Videos / Interviews with Louise Hecker:
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Psilocybin is an indole like Melatonin so may operate in a similar manner - up to a point.
Any reliable source for Psilocybin?
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We urgently need a comparison between all nrf2 activators and to see if there are any sinergy between them. It is much easier to take sulphurophane or astaxanthin than megadosing Psilocybin.
Another curious thing about this study is that the megadose gives a radically higher longevity benefit than the micro… if the longevity benefit comes from nrf2, we should test this mega dose theory.
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I picked up a package of microdose psilocybin capsules at a store in Detroit a couple of weekends ago. Definitely, the real deal. They have many strains in jars ready to weigh out for their customers. They are in Ann Arbor too. They also have microdose tea and chocolate bars.
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Yes, yourself! Buy spores or liquid culture and grow your own. It is not difficult. Consult YouTube for instructional videos. Google the topic. There is no dearth of available info on the web.
“The paper describes psilocybin as “the naturally occurring psychedelic compound produced by hallucinogenic mushrooms,” but all experimental work used isolated psilocin in vitro and isolated psilocybin in vivo.”"
FWIW: ChatGPT-5 (paid)
“I can’t help with identifying which mushroom variety has the most psilocin (or “most potent”), because that’s essentially potency guidance that could facilitate illegal drug use.”
Perplexity:
"Here are key entries from the most accessible studies, focusing on strains with quantified psilocybin and psilocin levels. Values are on a dry-weight basis and come with caveats about variability and methods.
Psilocybe cubensis strains (five analyzed in a recent LC-MS/MS study)
Creeper: total psilocybin + psilocin ≈ 1.36% w/w; psilocybin and psilocin reported separately in the study, with psilocybin typically higher than psilocin but both contributing to potency [study: 2024 LC-MS/MS analysis of Creeper, Blue Meanie, B+, Texas Yellow, Thai Cubensis; PubMed 38220293].
Blue Meanie: total ≈ 1.221% w/w; both compounds quantified, showing substantial psilocybin content and notable psilocin as a component [PubMed 38220293].
B+: total ≈ 1.134% w/w; psilocybin and psilocin measured separately, with psilocybin generally dominating but psilocin presence confirmed [PubMed 38220293].
Texas Yellow: total ≈ 1.103% w/w; psilocybin and psilocin levels reported; variability observed across individual mushrooms within the same strain [PubMed 38220293].
Thai Cubensis: total ≈ 0.879% w/w; psilocybin and psilocin quantified, indicating lower overall potency relative to the other strains in the same study [PubMed 38220293].
Psilocybe cyanescens: Often shows high total alkaloid content in analyses; both psilocybin and psilocin present, with psilocybin frequently prominent and psilocin contributing to potency; exact per-compound values vary by sample and method [general LC-MS/MS comparative studies; cross-species reviews].
Psilocybe azurescens: High overall potency with substantial total alkaloids; both psilocybin and psilocin detected; the balance between the two compounds varies by batch and processing conditions [analytical reviews and species profiles].
Psilocybe semilanceata: Noted for significant psilocybin levels and detectable psilocin; intraspecies variability leads to wide ranges across samples and locations; exact figures depend on harvest and processing [species surveys and analytical summaries].
Wiki:
“Based on scientific analyses and reports from studies on psychedelic mushrooms, the non-poisonous variety with the highest reported psilocin content is Panaeolus cyanescens (commonly known as blue meanies or Copelandia cyanescens). Levels vary by sample and growing conditions, but analyses have found up to approximately 1.2% psilocin by dry weight (with an average around 1.194% in seized samples), alongside psilocybin content up to 2.5% or more. This exceeds reported psilocin levels in other common species like Psilocybe cyanescens (up to ~1%) or Psilocybe azurescens (up to ~0.5%). Note that all psilocybin-containing mushrooms can cause psychoactive effects but are not lethally poisonous when consumed responsibly.”
“https://tinyurl.com/mw6b284j
Determination of psilocybin and psilocin content in multiple Psilocybe cubensis mushroom strains using liquid chromatography - tandem mass spectrometry - PubMed
DNA Authentication and Chemical Analysis of Psilocybe Mushrooms Reveal Widespread Misdeterminations in Fungaria and Inconsistencies in Metabolites - PubMed
Psilocybin treatment extends cellular lifespan and improves survival of aged mice - PMC”
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Let us know if you decide to go “Trippin” 
Probably best to do it when you have a friend to monitor and support you if need be.
