reducing amphetamine neurotoxicity

[Amu]

Are we sure about the implications of using anti-oxidants to reduce stimulant neurotoxicity?

See the following:
http://www.ncbi.nlm.nih.gov/pubmed/17327526
http://www.ncbi.nlm.nih.gov/pubmed/16242247
http://www.ncbi.nlm.nih.gov/pubmed/17908557

In essence, for constant low-dose stimulant dose, using anti-oxidants might cause unwanted neural adaptation, not to mention how it is impossible to predict whether any of the anti-oxidation supplements we take might act as pro-oxidants in essence.

 

[Dysphoric]

Obviously Methamphetamine is more neurotoxic, but I have a question.

Would taking even 20-30mgs of Desoxyn a day be that much more neurotoxic than 40-50mgs of Adderall a day?

Cause I'm planning on taking my Desoxyn once I start school in Spring of next year. Can the neurotoxicity from Methamphetamine be reduced by quite a bit with some of the listed stuff, mainly Selenium? If not then I might just switch to Adderall again, although I don't feel Adderall as much as Desoxyn, on top of the fact that Desoxyn is way more smooth.

 

[Amu]

Obviously Methamphetamine is more neurotoxic, but I have a question.

Would taking even 20-30mgs of Desoxyn a day be that much more neurotoxic than 40-50mgs of Adderall a day?

Cause I'm planning on taking my Desoxyn once I start school in Spring of next year. Can the neurotoxicity from Methamphetamine be reduced by quite a bit with some of the listed stuff, mainly Selenium? If not then I might just switch to Adderall again, although I don't feel Adderall as much as Desoxyn, on top of the fact that Desoxyn is way more smooth.

Neurotoxicity is a concept related to permanent changes in the brain, behavioral consequences might or might not follow, and considering that Desoxyn has been approved since 1943 and no behavioral changes per se have been documented, except for the occasional user complaining of worse ADHD symptoms related to receptor/transporter sensitivity changes, I highly doubt 20-30 mg per se will produce enough free radical damage to be noticeable as long as the user gets appropriate sleep and nutrition. Nonetheless, it is POSSIBLE, and especially dangerous for adolescents and children, which is why dextromethylphenidate, a highly under-rated agent, should be used in that age group if a stimulant is required. Of course, proper hydration is required, since if hyperthermia occurs, neurotoxicity will occur, but 20-30 mg spread throughout the day isn't going to cause massive release of serotonin and cause direct hyperthermia, and I think users noticing enhanced mood different from dextroamp are probably experiencing smooth dopamine increases, which dextroamp doesn't cause without releasing a large amount of anxiogenic NE, or perhaps they are sensitive to small amounts of serotonin increase, but again, the SERT is not reversed until enough SER is present in the synpase.

 

[thikal]

And what about Ketamine to reduce oxydative stress?

With respect to the pharmacodynamic action providing neuroprotection, NMDA-receptor antagonism may be just one of several mechanisms; others include scavenging of free radicals, a central sympatholytic effect and augmentation of dopamine metabolism in the caudate. The suitability of ketamine for neuroanaesthesia, which must also take account of its effects on ICP, CBF and CMRO2, is--for the time being--questionable.

http://www.ncbi.nlm.nih.gov/pubmed/7840413

 

[Amu]

And what about Ketamine to reduce oxydative stress?



http://www.ncbi.nlm.nih.gov/pubmed/7840413

Well ketamine would be quite harmful to the prefrontal cortex of an ADHD user, some have said that ketamine use early on in life can even cause ADHD, I'm not sure about the latter, but ketamine is probably useable by non-ADHDers to reverse tolerance during breaks, it is very psychoactive though, not practical for even weekly use, and gets extremely addictive in some cases.

 

[Vaya]

In essence, for constant low-dose stimulant dose, using anti-oxidants might cause unwanted neural adaptation, not to mention how it is impossible to predict whether any of the anti-oxidation supplements we take might act as pro-oxidants in essence.

