27 replies to this topic

[Cew27]

Hey guys, i have been using dexamphetamine at a dose of around 15mg a day for 6 months for the end of my honors degree.
I am diagnosed with ADHD so my use has been legitimate and generally as prescribed.

To get to the point, i have read quite a bit about amphetamine neurotoxicity and prevention though i feel my knowledge is lacking and full of holes.

I occasionally used Dextromethorphan at night to ensure the efficacy of my next dose of dex and i am aware of a study that hints that DXM and other NDMA receptor antagonists may induce dopamine receptor (D3) synthesis.
This has me wondering if NDMA receptor antagonism could help my return to normality following an extended period of stimulant use with no breaks.

I have legitimate access to DXM and i am also aware of how DXM and Ketamine are very similar in their NDMA antagonizing effect, though i wonder which is more effective.

Lets just say i can legitimately obtain what i need - should i need it.

Sulbutamine also seems promising in increasing the density of D1 and D2 receptors so i read - with uridine offering similar effects.

I have also seen some evidence showing that amphetamine use lowers levels of GDNF, NGF and BDNF though i did read it elevated them short-term.
I have noopept and a pre-mixed nootropic stack containing piracetam, aniracetam, sulbutamine, l-tyrosine, GABA, choline, l-phenylalanine, L-Leucine, DMAE and Alpha-GPC.

In summary i am looking for some clarification and advice on:

NDMA receptor antagonists - will they help my recovery? which is preferred? (i can easily obtain the two mentioned above, i have not yet tried to obtain memantine)

Will nootropics be of benefit to me due to their effects on GDNF, NGF and BDNF and if so - what ones? (is noopept better than the other stack mentioned above?)

Should i go and get myself some uridine and sulbutamine to try restore dopamine receptor density?

Are there any products like "Reset AD" which are effective at improving the adrenal systems health?

Lastly, i use cannabis on an evening - vaporized indica strains. I have seen a-lot of evidence that cannabis reduces if not negates a lot of the neurotoxicy of stimulants and was wondering if anyone had any oppinions on this matter?


I appologize for my scatty presentation - i am operating at less than optimum levels at the moment, hence this post.

Thanks to anyone who managed to read that and comprehend that.

Any responses or advice is greatly appreciated and highly valued!

Thanks again





 

Edited by Cew27, 09 May 2015 - 02:57 PM.

[OneScrewLoose]

A lot fhe "negative effects" of ADHD medication that we take for granted were started by scientology in the 90s as part of their efforts to discredit psychiatric medication altogether (it's agaisnt their beliefs, it's all about removing thetans to them (seriously)) Read this.

Here's some more recent studies:
http://www.ncbi.nlm....pubmed/22805599

And some positive ones:
Amphetamines may assist recovery from stroke

Long-term Sstimulant use might help 'fIx' the parts of the brain responsible for ADHD.

You're fine dude. Part of what you might be experiencing is the full force of your ADHD coming back when you went of the amph, which you are no longer used to. A better alternative would be to post your general cognitive issues, and post how they were before and after stopping the medicine. Then I could make some recommendations.

And one more thing. 15mg per day is a small dose. I've previously been prescribed 90mg/day, which I took for a year.

[Cew27]

I'd be grateful to heat any other opinions? 

I plan to switch back to methylphenidate and use only twice weekly for the next two years while i get my career going.

I have also managed to obtain memantine legally so i do have that option. 

Any advice would greatly aid in easing my mind. 





 

[gamesguru]

Keep the cannabis use to the evening, otherwise there will be career problems.

http://www.longecity...n-amphetamines/

 

 

See my profile for an herbal ADHD stack.

 

Can't say much about methylphenidate/atomoxetine/guanfacine/clonidine

Edited by gamesguru, 10 May 2015 - 08:18 PM.

[Cew27]

Keep the cannabis use to the evening, otherwise there will be career problems.

http://www.longecity...n-amphetamines/

 

 

See my profile for an herbal ADHD stack.

 

Can't say much about methylphenidate/atomoxetine/guanfacine/clonidine

Thanks for that, ill take note of the stack! 

Im intrigued for insight about your cannabis recommendation?  (funny, because i work in the cannabis field haha)

 

[gamesguru]

It's disruptive of learing, demotivativing.  Especially for the youth, it is best enjoyed in moderation.

[Cew27]

It's disruptive of learing, demotivativing.  Especially for the youth, it is best enjoyed in moderation.

Each to their own, however i find it no hinderance to my learning, i am prescribed a cox-2 inhibitor for back pain and substitute that with a cbda (cannabidiolic-acid) oil preparation when i can for its selective and side-effect free cox-2 inhibition. 
This negates the deleterious effect on memory. 

i use it for its reflective properties which actually improve my motivation and metacognition in such a reliable manner its actually surprising given the duration of usage. 

