• N&PD Moderators: Skorpio | thegreenhand

Dextroamphetamine Tolerance, Neurotoxicity, and General Advice

lbass

Greenlighter
Joined
Nov 14, 2017
Messages
6
Hi everyone,

For some background: I have post-concussion syndrome (a few years since the sporting accident). A nutritional GP is helping me with supplementation for the concussion. A recent SPECT scan showed significant hypoperfusion to my temporal lobes, and I was recommended to start dextroamphetamine to help improve my quality of life. Dextroamphetamine has been the only thing that I have found helpful out of everything I have tried. I am concerned about Neurotoxicity given the condition my brain is already in, and I am equally concerned about building up a tolerance to the dextroamphetamine. My issue is that my nutritional GP does not prescribe dextroamphetamine and is unfamiliar with neurotoxicity, tolerance, vitamin interactions, etc. I have been modifying my old regime to be more appropriate around the timing of the stimulant, as well as adding a few vitamins which seem to be quite beneficial (R-Alpha Lipoic Acid, L-Theanine, L-Arginine, Selenium, L-Tyrosine, Melatonin). This is what I have come up with:

6:15am
Banana
Thorne Basic B Complex
Vitamin B6 100 mg
Brain Active LongVida (Curcumin) 400mg
Vitamin D3 2000 IU
Treadmill

7:30 am
Acetyl-L-Carnitine 500 mg
R-Alpha Lipoic Acid 100 mg
Ubiquinol QH+ PQQ
L-Theanine 100 mg
L-Arginine 500 mg

8 am Breakfast
Dexamphetamine 3.33 mg slow release compounded from powder.

10 am
Acetyl-L-Carnitine 500 mg
N-Acetyl-Cysteine 600 mg

10:30 am
Apple
Pristiq 50mg

Lunch 12:00 pm

2:30pm
N-Acetyl-Cysteine 600 mg
Acetyl-L-Carnitine 500 mg
L-Theanine 100 mg
L-Arginine 500 mg
R-Alpha Lipoic Acid 100 mg

Dinner 6:30pm
Vitamin C 1500 mg
Mixed Tocotrienols and Vitamin E
Zinc Citrate 25 mg
Fish Oil (EPA 400 mg/DHA 200 mg) x 3
Magnesium Chelated 400 mg
Selenium 200 mcg
Fusion Probiotic (High Lactobacillus)

8pm
L-Tyrosine 500 mg

8:30pm
Topiramate 12.5 mg

9pm
Melatonin 3mg 6 hour time released

My questions are:

  1. Is the timing of my vitamins appropriate around the dex? Could any of my timing interfere with it?
  2. Could any of my dinner time vitamins be moved to lunchtime without interfering with the dex? The ones I currently have with dinner are the ones I am concerned with, but I am taking too much with dinner.
  3. Is it safe to take L-Tyrosine and dex? I read a recommendation to only take it on dex off days, but I don't have any off days.
  4. Is there anything glaringly wrong with my L-Theanine or L-Arginine use? These I have not had cleared by the doctor.
  5. I think that the Dex loses potency after taking the Pristiq. Is this possible?
  6. I have not liked taking Melatonin. I have had very vivid dreams with it. I saw 5-htp is an alternative but this might interact with the Pristiq. Any ideas?
  7. The one side effect I have from the dex is increased migraine severity and frequency. My doctor put me on Topiramate for this, but I have found it very fatiguing. It has also made my memory issues worse. Does anybody know of an anti-migraine that would pair well with dex? My lead one at the moment is propanolol but this seems as though it would counteract the dex. Other options are lyrica and neurontin but I do not like their side effect profile.
  8. I read a study showing Adderall was better absorbed without food versus a fatty meal. I think I probably get a better result on an empty stomach also, but I find this hard to time around my mornings. Is it particularly detrimental to have dex with breakfast?
  9. During one month of taking dex, my tolerance has already built. There is a recommendation for taking off days during the week. My issue is that I am bed bound without it, but I still will probably end up taking weekends off. So many people support taking Memantine with dex. Would you recommend this?

