Health Psilocybin treatment extends cellular lifespan and improves survival of aged mice

[perpetualdawn]

@iom apparently that was his first mushroom trip ever. I think he has tripped on ketamine before, but surprisingly it seems like that was his first foray into classic psychedelics. I always assume that all of these silicon valley tech bro types have tripped before, but I guess that's not the case.

As much as I'd like to think that getting the super rich to trip would lead to a positive global transformation, I expect their experiences will simply reinforce their existing attitudes

I think you're right, but I do hold out some faith that these experiences can nudge people in a positive direction, and that billionaires tripping on psychedelics is probably better than billionaires tripping on cocaine and whisky or whatever. If I had a button to prevent guys at Davos from going to the ayahuasca "healing" I wouldn't press it. Would you?

Psychedelics can catalyze transformative perspective shifts, jumping past local maxima. But I do take your point and agree that they also tend to amplify people's existing traits, character, goals.

I also rather doubt that he will make a good anecdote for study because he is not very representative of the "average" human---he's already doing all kinds of other "aging interventions" that aren't being controlled for.

I think that if there are measurable longevity benefits to psilocybin mushrooms, it's likely that they overlap with some of the treatments that he's already doing, so they will probably not be as strong a signal as they would be for the average joe tripper.

it is a mistake to assume that any 5-HT2A agonist will do. I like to think of a receptor like 5-HT2A as more like an access panel, which allows activation of multiple effects, depending not just on the drug but also the environment of each individual receptor in the body (i.e. pH, presence of co-factors. etc.). Throw in pharmacokinetic effects, and the array of possible effects mediated by a "5-HT2A agonist" may be very vast indeed.

Interesting thought and good point. I think the overall hypothesis right now is that any (trippy?) 5-HT2A agonist will do, but there could definitely be a more complex underlying picture like you describe

 

[perpetualdawn]

From Bryan Johnson's recent post:

Three exciting longevity results came back from my first dose of mushrooms: >35% decrease in inflammation, a deeply relaxed state and neuroprotective effects.

Inflammation (hsCRP)
My systematic inflammation levels dropped from elite to undetectable. This decrease is significant, aligning with clinical reports of reduced inflammation markers (CRP, TNF-alpha, and IL6) seven days post high dose psilocybin.
+ pre-mushrooms: 0.23mg/dL
+ post-mushrooms: < detection limit 0.15mg/dL
+ >35% decrease

Deep low stress state (HPA Axis)
My cortisol and DHEA-S dropped by 42% and 45%, respectively, suggesting a profound inhibition of the Hypothalamus-Pituitary-Adrenal (HPA) axis, which corresponds with the "after-glow" effect.
+ DHEA-S: 287µg/dL to 157 µg/dL
+ morning cortisol: 10.3 µg/dL to 5.9 µg/dL

While cortisol spikes acutely during the trip, the post-session drop indicates a shift from sympathetic to parasympathetic dominance. This aligns with my sustained relaxed and joyful state.

Neuroprotection (Estradiol)
Estradiol increased 3x (11.3 to 36 pg/ml). This may be due to peripheral activation of 5HT2A receptors stimulating aromatase activity, the enzyme that converts testosterone to estradiol.

A study has shown 5HT2A stimulation in human placental cells can drive aromatase gene expression and activity. My testosterone levels remained unchanged, indicating my body compensated for the minor conversion to estradiol.
The increase is within the normal male range and is generally positive, as estradiol provides anti-inflammatory, neuroprotective and cardiovascular protective effects.

Conclusion
Taken together, these data suggest that a single high dose psilocybin experience can transiently push my biology into a low inflammation, low stress configuration that is theoretically favorable for longevity.
Measurement window: 4 days before vs. 5 days post-dose

 

[Allylbenzene]

there could definitely be a more complex underlying picture like you describe

5HT7 looks to be as important as 2a. There's a good video presentation about this on Shulgin's publisher site:

Breadth and Depth - TransformPress

Tom Ray builds on the work of the Shulgins, taking the next steps they envisioned:

transformpress.com

Tom Ray had 25 psychedelic drugs from Shulgin’s toolkit broadly assayed by the National Institute of Mental Health – Psychoactive Drug Screening Program. By synthesizing the subjective experience and molecular affinity data, he has been able to realize the Shulgin’s vision of using their toolkit of drugs to advance our understanding of the relationships between the brain, the drugs, and the mind; and most importantly, our understanding of ourselves.