indole-acetic acid in two human urine samples. In the rat the profile is reversed, which forbids transposing rodent metabolic data. And a hole sits at the centre: in the only published death, urinary 5-OH-DiPT is sixteen times more abundant than the parent compound, so this metabolite dominates excretion, and it is not known whether it is active. The whole question of CYP2D6 interactions passes through this unknown.

One last point, because it circulates: 5-MeO-DiPT does not inhibit monoamine oxidase. No source supports it, and it is rather, in part, a substrate of it.

What the sexual and tactile reputation supports, and what it does not

Three distinct objects, not to be mixed together.

The first is Shulgin's trials, the source of all the phenomenology in circulation, marked tactile effects, erotic exaltation, low visual load. They could not be read for this page: the 1980 article appeared in a journal that has disappeared and has no indexed abstract, and the TIHKAL entry is hosted by Erowid, whose licence forbids republication. What reaches here comes through a tertiary source. Status: uncontrolled author reports, small group, unblinded, fifty years ago.

The second is a hard epidemiological fact. Japanese national survey of 2003 on 2,062 men who have sex with men: 5-MeO-DiPT is the second most used substance for lifetime use, 9.3 per cent, behind amyl nitrite at 63.2 per cent. In Qingdao in 2015 and 2016, 288 of the 431 men who have sex with men had taken it in the previous six months, that is 66.8 per cent, and none of the 603 other users of new substances, ever. In this context the molecule is an almost perfect population marker.

The third is a set of self-reported measures of effect, uncontrolled. In Tianjin in 2016, among the 31 users of the molecule in a cohort of 302: 83.9 per cent had sex after use, 87.1 per cent report an increase in pleasure and desire, 83.9 per cent a lengthening of the duration of each act. Cross-sectional, without blinding or placebo, thirty-one people who knew what they had taken.

None of this is controlled: there exists no controlled study, no validated sexual function questionnaire, no psychophysics of the tactile threshold, in humans as in animals. What is missing is the control, not the measurement. And no opposition should be manufactured between the two halves of the record: a serotonergic profile predicts delayed orgasm, and delayed orgasm, seen from the user's side, is called an act that lasts longer, which 83.9 per cent of them report. The two statements probably say the same thing in two vocabularies.

It remains that what emergency departments see is not what use reports describe. Four published clinical cases: a man of 21, mild hallucinations and inability to move the limbs, with a codeine co-ingestion that weighs on attribution; a man of 23 who presents not with visual or auditory hallucinations but with sensory hallucinations, formication and paranoia; a man of 19, hypertension, tachycardia, mydriasis, catalepsy; a woman of 23, disoriented, Glasgow 13, echolalia, whose urine contained three tryptamines, one of them unidentified. The only somatosensory side documented outside testimony is therefore formication and immobility, which is not a tactile exaltation.

What has been measured in the rodent, and what does not transpose

The convulsive signal is striking. In the rat, four subcutaneous injections of 10 mg/kg two hours apart, under EEG: myoclonus from the first dose, and all the animals convulse from the second. In the same protocol, MDMA produces no EEG abnormality and methamphetamine myoclonus in about half the animals.

It does not produce acute hyperthermia, and this is doubly measured: hypothermia in the rat during administration, followed by a mild and delayed hyperthermic rebound; dose-dependent hypothermia in the mouse, attenuated by a 5-HT1A antagonist, with a correlation between 5-HT1A affinity and hypothermic potency.

Rodent neurotoxicity exists and is not a human fact. Single and double strand DNA breaks persisting up to 60 days, and, after exposure in adolescence, lowered baseline dopamine and serotonin levels in adulthood. But these rats receive 2.5 to 20 mg/kg when a human dose of 6 to 20 mg in a person of 70 kg comes to 0.09 to 0.29 mg/kg: a factor of 10 to 200 before any interspecies scaling. The same caution for cellular cytotoxicity, whose EC50 lies between 0.6 and 0.8 mM, that is 400 to 500 times the blood concentration of the only human death, about 1.5 µM.

