Nootropic Stack Progress

Hi Beautiful people, I wanted to create a progress log for my Nootropic stack. I thought might be helpful for me to create a post so as to track my progress as I think it might help keep me accountable. I have been guilty of adding far too many things to my stack in the past and so I wanted to scale it back and start from the ground up.

For background my primary diagnosis is Schizophrenia. I have depression although much of what I experience could just be the negative symptoms. I have recently been diagnosed with ADHD as an adult, make of that what you will. I suspect I’m slightly on the spectrum but nothing to warrant a diagnosis. I have also experienced crippling anxiety in the past, this has all but completely self resolved. While I experienced mixed states during my psychotic episodes, I have also experienced mood elevation without concurrent psychosis, which I likely attribute to the medication. I rarely experience positive symptoms anymore, they appear about once every month or so although my ‘thinking style’ still has a notably paranoid flavour to it all. My stack focuses mainly on improving cognition and combatting negative symptoms. The dopaminergic drugs that I take have a propensity to cause slight exacerbations in positive symptoms as such my risk tolerance is on the higher end. Since negative symptoms are also likely caused by a dopaminergic pathway it’s not a careless approach, moreover, it requires a very fine balance. My schizophrenia is of a paranoid subtype.

I’m scaling back to just the pharmaceutical but I thought however there are still some interesting talking points in my current stack.

Latuda 60mg (night)
I’ve seen some studies that show diminishing returns in response above 80mgs. 40mg didn’t work for me previously. Individual response to antipsychotic medications in particular is SO varied, honestly, you just have to try a few and find what is right for you. Here I opted for something with low weight gain/low sedation. I lost at least 20kg after I switched from the previous antipsychotic. I’m still keen to try brexpiprazole again later down the track. In the short term looking to lower this down to 40mg.

https://www.thelancet.com/article/S0140-6736(19)31135-3/fulltext?fbclid=IwAR2FyHbWWLdmUr5zCuBjsYgumaIs3Pw9tWqzV5QMbO7Nd_Xi1JgvBUFPk7k

Bupropion 225mg (morning)
Adjunctive antidepressants show some promise. I tried 4 or 5 SSRIs before ending up at this one. For me it’s honestly a godsend and I could not recommend it enough. It gives me enough energy to counteract the depression and negative symptoms. It’s an NDRI so maybe it’s playing with fire a little but it changed my life. In the past, it has given me hypomania here and there. It never developed into full-blown mania so it was only ever ‘the fun bit’ and Drs wouldn’t diagnose a mood disorder despite my suggestion. As a result, I have gotten a bit off the leash on this medication before in the past, and all at my prescribed dose of only 300mg. I can confidently say this now but in my experience it often takes a lot longer to nut out the full effects of a medication has when you take it as prescribed which I always do as you will end up vary the dosage very infrequently. I now know this medication has a profound effect on my mood but was also likely the cause of my previous hypomanic state. All in all, it is a favourite medication of mine and like many others, I have tried a fair few.

Ritalin 5mg up to 3x a day (as required)
This is a medication that does what it says it will do, it gives you focus. It doesn’t motivate you in the same way that Bupropion does. This stuff could easily make you psychotic as it has for me when I have stacked the dosage too close to my Bupropion in the past. Works for cognition, maybe less so for negative symptoms. Stimulant medications are powerful and probably not worth it if you experience a lot of positive symptoms. On balance it is an equally powerful tool if you can use it right. Due to the risk of psychosis, this is a hard medication to titrate.

Clonidine 100mg (night)
A surprisingly mild drug prescribed for ADHD I feel it has an anti-anxiolytic effect and is calming in a warm way. By far the most intriguing drug I have ever tried as its effects are quite subtle somewhat like how SSRIs were for me. I feel the effect size in providing focus is really quite small. Due to the small effect size, I’m not sure it warrants long term continuation.

Melatonin 2mg (night)
It works and I feel it has little downside so is worth continuing to take. If you sleep fine already I wouldn’t bother. Some people have opposing views about melatonin but personally, I think there are worse things you could take.

The first thing I will add to my stack is a multivitamin which I will run for 1 month on, 1 month off.

Wishing you luck in your journey, see you then crew.

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Welcome.

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@ZombieMombie , @ninjastar , @Moonbeam, @rogueone, and @Bowens

Enjoy your stay with us!

Melatonin is a good supplement for sleep.

It’s warned not to take it long term, like many months in a row might be too much, but I don’t know if that applies to me. The zyprexa I take is already inhibiting serotonin(which produces melatonin naturally), so it can’t really disrupt natural production under these circumstances.

