I think I’ll go with the annoyingly negative review that Vera Health generated on this topic. I find Vera-Health.ai to be pretty skeptical on everything; but their analysis seems pretty solid.
Human evidence that maraviroc (CCR5 antagonist) improves memory or slows neurocognitive decline is weak/inconclusive: one very small pilot RCT suggested possible benefit, while multiple larger and better-controlled RCTs show no meaningful neurocognitive advantage.
Human interventional studies directly testing maraviroc with neurocognitive outcomes (key evidence)
Study (population)
Design / n
Cognitive outcome
Bottom line
Clinical Evidence
Letendre et al, 2023 (A5324; virally suppressed PWH with NCI)
No major benefit vs control; exploratory memory-domain improvement only in subgroup with ↑CNS penetration effectiveness
MVC is bundled with a regimen switch; cannot isolate MVC’s independent cognitive effect; small and largely negative 6
What this means clinically
As a treatment for memory loss/neurocognitive decline in humans, maraviroc is not supported by high-quality clinical evidence: the largest placebo-controlled RCT is negative for MVC-containing intensification in PWH with NCI 1.
Any suggestion of memory benefit is limited to small pilot/exploratory signals that have not replicated in larger trials and often cannot isolate MVC from other regimen effects 56.
Scope note (important for ED/clinical interpretation)
The available human evidence is almost entirely in HIV-associated neurocognitive disorder contexts (ART intensification or regimen switching), not in Alzheimer disease or general age-related cognitive decline. Mechanistic/preclinical rationale exists but does not establish clinical efficacy in humans (e.g., CCR5 blockade theory/review) 7.
Thanks. I am always up for definitive negative evidence reports as long as it is not just one report refuting the preponderance of evidence. So, I think I will be skipping maraviroc.
I don’t think I need still another supplement or drug with questionable results.
You are absolutely free to skip it but I caution you NOT to. For me it is by miles the most beneficial substance I have ever tried and yes I’ve tried at least 100-150 supplements and at least 20 FDA approved drugs and about 20 different peptides. As far as what it is doing for me, well as I had indicated earlier in other posts, I lost a lot of muscle and became very weak on GLP1 and my motivation to do anything tanked. I started HGH and it helped some maybe a 20% improvement, but boy did Maraviroc ever fix it all for me. My strength is back to normal 100%. Plus, my motivation and drive are back to my normal levels and even a bit better. I really thought I was effed for life and thank God to whoever started this thread on Maraviroc. I do 37.5mg every other day with dinner. I don’t think I have noticed any negatives.
As far as neurocognitive effects, I can’t say much there as I was relatively ok and wouldn’t know if helped or not. I am tempted to think my memory is a bit better, but I do take other stuff and can’t necessarily pinpoint it. So, yes if you want it for strength, muscles, motivation and endurance go right ahead and take it. Well, you have taken and are taking like 100 other drugs what the heck just try one more LOL.
p.s. I think it is worth noting that I started at my lowest point thus it really was a miracle intervention in my case. Perhaps someone who is at his best (already) may or may not feel any discernable benefits.
At my age I am primarily interested in cognitive effects. The gym, rapamycin, and my polypharmacy interventions maintained my strength.
As I mentioned in another thread, modafinil is a life-changing drug for me. The motivational effects from modanfil was something I didn’t expect.
I haven’t necessarily written off maraviroc, but the studies don’t seem to indicate that it would have any cognitive effect for me.
As the hippies used to say “Different strokes for different folks.”
Every time I promise myself, I’ll NEVER try another drug then you show up with something like this LOL. I am afraid I’ll have to try at least one more. I’ve been searching for something to help me in motivation department (for a long time) so hopefully modafinil will be the answer or at least part of the answer.
I noticed the wakefulness and mental effects of modafinil from the first dose. I didn’t notice the motivational effects for a few weeks. Modafinil has increased my productiveness tremendously.
There is another drug, “armodafinil,” which is the enantiopure (R)-(–)-enantiomer of the racemic mixture modafinil. Both enantiomers of modafinil are active as dopamine reuptake inhibitors and wakefulness-promoting agents, but armodafinil is more potent and longer-acting" Which I plan on trying when I run out of my modafinil supply. The effects of modafinil last me approximately 6 + hrs. I cannot take it in the afternoon without it affecting my sleep.
Armodafinil has a longer half life and will last longer into the day.
“Research reviews suggest modest improvements in attention, executive function, and complex task performance in both sleep-deprived and non-sleep-deprived individuals…”
Commonly reported subjective effects from social media, such as Reddit:
Commonly reported benefits
“Huge improvement in both fatigue and brain fog.”
“Improving attention and reducing impulsivity similar to Ritalin.”
