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Wellbutrin

wellbutrin brain fog depression

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#1 James88

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Posted 10 January 2018 - 12:19 AM


I’m curious as to why I would respond so badly to Wellbutrin. I’ve had ADHD and depression from ever since I can remember. All signs point to a lack of dopamine. But Wellbutrin and other ADHD medications (Concerta, Vyvanse etc) make me feel awful. I can barely put two words together in my head, full of fog, irritable, they make me unbelievably clumsy and stupid, and my depression gets worse than ever. Literally turn me into a walking talking depressed zombie. Anybody have any theories on why this might be?

#2 jack black

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Posted 10 January 2018 - 12:00 PM

waiting for any good responses. I have a family member like that officially (mis?)diagnosed with ADHD and depression who had a bad response to either Wellbutrin or Concerta. IMO, her problem was more like social anxiety and maybe Asperger's. She got better on her own, but it took a lot of time and moving to a different country. she had some problems with thyroid too, not sure if related.

 

there was a discussion in another thread and one member voiced opinion that bad response to stimulants is either bipolar or schizophrenia and one should take atypical antipsychotics instead. not sure of that, but I had a good response to anti-5HT2a meds once.



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#3 James88

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Posted 10 January 2018 - 12:36 PM

Which meds are anti ht2ra? Are there any supplements that do a similar job?

#4 jack black

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Posted 10 January 2018 - 01:02 PM

google is your friend. I took serzone, but it's gone from the market in USA.



#5 Mind_Paralysis

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Posted 10 January 2018 - 08:34 PM

 I would say, if you react in such a way, then it's likely that impaired dopaminergic signalling is not the key component to your symptoms - something else is probably amiss.

 

I do believe there are reports of stimulants causing sedation in ADHD-ers though... something which is sometimes seen as a key marker in getting a diagnosis even! Because regular people are not calmed down by stimulants - they are, stimulated.

 

Let's assume that ADHD is your correct diagnosis - as such, I would suggest you try Amphetamine instead of Reuptake inhibitors like MPH (concerta) and Buproprion (wellbutrin). I knew a woman with ADHD whom tried out concerta but had to give it up because it was so sedating - to the point of accidents happening - she responded much better to releasing agents like Amphetamine.

 

 

Which meds are anti ht2ra? Are there any supplements that do a similar job?

 

There are no supplements, as in vitamins, amino acids or nutrients which do a similar job.

 

The only thing similar would be a diet which eliminates tryptophan-sources - that's the building-block which turns into serotonin. Once your body is depleted of Tryptophan, your serotonin will start to sink, and signalling out of ALL 5ht-receptors will lower - this is in essence antagonism, just an indirect form.

 

Such a diet is not recommended unless you have some kind of extreme symptoms though - it's an extreme "natural" measure, with a lot of side-effects - tryptophan is an important amino acid.

 

 

Trazodone and Mirtazapine are two famous and widely available 5ht2a-antagonists.

 

https://en.wikipedia...ent_antagonists


Edited by Stinkorninjor, 10 January 2018 - 08:39 PM.


#6 James88

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Posted 10 January 2018 - 08:41 PM

I don’t think I’d do too well with that then. My depression is pretty heavy most of the time and if I ever go on any diet that is low in carbs I get suicidal pretty quickly. And from what I read, carbs are a huge source of getting tryptophan into the brain to form serotonin. So whatever the underlying reason is for my awful, horrible horrible depression, I’m sure that the tryptophan pathway is something to do with it. Although 5htp does nothing for me. Actually just makes me numb, bored and completely unmotivated, so I don’t know really!! The quest goes on!!!

#7 jack black

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Posted 10 January 2018 - 11:36 PM

there are many different 5HT receptors with many different functions. globally lowering or increasing 5HT is not a solution; selective blocking 5HT2a or stimulating 5HT1a is. one of the supplements with that supposed action is Ginkgo. i guess you can try it first before deciding on med treatment later.

 

read more here: https://selfhacked.c...blems-and-cirs/


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#8 James88

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Posted 11 January 2018 - 01:37 PM

I actually have a heterozygous mutation in my htr1a and a homozygous mutation in my htr2a. Not entirely sure what that means though, but I’m guessing it’s not positive!!

#9 jack black

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Posted 11 January 2018 - 02:29 PM

I actually have a heterozygous mutation in my htr1a and a homozygous mutation in my htr2a. Not entirely sure what that means though, but I’m guessing it’s not positive!!

 

which RS# are those? I'll search my genetic results, I have them for most of my family members.