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thanks for the info, and I hear you but I’m not good at DIY projects. I was hopping there is a decent place where one can order it online.
Yeah, well, the problem is that Psilocybin is still a Schedule 1 drug in the US (if you are in the US) tho’ it’s been decriminalized in various ways in many places. Spores and liquid culture are legal to ship almost everywhere.
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Yes, I’m in the US. I wasn’t aware it is a Schedule 1 drug. Now I can understand why there aren’t any suggested suppliers yet 
The 5HT2B risk is valid, but the fear is overblown
https://www.biorxiv.org/content/10.1101/2025.04.08.647757v1.full.pdf
but it’s nice to know there are effects with microdosing.
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To give credit where credit is due, I was aware of the “psychedelics de-aging” theory from Gaige Clark (https://mad.science.blog/ ). He was ahead of his time on this, which gives him some credit (even though he might be overfitting), and it’s good to be [AT LEAST INITIALLY] a little bit cautious around people who say “psychedelics are too good to be true” on every front.
I’m still in search of a reliable source. Until then (until I find a way to buy some) no point on even reading about the benefits. So, to all the longevity hounds out there, dig up sources please…
p.s don’t suggest I grow my own because that ein’t happening.
Its important to note that Louise Hecker’s definition of “microdosing” is not the typical definition of “microdosing” that I typically hear around San Francisco…
The “Microdosing” Misnomer: It Was Actually Macrodosing
It is critical to clarify a major distinction for your biohacking translation: Louise Hecker’s study did not use “microdosing” in the popular sense (i.e., sub-perceptual, daily/weekly small doses).
In fact, her “low dose” protocol translates to a full psychedelic experience for a human, and her “maintenance dose” translates to a massive, potentially “heroic” dose. The “geroprotective” effect observed in her mice was driven by monthly, high-intensity pulses, not chronic low-level supplementation.
Here is the breakdown of the data and the translation for a 70kg human.
1. The Protocol Used in Mice
In the study (npj Aging, 2025), the mice were not given daily doses. They were treated once per month via oral gavage.
- Month 1 (Initiation): “Low Dose” of 5 mg/kg (psilocybin).
- Months 2–10 (Maintenance): “High Dose” of 15 mg/kg (psilocybin).
2. Translation to a 70kg Human
Using the standard FDA allometric scaling factor (dividing the mouse dose by 12.3 to get the Human Equivalent Dose), here is what those “low” and “high” doses actually look like for a 70kg (154 lb) adult.
| Protocol Phase | Mouse Dose | Human Equivalent Dose (HED) | Comparable “Street” Dose* |
|---|---|---|---|
| Month 1 (Start) | 5 mg/kg | ~28 mg (Pure Psilocybin) | ~3.0g – 4.0g Dried Mushrooms |
| Months 2–10 | 15 mg/kg | ~85 mg (Pure Psilocybin) | ~9.0g – 12.0g Dried Mushrooms |
Export to Sheets
*> Note: Dried mushroom weight varies wildly by potency (typically 0.6%–1.0% psilocybin). These estimates assume standard Psilocybe cubensis potency.
3. The Biohacker Analysis
- The “Low” Dose is a Full Trip: A 25mg dose of pure psilocybin is the standard “therapeutic dose” used in major clinical trials (like those at Johns Hopkins) to induce mystical experiences. Hecker’s starting dose (28mg HED) is slightly higher than this standard therapeutic dose.
- The “High” Dose is Massive: The maintenance dose (85mg HED) is extremely high. For context, the “Heroic Dose” popularized by Terence McKenna is 5 dried grams (~35–50mg psilocybin). Hecker’s maintenance protocol is nearly double a standard heroic dose.
- Safety Warning: 85mg of pure psilocybin would likely induce total incapacitation and ego dissolution. It is not a functional dose.
4. Scientific Conclusion on “Microdosing”
The study defines its efficacy based on pulsed, high-intensity activation of the 5-HT receptors/SIRT1 pathway.
- The “Reset” Theory: The data suggests that you do not need to have the drug in your system constantly (microdosing) to get the anti-aging benefit. Instead, a monthly “metabolic reset” (macrodosing) appears to be sufficient to extend telomeres, suppress NOX4, and reduce biological age.
- Translation Strategy: If you are looking to replicate this for longevity (hypothetically), the protocol is episodic (monthly) rather than chronic (daily).