Finally, it is neither an MDMA nor an LSD: generalisation to LSD in the trained rat is only intermediate, 75 per cent, and the direct comparison with MDMA concludes that the pattern of effects is distinct.

Duration, dose, tolerance

The oral route is the only one for which figures exist, and they contradict each other:

Source	Threshold	Active dose	Onset	Duration
Shulgin, via TIHKAL, not read	4 mg	6 to 12 mg	20 to 30 min	4 to 8 h
Shulgin, quoted by a review that was read		6 to 10 mg	20 to 30 min	3 to 6 h
DEA, quoted by an article that was read, primary document not read	4 mg	6 to 10 mg effective, 6 to 20 mg used		about 6 h
PsychonautWiki, community document	3 mg	10 to 15 mg common, 15 to 20 mg strong	20 to 40 min	4 to 8 h, plus 2 to 6 h of come-down

The useful fact is in the gap, and it holds without any toxicity figure: the dose called common by the community source begins above the full dose of the only primary source. And nobody here has read that primary source first-hand: everything that circulates about the doses of this molecule descends from it by a chain of citations.

No peer-reviewed source gives a dose for another route, not smoked, not insufflated, not rectal. The only published rectal administration is that of the death, and the quantity there is not established; a value of 100 mg circulates through a press page, it is not verified and must not be taken up.

There is no human pharmacokinetics: no Tmax, no half-life, not a single concentration-time curve. Tolerance has never been studied, in any species: a user guide describes a wait of several days to a week and a cross-tolerance with LSD, community document not read, while a publication goes the opposite way in speculating a sensitisation in a former user. The only two statements available contradict each other.

The only published human concentrations are one-off: a serum level of 0.14 µg/mL corresponds to a discharge without sequelae, a blood level of 0.412 µg/mL to a death. A factor of three between two isolated cases, on two different routes, which defines no threshold.

Harm reduction

The only published death lies in a situation, not in a dose. A man of 29, aqueous solution administered rectally, by pipette, by his partner, in a context of seeking sexual pleasure. Very intense agitation, death about three and a half hours later, autopsy showing myocardial ischaemia and pulmonary haemorrhage. Three things come out of it: the rectal route is the only route for which an outcome is published, and that outcome is a death; there is no dose landmark for it; and it is an administration by a third party, where the person receiving controls neither the quantity nor the pace. The detail of the context comes from secondary abstracts, the full text could not be read.

A rhabdomyolysis is documented, in a healthy man of 23, with transient acute renal failure after ingestion. No figure accompanies this case in the only readable piece, and the dose and creatine kinase values that circulate come from a demonstrably false chain of transmission: they are not taken up here. What is usable is a sign, not a threshold: muscle pain and dark urine, which require hydration and medical advice. Worth knowing too that rhabdomyolysis in hallucinogen intoxication is classically secondary to agitation and muscular hyperactivity, and that it is frequent in this population for other reasons.

A single human case of severe hyperthermia exists, a neuroleptic malignant syndrome in a man living with HIV. The body of that article is a PDF that has not been opened: dose, co-medications, temperature, treatment and outcome are unknown. Yet malignant syndrome and serotonin toxicity overlap clinically, and without that text one cannot say which of the two was at work. It is the missing document that would decide the direction of this guidance, and it is better to say so than to choose.

On convulsions, no human case is attributed to 5-MeO-DiPT alone, those of a Japanese case being attributed by its authors to a multiple intake. What makes it count among the ten substances of this corpus, out of fourteen, that carry a convulsive signal, is therefore the rat EEG and nothing else: it is one of those, four out of these ten, whose support remains animal, isolated or unquantified, and not one of the six that line up counted human cases. It counts there all the same, and animal support does not exempt it from the rule of the ten, which is that one never brings the same threshold down twice without consequence.