I use it in moderation as you stated for its medicinal and mood enhancing properties. 
The green goddess will treat you well if you show her respect.

[gamesguru]

Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale)

 

I had progressed to the point of consuming 3.5 grams daily before the age of 21, the hinderance was undeniable.

[OneScrewLoose]

A small dose of Selegiline, 1mg/day, will do a lot to prevent any neurotoxicity of dopamine related excess. Be careful though, any higher and the selegiline will potentiate the Methylphenidate. On the flip side, you might be able to take less methylphenidate this way. But, honestly, you have to be extremely careful in doing this kind of thing.

Memantine may help too, but it takes a lot of patience to really get stable on it. Try going 2.5mg > 5mg > 10mg and if you want to > 15mg and then 20mg max. Because of its effect on Acetylcholine a7 receptors, I would honestly wait 2 weeks between each dose increase. I have the experience to back this up; I'm on 35mg for neuropathic reasons.

Have you tried Vyvanse?

[gamesguru]

Vyvanse is also an amphetamine, or no?

 

Probably the suggestion of low dose selegiline and methyphenidate is a good one to try.

[OneScrewLoose]

Vyvanse is a brilliantly designed amphetamine. It's only the dextro isomer. However, instead of being time-releases, it's attach to a lysine molecule. Your body can only cleave so much of that lysine per unit time, giving you a very even and study amount of amphetamine through it's duration of half life, instead of peaks and valleys. It's considered the amphetamine with the least potential for abuse. I feel it's the first new amphetamine/methylphenidate drug in decades that doesn't qualify as evergreening.

[RoyBatty]

A lot fhe "negative effects" of ADHD medication that we take for granted were started by scientology in the 90s as part of their efforts to discredit psychiatric medication altogether (it's agaisnt their beliefs, it's all about removing thetans to them (seriously)) Read this.

Here's some more recent studies:
http://www.ncbi.nlm....pubmed/22805599

And some positive ones:
Amphetamines may assist recovery from stroke

Long-term Sstimulant use might help 'fIx' the parts of the brain responsible for ADHD.

You're fine dude. Part of what you might be experiencing is the full force of your ADHD coming back when you went of the amph, which you are no longer used to. A better alternative would be to post your general cognitive issues, and post how they were before and after stopping the medicine. Then I could make some recommendations.

And one more thing. 15mg per day is a small dose. I've previously been prescribed 90mg/day, which I took for a year.

 

Do not ever take above 20mgs of amph, period. Not to say 90mgs of amphetamine is enough to fuck you up very rappidly
 

[OneScrewLoose]

Source, please?

[Cew27]

I said amphetamine use to generalize as i use vyvanse and dexamphetamine. 

I generally take 30mg of vyvanse and then supplement this with up to 7.5mg of dexamphetamine although this was while i was studying 12 hours a day. 

Now i hope to be able to drop to just the 30mg on days i require it and use the 5mg IR tablets for smaller tasks rather than medicating a whole day with vyvanse. 

I understand the neurotoxicity of amphetamine to be dose dependent so i generally try keep the dose as low as i can get away with for the work i must complete. 

Two days of abstinence had me dead on my feet, so i know that my 4 months useage will require some careful recovery. 

[OneScrewLoose]

I haven't seen any good data yet on exactly where doses of amphetamines start to become neurotoxic. I'm sure it's out there, if anyone wants to take a look. I can guarantee, however, that it's much greater than 30mg. Also the type of neurotoxicity we would be worried about is called excitotoxicity. This occurs when glutaminergic activity elevates to high and starts damaging brain cells. If you are genuinely worried about this, look into Memantine, its mechanisms are designed to counter excitotoxicity (its primary use is preventing it in Alzheimer's patients).

If you really want a smooth way to ease off of amphetamines, look into wellbutrin. It's a weaker DAT inhibitor, and will compete with amphetamine at the DAT site, reducing the overall effect. Due to the Wellbutrin also being a strong CYP2D6 inhibitor, it will also make the amphetamines last longer. So, you get weaker and long, less of a high and a more steady feeling throughout the day. This can help in reducing it, if you want to.

[Flex]

Whats about nerve terminal damages ?

A reduction of Vmat2, DAT & etc could reflect that.

Furthermore, even if Vmat2 is just downregulated (afaik) Your detox system is impaired as well as Your dopamine content.

 

and this, besides the changes of gene expression that are caused by Amphetamine.

 

Edited by Flex, 14 May 2015 - 01:43 AM.

