Rapamycin and Ketamine

I’ve heard that Rapamycin intefears with the effects of Ketamine, because some of the effects that Ketamin has are interupted by inhibiting the mTORC1 pathway, where Ketamine’s action realies on interfering with the downstream pathway activities of this pathway, which basically gets turned off.

I’m guessing this could also explain the ulceration seen in the bladders of chronic Ketamine users; is Ketamine’s interference in the latter parts of this pathway perhaps inhibiting the rate of cellular turnover in the blader? In the same way Rapamycin can cause mouth ulcers, by posissbly inhibiting cell turnover in the mouth.

Can anyone provide more detials on how Rapamycin interfears with Ketamine’s actions and how Ketamine interacts with the same pathways Rapamycin interacts with?

Details here:

The results were a real surprise, in two major respects. First, results of the rodent experiments were not confirmed in people: patients who received 6 mg of oral rapamycin received just as great a benefit from ketamine after 24 hours as those who received placebo. Rapamycin blocks mTOR1, but does not in itself prevent ketamine from exerting rapid antidepressant effects.

The second surprise delighted the research team. When patients took rapamycin prior to receiving ketamine, 41% still showed a clinical antidepressant response after two weeks, with 29% in full remission. This compared with 13% response and 7% remission when placebo was given prior to ketamine instead of rapamycin. In other words, rapamycin pretreatment apparently extended ketamine’s antidepressant effectiveness, for at least some patients.


For what purpose are you using Ketamine?

When I first tried Rapamycin I got very strong beneficial effects:

  • Vastly better attention span including better long term goal planning, ordering of task and not feeling like I needed to do everything all at once, but could order my to-do items and work my way thought a list sequential, I was very productive during this period. Normally it can take me weeks or months to get round to things.
  • Felt calm and on top of things.
  • Excellent mental energy reserves, not speedy like caffeine or amphetamines, but when I needed to call on my energy it was there. I also had energy for three four hour bursts of concentration a day, where as, normally, I can only manage a two hour burst every other day.
  • Better body awareness and energy, I felt like I could move more easily and get off the sofa. I normally have very low energy, possibly post Covid.
  • Significantly reduced rate of breathing, I was taking 3 to 6 berths a minute, I usually take about 20.
  • Improved postural tone, I sat in a class upright for two four hour stretches, I usually slouch after about 30 minutes.

Sadly these did not occur during the second cycle when I took Rapamycin. I understand that Ketamine interferes with some of the same mTORC1 pathway. So I’m wondering if ketamine therapy might help get me back to this state. As I look at others my age and they are not suffering form such a severe energy decline, so I suspect it could also be linked to depression, autoimmune problems and possibly even things like PTSD post boarding school.

I have an adult diagnosis for ADHD in the UK. I’m acutely aware that my frontals and motor-strip (just behind them) of my brain, are very down regulated. But getting these to wake up is probably going to involve in-direct intervention that targets something else, and not those, like resting the default mode network or psychedelic intervention. I’ve tried stimulant medication from the NHS and neurofeedback, but both only seem to provide sporadic or temporary relief.


Many thanks for these.

What was your experience with neurofeedback? Was it in a clinical setting? How often did you do it and for how long? I ask because I’ve been researching it and comparing home devices with apps like muse, mendi, and focuscalm vs clinical neurofeedback.

You might find this ketamine interview interesting

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Or just this section of the discussion:

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Thanks! Randomly I was just listening to this.

I’ve booked a series of ketamine infusions at a reputable clinic; I’m wondering if there is any guidance on taking Rapamycin along side this, in terms of dose and spacing of dose?

Many thanks.

Ok, Dr John Krystal actally says it in the vide, when asked the dose they used in the studdy by Tim Ferriss he answers 6mg and:

“…We may have stumbled onto something by giving that dose. What I mean by that is that we thought it should get into the brain at six milligrams. And we were pretty confident that it would get in the brain. It would have some effect in the brain. But rapamycin turns out to be actively pumped out of the brain. And so, the concentration that we achieved was probably kept quite low by this active clearance mechanism. And so, what we think we did was to stumble on a combination that was in a sweet spot, high enough to interfere with the gobbling up of the synapses but not so high to interfere with the antidepressant effects. So, a little bit of serendipity.”

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I’ve been researching neurofeedback for about seven years now and I would say that, as a rule of thumb its not worth getting the cheaper devices as they don’t do much or do just one very specific thing and you need a range of features to improve brain health. A generic neurofeedback setup is much more effective, but also more expensive. I’d also note that neurofeedback is not well publicised, but having testing on all my friends and filmily I can attest that it does work very well.

The good news is if you can find a practitioner who works remotely they will likely lend you a device which you pay a monthly free for, so you can use it at your leisure and rental makes the price more accessible.

I use the Othmar system which includes ultra high frequencies other neurofeedback system can miss. There are a few good systems out there so do take a look.

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Yeah, I think he says in there somewhere or I found it that they gave them the 6 mg rapamycin 2 hours before the ketamine. He is quick to point out this is initial info and they still need to do more work before people should go try this.

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