Thanks for the details. I would be very happy with 4-6 hour improved focus and increased motivation (to complete daily tasks). No need to be an energizer bunny 24/7 LOL. So, I’ll be ordering modafinil sometime next week.
Did you not say in the other thread that its amazingness was wearing off somewhat with continued use or did I imagine that? My ChatGPT “adviser” keeps trying to steer me off it, and told me tolerance would kick in soon but did admit it could be useful for very rare days when I need to perform my absolute best. Anything beyond this one-off case seemed to be counterindicated according to it. But I remain curious. My drive to get stuff done is indeed under strain now that I’m on tirzapetide and hasn’t been amazing for years even before that.
Of course, but the same thing happens with coffee. A first-time coffee drinker might not even sleep well the first time they try coffee. But with our acquired tolerance, we still feel and enjoy the effects of coffee. At least I do.
Gemini:
Standard Dosing: For narcolepsy and OSA, a common daily dose is 200 mg, taken as a single dose. Studies indicate that doses exceeding 200 mg may not provide significant additional benefits for all patients.
Clinical Evidence: Large, long-term studies (up to 40 weeks) in narcolepsy patients generally show no significant evidence of tolerance developing; most patients maintain effective wakefulness without needing to escalate their dose.
Acquired Tolerance: Despite clinical trial data, some long-term users report a “wearing off” effect over time."
I am currently taking it every day, sometimes 100 mg and sometimes 200 mg. This is purely subjective, depending on how I feel when I wake up.
So, yes, it doesn’t provide the jolt it did when I first started taking it. We are all looking for the magic pill that cures some real or perceived need. In my case, I have always been what D. Trump would describe as a "low-energy person."I can’t help it. “I was born that way.” Also, in recent years, while not feeling depressed, I tend to feel unmotivated.
Modanil has been a real lifestyle changer for me. I am no longer just a gym rat; I participate in many more social activities and get much more work done.
I am not sure how much modafinil affects younger people with naturally higher energy and motivation levels than mine. But I think it’s something most older people should give a try.
Over the years, I have spent many a buck at Nootropics Depot and other purveyors of nootropics. But for me, it was money wasted. Not one racetam or other nootropic did anything significant for me.
Because of my age and other factors, I get blood work done at least every 3 months. The only thing to keep in mind when using modafinil is that you should have good liver function. It can raise blood pressure and resting heart rate. Though I did not detect this at the doses I am taking.
Then this goes into my bucket list to try later on. Right now I’m juggling too many variables but I too am a rather “low energy” person. Always healthy, almost never sick, great markers, but never the energizer bunny. When the environment is interesting that alone can draw me out and stimulate me. Since I’ve moved to the suburbs or rather the country, I lack that stimulatory effect of city living and am much more prone to foot dragging about everything. So it sounds like we have similar temperaments and it might help me too. I’m actively working on lowering my RHR though from glp1a so this will be on my next tier bucket but will likely get to it this year.
This is exactly how I am… if I’m in NYC, I go go go with no breaks from the second I wake up until I go to bed… when I’m here… nope… for me, I think it’s related to ADD… if I’m interested, nothing can stop me… and if I’m not, it’s hard to get motivated… (ss-31 has been helping me in this regard, but so far, I’m not seeing this report from other people, so I’m not suggesting it and only sharing).
Modafinil at doses of 200 mg a day does not affect my resting heart rate in any detectable way. The thing that affects my resting heart rate the most is recent physical activity. The more active I am and the more exercise I do, the lower my resting heart rate is.
“Years of consistent moderate exercise accumulate real cardiovascular benefit. The heart adaptations built over decades don’t disappear quickly”. I am definitely benefitting from this, as I no longer exercise at the level that I did for many years. Exercise and going to the gym are not my favorite interventions. But I do them anyway.
The way the GLP-1s affect RHR is through significant weight loss. “The effect tends to be dose-dependent—greater weight loss correlates with greater RHR reduction.”
I think that GLP-1s combined with exercise would likely produce a significant reduction in RHR. I really do think that modafinil would definitely improve a person’s motivation and ability to do more exercise.
Yes but in my case I’ve lost just around 10 lb (I’m on the lowest dose) but have experienced higher RHR. GLP1s affect that metric by raising sympathetic tone too. That’s been the problem for me and the solution is to work out. Maybe need modafinil for the motivation piece to do that
Matt interviews Dr. Christin Glorioso, neuroscientist, physician, and founder of NeuroAge Therapeutics. They have an interesting test that includes imaging, blood, genetic, and online cognitive testing. It’s about $1300 for the package, so I’m not rushing out to try it, but I’ll look into the free online test.
I don’t want to take this daily, so I’m considering 150 mg once per week or perhaps 75 twice per week, as a start, then perhaps titrate up. Anyhow, need to take my cognitive test first.
