My six month experience with ISRIB — the most powerful nootropic I've tried

☠ High Risk

TL/DR: ISRIB worked amazingly well for many months (taken orally, mixed with DMSO inside of fish oil gelcaps) by giving me ridiculous amounts of energy and a silver tongue, stopping my depression, procrastination and offering tremendous insight into my life along with my ability to socialise with others. It stopped working after roughly six months and I have since returned to my previous brain fogged state; I am not sure whether this was because I became a bit obsessed with dosing ISRIB too often/recklessly (potentially causing pancreatic issues), or if the positive aspects of the experience were simply because of my potential underlying (yet to be diagnosed) mania it may have induced and I have now returned to my pre-ISRIB baseline.

I didn't keep logs or record my dosages, I just took more gelcaps whenever I felt like a boost. There were weeks I went without taking ISRIB and the cognitive benefits more or less remained the same.

Since June last year, I have consumed about 2.5 grams of ISRIB. Additional doses now seem to cause increased brain fog.

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I first reported about my experience with ISRIB on reddit sometime around the middle of last year. I soon deleted this post because I was frustrated with how much effort I put into writing it compared with the lack of feedback I received from posting it.

I began taking ISRIB due to the problems with my inability to process conversation and provide witty feedback. Along with the constant brain fog, aphasia, depression/anhedonia and tiredness, my life was a complete mess. I had always felt like it was my responsibility to fill the conversational gaps during my interactions with people as the awkward silences that followed were my fault.

...Anyway, the initial report I deleted went something like me diluting 100mg of ISRIB into 5ml (the size of the syringe I was using) of DMSO. Because I was so eager for it to work, I megadosed it from the beginning. Being the idiot I was/still am, I didn't bother reading literature which clearly stated its solubility in DMSO is something like 1mg/1ml. I injected this milky and totally undiluted solution via intramuscular injection into my thigh. This injection created a rather intense burning sensation, and within about ten minutes I noticed a rather dull headache. From what I had read from a post back in 2014 over at Longecity, there was a person who also experienced nootropic benefits from this compound, along with the headache when taken orally with DMSO.

Over the next few days post I.M. injection, I experienced rather delightful benefits from ISRIB — much more spacial awareness of my surroundings, and the previously unconscious ways in which I held my body and posture became more conscious to me. There were other noticeable benefits, but not enough for me to write off (at that moment in time) as being placebo.

I reached out to another person who was also trialling ISRIB around the same time as me. I expressed to him the annoyance of having to do multiple I.M. injections (which hurt even when properly diluted) during the day. His solution was to pierce a fish oil gelcap with a needle, squeeze the oil from out of it, and then refill the gelcap with the DMSO/ISRIB solution, along with some propylene glycol (because I couldn't find PEG 400) to aid in assisting oral bioavailability.

Several weeks passed as I continued consuming ISRIB via the gelcap method; I completely stopped procrastinating, socialised to new heights that I had previously considered impossible, sorted out my life affairs and moved onto a new city. This was totally reminiscent of my Piracetam experience back in 2012, during which time I believe the cognitive benefits arose, in retrospect, entirely from Piracetam mania. Piracetam has since permanently stopped working for me.

I continued taking ISRIB (mostly via the gelcap method but sometimes I.M.) and felt like I reached my peak cognitive level within about two or three months of taking dosages several times times a week (anywhere from 10-100mg of doses spread throughout the week). Again, due to my extreme stupidity (in hindsight), I didn't bother keeping logs nor monitoring the doses.

In terms of benefits, I would say that my social skills (at least the extent to which I perceived them) sky-rocketed. Often I would be conversing with people and find myself blurting out the very word/s that they would be searching for before they even realised they needed to say it. I guess this played one of the largest parts (beside my near constant state of extroverted excitement and euphoria) in my percieved intellect and charisma through the eyes of others. People seemed drawn to me. I won't go into a lengthy explanation here because my behaviour was situational and I'm sure you get the gist — typical manic shit.

My confidence in pretty much every conceivable aspect accelerated. I also felt as if I had regained long-lost memories of events that had vanished. I felt as if everything interested me — this lead me down a kind of "ADHD" rabbit hole in which I had many tabs open on my phone and was looking through multiple sources of obscure areas of interests to pass the time. I felt like I knew who I was, fell completely in love with myself (narcissism), and would often fall into fits of laughter over minor things. Typical mania — but it all felt wonderful. I began writing (one of my favourite past times) and the words simply flowed from out of me. I wrote several short stories, which I now read and can barely believe that I myself wrote them. All of this, too, reminded me of my experience with Piracetam.