#10 James88

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Posted 11 January 2018 - 03:26 PM

Thanks mate.

htr1a:

rs6295 +/-
rs10042486 +/-



htr2a:

rs12583882 +/+
rs5443 +/+
rs9316233 -/+
rs7997012 +/+

#11 Kinesis

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Posted 11 January 2018 - 07:10 PM

ADHD is a symptomatic diagnosis ... not specific to molecular mechanism. Although it often is helped by stimulants, there are exceptions as your experience proves.  If you don't respond well to drugs that upregulate catecholamine function, that just means your ADHD symptoms may not have anything to do with low catecholamine function ... possibly you're already in the upper end and more just makes you feel worse.  If so, it's time for a paradigm change.  Start looking for other possible issues.  Maybe a drug or supplement that actually tones down catecholamines would help.  Or something serotonergic.  Since we can't just look inside your synapses to see what's going on at a molecular level, all the information we really have is your symptoms and how you respond to typical ADHD meds.  Some trial and error is inevitably involved ... maybe try one of these other angles and see how you do.  When you hit upon the right strategy, you'll know it.



#12 jack black

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Posted 11 January 2018 - 08:27 PM

Thanks mate.

htr1a:

rs6295 +/-
rs10042486 +/-



htr2a:

rs12583882 +/+
rs5443 +/+
rs9316233 -/+
rs7997012 +/+

 

 

rs5443 C825T – GNB3

This SNP codes for GNB3, which in turn codes for a second messenger complex associated with 5HT2A receptor signaling (R).

 

looks like the rs5443 +/+ puts you at higher 5HT2a signaling indeed. We don't have it in our family, but it's fairly common. How about the other 5HT2aR results?

 

 

rs6311 -1438 G/A

The “T” allele results in more receptors/increased gene expression and more active receptors (R,R2).

TT is associated with depression, panic disorder, and a higher stress response.

The T allele was associated with a reduction in general health, vitality, and social
function (p=0.0031-0.040) (R).

The T allele is associated with IBS (R) and CFS (R).

The C allele is associated with an extraverted personality, rheumatoid Arthritis and novelty seeking.

CC=3.6x increased risk of sexual dysfunction when taking SSRI Antidepressants ®.

This SNP correlates perfectly with rs6313, as in the T allele here will result in the A allele by rs6313 (R).

rs6313 T102C or C102T
The A allele was associated with lower general health and social function scores (p=0.0032–0.034) (R).

GG is more common in suicide attempters (R).

The allele has been associated with higher extraversion personality scores among borderline personality disorder patients and the presence of visual and auditory hallucinations in patients with late-onset Alzheimer’s Disease (R).

In schizophrenia, GG tends to do worse on working memory tasks than do individuals with an allele (R).

This SNP correlates perfectly with rs6311, as in the A allele here will result in the T allele by rs6311 (R).

rs6314 C1354T His452Tyr

~7% of the alleles in the global population are “A“. So GG is the common version.

The A allele had reduced ability to activate the receptor or cause downstream signals.  This means it causes a blunted signal after activation (R). (Technical: reduced ability to activate phospholipases C and D, suggesting that signaling through both G(q) and G(13) pathways is hindered) (R).

AA had significantly greater mental fatigue scores than the AG (and greater than GG)
(p=0.026)  (R).

AG is associated with ADHD, better response to antidepressants, worse memory (R).

AG was associated with better response to the SSRI paroxetine (Paxil) (R).

GG had a better memory (R).

Although common, GG or AG has higher rheumatoid arthritis risk ®.

(Tyr=A, His=G)



#13 James88

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Posted 11 January 2018 - 09:08 PM

So does that mean I should be looking to decrease the htr2a receptor? Another theory I had after many hours of research was excess glutamate, which would mimic the symptoms of ADHD.

#14 jack black

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Posted 12 January 2018 - 02:50 AM

Another theory I had after many hours of research was excess glutamate, which would mimic the symptoms of ADHD.

 

I guess it's possible, but would it explain the bad response to ADHD treatments?

maybe to sort it out you need a trial of tianeptine (anti-NMDAR) and anti-5HT2aR of your choice? Since you're UK based, nefazodone should be readily available (by prescription of course).

 

BTW, what are your COMT and MAO-A/B genes. Any clues there?

any problems with folate metabolism?



