23 replies to this topic

[edward]

This is an old study but it pretty definitively shows the anticholinergic effects of Wellbutrin. This has been mentioned in various places on this forum and I have seen references to it having this effect but I wanted to do some digging and see if I could find an actual study (I'm sure there are more, I just stopped here). I was on Wellbutrin in the past but found memory and verbal fluency issues which my doctor at the time didn't believe. I dropped the Wellbutrin and they went away. Now I cover my dopamine and norepinephrine bases with low dose deprenyl and modafinil and my memory is better. Anyway, its nice to know that the memory issue was not all in my head, ha ha.

http://jpet.aspetjou...nt/288/1/88.pdf

[rfarris]

...the anticholinergic effects ...

Sorry, but what does that mean?

[edward]

Bupropion/Wellbutrin is an antagonist at the nicotinic acetylcholine receptors in both the brain and skeletal muscle.

The net effect is that it will be doing the opposite of nootropic drugs that affect the acetycholine system positively (agonists, acetylcholinesterase inhibitors, precursors etc.) do and thus could potentially cause memory problems. (now I am oversimplifying things because I don't want to type out an intro to neurochemistry text all in one post)

[Rags847]

Bupropion/Wellbutrin is an antagonist at the nicotinic acetylcholine receptors in both the brain and skeletal muscle.

The net effect is that it will be doing the opposite of nootropic drugs that affect the acetycholine system positively (agonists, acetylcholinesterase inhibitors, precursors etc.) do and thus could potentially cause memory problems. (now I am oversimplifying things because I don't want to type out an intro to neurochemistry text all in one post)

Edward, great info! Is Wellbutrin unique in being a substance that is an antidepressant and an antagonist at the nicotinic acetylcholine receptors or do other anti-depressants have this mechanism? I was considering trying Wellbutrin because it doesn't have sexual or weight gain side effects like many other anti-depressants. But if it is an anti-nootropic then forget it. I'll try Rhodiola, St.John's Wort or SAMe for a mood boost (none of these are anti-nootropic, right?). And then work out my intellectual and motivation enhancing through Piracetam and CDP-Choline or ADHD drugs (which I'm considering trying).
Thanks for any useful knowledge.

[rebuild101]

Bupropion/Wellbutrin is an antagonist at the nicotinic acetylcholine receptors in both the brain and skeletal muscle.

The net effect is that it will be doing the opposite of nootropic drugs that affect the acetycholine system positively (agonists, acetylcholinesterase inhibitors, precursors etc.) do and thus could potentially cause memory problems. (now I am oversimplifying things because I don't want to type out an intro to neurochemistry text all in one post)

Edward, great info! Is Wellbutrin unique in being a substance that is an antidepressant and an antagonist at the nicotinic acetylcholine receptors or do other anti-depressants have this mechanism? I was considering trying Wellbutrin because it doesn't have sexual or weight gain side effects like many other anti-depressants. But if it is an anti-nootropic then forget it. I'll try Rhodiola, St.John's Wort or SAMe for a mood boost (none of these are anti-nootropic, right?). And then work out my intellectual and motivation enhancing through Piracetam and CDP-Choline or ADHD drugs (which I'm considering trying).
Thanks for any useful knowledge.

Whoa, hold on now... I wouldn't exactly slap the "anti-nootropic" label on Wellbutrin =) In fact, for some of us, it certainly does work as nootropic (speaking from personal experience). Cognition consists of more than just memory even IF you had a negative effect as mentioned prior, and remember that we all can have very different results. For me, I had the opposite effect that edward had: my memory and verbal fluency increased. So it really is YMMV...

Wellbutrin is a bit unique in its mechanism. As I understand it, it targets more of the norepinephrine (motivation, etc.) side of things where as SSRIs go more for serotonin. SSRIs also has more sexual side effects than Wellbutrin as you seem to already know. The only other types of antidepresants that *might* be close to Wellbutrin could be tricyclics -- but someone correct me if I'm wrong there.

So while we're on the subject, would taking a choline supplement help counter act any acetylecholine blocking problems caused by the medicine? Or would it be more of a complete waste of Choline?

