http://journals.plos...069964-Kilgore1
In the end claim saha (vorinostat) has no effect on cognition due to his inability to cross bbb (in unaffected brains)
Vorinostat definitely has an effect on cognition, but maybe it's limited by blood brain barrier.
Somebody should snort it and report back. It seems a little risky though imo.
Stevespetrat had no problems snorting his. I have the courage to try this out with my vorinostat, but I probably won't trial this until I get over this cold I have.
Stevespetrat
OK, I'll share my vorinostat experiences. Keep in mind this is not a very clean trial. I've tried probably well over 100 different noots and supplements the last couple years. My current stack/diet has a variety of vitamins, minerals, probiotic foods, nearly 1:1 ω3:ω6 ratio, no grains and relatively low carbs, natural and supplemental ACh and dopamine precursors, 5α-reductase enhancers, etc, etc, not to mention NSI-189, a few doses of Dihexa, and I'm probably forgetting plenty.
I have to describe the circumstances that led me to snorting lines of vorinostat and then sitting down at a poker table for the results to make much sense. After getting jaundice and very elevated liver enzymes from a prescription drug, my physical and mental health spiraled out of control for over a year. My extremities got cold, I lost sensation in my skin, my eyes dried out, I stopped sweating, 100s of splinter hemorrhages appeared in my finger- and toenails, I couldn't recognize myself in the mirror, I lost my sense of balance and dropped things constantly, experienced near constant muscle pain-- at one point my pee turned brown and my muscles literally shrank over the course of a few days as I had the sensation of barbed wire being pulled through them -- I had first a 3 week period and then a 2 month one of not being able to sleep more than 2 hours a night (and usually an hour at most), my guts locked up to the point where it felt like steel wool was passing through them, for 2 weeks my heart rate never dropped below 100 day or night (I know this because I got one of those little pulse oximeters and wore it in my "sleep") and then I developed POTS / orthostatic problems, and my startle reflex was so heightened that birds chirping would make me jump every single time they made a peep (yet at the same time very nearly being hit by a car made me do nothing but chuckle slightly, go figure). There are plenty of things I'm leaving out, but you get the idea. And of course for months and months, virtually every waking moment was filled with the sensation that I would die at any second, nothing would ever improve, there was no hope. In this darkest moment, doctors offered antidepressants that made everything worse and benzos that dulled me past the point of having anything even resembling human cognition (not that I was cogitating much to begin with), and the support offered by my parents was to put me up in a nice institution for a while where I was convinced (and not without reason) that drug after drug would be added to the blindfolded-dart-throwing psych treatment protocol until the last remaining bit of my personality was totally eradicated.
So eventually I implemented a highly restrictive diet that eliminated the outright terror and reduced the anxiety enough to where I was able to continue combing through medical literature, ultimately stumbling upon a paper on acute stress and epigenetic changes in ACh synthesis. Recognizing that solidly 80% of my symptoms could be linked to ACh deficiency, boosting its synthesis caused a rapid improvement in my mental state and a reduction to some extent of the physical symptoms.
I had recovered enough to fall utterly head over heels for a girl for the first time in my life. Experiencing this for the first time in my mid 30's, I didn't handle it very well, and she left after a month. This plunged me into a depressive episode that none of my tricks could reverse. Unable to sleep, eat, focus, or act for a week during a time when I was unemployed and low on funds, I literally could not afford to feel that way, so I dusted off the NSI-189 that had been stashed in my "medicine cabinet" for almost a year. The reversal of not just the immediate depression but years of previous funkiness was amazingly rapid.
But of course my experiences had left their mark on my psyche. Any time I felt too happy, my mood crashed to painful despair. Any time I thought about the stuff I'd gone through, pain. Any time I thought about the girl I'd briefly known, pain. And while (for me anyway) pain can be an excellent motivator and a catalyst for change and growth (a source of eustress), this pain that I could not adapt to or learn from simply caused distress.
OK, that's out of the way. So, one thing I'd done when money was tight was go play poker. When I first started playing years ago, I was cool as a cucumber. But, after taking enough bad beats and experiencing the concomitant surge of adrenaline, my body "learned" to be excited during big hands. Even though, psychologically, I didn't experience it as fear, the physiological adrenaline rush had some hallmarks of a conditioned fear response. It certainly impaired my cognition and caused me physical and mental fatigue as repeated surges kicked in over the course of a play session. This limited play time and also caused me to make sometimes costly mistakes as my thinking wasn't as clear as it could have been. Propranolol (a β-blocker) had been somewhat effective in countering the physical symptoms, though it left me somewhat mentally dull and emotionally depressed.
I thought maybe vorinostat could help me "unlearn" my response at the poker table, so I took 50 mg up the nose and 50 mg sublingually, along with an extremely low dose of propranolol (2 mg, lowest prescribed is 10 mg, and I usually take 5 - 10 mg for performance enhancement) to take the edge off. I sat down, eventually got into a big hand, and felt... nothing. Because of everything that happened the past couple years, I've developed an acute and continual awareness of my emotional and cognitive state, the same way a golfer might be aware of his swinging mechanics. And so I was sitting there, clearly processing the hand, $250 on the line, experiencing no stress whatsoever, and really realizing how impaired my thinking had been even those times when I'd taken propranolol. And the next time I played poker, same deal -- without the vorinostat.
Now, if that were it, I wouldn't have written so damned much. But at the end of the night (I was only up $40. There was a big hand where I lost ~$100 on a 12% suck out by my opponent; sadly, vorinostat didn't improve my luck any), I went back to the parking lot. Unbidden, a memory of the girl I'd dated 5 months before floated to my mind. And for the first time in all those months, I could feel it lose its emotional salience. The pain was dulled. I ran into her a few weeks later, and, for the first time since our first kiss, I wasn't flustered and rendered stupid by her mere proximity.
Other things have changed. I no longer feel my mood crash out when I get too happy. Unless I'm very sleep deprived or under inordinate stress, I can reflect on the events of the past couple years without mental anguish. I banged my funny bone really hard while I was hitting my punching bag. As I sat there writhing in pain, I thought, "Hmm. Maybe I can get rid of this." And, with a few moments of calm meditation, the pain was gone. Maybe it's placebo; maybe it's some special effect of being on NSI-189 for 6 months. But I think it was from the vorinostat. I've since used it in other situations where I felt intense emotions were causing cognitive impairment with similar effect.
If it were only my experience, I might not have bothered sharing. But I ended up giving some to a friend of a friend who was experiencing severe test anxiety and cognitive impairment. She sat there and took a practice test. Afterwards, I asked her how she felt. "Well, I felt like panicking, but then I didn't panic." She'd also had an interview that had gone badly a week or so before. I asked her if it bothered her. "Yeah, every time I think about it, I still get upset." I asked her how she felt about it now. ".... Huh. I don't feel anything about it this time."
I think back to when I was a kid. I would get physically or mentally hurt, yet bounce back in no time at all. But at some point during adulthood, my mind learned to take "bad things have happened" and use that data to predict "bad things are going to continue to happen." Pain is a part of life. But when we ruminate on that pain, when we imagine that it will continue indefinitely, that's when it becomes distress. Crudely peaking, while NSI-189 helped me cope with the emotional baggage, I feel like vorinostat turned off that learned response and reset it to the more youthful resilience.
Take this highly uncontrolled pair of anecdotes for what you will.
