8 replies to this topic

[Mind_Paralysis]

I need some quick answers.

I am about to move across the country - hundreds of miles. I cannot complete the move because I am non-functional as a result of shut-down from anxiety related to inability to organize - I have Sluggish Cognitive Tempo / ADHD-PI.

 

The response was triggered because my Vyvanse - even in combination with Agomelatine and Modafinil, is not sufficient to help me complete such a complex and non-stimulating task.

 

 

I have used 300 mg Wellbutrin in the past, even with Agomelatine in combination, it was well-tolerated - except for two specific side-effects.

 

 

Loss of verbal and working memory - I had problems speaking and remembering things. Most definitely related to it's anticholinergic effects. (nicotine-receptors)
 

Aggression / irritability - after continued use, say 4-5 days, I become highly volatile - violent almost. It is not an anxious form of aggression - I have had this in the past and I know the difference - I do not feel any more anxious than usual - I simply hate all life. Could this also be related to anticholinergic effects?

 

The aggression abates with time - it usually takes about 2-3 weeks for this side-effect to decrease and then suddenly go away. The verbal memory problem never goes away - it is continuous.

 

Now, smoking cessation is known to cause aggression as well - this is why I suspect the antinicotinic effect as the root cause of this. Interestingly, I do NOT experience anxiety or aggression when I cease Bupropion - so it's not like Methylphenidate or amphetamine -induced anxious irritability, or withdrawal - this is different.

 

I have genes which are supposedly related to increased nicotinic dependency - I have never used nicotine, but my mother is a heavy smoker and has always had trouble quitting.

 

 

Once again, I feel that aggression and decreased memory is related to the antinicotinic effects. Now, for something else...

 

Does Bupropion LOWER SEIZURE THRESHOLD THROUGH NICOTINIC ANTAGONISM?

 

The reason I'm asking is because I have a high suspicion that Norepinephrinergic medication could treat my symptoms - and Bupropion is such a medication. However, it is a less potent medication than Strattera, hence I would say in order for me to properly test it, I need to try higher doses.

 

I know the release is important - XL, XR, LA all have less incidence of seizure.

 

If ALL of these effects are a result of nicotinic antagonism in susceptible people, then IMHO, it stands to reason that adding nicotine gum should pretty much ABOLISH these effects COMPLETELY.

I would then be left with an NdRI which could treat my symptoms.

 

Please respond. I must know.

 

 

A final sidenote is that when I used the antihistamine/anticholinergic Promethazine at higher doses, I experienced COMPLETELY FLATTENED AFFECT. All emotions were numbed. Is this another sign towards me being sensitive to anticholinergic effects?

[jack black]

happy to help. here is your answer:

 

 

The mechanism of bupropion HCl-induced seizures is unknown [21, 22].

 

source: https://annals-gener.../1744-859X-7-11

 

 

here is some speculation:

 

 

Bupropion’s sympathomimetic amine structure suggests that it may act via catecholamine release in the central nervous system and may possibly lead to hypothalamic stimulation. This mechanism may be partially responsible for the seizures seen in cases of bupropion overdose.

 

source: http://www.ncbi.nlm....les/PMC4115959/

Edited by jack black, 23 July 2016 - 11:12 PM.

[Mind_Paralysis]

You da' man JackBlack! : ) Cheers for the reply.

Hmm... the hypothalamus, eh? I'm curious though - do we know why TCA's are more ceizure-inducing than SSRI's and just about every newer antidepressant?

Because from where I'm standing, the one similarity between them is that they are ANTICHOLINERGIC!

Well, that and TCA's actually affect dopaminergic and norepinephrinergic signalling to a greater extent than SSRI's.

As I recall these were the seizure-risks with the different classes:

SSRI's : 0,1%
TCA's : 0,2 %
Bupropion: 0,4% (!)

Yet curiously, extended release bup has only 0,1% - as long as you don't go past 450 mg.

Btw, I'm on 600 mg Wellbutrin + 2 mg nicotine today, and even though I'm not feeling as motivated and enhanced as last evening - where I actually completed a significant amount of packing, including 5 different repacks...!
I am definitely feeling it to an extent - I've already completed the task of puttying shut drill-holes in the wall - which was another task I had gotten stuck on.

Actually feeling a bit "jacked" today though, experiencing more of a body-load than from instant-release.

Might be needing some nic right about now as well - the sh*t only lasts for two hours...! Now that is a bit of a bother - having to re-dose nic all the time.

No signs of enhanced aggression yet, or impaired verbal memory - but we'll see.

[Finn]

You da' man JackBlack! : ) Cheers for the reply.

Hmm... the hypothalamus, eh? I'm curious though - do we know why TCA's are more ceizure-inducing than SSRI's and just about every newer antidepressant?

Because from where I'm standing, the one similarity between them is that they are ANTICHOLINERGIC!

Well, that and TCA's actually affect dopaminergic and norepinephrinergic signalling to a greater extent than SSRI's.

As I recall these were the seizure-risks with the different classes:

SSRI's : 0,1%
TCA's : 0,2 %
Bupropion: 0,4% (!)

Yet curiously, extended release bup has only 0,1% - as long as you don't go past 450 mg.
 

 

http://www.ncbi.nlm....pubmed/10452441

 Aside from the sinus tachycardia due principally to anticholinergic effects, TCA-toxic changes seen on the ECG are attributable primarily to the sodium channel blockade caused by these agents.

 

http://lifeinthefast...-conundrum-022/

 

Cardiotoxic effects primarily result from blockade of inactivated fast sodium channels in a use-dependent manner (blockade is higher at faster heart rates).