[niner]

Edward, what dose and formulation (SR, XR, or quick release) did you experience the memory issues with? Bupropion has been investigated up the wazoo, so I don't think this is likely to be a huge problem, though it may well be a low level side effect. The experiment described in the paper was in vitro, and the IC50 for bupropion appeared to be about 10 uM from the graph. Without looking at bupropion PK, I would say that it's not crazy to think that there might be enough of an effect for some people to notice something at higher dosage levels.

[edward]

Edward, what dose and formulation (SR, XR, or quick release) did you experience the memory issues with? Bupropion has been investigated up the wazoo, so I don't think this is likely to be a huge problem, though it may well be a low level side effect. The experiment described in the paper was in vitro, and the IC50 for bupropion appeared to be about 10 uM from the graph. Without looking at bupropion PK, I would say that it's not crazy to think that there might be enough of an effect for some people to notice something at higher dosage levels.

I have tried different doses over the years. I have gone back to it only because: a. it is a wonderful antidepressant, it really knocks out depression and activates without major anxiety, b. I kept thinking that the memory and cognitive issues were just my imagination so I gave it multiple tries. The last dose I tried was 300 mg of the XL and yes the same effect. Takes a little while to notice but the same thing. Perhaps in lower doses it might be ok but 300 mg per day, either 2 150 XR, 3 100 immediate or 300 XL seems to be the dose where the antidepressant effect kicks in for me. Its really sad because its a great drug other than this effect.

I have discussed this effect with two different physicians and they both have had patients that have complained of this effect especially with regards to verbal fluency so it is not unheard of, I just think that maybe some are more sensitive than others.

[edward]

I tried every way I could think of, choline supplementation, Hup A, Nicotine, Piracetam and nothing made this particular side effect go away other than stopping the drug and even with that it takes about 2 weeks for the effect to fade.

[rebuild101]

Edward, what dose and formulation (SR, XR, or quick release) did you experience the memory issues with? Bupropion has been investigated up the wazoo, so I don't think this is likely to be a huge problem, though it may well be a low level side effect. The experiment described in the paper was in vitro, and the IC50 for bupropion appeared to be about 10 uM from the graph. Without looking at bupropion PK, I would say that it's not crazy to think that there might be enough of an effect for some people to notice something at higher dosage levels.

I have tried different doses over the years. I have gone back to it only because: a. it is a wonderful antidepressant, it really knocks out depression and activates without major anxiety, b. I kept thinking that the memory and cognitive issues were just my imagination so I gave it multiple tries. The last dose I tried was 300 mg of the XL and yes the same effect. Takes a little while to notice but the same thing. Perhaps in lower doses it might be ok but 300 mg per day, either 2 150 XR, 3 100 immediate or 300 XL seems to be the dose where the antidepressant effect kicks in for me. Its really sad because its a great drug other than this effect.

I have discussed this effect with two different physicians and they both have had patients that have complained of this effect especially with regards to verbal fluency so it is not unheard of, I just think that maybe some are more sensitive than others.

Did you ever try the SR or instant release versions? If not, I'd give it a shot. It can be a difference of night and day.

Have you or any others experienced any tinnitus (ringing in ears) from Wellbutrin? Maybe I'll have to start a separate thread for that tho. I should double check, but I thought for sure I read something about piracetam helping reduce tinnitus. That would kind of make sense. If Wellbutrin inhibits or is anticholinergic and Piracetam uses or increases acetylcholine, wouldn't a similar effect on the tinnitus be expected? You mentioned a two week delay after stopping the medicine before the cognition cleared up. Maybe a choline/piracetam combo could at least reduce that two week period?

[flatline]

Hmm, how topical. I was just researching this issue. I have been on 150mg XL for about six weeks now. The memory effects have subsided. I think that a further increase will have to be performed VERY slowly, most likely by increasing my tolerance with small doses of immediate release, which comes in 75mg (and if my doctor allows it, I would like to split this pill for half that dose, because the memory effects are really awful). It's not just memory -- it just makes you a complete air-head!