[OneScrewLoose]

It looks like in vivo studies are giving different results:

http://www.ncbi.nlm....les/PMC3134290/
http://www.ncbi.nlm....les/PMC3711765/
 

 

Across similar time courses, electrically-evoked dopamine responses were enhanced in vivo, rather than compromised as in in vitro studies, by AMPH. The dominant component underlying this potentiation in vivowas up-regulated exocytotic dopamine release, which is in sharp contrast to the marked depletion of readily releasable vesicular dopamine stores demonstrated in vitro.

Also, by gene changes, I think you mean epigenetic changes, as your genes themselves don't change unless you are exposed to radiation or you grow old and your telomeres run out. Don't worry though, new evidence shows that these kinds of changes can reverse themselves:

http://bit.ly/1ExNnRO

Don't worry so much about very little substance. Unless you're going down a road of serious abuse, the human body is remarkably resilient. Somewhat related, there are towns in northern Russia where winter temperatures average -50 degrees! We just fucking adapt like a boss.

Edited by OneScrewLoose, 14 May 2015 - 03:08 AM.

[Flex]

Yes I meant the epigenetic one. Excuses for the mistake.

 

Dont know.. epigenetic changes due to Depression or Trauma might be reversible on they own or by good experience, coping & etc. So by anything that works like a behavioral therapy (CBT)

but are also heritable to the next generation.

Epigenetic changes that are induced by drugs (cocaine, Amphetamine), might be very long lasting or, at least nowadays, even perresistent.

 

Your body is resilent but its hard to determine how much exactly and some (epigenetic) changes are not allways noticable, which can be tricky.

 

The Epigenetic Mechanisms of Amphetamine

http://www.avensonli...178-S1-0001.pdf

 

1)  both  sense  and  antisense  RNA  preparations

can cause interference and reduce gene expression, and

2) RNA interference  persisted  well  into  the  next  generation  [57].

 

Persistent gene expression changes in NAc, mPFC, and OFC associated with previous nicotine or amphetamine exposure

http://www.researchg...63084000000.pdf

Edited by Flex, 14 May 2015 - 06:16 PM.

[OneScrewLoose]

Goddamnit I hate you, and everyone on this forum. Too many great studies to read., and you fuckers are providin' and sucking up all my time...I'll get back to you.

[axonopathy]

Here's a relevant article about mitigating neurotoxicity risks of amphetamine: http://www.brainprot...otoxicity-risk/

 

Although damage control while on amphetamine is probably a different issue from facilitating recovery.

[Flex]

Goddamnit I hate you, and everyone on this forum. Too many great studies to read., and you fuckers are providin' and sucking up all my time...I'll get back to you.

Thanks

the same can be applied on this post    :

Here's a relevant article about mitigating neurotoxicity risks of amphetamine: http://www.brainprot...otoxicity-risk/

 

Although damage control while on amphetamine is probably a different issue from facilitating recovery.

 

Really interresting site

Edited by Flex, 14 May 2015 - 10:09 PM.

[TiredAt45]

I haven't seen any good data yet on exactly where doses of amphetamines start to become neurotoxic. I'm sure it's out there, if anyone wants to take a look. I can guarantee, however, that it's much greater than 30mg. Also the type of neurotoxicity we would be worried about is called excitotoxicity. This occurs when glutaminergic activity elevates to high and starts damaging brain cells. If you are genuinely worried about this, look into Memantine, its mechanisms are designed to counter excitotoxicity (its primary use is preventing it in Alzheimer's patients).

 

Yes, I am getting annoyed at all the talk of amph. neurotoxicity.  When I was prescribed it I looked through the research and the conclusion I came to was: there is very little scientific understanding out there about a drug that has been with us for over a century!  Specifically, (at the time) all the research that showed "bad" effects were with the doses used by recreational users (4-10x therapeutic doses).

 

I think amph. may be non-linear, in that at higher doses than typically used therapeutically, different neuro-chemical effects occur.

 

What I really want to see is:  1. is there evidence for neuro-toxicity at therapeutic doses?  1b.  If so, is the harm caused by the amph. or secondary effects (reduction of sleep, etc.)  2. Is there evidence for positive effects?  3. is there evidence of long-term inducement of motivational problems?

[axonopathy]

 

I haven't seen any good data yet on exactly where doses of amphetamines start to become neurotoxic. I'm sure it's out there, if anyone wants to take a look. I can guarantee, however, that it's much greater than 30mg. Also the type of neurotoxicity we would be worried about is called excitotoxicity. This occurs when glutaminergic activity elevates to high and starts damaging brain cells. If you are genuinely worried about this, look into Memantine, its mechanisms are designed to counter excitotoxicity (its primary use is preventing it in Alzheimer's patients).

 

Yes, I am getting annoyed at all the talk of amph. neurotoxicity.  When I was prescribed it I looked through the research and the conclusion I came to was: there is very little scientific understanding out there about a drug that has been with us for over a century!  Specifically, (at the time) all the research that showed "bad" effects were with the doses used by recreational users (4-10x therapeutic doses).