This is precisely what the article Exacerbation of Methamphetamine-Induced Neurochemical Deficits by Melatonin. Essentially the article demonstrates that, contrary to the researchers' expectations, the endogenous antioxidant melatonin became a pro-oxidant when co-administered with methamphetamine, augmenting methamphetamine's neurotoxic profile. In the Discussion, the authors make a pretty interesting point:

The possibility that melatonin alters the METH effects due to changes in the cardiovascular system should also be considered. Viswanathanet al. (1986) observed that melatonin decreases norepinephrine turnover in the heart. If melatonin suppresses sympathetic activity to the vasculature causing vasodilation, it is possible that as a consequence more METH is delivered to the brain and hence increases the neurochemical deficit induced by the METH. We are currently investigating other possibilities to explain why melatonin enhanced the METH-induced monaminergic effects, including possible pharmacokinetic alterations of METH by melatonin.

Melatonin is currently promoted in some countries as an over-the-counter “natural” medication for insomnia and other sleep disorders (UC Berkeley Wellness Letter, 1995). Because insomnia is one of the sequelae experienced by METH abusers, it is conceivable that they may perceive melatonin as a safe sleep-aid (UC Berkeley Wellness Letter, 1996) to overcome the insomnia associated with the “high” experienced during the METH “rush.” Moreover, because those who abuse METH are often knowledgeable about the potential neurotoxic effects of METH and its congeners, it is conceivable that they might use melatonin to protect against the possible oxidative neurotoxicity associated with the use of these central nervous system stimulants. Because we report that the neurotoxicity of METH is markedly potentiated when administered with melatonin, the potential implications of this drug interaction are self-evident. It is true that the doses of both METH and melatonin used in this investigation exceed those used by the naive abuser; however, as tolerance develops the dose of METH is markedly escalated and may approach the high doses used in these studies.

Felt that went along with your thinking here, Amu.

~ vaya

 

[Dysphoric]

I believe this is slightly misinformed - or, rather, DA reuptake inhibition is but a symptom of the pharmacology of amphetamines. Take a quote from THISwebsite, for instance: " Amphetamines’ 3 main effects on dopamine transport are depletion of vesicular dopamine (DA), reversal of DAT (efflux of DA into synaptic cleft), and DA uptake inhibition (Caron et al, 1998).. Methylphenidate is a DATI (dopamine transporter inhibitor), whilst amphetamine and its derivatives and analogues work by DAT reversal. Interestingly enough, I did some research a little while back and discovered that methylphenidate, as a DATI, can actually help prevent amphetamine-induced DA deficiencies! How 'bout that? Solving your amphetamine problems with Ritalin, what a world. But, see for yourself, the following is from a file I wrote up myself with links just so I could wrap my mind around the idea; the links and/or citations following the verification statements, as they are, ought still be valid:

A. Premise:
1. DAT-Inhibitors (DATI's) protect against METH-induced DA deficits
and…
2. Methylphenidate is a DATI
therefore...
3. Methylphenidate should protect against METH-induced DA deficits
----------------------------------------------------------------------------------------------
B. Verification:
1. DAT-Inhibitors (DATI's) protect against METH-induced DA deficits
"Methamphetamine Toxicity and Messengers of Death." Irina N. Krasnova, Jean Lud Cadet. Molecular Neuropsychiatry Research Branch, Intramural Research Program, NIDA/NIH/DHHS, 251 Bayview Boulevard, Baltimore, MD 21224, USA
Accepted 16 March 2009
Available online 25 March 2009
http://www.toxicology.tcu.edu.tw/files/class_0981/神經毒理學特論/980923.pdf
2. Methylphenidate is a DATI
"Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications."
http://www.ncbi.nlm.nih.gov/pubmed/11793423
3. Methylphenidate should protect against METH-induced DA deficits
"Methylphenidate Alters Vesicular Monoamine Transport and Prevents Methamphetamine-Induced Dopaminergic Deficits." Veronica Sandoval, Evan L. Riddle, Glen R. Hanson, and Annette E. Fleckenstein. Department of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah. Received October 3, 2002; accepted December 4, 2002.

And the last bit from the document I typed up, I apparently didn't deem it necessary to validate this with a reference, but I remember happening across the information (pertinent or impertinent to this discussion, you make the call) as I was doing more in-depth research on the aforementioned subject:

Methamphetamine is a DA reuptake inhibitor.
>Methamphetamine decreases reabsorption of DA by synaptic vesicles, resulting in more DA in the synapse and less DA in the vesicles.
>METH causes DAT (dopamine transporter) upregulation (increase of a cellular component)

Therefore, because methylphenidate works against the DA transporter - and methamphetamine's neurotoxicity is caused in part by its ability to promote the activity of said transporter - methylphenidate fights the neurotoxicity caused by meth on the battleground occupied by these DAT's.