I might have experienced some alleviation of the memory effects by using Centrophenoxine, an acetylcholine acting nootropic. I only did this once or twice, so I can't say anything definitive. I will certainly experiment with this more if I run into the memory effects again.

[Pittguy578]

Wow I did not log on here for a month or two...and was just saying to myself the other day something is wrong with my memory..I am forgetting names/etc that I have known for years..not people currently in my life but people from my fraternity..etc..I looked at this one guys pic on myspace and could not remeber his last name for the life of me..
I just started WB about a month ago..started on the regular stuff for MAJOR Depression.now I am on XL..450 MG.I am talking about suicidal ideations. isolation.sleep problems..etc. I actually had to go on short term disability since I was not able to work..I had gotten depressed before but this is the first time I ever had anything like this. just had a bunch of stuff happen at one time..I hope to go back to work in the next week or two...It is the only thing that started to make me feel normal again..I am hoping these memory issues go away..but my focus is better though..I also have ADHD..very weird..I am supplementing with choline and piracetam now to help get my memory back.

[flatline]

Yeah, I've gotta throw my anecdotal support behind centrophenoxine. It is a powerful choline agent. James South (supplementalist) touts it as superior to other Choline supplements. Read for yourself here: http://www.smartnutr...rophenoxine.htm

How's your situation going, James?

Edited by flatline, 05 April 2008 - 11:31 PM.

[DairyProducts]

When I used Bupropion, my memory became much better. I could remember short term thing better and memories from long ago came back seemlessly. Best memory of my life. Am I the only that happened to?

[chris76]

Untreated depression is bad for cognitive functions. In that perspective antidepressants should be good for memory and other cognitive functions.
On the other hand if the depression is due to a stressful situations/problematic past/upbringing remembering is not a good thing.
For example SSRI and Venlafaxine helps people with post-traumatic-stress-syndrom (eg. helps them forget?)

[Animal]

I seem to have more then enough acetylcholinergic activity to compensate for the potential cognitively detrimental effects of Wellbutrin. Thus I have never suffered from any deterioration in ability due to my use of Wellbutrin fortunately, and I used the maximum recommended dose of 450mg/day.

In fact, the application of acetylcholinesterase inhibitors and cholinergics in general cause a rather unpleasant depressive state for me.

[brentpeters]

I have been prescribed Wellbutrin but am uncertain about its long-term effects. Does it increase endogenous dopamine production, or does it act like an SSRI, by preventing its elimination? And is it sustainable? In general, I am opposed to pharmacological drugs, so I do not expect to be on Wellbutrin for long, but nonetheless I would like to know more of its safety. The brain is so delicate; the prospect of tampering with its neurotransmitters is cause for concern.

The potential for memory loss, no matter how slight, is also worrisome. How best might this be avoided?

I also read this article on Livestrong, but I think the author got Wellbutrin confused with SSRIs: http://www.livestrong.com/article/136648-the-long-term-side-effects-wellbutrin/

[addisonmelton]

I know nobody has touched this thread for a while, but I was doing research on this subject myself just now and came across the following bit by a doctor explaining in simple terms the relationship between dopamine and acetylcholine

"Acetylcholine opposes/moderates dopamine transmission, in some parts of the brain. An excellent example that demonstrates the relationship between dopamine and acetylcholine is the difference between Parkinson's disease and Huntington's Chorea. An oversimplified explanation is that in Parkinson's disease dopamine is deficient. In Huntington's chorea, acetylcholine is deficient. One of the lead-in symptoms of Parkinson's disease is depression."

In other words, increasing one is going to reduce the influence of the other in the brain, kind of like a see-saw. Don't know how right she is but subjectively it matches my experiences having taken wellbutrin, choline, and adderall in various combinations over the years.

Here's the full link: http://www.doctorslo...opic-16975.html

[NeuroNootropic]

I found these studies using Google scholar:

In Alzheimer's disease (AD) and Parkinson's disease (PD), dysfunction in the basal forebrain cholinergic system is accompanied by a consistent loss of presynaptic cholinergic markers in cortex, but changes in cholinergic receptor binding sites are poorly understood. In the present study, we used receptor autoradiography to map the distribution of nicotinic [3H]acetylcholine binding sites in cortices of individuals with AD and PD and matched control subjects. In both diseases, a profound loss of nicotinic receptors occurs in all cortical layers, particularly the deepest layers.