#15 James88

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Posted 12 January 2018 - 08:22 AM

Thanks for the advice mate. COMT are as follows:

COMT:
 
rs4680 -/-
rs4633 -/-
rs6269 +/+
rs2239393 +/+
rs4646312 +/+
rs6267 -/-
rs737866 +/-
rs165599 +/-
rs737865 +/-
rs4646316 +/-
rs769224 -/-

MAO A was not reported, I have no idea why, it wasn’t on any program that I ran my raw data through, and i tried A LOT of them. But I do have an MAO B mutation. In terms of folate, I am heterozygous for both MTHFR C677T and A1298C. But when I take methylfolate I respond terribly. Just about as badly as ADHD meds. I started really small as well (quarter of a tablet) and still reacted really badly.

I take methyl B12 for MTRR mutations and do fine with that, it’s definitely been a positive.

#16 jack black

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Posted 12 January 2018 - 03:25 PM

. In terms of folate, I am heterozygous for both MTHFR C677T and A1298C. But when I take methylfolate I respond terribly. Just about as badly as ADHD meds. I started really small as well (quarter of a tablet) and still reacted really badly.

I take methyl B12 for MTRR mutations and do fine with that, it’s definitely been a positive.

 

have you seen that monster thread?

http://www.longecity...ohol-hangovers/

 

that smart chap Chadwick have similar folate mutatations to yours and figured out that high dose of methylfolate ~10mg + some hydroxycobalamine (but not methyB12) fixed all his problems. He is probably practicing medicine in Sweden by now. BTW, low dose methylfolate and/or methyB12 gave him bad reaction, just like for you and countless others, even he doesn't understand why.


Edited by jack black, 12 January 2018 - 03:27 PM.


#17 jack black

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Posted 12 January 2018 - 05:46 PM

COMT:
 
rs4680 -/-
rs4633 -/-
rs6269 +/+
 

 

the first 2 confer high COMT function, the last is low COMT function. Overall, going by the COMT results, your dopamine, NE, and 5HT levels could be low indeed, but we don't know the MAO-A side of it. is the MAO-B mutation Rs1799836?

 

this is similar to Chadwik's so far. you should use his regimen.



#18 jack black

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Posted 12 January 2018 - 07:24 PM

OMG!

 

Now, I'm not so sure I understand the COMT SNPs anymore. Looks like there is a lot of bad science and lack of understanding on COMT published everywhere.

I just found out by checking references, according to this study: http://science.scien.../5807/1930.full

COMT SNPs are inherited as haplotypes and looks like the OP combo is homozygous for low activity and this would explain the history of poor stimulant response.

Could someone please read that linked paper and double check my reasoning?

 

That changes it some for my family as well.

 


Edited by jack black, 12 January 2018 - 07:37 PM.


#19 James88

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Posted 12 January 2018 - 08:19 PM

Yeah I got super confused about the high/low dopamine issues too. I figured it must already be high due to the fact I respond so badly to anything that raised it. (Except for coffee and cocaine) which I respond brilliantly to for about an hour. I’m gonna check that folate thread out then!!

Literally started the Charlottes Web about 10 minutes ago by the way, fingers crossed it actually has a positive impact on my life and not a let down like all the rest. I am very cautious being an addict with nearly 4 years recovery under my belt. Please don’t be addictive!!!

#20 jack black

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Posted 12 January 2018 - 09:39 PM

CBD should stimulate 5HT1aR and those are inhibitory, so it should be equivalent to inhibiting 5HT2aR, like we discussed. keep us posted.

the only concern i have now is less 5HT stimulation = more dopamine stimulation (they are inversely correlated) and yours is too high already?

 

on the other hand, THC stimulates 5HT2aR and produces the opposite. Any experience with that?



#21 James88

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Posted 12 January 2018 - 10:15 PM

Thanks mate, i’ll keep you updated on how i get on with it. I am very sensitive to nearly all new supplements and regularly have paradox reactions so I’m starting at a tiny dose and going to work my way up slowly, but so far so good this evening, hoping it gives me a decent sleep!!

My experience with THC was always bad (which is why I made sure the CBD I got had the lowest THC possible.) I smoked weed when I was in my early teens and it would give me panic attacks, I just forced myself to smoke it because it was what everyone was into at the time but I hated it. Alcohol and cocaine together were my perfect combo, they took care of everything, depression, lack of confidence, social anxiety you name it. Which is obviously why I fell into addiction. Went to rehab in 2014 and have been clean since, still crazy on nicotine though. I honestly don’t think I could function without it!!

#22 Mind_Paralysis

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Posted 13 January 2018 - 11:06 PM

Hmm... so you're big on smoking? Well, that could explain why you don't respond well to Buproprion (wellbutrin, voxra) at least - if you've got some kind of naturally lowered nAch-activity, then lowering it further will be terrible. On the other hand you got the same side-effects from stimulants, and they affect dopamine much more...