Anyway, I hope what I've said makes sense; sorry to resurrect such an old thread but I found myself doing a bit of investigative research for my own purposes and thought I'd chime in.

~ vaya

So, If I take Dexmethylphenidate it can prevent most if not all damage done after taking Desoxyn? I'm interested. If this is true, when do I want to take the D-MPH to prevent said damage? After the Desoxyn where's off, during, the day after? When?! And what would be a good dose? I'm very interested.

 

[Amu]

So, If I take Dexmethylphenidate it can prevent most if not all damage done after taking Desoxyn? I'm interested. If this is true, when do I want to take the D-MPH to prevent said damage? After the Desoxyn where's off, during, the day after? When?! And what would be a good dose? I'm very interested.

Taking dextromethylphenidate before desoxyn will reduce neurotoxicity but also reduce the effectiveness of desoxyn because it prevents some of the desoxyn from binding to DAT. It is similar to taking an SSRI before MDMA usage.

 

[Vaya]

Yes, It Can!

So, If I take Dexmethylphenidate it can prevent most if not all damage done after taking Desoxyn? I'm interested. If this is true, when do I want to take the D-MPH to prevent said damage? After the Desoxyn where's off, during, the day after? When?! And what would be a good dose? I'm very interested.

Well, first thing's first, the study used racemic (dextro- and levo-) methylphenidate, not dexmethylphenidate alone. It's the same situation with the methamphetamine; under materials they list +/- (or dextro- and levo- / racemic) methamphetamine, so the results wouldn't specifically correlate to Desoxyn, either (but I may just be being nitpicky ) Backed up by their chemical chirality, so too do most accounts (very much including my own) pin Dextro-Methylphenidate as differing so markedly from the effects of its levo-isomer that I would hasten to wager that the differential nature of its impact on meth toxicity vs. that of racemic methylphenidate would warrant its own study paradigm. Regardless, I'm sure for at-home experimentation the substitution would no doubt prove at least as effective at helping heal your brain.

I've also amended that post of mine to include the link to the third article under Verification; it will be instrumental for you to understand this article in order to wrap your mind around this entire concept of "methylphenidate-intervention"!! I admit it, it took me a few reads, and some of those charts are just damn confusing.
In fact, here it is
Methylphenidate Alters Vesicular Monoamine Transport and Prevents Methamphetamine-Induced Dopaminergic Deficits (PDF)
Methylphenidate Alters Vesicular Monoamine Transport and Prevents Methamphetamine-Induced Dopaminergic Deficits Full-Text (you can enlarge the Results section images more accurately with this format to see exactly what they were measuring and how the values changed with time).
Now, then, let's analyze the data!
---------------------------------------------------------------------------------------------------------------------------------------

...when do I want to take the D-MPH to prevent said damage? After the Desoxyn where's [sic] off, during, the day after? When?!

From the abstract:

...we hypothesized that methylphenidate post-treatment [with methamphetamine] might protect against the persistent striatal dopamine deficits caused by methamphetamine by rapidly affecting VMAT-2 and vesicular dopamine content. Results reveal that methylphenidate post-treatment both prevents the persistent dopamine deficits and reverses the acute decreases in vesicular dopamine uptake and VMAT-2 ligand binding caused by methamphetamine treatment. In addition, methylphenidate post-treatment reverses the acute decreases in vesicular dopamine content caused by methamphetamine treatment. Taken together, these findings suggest that methylphenidate prevents persistent methamphetamine-induced dopamine deficits by redistributing vesicles and the associated VMAT-2 protein and presumably affecting dopamine sequestration.

Simply put, you would take methylphenidate as a preventative measure up to several hours after you've taken your last methamphetamine dose.