→ source (external link)

The presence of distinct nicotinic acetylcholine receptor (nAChR) subtypes in specific central nervous system (CNS) areas offers the possibility of developing targeted therapies for diseases involving the affected brain region. Parkinson's disease is a neurodegenerative movement disorder characterized by a progressive degeneration of the nigrostriatal system. α6-containing nAChRs (designated α6*1 nAChRs) have a relatively selective localization to the nigrostriatal pathway and a limited number of other CNS regions. In addition to a unique distribution, this subtype has a distinct pharmacology and specifically interacts with α-conotoxinMII, a toxin key in its identification and characterization. α6* nAChRs are also regulated in a novel manner, with a decrease in their number after nicotine treatment rather than the increase observed for α4* nAChRs. Striatal α6* receptors were functional and mediate dopamine release, suggesting that they have a presynaptic localization. This is further supported by lesion studies showing that both α6* nAChR sites and their functions are dramatically decreased with dopaminergic nerve terminal loss, in contrast to only small declines in α4* and no change in α7* receptors. Although the role of nigrostriatal α6* nAChRs is only beginning to be understood, an involvement in motor behavior is emerging. This latter observation coupled with the finding that nicotine protects against nigrostriatal damage suggest that α6* nAChRs may represent unique targets for neurodegenerative disorders linked to the nigrostriatal system such as Parkinson's disease.

→ source (external link)

Bupropion is a noncompetitive antagonist of the nicotinic acetylcholine receptors so what implications does this have on Parkinson's disease?

Do the nicotinic receptors upregulate density or are new nicotinic receptors formed? What if the nicotinic receptors die out because they're not getting stimulated?

Can someone more knowledgeable than me please explain whether bupropion increases nicotinic receptors or whether it decreases them?

[majkazuki]

Bupropion is a noncompetitive antagonist of the nicotinic acetylcholine receptors so what implications does this have on Parkinson's disease?

Do the nicotinic receptors upregulate density or are new nicotinic receptors formed? What if the nicotinic receptors die out because they're not getting stimulated?

Can someone more knowledgeable than me please explain whether bupropion increases nicotinic receptors or whether it decreases them?

Bupropion helps with motivation and an ability to feel reward; my life is better with it. Without, I'm a dysthymic downer uninterested in anything.

It does mess with verbal fluency a bit, and maybe with short term memory...

I'm also concerned about the effects of long term use. Going on two years use at 200mg SR/day.

Anyone else here on bupropion long term? Or have any warnings regarding long term use?

Edited by greg45, 03 February 2013 - 05:23 AM.

[NeuroNootropic]

I too suffer from dysthmia and when I took 150 mg Wellbutrin XL it helped for the first 2 weeks and then made me worse after that. I gave it 5 weeks before quitting. It also gave me many side effects. I also tried upping it to 300 mg XL but that just gave me even more side effects without any benefits.

If you don't mind me asking, what symptoms do you have and what meds did you try before taking bupropion? Also, what dosage and release variations of bupropion did you try before settling at 200 mg and aside from impaired short term memory and verbal fluency, do you have any other side effects?

[nupi]

Bupropion helps with motivation and an ability to feel reward; my life is better with it. Without, I'm a dysthymic downer uninterested in anything.

It does mess with verbal fluency a bit, and maybe with short term memory...

I'm also concerned about the effects of long term use. Going on two years use at 200mg SR/day.

Anyone else here on bupropion long term? Or have any warnings regarding long term use?

I was on it for like 8 months before I kicked it, it definitely screwed with my memory and gave me anxiety, sleep problems and horrible constipation. It was great for 3 months, after that it was down hill from there...

[majkazuki]

I too suffer from dysthmia and when I took 150 mg Wellbutrin XL it helped for the first 2 weeks and then made me worse after that. I gave it 5 weeks before quitting. It also gave me many side effects. I also tried upping it to 300 mg XL but that just gave me even more side effects without any benefits.