MAOIs, and Syrian rue first. No human case exists, and the inference remains the most serious on this page. It rests on four supports not to be confused: full 5-HT2A agonism at nanomolar affinity; the 5-HT1A brake, which is the strong argument because it is sourced, extracellular serotonin being held back only by its own autoreceptors and the authors of that measurement concluding that anything inhibiting their function would produce greater effects; the existence of an MAO route of elimination, minor, blocking which closes off an exit route; and the fact that the closest analogue, 5-MeO-DMT, has a published death and a published serious case with harmala alkaloids, harmaline very strongly potentiating its hyperthermia in the mouse.

To which is added a published field fact. Out of eleven Japanese products sold as Amanita muscaria, four liquid extracts, and they alone, contained almost no ibotenic acid or muscimol but 5-MeO-DiPT and 5-MeO-DMT together with harmine and harmaline, plus atropine and scopolamine, none of these compounds being declared or quantified, which forbids any conclusion about dose. A liquid extract can contain the tryptamine, its MAOI and an anticholinergic with nothing to indicate it. The seven whole mushrooms in the same work were authentic.

CYP2D6 inhibitors, diphenhydramine among them, and the direction nobody knows. CYP2D6 is the only enzyme capable of O-demethylation, with no backup route. Diphenhydramine is a CYP2D6 inhibitor measured in humans, metoprolol clearance being halved by it; paroxetine, fluoxetine and bupropion are inhibitors too; and a poor metaboliser by genetic polymorphism is in the same situation without having taken anything. The beta-carbolines of Syrian rue further inhibit, in vitro, CYP2D6 and CYP3A4, that is, the two elimination routes of this molecule in addition to MAO. But the clinical consequence is established neither in its magnitude nor in its direction: it is not known whether 5-OH-DiPT is active, while it is the dominant metabolite. Do not write that closing this route makes things worse. Nobody has measured it.

Ritonavir and cobicistat, the two boosters of antiretroviral regimens, potently inhibit CYP3A4, and ritonavir also CYP2D6, and CYP3A4 is one of the three major enzymes of the second route. No study has examined this interaction, it is an inference, but it targets exactly the user population best documented for this molecule, and the only published case of malignant syndrome concerns an HIV-positive man.

On the other serotonergic agents, no published case with an SSRI, an SNRI, tramadol or linezolid, and this zero was looked for. The mechanism remains, additive transporter blockade plus direct agonism. A community page flags tramadol and AMT; the mechanism there is real, AMT being both a serotonin releaser and a reversible monoamine oxidase inhibitor, which stacks the same risk twice, but nothing documents it. On AMT the support does not reduce to that community page: one team compared, in the mouse and under identical conditions, AMT, 5-MeO-AMT and 5-MeO-DiPT, and reports that AMT and 5-MeO-DiPT both show acute toxic effects, all three otherwise inhibiting locomotor activity. Reading caveat: the three molecules were administered separately there, this work compares two toxicities and does not measure their combination.

On the stimulant side, in vitro, 5-MeO-DiPT prevents the releasing action of methamphetamine; the in vivo consequence is unknown and is not a piece of advice. What is established is epidemiological: after the Japanese bans, 29.9 per cent of users used substitute products, of whom 60.7 per cent methamphetamine, and those who substituted report more unprotected sex. Caveat: this survey bears on a combined shortage of several products, not on this molecule alone.

Nobody will be identified in the emergency department, and screening can lie in both directions. There is no screening immunoassay for the tryptamines, and they do not appear in routine panels: identification requires GC-MS or LC-MS/MS. In one published case the urine was positive for phencyclidine and cocaine, and negative for 5-MeO-DiPT. If diphenhydramine is present, it too figures among the drugs giving false positives for phencyclidine. A negative screen excludes nothing, a PCP positive can be false, and saying what has been taken and keeping the bag materially changes the management. For the interpretation of a late assay: the urinary concentration falls by 22.8 per cent in 24 hours at 25 degrees and by 38.2 per cent in 7 days at 4 degrees.