 

I think amph. may be non-linear, in that at higher doses than typically used therapeutically, different neuro-chemical effects occur.

 

What I really want to see is:  1. is there evidence for neuro-toxicity at therapeutic doses?  1b.  If so, is the harm caused by the amph. or secondary effects (reduction of sleep, etc.)  2. Is there evidence for positive effects?  3. is there evidence of long-term inducement of motivational problems?

 

 

 

These are great comments.

 

There are numerous factors at play with amphetamine neurotoxicity. On the one hand, evidence from neuroimaging studies in humans suggests that amphetamine rescues alternations in brain structure in patients with ADHD who take psychostimulants vs. unmedicated controls. There is also evidence that amphetamine facilitates recovery after a stroke and some other neurological insults. Anecdotally, we also know that some very bright people can get away with essentially continuous amphetamine use well into old age, e.g., Paul Erdos. 

 

On the other hand, there are studies in primates and rodents showing that amphetamine (at doses which correspond to therapeutic doses in humans via adjustment for organism surface area), cause (1) persistent down-regulation in tyrosine hydroxylase (TH) expression, the rate limiting enzyme in the endogenous biosynthesis of dopamine, (2) increased markers of oxidative stress, lipid peroxidation, abnormal protein adducts, (3) damage to axons, (4) depletion of antioxidant defense, e.g, glutathione (5), direct damage to dopaminergic synaptic terminals. Another aspect to consider is the cardiovascular effects of amphetamine. Hypertension is itself associated with cognitive dysfunction, and amphetamine is a potent sympathomimetic that elicits significant increases in blood pressure, enhanced vasoconstriction, in addition to positive inotropy, chronotropy and dromotropy. 

 

All this being said, it is unlikely that amphetamine kills neuronal cell bodies. These effects are also unlikely to be secondary, because much of the neurotoxicity is mediated by excess dopamine itself. Excessively elevated dopamine concentrations is intrinsically neurotoxic because it promotes the formation of 6-hydroxydopamine which interferes with vesicular storage of dopamine and trashes the synapse. 

 

I also suspect there are genetic factors that modulate susceptibility to neurotoxicity. For example, amphetamine likely elicits much more robust dopamine release in individuals on the schizophrenic spectrum, which makes sense because this patient population is already predisposed to psychosis. 

 

Taken together, I think it stands to reason that low-dose amphetamine is therapeutic for the people who need it (ADHD, narcolepsy, treatment resistant depression, stroke recovery), and neurotoxic for the people who abuse it. Lifestyle factors clearly play a role (sleep, dietary enrichment with flavanoids, exercise), but I suspect that even if you took perfect care of yourself despite taking large doses of amphetamines, it wouldn't mitigate all of the deleterious effects in the brain.

[John250]

I read on ncbi that chlorella vulgaris helps with neurotoxicity. I ordered some powder from nuts.com

[Eryximachus]

I read on ncbi that chlorella vulgaris helps with neurotoxicity. I ordered some powder from nuts.com

 

Dude, amphetamine has been used for 100 years.  15mg per day is totally and non-toxic.   

 

There are all manner of scientists and mathematicians who used larger doses of dexedrine than that when it was over the counter, and did so for decades.  

[John250]

Dude, amphetamine has been used for 100 years. 15mg per day is totally and non-toxic.

There are all manner of scientists and mathematicians who used larger doses of dexedrine than that when it was over the counter, and did so for decades.

Unfortunately 15mg wouldn’t do a dent for me. On total I use about 60-80mg/day

I am 6 foot 240 pounds though so I’m not sure if body mass has anything to do with it. I’m also a Cpy2DC ultra metabolizer.

[You_cant_handle_the_truth]

Definitely enhanced absorption Curcumin. I use Curamed from Terry Naturally--> https://br.iherb.com...-softgels/23136

 

It's Curcumin BCM-95 with the following in order to enhance absorption

   

    - Phospholipids (Sunflower)

    - Turmeric Oil

    - MCT

 

 

 

 

You can also use Lion's Mane, Boswellia, Magnesium L-Threonate and Melatonin

 

 

Furthermore, always use Curcumin when using Amphetamines, because it will protect your Brain and whole body. Even if you have to increase the dosage of the Amphetamine, use Curcumin

 

 

You can find a lot of information about these supplements on the websites below and the good thing is that they have links to the Studies about the substances

 

    - www.selfhacked.com

    - www.examine.com

    - www.mybiohack.com

 

[John250]

Seems like Life Extension’s Dopa-Mind(Neuravena wild green oat extract) hold some promise as a strong MAO-B

Edited by John250, 10 July 2018 - 11:54 PM.