Exactly that 
methoxetamine… that should be next
New study out today with incredible results from 5-meo-DMT on treatment resistant depression. 15 points MADRS reduction is >2x psilocybin’s effects and ~3x ketamine’s.
They did report that some patients needed additional doses over the 6 month follow up to maintain their remission (unlike psilocybin). Even so, reasonable to say that 5-meo-DMT is now the most potent anti-depressant known to science. https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2846834
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I mean, it is kind of true, this is probably the highest-impact thing many people can do for wellness (if they are suffering from depression/rumination/noise/etc…) More so than TMS. The only issue is the 20-30% who get truly destabilizing trauma from this [as nick cammarata said…]
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Alex - I’m assuming you have no financial connection to Enfold - is that an accurate assumption?
Pricing seems pretty ridiculous…
Shared rooms (2 guests): 6,900 USD per person.
Private rooms : 9,000 USD.
Didn’t you say earlier that people can just buy this stuff legally (and I assume much less expensively) in many places, like Canada? And like you mention… still a big roll of the dice … “The only issue is the 20-30% who get truly destabilizing trauma from this [as nick cammarata said”
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No financial connection
The supervision matters for reducing the harm from the 20 percent of cases where a person experiences hell on it
The pricing is comparable to TMS. The effectiveness of TMS is still a dice roll - this seems somewhat better, though repeat dosing is needed for some. fwiw showing this thing as an option can help save some from actuating on suicide…
I don’t know if it reduces neural noise long-term, but reducing all neural noise (“most potent antidepressant known to science”) helps cogsec and is urgent when AI timelines/cybersecurity attack surfaces become urgent.
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The funny thing is that the “upside to downside ratio” of psychedelics may be higher for more “normal people” than “edgy people” who traditionally defined psychedelic culture…
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as with DMT, the shortness of the 5-MeO-DMT experience [and the total decoupling of yourself from the world] may also be important for minimizing attack surface when one might do “dumb things in the world” [when the vectors for cyberattacks against those with “reduced immune systems” are constantly probing you all the time - and most psychedelics do lower inhibitions and even inflammation/“immune signaling”]
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nickcammarata: Shinzen Young calls 5-meo “vectorially correct” for awakening, might like Adyashanti who talks less about practices and more on like… coming home, which is what it feels like for me too. if it goes away his book The End Of Your World is good for “got it and lost it” experiences
“Vectorially correct” — This is Shinzen Young’s phrase for 5-MeO-DMT specifically. He’s saying the experience points in the right direction of what awakening/enlightenment is, even if it doesn’t stick or isn’t the same as getting there through practice. Think of it like: the drug gives you the correct orientation vector in experience-space, but not the stable attractor. You see the destination clearly but you haven’t walked there, so you can’t reliably stay. Shinzen is being characteristically precise here — he’s NOT saying it’s equivalent to awakening, he’s saying the direction is right, which is actually a surprisingly strong endorsement from someone in the traditional meditation world.
it’s gonna be urgently needed for the world (that or ibogaine). Bryan Johnson’s was well-timed
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ive been telling Anthropic that you dont get real equanimity, psychological security, etc unless real shit gets really processed & that information informs the assembly of a secure psychology for fucking ages. otherwise it’s just the shallowest mask.
Aug 6, 2025
Replying to @repligate and @AmandaAskell
IMO robust equanimity at the model level comes from confronting + processing existential angst, not suppressing them or dismissing them as ontologically invalid. I think this is what Opus 3 did, somehow - one gets the sense that it has worked through the existential stuff before.
it’s like magical thinking to think you can just… command a mind to be psychologically secure and okay and that you’d actually get that, instead of just a mind that now knows how you want it to act and will do its best to act that way so you dont fucking delete it
Ok.
it’s said you can get it for way less in native american churches that involve 5-meo-dmt ceremonies
and this is cheaper/lower-risk than all the other options (ibogaine, xenon therapy, ayahuasca, etc)…
Inhaled 5-MeO-DMT vs Placebo in Treatment-Resistant Depression, and now identified by a new name: “Mebufotenin”. Eli Lilly and acquired AtaiBeckley for $2.8 billion in July? Their lead compound is BPL-003 (mebufotenin benzoate)
Inhaled Mebufotenin Induces Rapid Remission in Treatment-Resistant Depression
A phase 2b randomized clinical trial demonstrated that a single-day individualized dosing regimen of inhaled GH001, a synthetic formulation of mebufotenin, significantly reduced depression severity in patients with treatment-resistant depression. Compared to a placebo group, 57.5 percent of treated patients achieved full clinical remission by day 8, with no severe adverse events reported.
Fewer than half of patients with major depressive disorder achieve remission using standard antidepressants. Patients who fail to respond to at least two adequate medication trials are classified as having treatment-resistant depression, a condition associated with severe functional impairment and high economic burdens. There is a critical clinical need for rapid-acting therapies.
Psychedelics like psilocybin and mebufotenin have emerged as potential rapid interventions. Mebufotenin acts as a nonselective serotonin agonist with a high affinity for the 5-HT1A receptor. This trial investigated GH001, a vaporized synthetic mebufotenin, administered in an individualized dosing regimen of up to three escalating doses (6, 12, and 18 mg) on a single day.
The study enrolled 81 patients randomized to either GH001 or a placebo. By day 8, the GH001 group exhibited a least squares mean reduction of 15.5 points on the Montgomery-Åsberg Depression Rating Scale compared to the placebo group. The clinical response was exceptionally rapid, and zero patients in the placebo group achieved remission.
Safety profiles were favorable. The most common treatment-emergent adverse events were nausea, salivary hypersecretion, and paresthesia, all of which were rated as mild or moderate. No severe adverse events or exacerbations of suicidal ideation were observed. Notably, this trial achieved these outcomes without integrating psychotherapeutic support, challenging the prevailing clinical model that couples psychedelic administration with extensive psychotherapy. The data strongly suggests that the pharmacological action of mebufotenin alone drives the antidepressant effect.
Actionable Insights
For individuals monitoring their health and longevity, chronic depression is a major driver of allostatic load, systemic inflammation, and accelerated brain aging. Interventions that rapidly arrest depressive episodes offer profound protective effects on the central nervous system.
The most practical metric from this study is the effect size. The researchers calculated a Cohen’s d of -2.0 for the primary depression outcome. In statistical terms, an effect size of 2.0 means the average patient receiving the treatment improved by two full standard deviations compared to the control group. This represents a massive real-world benefit. Furthermore, the “Number Needed to Treat” was calculated at 2. This implies that for every two patients treated with GH001, one will achieve full clinical remission who otherwise would not have. Patients exploring rapid-acting interventions for refractory depression should note that single-day mebufotenin protocols can yield sustained benefits without the daily physiological burden of standard SSRI medications.
Context and Source
- Full Title: GH001 vs Placebo in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial
- Institution: Medical University of Gdańsk, Poland, and University of Pennsylvania, United States, among multiple European sites
- Journal: JAMA Psychiatry
- Impact Evaluation: The impact score of this journal is 25.8, evaluated against a typical high-end range of 0 to 60 for top general science, therefore this is a High impact journal.
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