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Interesting theory. I’m assuming that as you meant as Zyprexa affects serotonin that there would be a down-regulation of serotonin production. My understanding is that antipsychotics occupy the receptor site at the neuron. These drugs work at the synaptic level so I’m not sure they are inhibiting the production or conversation of neurotransmitters they are just blocking their effects in the brain.

I found a paper, I can’t link it because apparently I’m a new user but you can find the whole article by googling: “Role of Melatonin in Schizophrenia”. The paper goes on to say

“Treatment with olanzapine, an atypical antipsychotic, did not affect the MLT circadian rhythm of a group of drug-free schizophrenic patients”

More generally because poor sleep is correlated with episodes of psychosis and positive symptoms I think it makes sense to take melatonin if you getting very poor quality sleep or experience insomnia.

@ZombieMombie , @ninjastar
I can’t post links?

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I think in the case of zyprexa there must either be downregulation of production of several different neurotransmitters or they are somehow destroying or detraining the brain receptors from working naturally.

There are thousands of stories online about people who have been on zyprexa, but when they try to quit the drug they experience severe insomnia from months to many years. Some may never recover natural sleep.

Melatonin helps a bit in conjunction with the zyprexa, but trying to sleep without zyprexa even though taking supplements, does not work for me. There was a time I could sleep even though not taking it though. But after about 7 years on it, there was like a switch one day, and suddenly I was dependent on the drug for sleep.

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I think my understanding is that taking antipsychotics unregulates dopamine receptors. I.e. as a result of blocking them your brain makes more receptors. I have heard of people using antipsychotic short term to upregulatie dopamine. The rebound effect does appear to be very common. The indications for which these drugs are prescribed schizophrenia, as well second and third line treatments for bipolar and treatment resistant depression. My feeling is that the majority of who require antipsychotics in the first place will be taking them chronically and will be prescribed them long term. As a result your brain will often have adjusted to these medications by the time someone trys to come off. The receptor upregulation combine with direct effects of these medications means that it is easy to become reliant and they are hard medications to come off. In effect you become dependent on them and they sensitise you once you come off. I also think that successfully coming of antipsychotics is a long process of carefully titrating the dose. E.g. zyprexa comes in 2.5mg as the smallest afaik, if you were to lower it then practically you would want to lower it buy 1.25mg every couple of months. Not many people do that so commonly they experience a rebound effect.

To your point though they do not know where or not antipsychotics are the cause of reduction in grey matter brain volume. It would be naive to think that taking antipsychotics for a long period of time will not induce at least some sort of permanent changes. That said it doesn’t necessarily mean any of the changes they make are harmful. They obviously shape your experience of the world in a powerful way for better or for worse.

In my experience antipsychotics don’t hit me anywhere near as hard as they used to years ago and tolerance is directly linked to dependence also.

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The problem I have with zyprexa personally is that if I get down to doses under 3.75mg, insomnia hits and I am forced back on the drug because of sustained insomnia that does not let up at all. Also sleep is not satisfactory on 5mg or below. Right now I’m doing 6,25mg which I think is a good dose for maintaining the sleep aspect.

I think in effect the only way to get off this drug is either to switch to a AP that also induces sleep, but works on fewer types of receptors. Zyprexa work on 17 different types of receptors, while for example seroquel works on 10 or less, don’t remember exactly. But that would give the brain opportunity to partially recover natural function for some receptors.

The other alternative is to simply quit zyprexa and try a heavy duty sleepmedication and hope that the brain is able to get some form of restitution and normalization over time.

Sorry about the late reply. I don’t get notified directly unless you hit the reply button under my post. If you hit the reply at the bottom of the screen you only notify the person that started the thread(unless you started it yourself). But luckily I saw there was a new post from the forum mainpage and checked it out :slightly_smiling_face:

I would really like to get rid of all those heavy negatives I’ve got, but because my positives are much more pronounced than my negatives; I have to take very calming drugs, that also worsens negatives much.

Your on a comparativly low dose so that is something to be happy about. I was only ever prescribed zyprexa for when I was experiencing acute psychosis. It felt like a really heavy medication made me sleep at least 11 hours just off adding an extra 2.5mg to AP. Zyprexa is shown to be one of the more effective medications and there is always a risk when swapping medication. I know seroquel is commonly in prescribed low dose specifically for sleep. I have been thinking about what you said and trying to optimise my sleep a bit myself. I tried a little extra melatonin and also low dose lithium 5/10mg. The extra melatonin made a slight difference but not noteworthy or significant really. I think sleep hygiene comes up trumps

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I would start with an antidepressant for negative side effects as I feel that’s really the only thing that both shows promise and is easily accessible. I think NAC is promising and memantine also but th3 verdict is still out even for the antidepressant. There are heaps of things that are worth trying which aren’t necessarily stimulating but often the effect size is small.