Well, have you tried anything Cholinergic? The classic combo of Piracetam + CDP-Choline is a god-send for some people with depression, as I understand it.

 

 

It does make me think though... do you have any of the candidate-genes for ADHD? You do have a lot of gene-data, it would appear, so it would be interesting to see what those results are. I also wonder, do you have any of the candidate-genes for... SCHIZOPHRENIA? Could your diagnosis be incorrect? Did you ever display hyperactivity? Were you one of the classic children who could never keep up with what the teacher said, always running around, cutting in when others spoke, stuff like that?

 

Reason I start asking, is because people on the schiz-spectrum often respond badly to both stimulants and anti-nicotinic drugs - recent data have revealed that the Nicotinic Alpha-7-receptor may play an important role in the immunologic aspects of the disease - hence, this may be why schizophrenics smoke like chimney's - they're self-medicating.

 

It should also be noted, that in certain parts of the brain, acetylcholine and dopamine have an antagonistic relationship to each other - lower one, and the other goes up, and vice versa.

 

 

Piracetam and a choline supplement are both fairly safe and easy to obtain compounds, when used with reason.



#23 James88

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Posted 14 January 2018 - 04:44 PM

Thanks for your input!! What you’re saying actually makes a lot of sense and is something I’ve been looking into. I do have some genetic traits for ADHD, they are as follows,

SLC6A3:
rs6347 +/-
rs27072 +/-
rs460000 +/-
rs6869645 -/-

DBH:
rs1108580 +/+
rs3025343 -/-
rs1611115 +/-
rs77905 +/-

I don’t really have any genetic traits for schizophrenia, however, other than anxiety and depression, I have suffered on and off with paranoia. Not really the psychotic kind, but an incredibly suspicious personality. I’m really interested in regards to choline. Almost all programmes that I have run my raw data through have said that I am in great need of choline due to my genetic dispositions. So a deficiency in acetylcholine could be a possiblity?

Only problem is, my nutritional therapist also recognised this and recommended alpha GPC. But I’m petrified to take it because all I ever see is people saying that it made them depressed, or any other choline supplement in general causing depression. And because my number one goal is to get rid of my depression, I get very afraid to take anything that could make it worse, it’s reasonably tolerable now, but when it drops I suffer severely to the point I can barely go on.

#24 James88

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Posted 20 January 2018 - 09:57 PM

Ok so update, I’m not getting on with CBD oil. The first few days I felt maybe slightly better on some level but nothing really noticeable, then after a few more days it’s pretty evident that it’s making my depression worse. Mood is more flat, less enthusiasm, more dark feelings and a sense of uneasiness in general.

I have stopped taking it, and felt better the last 24 hours, but obviously I never felt great in the first place, still depressed, but not to a level that is too much for me to handle. Back to the drawing board. I honestly have no idea where to go from here, feeling quite lost, I had such high hopes for the CBD.

#25 NeuroNootropic

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Posted 21 January 2018 - 08:17 PM

Hey James, I'm a little bit like you. A lot of times stimulants just make my depression and ADHD worse than baseline. But, Wellbutrin alone usually elicits a positive response after taking it for a few days. What I've found to be helpful in inducing a positive response to stimulants includes:

  • Agmatine - After about 2 weeks it seems to induce an antidepressant-like effect but at the same time it reduces the negative effects of stimulants, like tachycardia and higher blood pressure, while simultaneously enhancing the positives like focus, mood, verbal fluency, and cognition in general
  • Maca - After a few weeks it definitely seems to make stimulants work better, but it's almost as though Maca increases the perceived dosage of the stimulants. So, instead of dexedrine 5 mg feeling like 5 mg, it feels like it's at least 2-3 times greater than that. I've only taken 10 mg of dexedrine once, but nothing above that so I can't really vouch for whether or not Maca really is increasing blood concentration levels or whether its acting in a very synergistic manner with the stimulants.  I'm guessing it's the latter considering Maca has been shown to have dopaminergic and noradrenergic actions itself.
  • Selegiline - After 2 weeks it makes stimulants really stimulating. I usually have fatigue even after I've taken a stimulant but on selegiline it's the complete opposite. Wakefulness is extremely enhanced on this combo. But, for cognition and focus there's only a mild synergistic effect

Also, I think you should stop taking the methylb12 and instead replace it with a high quality multivitamin like Life Extension Two-per-day. I think the reason why chadwick responds more positively from a high dose of methylfolate might be because at high doses it probably increases BH4, which is a co-factor in the production of dopamine and serotonin and subsequently noradrenaline and melatonin, respectively. But, at low doses I think it mainly increases methylation which has a double-edged effect on dopamine, noradrenaline, and serotonin by increasing SAM-e. It's all dependent on your genetics, but SAM-e increases production of those neurotransmitters while simultaneously increasing their metabolism or breakdown. For this reason, I think it's important to not mess with the methylation cycle as it's extremely complex. This is further supported by his use of hydroxocobalamin, which decreases methylation, and not methylcobalamin, which increases methylation.