I think this is a great forum. I have found old posts incredibly useful. Thank you very much for any information.Dextroamphetamine Tolerance, Neurotoxicity, and General Advice
 
Last edited:
Dextroamphetamine does not produce neurotoxicity at therapeutic doses. 3.33 mg of pure dextroamphetamine is also an incredibly low therapeutic dose.
 
Dextroamphetamine does not produce neurotoxicity at therapeutic doses. 3.33 mg of pure dextroamphetamine is also an incredibly low therapeutic dose.

http://adderallsafety.org/what-is-neurotoxicity/

I thought therapeutic doses were neurotoxic?

Yes it is a very low dose. I was on 1.25mg to start. I will probably end up on 5 mg. I am very sensitive to the dex and a little goes a long way. I am not finding the slow release to be quite as effective as the IR though.
 
As Seppi has pointed out, that is a very low dose, especially for an adult. I wouldn't lose sleep over worries of neurotoxicity.

Therapeutic doses (e.g. 10mg daily to an adolescent for years) will certainly have an effect on the brain in the long term but I wouldn't jump the gun and say its a neurotoxic effect. The concerns are things like sleep pattern disruption, escalation of use, weight loss and effects on the developing brain.

The evidence is far from conclusive that therapeutic use of amphetamine is neurotoxic, the markers that scientists use to look at amphetamine's effect on the brain can't actually tell us if there is injury to brain cells or not because many of the noted differences in amphetamine users vs. controls could be due to a homeostatic compensation of the brain, rather than neurotoxicity that the amphetamine user sustained.
 
http://adderallsafety.org/what-is-neurotoxicity/

I thought therapeutic doses were neurotoxic?

Yes it is a very low dose. I was on 1.25mg to start. I will probably end up on 5 mg. I am very sensitive to the dex and a little goes a long way. I am not finding the slow release to be quite as effective as the IR though.

http://adderallsafety.org/what-is-neurotoxicity/ is a blog run by a moron who is trying to generate ad revenue.

The only evidence I've seen in reviews and meta-analyses of the effects of long-term use of ADHD stimulants (i.e., amphetamine and methylphenidate) at therapeutic doses in humans with ADHD is an increase in gray matter volume in a handful of brain regions. That would be a neurotrophic, not a neurotoxic, effect. Reviews and meta-analyses of binge use and recreational use find that the opposite occurs: gray matter volume decreases.

I use 60 mg Adderall IR every day. Honestly, I'm not sure if I'd even notice a clinically notable effect from taking 5 mg of pure dextroamphetamine. In any event, amphetamine tolerance tends to build up to a certain point, and then just stops. E.g., I haven't needed an increase in my daily dose for the past 8 years despite taking amphetamine nearly every day during that time.
 
Last edited:
To answer your original questions:
1. Assuming they make any difference on amphetamine's treatment effects, taking a multivitamin before or concurrently with amphetamine use would probably be the best option.
2. Vitamins don't affect the pharmacodynamics of amphetamine. They might affect neurotransmitter synthesis, but that would only be the case if a multivitamin were taken before or concurrently with amphetamine.
3. Yes. Ignore whoever recommended that.
4. Amino acids are present in proteins. You'll get L-theanine and L-arginine from food even if you don't supplement it. You could also just eat more protein to obtain the same amount as you would from supplements. It makes no difference unless you have an inborn error of metabolism (i.e., rare genetic disorders) involving amino acid metabolism.
5. Yes. That drug is an SNRI. DRIs and NRIs have pharmacodynamic interactions with amphetamine because they inhibit amphetamine uptake at the dopamine and norepinephrine transporters. It would probably be a better idea to take a higher dose of amphetamine and use an SSRI, assuming the noradrenergic effects of desvenlafaxine (i.e., Pristiq) are necessary/helpful for you. If they aren't, switching to an SSRI and using the same dose would probably be a better option.
6. If you're taking melatonin because someone said it protected against amphetamine neurotoxicity, just don't take it. Therapeutic doses of amphetamine don't cause neurotoxicity, so using purported "neuroprotectants" is just a waste of money.
7. I've been taking amphetamine for almost 20 years; I used to get migraines once or twice a month in my early teenage years when I was on it, and, from what I remember, caffeine helped somewhat. Your case may be different.
8. Eating food with amphetamine doesn't impair its absorption so much as it just slows it down. If you wanted to speed it up, you could just hold the powder/tablet/capsule in your mouth and let it absorb through your oral mucosa. Amphetamine formulations tend to taste awful though.
9. Zinc (30 mg/day; personally, I take 100mg/day) is the only substance I know of which has been found to have a clinically and statistically significant effect on amphetamine tolerance in clinical trials. See https://en.wikipedia.org/wiki/Amphetamine#Interactions