The product is not what it announces, and field tests will not say so. Out of 99 kinds of product bought in Japan as psychoactives, 5-MeO-DiPT was found undeclared in 8. The Scott test, specific for cocaine, does not distinguish crack from 5-MeO-DiPT. And colorimetric reagents separate no tryptamine from another: AMT, DPT and 5-MeO-DiPT are all indoles, hence all Ehrlich-positive, whereas their active doses have nothing in common. A reagent says at best what a substance is not.

Populations to exclude or to warn. CYP2D6 poor metabolisers, people on MAOIs, SSRIs, SNRIs, tramadol or linezolid, people on boosted antiretrovirals, adolescents with the dose caveat stated above. On the cardiac side, the autopsy of the only death shows myocardial ischaemia and the toxicology series reports tachycardia and hypertension; as for long-term valvular risk, a screen did measure 5-HT2B for this molecule, but its values are in supplementary tables that have not been read, so that the risk can be neither asserted nor ruled out, for a molecule that identified populations consumed regularly for some fifteen years.

Signs that should prompt a call. Very intense agitation. Catalepsy or inability to move the limbs. Formication and sensory hallucinations. Echolalia, disorientation, lowered consciousness. Muscle pain and dark urine. Sustained hyperthermia with rigidity. Myoclonus, convulsion.

On persistent effects, the only published reference on flashbacks induced by this molecule is a 2005 letter that could not be read. A case of prolonged delusional state of two months concerns a former user, but the acute trigger there was another product and the sensitisation invoked is a hypothesis of the authors, not a measurement. The frequency of persisting perception disorder is unknown.