If you don't mind me asking, what symptoms do you have and what meds did you try before taking bupropion? Also, what dosage and release variations of bupropion did you try before settling at 200 mg and aside from impaired short term memory and verbal fluency, do you have any other side effects?

Sorry for taking so long to respond.

I was prescribed Buproprion SR, titrating from 150mg, to 200mg. I was wired for the first few weeks, taking 75mg SR tablets once in the morning, once in the early afternoon. The first week was especially unpleasant, as I didn't get much sleep and was irritable. I was able to keep a lid on my emotions and reactions--I did everything I could to not lash out at anyone.

The original plan was to continue up to 300mg, but I found the med so stimulating that I was hesitant to do so. I made a pledge to myself that I was going to give the medication at least 8 weeks, if not 12. I started to feel a significant lift in mood after about six weeks. I've remained at 200mg for probably a bit over a year now.

My doc doesn't understand how I get an antidepressant effect at anything less than 300mg. She's mentioned titrating higher, but I'm very hesitant. I like where I'm at now. I'm awake, can focus, and have motivation. If it matters, my BMI is 18.7, so perhaps that's why such a low dose works?

I'm taking a generic Buproprion SR, two 100mg pills. I never tried another form of Buproprion.

I had tried Methylphenidate and Adderall, but I didn't like how fast my body adjusted to those meds. I felt irritable after the Methyphenidate would wear off and spacy after the Adderall wore off. Both meds exacerbated some OCD tendencies. I think they are okay to use short-term, but I felt like I'd be digging myself a hole if I continued down that road long-term.

Quite a few years ago I had tried Lexapro, but not for enough time to give the medication enough time to create a level, consistent antidepressant effect.

I'm not quite sure what symptoms you're asking about, though? If you're asking what I'm trying to treat, it would be dysthymia, low drive/motivation, and social anxiety. I've been that way for a long time--at least since I was 8 (yikes, almost 20 years). I'm also looking to maximize my potential, intelligence, and overall health.

Buproprion also curtailed addictive tendencies. I've totally given up nicotine, I hardly drink anymore, and I no longer partake in any other recreational highs... My addictive nature remains, but it doesn't rule my life the way it once did.

I have found that steady blood sugar with supplementation of 250mg CDP-Choline has significantly helped my memory, mentation, and verbal fluency. I'm considering bumping up to 500mg CDP-Choline per day to see if the impact of these benefits could be even greater.

Bupropion helps with motivation and an ability to feel reward; my life is better with it. Without, I'm a dysthymic downer uninterested in anything.

It does mess with verbal fluency a bit, and maybe with short term memory...

I'm also concerned about the effects of long term use. Going on two years use at 200mg SR/day.

Anyone else here on bupropion long term? Or have any warnings regarding long term use?

I was on it for like 8 months before I kicked it, it definitely screwed with my memory and gave me anxiety, sleep problems and horrible constipation. It was great for 3 months, after that it was down hill from there...

Again, sorry for taking so long to respond. Thanks for your input. It's funny, I had those issues--minus the constipation--for the first couple of months, but then things became smoother.

Edited by greg45, 22 February 2013 - 02:13 AM.

[Axmann8]

Sorry for necroposting, but there aren't many bupropion threads on Longecity so I figured it would be better to keep it in this one (plus, this one shows up when it is searched in Google :D)

 

I just wanted to point out that, while substances increasing the activity/effectiveness of acetylcholine do, in general, have a positive effect on cognition and memory, excesses in acetylcholine can also induce cognitive deficits. In fact, Alpha-GPC gave me absolutely terrible brain fog, depression, lethargy, and memory problems.

 

If anything, I've noticed improvements to my memory in the short time I've been on Wellbutrin. At the very least, it has reversed some horrible depersonalization/derealization I've been having lately, which may have possibly even been induced by overuse of nootropics (high doses of CDP-Choline daily for about 4 months).

Edited by Axmann8, 26 November 2015 - 12:44 PM.

[theCLK]

I'm thinking about trying Wellbutrin for focus, not sure if my short term memory could be any worse at this point