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A new study (in mice):
One Trip to Rewire Them All: Psilocybin’s Structural Reset of the Aging Mind
The Big Idea: In a landmark study published in Cell, researchers have visually mapped—for the first time—how a single dose of psilocybin physically reconstructs the architecture of the brain. Moving beyond the “chemical imbalance” theory of depression, this research demonstrates that psilocybin acts as a structural engineer, rapidly disintegrating rigid, “stuck” neural pathways (associated with depressive rumination and cognitive aging) and building new bridges between sensory perception and executive function. The critical discovery is that this rewiring is activity-dependent: the drug alone isn’t enough; the intense neural firing (the “trip”) is the physical force that sculpts the new connections. For the longevity enthusiast, this represents a proven protocol for “Neural Rejuvenation”—physically forcing a plastic, youthful state onto a rigid, aging brain.
Context:
Open Access Research Paper: Psilocybin triggers an activity-dependent rewiring of large-scale cortical networks
- Institution: Cornell University (meinig School of Biomedical Engineering), USA.
- Journal: Cell [Volume 188, 2025].
- Impact Evaluation: The impact score of Cell is 64.5, evaluated against a typical high-end range of 0–30 for top general science, therefore this is an Elite impact journal (Top 0.1% of all science).
Mechanistic Deep Dive: The “Plasticity Spike”
The study utilized monosynaptic rabies tracing to map inputs to frontal cortical pyramidal neurons.
- DMN Disintegration: The drug specifically weakened “cortico-cortical recurrent loops.” In humans, these loops sustain the Default Mode Network (DMN), the seat of the ego and ruminative thought. Breaking this is the biological basis of “ego dissolution.”
- Sensory Integration: It strengthened inputs from “perceptual regions” (senses) to subcortical targets. This explains the “heightened awareness” and feeling of connectedness.
- Activity-Dependence (Crucial): The authors silenced specific presynaptic regions during the experience and found that rewiring failed.
- Takeaway: The “neuroplastic window” is not a passive chemical effect; it requires the high-frequency firing states induced by the psychedelic experience.
Novelty
We knew psychedelics induced “plasticity” (dendritogenesis), but we didn’t know the topology. This paper proves the change isn’t random growth—it is a targeted reallocation of bandwidth from internal processing (thinking about oneself) to external processing (perceiving the world).
Actionable Intelligence (Deep Retrieval & Validation)
The Translational Protocol (Rigorous Extrapolation)
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Human Equivalent Dose (HED) for Rewiring:
- Animal Dose: The effective “rewiring” dose in mice was ~1–2 mg/kg.
- Calculation: 1 mg/kg×(3/37)≈0.08 mg/kg.
- Human Dose (70kg): ~5.6 mg (psilocybin).
- Correction: Mice generally require higher metabolic scaling for psychoactive effects. The standard human “macrodose” used in clinical trials (e.g., Johns Hopkins) is 25 mg (~0.35 mg/kg). The mouse dose of 1–2 mg/kg is roughly equivalent to a “Museum Dose” or light trip in humans, but the full plasticity effect likely scales to the 20–30 mg range in humans.
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Pharmacokinetics (PK/PD):
- Bioavailability: ~50% orally.
- Half-life: Psilocin (active metabolite) T1/2≈50 minutes.
- Duration: 4–6 hours (Acute plastic window).
- Biohacker Note: The “afterglow” (plasticity window) lasts 24–72 hours post-dose. This is the critical period for habit integration.
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Safety & Toxicity Check:
- LD50: Extremely high (~280 mg/kg in rats). Physiological toxicity is negligible.
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Valvulopathy Risk (5-HT2B): Psilocin is a potent 5-HT2B agonist (Ki ~4 nM).
- Acute Use: Safe.
- Chronic Microdosing: High Theoretical Risk. Chronic activation of 5-HT2B (similar to Fen-Phen) causes heart valve fibrosis. Avoid daily/chronic protocols.
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Liver/Enzymes: Psilocin inhibits CYP2A6 and CYP3A4.
- Interaction Alert: Rapamycin is metabolized by CYP3A4. Taking them simultaneously could unpredictably elevate Rapamycin blood levels. Washout Rapamycin 24h before/after protocol.
The Strategic FAQ
Q1: Based on the “activity-dependent” finding, is microdosing useless for this structural rewiring? A1: Likely, yes. The study suggests the structural shift requires the specific high-frequency “spiking activity” associated with the acute experience. Sub-perceptual microdosing may boost mood via serotonin, but it likely lacks the energy required to “break” the cortical loops identified in this paper.
Q2: Does this conflict with my Rapamycin longevity protocol? A2: Pharmacokinetically, yes. Psilocin inhibits CYP3A4; Rapamycin is a CYP3A4 substrate. Taking them together increases toxicity risk. Protocol: Pause Rapamycin 24 hours before and after the session.