 

So high dose methylfolate + hydroxocobalamin might balance the methylation cycle since methylfolate increases methylation and hydroxocobalamin decreases it. The end result is increased neurotransmitter production with minimal effect on metabolism.


Edited by NeuroNootropic, 21 January 2018 - 08:20 PM.

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#26 James88

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Posted 21 January 2018 - 10:31 PM

Thank you,

Is there anyway to increase BH4 without a ton load of methylfolate? I’m also still wondering if high dopamine - low serotonin is my issue. Along with high glutamate - low gaba. I’m not really educated on any of this, just two years worth of google research. I understand that it’s much more complex than just high and low neurotransmitters. But I’m just desperate to find an answer. I’ve just tried Ginkgo Biloba for 4 days, it has given me a similar bad reaction and has actually made my anxiety worse!! That’s another dopamine raising supplement that makes me feel like trash. But then again, raising serotonin through 5htp just made me feel flat and numb. Urghhhh so frustrating!!!

#27 Mind_Paralysis

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Posted 22 January 2018 - 12:30 PM

Thank you,

Is there anyway to increase BH4 without a ton load of methylfolate? I’m also still wondering if high dopamine - low serotonin is my issue. Along with high glutamate - low gaba. I’m not really educated on any of this, just two years worth of google research. I understand that it’s much more complex than just high and low neurotransmitters. But I’m just desperate to find an answer. I’ve just tried Ginkgo Biloba for 4 days, it has given me a similar bad reaction and has actually made my anxiety worse!! That’s another dopamine raising supplement that makes me feel like trash. But then again, raising serotonin through 5htp just made me feel flat and numb. Urghhhh so frustrating!!!

 

Again... since Dopamine makes you feel bad... why don't you try raising ACETYLCHOLINE? (dopamine's nemesis)

The one common thing you haven't tried yet - you've already had multiple bad reactions to supplements, so you should be used to, and able to pick up on the bad signs by now, yes? Then, I don't see why Piracetam + CDP Choline wouldn't be a good idea.



#28 James88

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Posted 22 January 2018 - 08:38 PM

I have some alpha gpc that I’ve been too worried to try, would that do the same thing? Is there no risk it could make my depression worse? Does it not lower serotonin as well?

#29 Mind_Paralysis

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Posted 23 January 2018 - 11:56 AM

I have some alpha gpc that I’ve been too worried to try, would that do the same thing? Is there no risk it could make my depression worse? Does it not lower serotonin as well?

 

Alpha GPC could work as well - the reason I want you to use it with Piracetam is beause that's a drug which increase acetylcholinergic activity in general, but also causes draining of Ach - that's why it's often taken with a choline-supplement. It also has some antidepressant properties which is being investigated as we speak, so that's a giant bonus. (it appears to increase production of BDNF)
 

If you're concerned about serotonin, you could always buy some 5htp and keep that ready, if you start to feel bad - but don't start using it unless you have a bad reaction.


Edited by Stinkorninjor, 23 January 2018 - 11:57 AM.


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#30 John250

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Posted 30 June 2018 - 12:29 AM

My doctor suggested possibly Wellbutrin to augment my other medication. Currently;
Lexapro 5-10mg/day
Abilify 2mg/day
Vyvanse 60mg/day(morning)
Adderall IR 30mg(afternoon)


My concern with Bupropion is its effects on amphetamines. I wouldn’t want it to decrease the amphetamine reward leading to higher doses.

Taken from Reddit:

“Since both of these drugs have relatively similar effects, I'm curious as to what the interaction would be. I can think of two major ways they'd interact.

Since amphetamine is dependent on transport through DAT and VMAT2 for its effects, and bupropion is a DAT/NET reuptake inhibitor, the combination would lessen the maximal effects of amphetamine

Since bupropion is a substituted amphetamine, it's reasonable to believe that the metabolism of amphetamine would be slowed?”

Any experience with this?





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