I have bad news to report myself, it’s a long story but I figured that the bupropion is giving me tinnitus. When I was at 150 it wasn’t noticeable at 225mg it blaring. It’s crushing that this drug is giving me these sides as I have been onnit for years. I love this drug to death and it has served me well but the tinnitus is an indication that it is ototoxic. So it’s not a good idea for to be on it long term. I’m going to have to go back on reboxitine which I have mixed feelings about as it isn’t well supported by the data

My cognitive abilities has diminished so I can’t even code a computer any more. A quite deadening feeling. I don’t even have the mental capacity to understand most of the things you write. You seem to be in a much better shape than I.

That’s alright at one point I couldn’t even read a paragraph without forgetting the words so there is hope. As it’s a chronic illness at one some point I had to accept that in terms of my recovery that I had reached my new normal/baseline also. That doesn’t mean you should ever give up though you can always improve as person illness or no illness. Most importantly be kind to yourself recovery is a looong journey. Make sure you find the medications that work for you as that and work closely with your supports, they were the things that made the biggest difference for me.

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I just wanted to give an update. I tried to come off the bupropion and lower my antipsychotic at the same time at the end of last year. Because latuda is also used in bipolar depression I think it was supporting my mood. Consequently when I reduced both my mood fell through the floor. I thought it would recover with time, as it takes time to readjust when you come off the antipsychotics. Also I think a bunch of lifestyle factors were contributing to my low mood. Being on the antidepressants so long my emotional connectedness was restored in a good way but my behaviour and routine changed for the worse.

As the bupropion was giving me tinnitus I decided I would try a ssri as I had heard that long term they can increase bdnf and facilitate neural connections. I cycled on to my second antidepressant before I restarted my nootropic stack as I figured it must have been helping when I was on it. I weeded out most of the side effect on the nootropic stack and cycled on a 3rd antidepressant. That didn’t work to I went back to bupropion.

I used to be super into my nootropic stack. Taking quite a large cocktail of things you think the stuff is going to work but the excitement wears off after a while. I take the same stuff everyday and make 1 or 2 changes every 2-3 weeks. Most of the stuff I take at what would be subtherapeutic doses.

I’m taking the nootropics over a lot longer period of time then the studies, I’m taking so much stuff already and it’s expensive. I had figured what does half the stuff do anyway? So I started to get lax with my refills.

I ran out of NAC for like a month or so. I heard a case report that NAC caused anhedonia. Having also read up about antiaddiction medication and knowing that it is used in ocd and ocd is hyperdompmenegeric state. When I reintroduced the NAC it flatlined my mood. I came to the conclusion that it’s obviously lowering dopamine which is why it works in addiction, schizophrenia and ocd. NAC is the only thing I’m actually bullish on and I dose it at 2400mg.

I had recently quit matcha tea which I drank religiously for 2 years because I read that it lowered testosterone. Subsequently I drank a few strong coffees and had some triggering days which allowed to more clearly depict what I had long suspected that coffee triggers my positive symptoms. I heard on a podcast that caffeine and adenosine inhibition has a downstream effect antagonising ndma recptor and since nmda is linked to the glutamate hypothesis I figued the caffine was no good for me. After I cut out caffeine I stopped getting positive symptoms altogether. Which is interesting since I take bupropion and ritalin which are both NDRIs.

I read a paper about grey matter changes in sz related to medication. That grey matter changes were also corollated improved outcomes in sz. As I personally felt I would rather not risk the chance that the medication could cause further changes and I was stable, not experiencing positive symptoms. I figured that ment maybe I had accumulated enough brain chnages from the medication that it had fixed me up a bit. So I figured since my positive symptoms are non-existent and my mood is flatline maybe I could get away with lowering my antipsychotic. I’ve tried lowering my antipsychotic like 4 or 5 times for reference.

I was on 50mg of latuda and lowered it by 10mg felt nothing so a couple days later lowered it lowered it another 10mg, which equates to a 40% total reduction in antipsychotics. The first couple of days were okay but then I notice I wasn’t sleeping right if basically at all. Then I figured I would stack on the sedatives I had on hand to so I could still sleep and cause inhibitory action in my brain. To lessness the likelihood of rebound psychosis and reduce any paranoia ect. I have benzodiazepines but since they are long acting they’re not ideal and they’re only their for emergencies. I really need to get some antihistamines since that’s the sedative part of antipsychotics. Anyway I added 5mg lithium and some ashwaganda. Which wasn’t enough so I added 150mcg clonidine and 6mg Melatonin. Which works okayish. I’m a week and a bit into my 40% reduction and haven’t experience any positive symptoms. The longest I lasted on this dosage is 3 weeks but granted by week one I was experiencing tiggering positive symptoms and by week 3 I was scared enough that I went back up to 50mg.