 

https://en.wikipedia...inic_antagonist

 

A nicotinic antagonist is a type of anticholinergic drug that inhibits the action of acetylcholine (ACh) at nicotinic acetylcholine receptors. These compounds are mainly used for peripheral muscle paralysis in surgery, the classical agent of this type being tubocurarine,^[1] but some centrally acting compounds such as bupropion, mecamylamine, and 18-methoxycoronaridine block nicotinic acetylcholine receptors in the brain and have been proposed for treating drug addiction.

 

 

Edited by Finn, 25 July 2016 - 05:57 AM.

[Mind_Paralysis]

I've chucked my dose down to 300 mg XR now - the effects of 600 mg XR was questionable - only on the days first dosing did I experience any productivity, and that may have been placebo.

I know that the effects of 300 mg IR was not placebo though! My fatigue was significantly reduced, I think I may even have experienced enhanced reaction-time while bicycling - and most telling: there's no way in h*ll I could have done 5 repackings in one night without chemical assistance!

@Finn:
I believe I know which effect the studies speak of - I believe I found a similar study regarding the Alpha-7 nicotinic receptor: apparently it's the one nic-receptor NOT involved in sympathetic response - which adds further proof that it's primary function is as regulator of emotional impulses from the amygdala.

Hmm... the effect is really weak with Bup though, but could alpha-7 antagonism be the cause of irritability while on Bupropion?

Going to take the days first nicotine gum now - should be about time.

[jack black]

Hi,

have you seen this: https://area1255.blo...nbupropion.html

 

 

I have found the most comprehensive approach to treating Wellbutrin-Induced Erectile Difficulties to be the trio-cocktail of .

 

• Viagra or Cialis ; which can be purchased =!HERE!=.
• + Arginine GLUTAMATE  {See Here}
• ++ YOH (Yohimbine) but only if no previous diagnosis of Anxiety (G.A.D, 300.OO <(Sv.Anxiety)> etc)

 

(**I've also found the above cocktail to alleviate Memory Issues resultant from Wellbutrin-Use**)

 

Edited by jack black, 26 July 2016 - 03:17 AM.

[Mind_Paralysis]

Hi Jack! : ) Hadn't seen that one.

Area-1255 is a somewhat questionable member of Longecity as I recall it though...

He has a vast amount of knowledge but it is obscured because he has used and abused so many substances through the years that it's hard to tell if they relate to anyone but him.

For starters, Erectile dysfunction is not a common side-effect of Bupropion (I don't have it, even at 600 mg), and Yohimbine is IMHO, a fairly dangerous compound - it hits a lot of receptors (for instance, it could affect me as an alpha-2-antagonist, and that could possibly make my CDD far worse) and the effects vary with dose.

That's why you don't see it in a lot of stacks - it's pretty complicated to keep track of.

It's worth having a look at the individual properties of the three drugs though! Might be I, and others, could use it to find the mechanism of counteracting Bupropion side-effects.

Btw, I want to reply to your excellent point in my KYNA-thread, but it's hard, as I've got pathological rumination regarding the subject - but I'll give it a try soon.

[jack black]

I found a nice review of bupropion (BP) here: http://www.sciencedi...357272509001757

 

Interesting tidbits:

 

Hydroxylation of the tert-butyl group of BP to hydroxybupropion (see both hydroxybupropion isomers in Fig. 2), one of the major metabolites, is produced by the isoenzyme CYP2B6. Thus, CYP2B6 polymorphism and drug-drug interactions might be risk factors increasing potential adverse events like seizures, which normally is very rear [sic!] (∼0.1%).

 

In addition, BP-induced blockade of non-α7 AChRs on GABAergic neurons may diminish tonic inhibition of VTA neurons (see Fig. 4),

 

 

 

Comparing these values with that found in other AChR types (see Table 2), we can conclude that the BP specificity for different AChRs follows the sequence: α3- > α4- ∼ α1- > α7-containing AChRs.

Considering the serum levels of BP attained after its oral administration (∼0.5–1 μM; Hsyu et al., 1997), the blockade of non-α3-containing AChRs is unlikely. However, hydroxybupropion, which has practically the same activity as BP for α4β2 AChRs (Damaj et al., 2004; see Table 2), can attain ∼10-fold the plasma concentration of the parent compound (Ascher et al., 1995 and Hsyu et al., 1997), increasing the possibility that α4β2 AChRs contribute to the clinical efficacy of BP.

 

Based on that, BP is a rather strong anti-ACh modulator.

Stinkorninjor, Maybe you have too low ACh levels in the first place? Alternatively, too much suppression of GABA for you?

How do you react to choline ot GABA supplements?

Edited by jack black, 03 August 2016 - 04:54 PM.

[Mind_Paralysis]

I would say it's very likely that I do have too low aCh-levels.

 

I also have that "warrior" -polymorphism, which actually means I have enhanced dopamine-synthesis - which could also explain why dopaminergics cause anxiety in me. This could lead to naturally lower aCh-levels.

 

I do also use stimulants with bupropion - which raises dopamine, which likely suppresses aCh even further.

 

 

 

And AWESOME work on that BP review!!

 

Now, we finally have the affinity-sequence for the NaCh-receptors of Bupropion. ^^ Too bad Alpha-7 is the lowest... (we can scratch Bup from the list of treatments of BPD now)

 

 

I have no idea what effect choline or Gaba-supplements have on me - I've never tried them.

 

What I can say, is that nicotine seems to be helping some with the cognitive problems Bup gives me - but not much. However, I'm using a rather low dose... usually only 2 mg's per day - most smokers use like 6-8 mg's. At times I have used 4 mg's, but I can't discern if it helped my problems more.

 

I suppose the easiest way to test this is to just get some Alpha-GPC, yeah? Any brands ya'll would recommend?