My energy levels felt absolutely phenomenal; I couldn't seem to be able to get more than six or seven hours of sleep because as soon as I woke up I instantly felt "wide awake" and I wanted to make the most of the day. I was happy as hell to just be alive. Note: I was also sleeping regular hours, so these benefits definitely did not arise from sleep deprivation. This is important for to emphasise, because before taking ISRIB I felt so utterly drained of energy regardless of whether I slept 7-12 hours.

I experienced a kind of emotionlessness rather quickly after taking ISRIB which never really bothered me. It was a kind of content emotional apathy, even though I felt euphoric for most of the time.

However, and this part concerns me the most, throughout the day I sometimes experienced brain fog if I didn't eat enough. I was eating a whole lot more than usual (compared to my pre-ISRIB state) yet I did not seem to be gaining weight... I was over-eating to counteract the effects of what I'd considered brain fog from ISRIB — and I assumed that this was because my brain now simply required more "energy"/calorie consumption because of my perceived increase in cognition (man, I must sound conceited haha). The fact that I remained more or less at the same weight (even though I was eating and drinking loads of sugary crap) was indeed very strange to me as it completely contradicted how I understood my metabolism to work — I put on weight pretty easily unless I count calories and exercise, so this raised some suspicion.

I talked to my friend who was also trailling ISRIB alongside me about this, and he told me that literature he read stated that ISRIB may potentially cause pancreatic dysfunction/damage. I wish I'd listened and stopped taking it once I'd reached what I had considered my optimal level of cognition, but every time I took it I felt a boost in my overall mood. Maybe it wouldn't have made a difference in the end... I guess I'll never know.

Fast forward a couple of months of me taking ISRIB inconsistently and I began noticing the brain fog much more often. The solution, I figured, in my idiocy, was to consume more ISRIB. I was also regularly taking a LSD (150-300mcg every couple of weeks for about two months) alongside ISRIB, and during the last trip I had (in December) it felt as if I was developing dementia—complete and utter aphasia and indescribable brain fog followed for the rest of the trip. This passed, but I still felt a little traumatised from the trip for a couple of days later. I have done much higher dosed trips in the past, but never experienced anything as frightening as that. I'm not sure if this has played a role in contributing to my brain fog.

The last few doses (as small as 5mg) I've taken over the past month seem to definitely offer diminishing returns... Additional dosing only seems to make the brain fog much worse... I'm not sure if this is because the ISRIB simply stopped working, or if I am experiencing side effects from it, or it has fucked, or is starting to fuck with my pancreas and the drug (and/or my brain) will work again once it has repaired itself (if at all possible). I am waiting for the results of my blood test (including insulin/glucose levels) to see if my doctor can offer any insight into what is going on. I am also considering starting a paleo diet and doing intermittent fasting to possibly help correct what may be underlying pancreatic dysfunction/disease.

I have tried intranasal insulin, but I didn't notice any benefits. I want to try injecting subq, but am concerned it may make me even worse.

Looking back, I can't help but ask myself what I really achieved whilst taking ISRIB. I definitely felt incredibly more intellectually, emotionally and conversationally available to my family, friends and the girls I pursued, and increased access to my vocabulary seemed much more pronounced. Things like the hysterical laughter over things that were rewlly not that funny, along with the "flight of ideas" makes me think that it could be entirely possible that the percieved benefits from ISRIB were simply just related to my potentially underlying mania.

It's hard seeing people I met during the heights of my ISRIB experience and meeting them again (through their eyes and my own) and being a totally different person. I have asked a few friends who I regularly interacted with during my ISRIB consumption what they thought of me before compared to my current state; some say that I simply seemed much more excited, another told me that I am not as enthusiastic/more depressed and not as talkactive and energetic.

I seem to have more or less returned to the brain fogged state I experienced before taking ISRIB. The anhedonia is back, as is my tiredness throughout the day and inability to hold long (and what I considered "intellectual" conversations) with others. Once again, I struggle with aphasia and finding the right word to suit the moment (what I identify as being my wittiness and charisma) along with my overall enthusiasm for life.

Apologies to those who have found this post convoluted; I will try to reply to any questions to be more specific.