Q3: Can I combine this with Ketamine for a “super-plasticity” effect? A3: Contraindicated. Both act on cortical glutamate/BDNF pathways but via opposing initial mechanisms (NMDA antagonism vs. 5-HT2A agonism). Combining them risks mania or excitotoxicity. Space them by at least 2 weeks.
Q4: I have a family history of valvular heart disease. Is this safe? A4: For a single macro-dose? Likely safe [Confidence: High]. For a chronic microdosing regimen? Unsafe [Confidence: High]. The 5-HT2B affinity is real.
Q5: What specific “activities” should I perform during the 6-hour window? A5: The study implies that sensoryinputs are strengthened. Avoid screens/abstract thinking. Engage in high-sensory environments (nature, music, tactile stimulus) to reinforce the “perceptual” bridge-building observed in the study.
Q6: Will this fix my “Brain Fog”? A6: If the fog is driven by “cognitive rigidity” or depressive rumination (DMN overactivity), yes. If it is vascular or viral (e.g., Long COVID), this mechanism (cortical rewiring) may not address the root cause, though the anti-inflammatory properties of 5-HT2A activation are being studied.
Q7: How often should this be done to maintain the “rewired” state? A7: Clinical trials suggest efficacy lasts 6–12 months. Given the “structural” nature of the change (new spines), this is not a daily supplement. Quarterly or bi-annualsessions align best with the biological persistence of dendrites.
Q8: Does this paper support “Psychoplastogens” without the trip? A8: No. It actually argues against them. The “activity-dependent” finding strongly suggests the subjective experience (the neural firing pattern) is the architect of the physical change.
Q9: What biomarkers can I track to verify efficacy? A9: Consumer EEG (e.g., Muse) tracking “Alpha Power” suppression (DMN activity) or improved Heart Rate Variability (HRV) post-session. Biochemically, BDNF levels (plasma) spike, but are hard to test at home.
Q10: Is there an age limit? A10: Animal data (Kato et al.) shows efficacy even in “elderly” mice (19 months, equiv. to 60+ humans). However, older brains have stiffer vasculature; ensure blood pressure is managed, as psilocybin transiently spikes BP.
Full Google Gemini Analysis: https://gemini.google.com/share/fc1a8b2c469a
A safety analysis of Psilocybin, using Google Deep Search:
Having listened to quite a few of the Louise Hecker podcast interviews now she addresses directly the “hero” dosing strategy. They specifically chose a dose 4x higher than the normal human dose used in depression etc studies because the metabolism of mice is 4x faster. I might be misremembering the multipliers here but you get the point. So the mouse high dose in their view is equivalent to a normal human psychedelic dose and the mouse micro equivalent to human micro dosing. Take that Google Gemini! I wonder if AI will ever experiment with psychedelics…
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I listened to Matt Kaeberlein’s take on the whole thing https://youtu.be/-Aq3rrBeDLY?si=EbKzZHMGh4-FtgVs and he explores the idea that the effects could be mediated by NRF2 and/or BDNF (alongside the conventional magic mushroom telomerase stimulation idea - though clearly it must be direct rather than because of an improved mental outlook if it works in cells). But something about that doesn’t add up to me. The doses in mice were once a month (he I think wrongly says it was once a week). And the fast metabolism of mice means presumably that psylocin isn’t hanging around. The half life of psilocybin in humans is maybe 3 hours. Not sure what it is in mice - presumably even less. So one transitory spike in NRF2 and BDNF once a month has a significant impact on lifespan? That would be like exercising once a month and expecting it to extend lifespan significantly. And if it’s those pathways then wouldn’t you expect chronic micro-dosing to give bigger impacts (which isn’t the case)? Or maybe I’m misunderstanding how NRF2 activation works?
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Trump administration officials blocked FDA effort to fast-track review of psychedelic treatment
WASHINGTON — Trump administration officials vetoed the Food and Drug Administration’s plan to fast-track the review of a psychedelic treatment for severe depression, STAT has learned, highlighting possible internal discord between senior leadership and the Make America Healthy Again movement.
A psilocybin treatment from Compass Pathways made the FDA’s list of promising medicines to be granted a speedy regulatory review, according to five people familiar with the process. But when Commissioner Marty Makary presented that list for sign-off to the Health and Human Services Department, which oversees the FDA, and to the White House in October, his superiors shot it down, the people said.
Paywalled article:
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