Sources

• L.B. Kozell et al. (2023), pharmacological activity of substituted tryptamines at 5-HT2A, 5-HT2C, 5-HT1A and SERT, JPET (human Ki and EC50 values).
• P. Puigseslloses et al. (2024), structure-activity relationships of 5-MeO-DMT derivatives, Mol Psychiatry (5-HT1A selectivity, second thermoregulation study, 5-HT1A brake on the head twitch).
• B.E. Blough et al. (2014), interaction of psychoactive tryptamines with serotonin transporters and receptors, Psychopharmacology (SERT IC50 of 646 nM, and the compared values of Sogawa and of Nagai).
• C. Sogawa et al. (2007), 5-MeO-DiPT, a selective serotonin transporter inhibitor, Toxicol Lett (absence of reverse transport; its qualifier of a potency comparable to cocaine is not supported by the numerical values published since).
• Y. Hagino et al. (2021), dual actions of 5-MeO-DIPT at SERT and the 5-HT1A receptor in the mouse, Neuropsychopharmacol Rep (source of the central fact of this page: striatal decrease, nothing in the SERT-lacking mouse, strong rise under a 5-HT1A antagonist).
• K. Noworyta-Sokołowska et al. (2016), neurotoxic effects of 5-MeO-DIPT in the rat, Neurotox Res (rise of serotonin in the rat, DNA breaks at 60 days).
• W.E. Fantegrossi et al. (2006), hallucinogen-like actions in the mouse and the rat, Pharmacol Biochem Behav (head twitch, intermediate generalisation to LSD, 5-HT1A selectivity in vitro).
• D.L. Graham et al. (2012), EEG and convulsant effects of repeated doses, Open Neuropsychopharmacol J (all the rats convulse from the second dose).
• K. Li et al. (2025), three tryptamines, acute toxicity, locomotor activity and hallucinogenic behaviour in the mouse, Behavioural Pharmacology 36(6):429-437. Abstract only read. Comparison of AMT, 5-MeO-AMT and 5-MeO-DiPT under identical conditions: acute toxic effects for AMT and 5-MeO-DiPT, inhibition of locomotor activity for all three, head twitch blocked by M100907. The three molecules were administered separately.
• M.T. Williams et al. (2007), body temperature, corticosterone and behaviour in the adult rat, Neuropsychopharmacology (hypothermia then a mild and delayed rebound).
• S. Narimatsu et al. (2006), oxidative metabolism by human liver microsomes and recombinant CYPs, Biochem Pharmacol (CYP2D6 alone for the O-demethylation).
• N. Tanaka et al. (2006), fatal 5-MeO-DiPT intoxication, Forensic Sci Int (only published death; abstract read, full text not read, 403 on two hosts; the quantity administered is not established).
• G. Alatrash, N.S. Majhail, J.C. Pile (2006), rhabdomyolysis after ingestion of foxy, Mayo Clin Proc. Abstract only read, full text 403 by four routes. This abstract contains no dose, no creatine kinase, no chronology: any figure attributed to this case is second-hand and is not taken up here.
• T. Kuwahara et al. (2008), problems in three Japanese drug users living with HIV, J Med Invest 55(1-2):156-160, DOI. Abstract read, body of the article not read, PDF. Carries the only human case of malignant syndrome; without it, neither the dose, nor the co-medications, nor the outcome are known.
• R. Meatherall and P. Sharma (2003), J Anal Toxicol, J.M. Wilson et al. (2005), Forensic Sci Int, S.C. Smolinske, R. Rastogi, S. Schenkel (2005), J Med Toxicol and M. Itokawa et al. (2007), Psychiatry Clin Neurosci (the four clinical cases, and the series of 41 exposures of which 26 moderate or major).
• S. Malaca et al. (2020), toxicology and analysis of psychoactive tryptamines, Int J Mol Sci (absence of immunoassay; screen positive for PCP and cocaine, negative for the molecule). Caveat: the synthesis this article makes of the work of Noworyta-Sokołowska is faulty, do not cite it for the phenomenology.
• K. Tsujikawa et al. (2006), analysis of Amanita mushrooms circulating in Japan, Forensic Sci Int (undeclared co-formulation with harmine and harmaline in the four liquid extracts, nothing quantified).
• Y. Tsumura, T. Mitome, S. Kimoto (2005), false positives and false negatives of a field test specific for cocaine, Forensic Sci Int and R. Kikura-Hanajiri et al. (2005), J Chromatogr B (8 products out of 99 containing the undeclared molecule).
• Y. Hidaka et al. (2006), BMC Public Health; D. Shan et al. (2017), Zhonghua Yu Fang Yi Xue Za Zhi 51(8):718-722, DOI; D.M. Li et al. (2018), Zhonghua Liu Xing Bing Xue Za Zhi 39(6):750-754, DOI; K. Hayashi et al. (2023), Int J Drug Policy. Abstracts read. These are the epidemiology of use and the only self-reported figures on sexual effect that exist.
• X. Yan et al. (2020), urinary assay by GC-Orbitrap, J Anal Toxicol (sample stability).
• Y. Fuse-Nagase and T. Nishikawa (2013), prolonged delusional state in a former user, Addict Sci Clin Pract (the acute trigger there is another product).
• T.S. Ray (2010), Psychedelics and the human receptorome, PLoS ONE 5(2):e9019, DOI. Page read; the supplementary tables S2, S4 and S6, which carry the values on 51 targets including 5-HT2B, have not been read. It is the only existing source of 5-HT2B for this molecule, and no value is published here until it has been read off by hand.
• A.T. Shulgin and M.F. Carter (1980), Commun Psychopharmacol 4(5):363-369, PMID 6949674, and A. Shulgin and A. Shulgin, TIHKAL, 1997, entry 37. Neither one nor the other has been read: a journal that has disappeared and has no indexed abstract for the first, Erowid hosting and a licence forbidding republication for the second. All the human doses in circulation descend from them by citation.
• DEA information sheet on 5-MeO-DiPT, deadiversion.usdoj.gov. PDF, not opened. Its figures reach here only by way of the citation made of them by an article that was read.
• A. Ikeda et al. (2005), flashbacks induced by 5-MeO-DiPT, Am J Psychiatry 162(4):815, DOI. Not read, no indexed abstract, paywalled text. It is nevertheless the sole reference for persisting perception disorder for this molecule.
• Erowid, 5-MeO-DiPT Vault and PsychonautWiki (community documents, to be read on site, cited without reproduction; source of the divergent dose range, of the unsupported claim of an MAO inhibition, and of the combinations flagged without any published case).