My mental state has been holding really well and if anything I feel a bit sedated. Since clonidine and guanfacine lower norephinephrine I wonder if that is helping hold the positive symptoms at bay. Since I’m so sedated and not experiencing positive symptoms I figure my plan is working so far. Which is pretty basic as far as a plan goes, replacing my antipsychotic with other sedatives so I can sleep while my receptors reacclimatise. I’m feeling pretty ambitious about having a plan that has cracked lowering my antipsychotic this time. I’m going for a further reduction taking my total from what was 50mg down to 20mg which is technically subtherapeutic.

Anyway this latest string of changes has given me the most hope I’ve had in years. It would be the lowest my antipsychotic has been in 2 years too. I’m holding my breath for the 3 week mark but even if it doesn’t work out this will become my new blueprint next time I lower my antipsychotic. It’s promising to feel like I have a new plan of attack in itself. And when I’m not feeling overly sedated my cognition and attention honestly feels like it has got an extra kick. I never realised how much the antipsychotics affected my ability to think. Heres to hoping I don’t fully lose my marbles in my latest round of experimentation. 20mg of latuda is really living life on the edge if you ask me

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I swapped L-Theanine from night to morning since I think it was affecting my sleep.
I lowered Lithium and now I’m just taking 5mg once a week. I figure this is just for good measure considering the epidemiological studies.
I changed Curcumin from once a day to once every 4 days since COX-2 inhibitors give me tinnitus.
I decrease melatonin from 8mg to 5mg.
I swapped Clonidine 150mcg + Guanfacine 2mg for Guanfacine 3mg.
I cut my B-Vitamin to 1/8ths since I felt it was causing pressure in my eyes/headache

The initial consequence being that I’m not sleeping anywhere near as good.

20mg vs 50mg latuda. Concentration is noticeably improved, that could just be from the increase Clonidine/Guanfacine hard to tell probably a bit of both. Problem-solving/cognition might have improved but personally sensing improved cognition is ethereal at the best of times. A few transient thoughts not exactly intrusive but maybe odd in context. Some passing ruminations that I was fixated on before I started APs popped up which is odd for me now but I wasn’t particularly bothered by them. Tempted to come off the latuda altogether but I’m going to consign myself to my better judgement.

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My thoughts on how to structure a stack

Glutamate receptor modulators
Glycine, D-serine, D-alanine, Sarcosine, NAC, and memantine all work.

Anti-inflammatories
Celecoxib, Minocycline, NAC, Asprin. Anything that is a Cox-2 inhibitor should help somewhat.

Antidepressants
Anything that is an SSRI but the evidence is scant in terms of which one is best. I would favour Vortioxetine or Bupropion simply because of the side effect profile.

Estrogen
Birth control if you’re female. SERMs if you are male, side effect profile of SERMs aren’t great.

Antioxidants
Ginko biloba, ALA, Vitamin C, NAC, heaps of options.

Different pathways
B vitamins, L-Theanine, Taurine, Lithium, Niacin

Maybe
Cholinergics, you could take Alpha Gpc. Statins they are mainly for weight gain and they also work through Anti-inflammatory pathways. CBD, I don’t think the evidence is good for this. Adenosine modulators, but why would you want to take something sedating.

Out of the above I think evidence points towards estrodial, memantine, NAC and an antidepressant.

You can also basically just pick a Glutamate receptor modulator, an Anti-inflammatory, Antidepressant and Antioxidant. Then take B vitamins, L-Theanine, Niacin and you can trial Lithium & Taurine to see if they make a difference for you.

After trialing guanfacine for 6 months, I’ve given up on it. It takes months to build tolerance and therapeutic mg/kg could theoretical be above 7mg which it is not tested for. 1 & 2 mg were painfully sedating but I pushed through because I wanted to believe it worked. I needed to get up to 4mg to be in the starting range for therapeutic dose but I know that’s just going to be more painful sedation. I do think it helps but just not a lot and in children sedation is a desirable side effect where as it just makes me unmotivated. I’m going to go down to taper down to 1.5mg and then aim for 1mg and reassess how I feel. I don’t think I’ll come off completely until I trial something else maybe memantine? I do feel the increased dose helped get me through the worst of the withdrawals when I lowered my antipsychotic. I think it is mainly just useful for blood pressure and sleep. When I started clonidine it got rid of my hypervigilance but it I don’t think the hypervigilance is coming back. Might just be more useful to take at the same time as stims but I also think the more meds you can do without the better