FWIW, I'd also suggest reading these two sections, since they're relevant to what I wrote in my last reply:
* https://en.wikipedia.org/wiki/Amphetamine#Medical
* https://en.wikipedia.org/wiki/Amphetamine#Toxicity
 
Last edited:
Thank you so much Seppi and Cotcha for taking the time. You have both put my mind at ease about taking amphetamine which I appreciate.

The information you provided on desvenlafaxine seems spot on. I am on it purely because of the noradrenergic effects. It seems though that about an hour after taking the Pristiq is tanks the effects of the dextroamphetamine. My doctor is making me run some trials over the next few days to see if this is the case. Then he is going to switch it to night if it is interfering and then probably get rid of it. I will look into SSRIs then. I really struggle with medications that have a fatiguing side effect though.

I get bad migraines from the concussion. I had just got them under control before starting the dex and then the dex has made the worse than ever. The topiramate has made it a lot more manageable but it makes me feel very spacey.

I will start increasing my Zinc dosage. That is great information thank you.
 
I started on instant release and it was very effective. My doctor like to convert people to slow release once he has worked out the correct dosage through instant release. For me 2.5 + 1.25 was too much and 1.25 + 1.25 was not quite enough. Both were very helpful though. I have swapped over to the slow release and it is like taking a sleeping tablet. My doctor upped the slow release dose to 5mg today and it still like a sleeping tablet. Seems like a very strange reaction after the instant release was so effective. Any ideas what is going on?
 
Any ideas what is going on?

What brand/formulations of instant- and extended-release amphetamine are/were you prescribed (or, assuming you take a generic version of an amphetamine pharmaceutical, what's the brand name equivalent)? The only real difference between different amphetamine pharmaceuticals is their pharmacokinetics, e.g., the rate at which they're absorbed in the intestine, excreted from the body, etc..

I'd be able to give you a more concrete answer if I know what the brand name formulations of the instant and extended release pharmaceuticals are.
 
What brand/formulations of instant- and extended-release amphetamine are/were you prescribed (or, assuming you take a generic version of an amphetamine pharmaceutical, what's the brand name equivalent)? The only real difference between different amphetamine pharmaceuticals is their pharmacokinetics, e.g., the rate at which they're absorbed in the intestine, excreted from the body, etc..

I'd be able to give you a more concrete answer if I know what the brand name formulations of the instant and extended release pharmaceuticals are.

I am in Australia so there may not be an equivalent to what we have over there. From my understanding the dexmphetamine (our name) is pure dextroamphetamine instant release. It is a 5 mg tablet and I was cutting it into quarters. On the label it says 'Dexamphetamine Sulphate, each tablet contains Dexamphetamine Sulphate 5 mgs. Sigma Pharmaceuticals.'

In order to get extended release dexamphetamine at my low dose, I go to a special compounding pharmacist. They make it specially for me. My understanding is that it would be most equivalent to dexedrine spansules in the US except that it is all extended release (I think the dexedrine spansules work by giving you half the dose first and then the rest is extended release). These are compounded from pure dexamphetamine powder. On the label it says "Dexamphetamine CR 5mg capsules".

I have had Post Concussion Syndrome for almost 3 years (it is almost completely disabling). I have had to stop work/uni/can't drive etc. I saw a neuropsychiatrist in Australia and after he saw my scans he thought that dexamphetamine could activate the parts of my brain that were in hypoperfusion. I was very skeptical to trying it as a core part of my concussion is the "Physiological Concussion". This is where you have a high resting heart rate and when you exercise you quickly become symptomatic at a heart rate much lower than your predicted age max. Autonomic nervous system dysfunction leads to a misregulation of cerebral blood flow during exercise and cognitive activity. It is similar, I guess, to having high anxiety. I have been trialled on beta blockers for example to try and calm this system (which helped) but lead to even more fatigue. All of this information is to say that I thought stimulants may be the exact opposite of what I should be taking.

Anyway, taking just 1/4 (1.25 mg) of dexamphetamine IR I felt like a new person. I could concentrate, drive, watch tv, read. It wore off by about lunchtime so we added a second 1/4 tablet. This worked amazingly for about 3 weeks. The negatives were that it severely increased my migraine headaches (so we added topiramate) and it did make the Physiological Concussion worse (higher resting HR, lower HR where I became symptomatic during exercise). I was fine with these side effects for the substantial improvement in quality of life. Once the effects started to dulled after 3 weeks I moved to a 1/2 tablet in the morning and 1/4 tablet at lunchtime. I ended up far too manic, with too high a HR, no sleep, with the introduction of just a 1/2 tablet so we thought my ideal dose was somewhere in the middle.

My psychiatrist prefers to switch patients to slow release after determining their dose with instant release. We decided to go with 3.33mg slow release. The slow release has been horrible. I do not know how the effects can be so different. I am more disabled than if I do not take it at all. I am so tired, huge amounts of brain fog, I cannot do anything. I have had a whole week of sleeping all day and staying in bed. We upped the dose to 5mg and it was just as bad. We also tried 5mg plus 1.25mg IR and still no good. It takes about 90 minutes to kick in and has soon as it does I am a zombie. We are probably going to try to keep increasing the dose but I am not confident it is going to work. Apparently some patients have responded like this for a few days but it does not normally last this long.
 
Last edited:
Hmm. I figured the ER drug might be lisdexamfetamine (brand name: Vyvanse in the US/Australia) since that's the only extended release drug which is produced in an ingestible tablet (and capsule) dosage form, but apparently that's not the case.

The only amphetamine ER mechanisms of which I'm aware are ion exchange resins (Adderall XR and Mydayis use a methacrylic acid copolymer; Dyanavel XR uses sodium polystyrene sulfonate; Adzenys XR-ODT uses both sodium polystyrene sulfonate and methacrylic acid copolymer), wax-fat coated pellets (formerly dexedrine spansules), prodrug formulations (Vyvanse), and gel-forming pellets that dissolve their contents slowly when exposed to water (currently dexedrine spansules, which use "hypromellose" to achieve this).
If the extended release tablet that you take doesn't swell/enlarge when exposed to water, it's probably not the same release mechanism as the dexedrine spansule beads. My guess would be that it uses a pH-dependent ion exchange resin which normally is released in the intestine, but I can't say for sure.

In any event, all of those formulations reach their peak effect, which is usually less pronounced relative to an IR peak effect, at least an hour later than IR formulations, although those milder effects do tend to last longer. So, it's not really surprising to me that you find the extended release formulation less effective overall. I don't like extended-release amphetamines for the same reason. I prefer IR formulations since they produce a marked and immediate effect right when I need it (i.e., whenever I take a pill). If your case is similar, I'd suggest just discussing the idea of using an IR formulation instead of the ER formulation with your psychiatrist. There's no real benefit to taking ER amphetamine dosage forms besides the fact that it permits you to take just 1 pill a day instead of 2 or 3.

Also, if you still want to know which of those release mechanisms that I mentioned (or possibly a different mechanism) is used in your ER formulation, you could ask your pharmacist. My advice is to just switch to an IR formulation though.
 
Last edited:
Thank you so much for the explanation.

I just spoke to the pharmacist. He said that their formula is that they fill the capsules with 40% filler methocel which breaks down when it comes into contact with liquid. I have spoken to a few compounding pharmacists this morning and they all use the same release mechanism. So it is a combination of the pure dexamphetamine powder and the filler.

I am thinking the IR might have to be the way to go as well. It is disappointing because I definitely liked the idea of having a smoother day than peak crash peak crash.
 
Glad to help.

As long as you time your dosing right, you shouldn't experience crashes with IR formulations.
 
Top