One measure of amphetamine neurotoxicity is a decrease in dopamine banding density. In the experiment, the researchers performed four injections at two-hour intervals on various rats with either saline solution (as the control group) or 7.5mg methamphetamine per kilogram; there are 2.2 pounds in a kilogram, so that works out to four injections of 16.5mg methamphetamine per non-control rat. Figure 1 demonstrates that decreases in DA banding density were causal factors of methamphetamine injection, because the saline/control rats' densities remained virtually the same whilst the METH-rats showed a density decrease.

Figure 3 indicates that

Rats received methamphetamine (METH; four injections; 7.5 mg/kg s.c.; 2-h intervals) or saline (Sal; 1 ml/kg s.c.). Some rats received one injection of methylphenidate 1 h after the final methamphetamine injection (e.g., METH/1XMPD). Others received two injections of methylphenidate 1 and 3 h after the final methamphetamine injection (e.g., METH/2XMPD). A third group of rats received three injections of methylphenidate or saline (1 ml/kg s.c.) 1, 3, and 5 h after the last saline or methamphetamine injection (Sal/3xMPD and METH/3xMPD, respectively).

Each methylphenidate injection was 5mg/kg, or 11mg racemic methylphenidate/pound.

It's 4:30 a.m. where I am right now so I'm just gonna quote the pertinent findings from the article itself, heavily edited of course to be concise and answer your question!:

Post-treatment with a single methylphenidate injection 1 h after the last methamphetamine administration partially reversed the 7-day striatal dopamine depletions caused by the methamphetamine treatment. Two or three injections of methylphenidate (1 and 3 h, or 1, 3, and 5 h, respectively) after the last methamphetamine administration completely prevented the persistent methamphetamine-induced striatal dopamine depletions (Fig. 2A). Methylphenidate post-treatment per se did not alter total dopamine levels 7 days after treatment, nor did it prevent the hyperthermia induced acutely by methamphetamine administration (Fig. 2B).
Results presented in Fig. 3 demonstrate that, as has been reported previously [...] multiple administrations of methamphetamine rapidly decreased vesicular dopamine uptake [...] as assessed in purified striatal vesicles prepared 1 h after the last methamphetamine injection. These effects persisted at least 6 h after treatment (Fig. 4). Post-treating animals with one, two, or three injections of MPD administered, as described for Fig. 2, during the initial 6-h period after methamphetamine treatment partially reversed these rapid methamphetamine-induced decreases in vesicular dopamine uptake [...] (Fig. 3). As reported previously [...] MPD treatment per se increased vesicular dopamine uptake...

In summary? Promising shit
'Night, all.

~ vaya

 

[Vaya]

It is similar to taking an SSRI before MDMA usage.

LOL I made that same comparison, but you finished your post sixty minutes before I finished mine so I edited it out You're quick on the draw, mon.
However, as my explanation of the study's findings explains, it's not before the Desoxyn you would take the Focalin... you've got a couple-hour optimal window after initial methamphetamine administration; you let the DAT reversal occur, and then via a DATI you reverse it back, either partially or near-completely undoing the process. I do not know if dexmethylphenidate would compete strongly enough with the dexmethamphetamine for the DAT, though, the way buprenorphine out-competes naloxone in Suboxone. Anyone know this?

~ vaya

 

[Dysphoric]

]

Wouldn't taking D-MPH a couple hours after taking D-MethAmp be a little sketchy? My concerns would be the impact on me physically, wouldn't that cause more side-effects? Like Tachycardia? High BP? Etc... Not to mention wouldn't it kind of kill the effects of The Amp?

IDK. I could understand taking the MPH like 12+ hours afterwords, but several hours? That would kind of freak me out. I think I'll pass.

 

[Vaya]

Wouldn't taking D-MPH a couple hours after taking D-MethAmp be a little sketchy? My concerns would be the impact on me physically, wouldn't that cause more side-effects? Like Tachycardia? High BP? Etc... Not to mention wouldn't it kind of kill the effects of The Amp?

IDK. I could understand taking the MPH like 12+ hours afterwords, but several hours? That would kind of freak me out. I think I'll pass.

I'm not advocating it either way, I merely found it an interesting topic to discuss. I have never taken dex/methylphenidate after dex/methamphetamine for the purpose of protecting myself from neurotoxicity. However, if I were to, I certainly wouldn't make it a large dose of dex/methylphenidate. Just *something* to instigate its DATI actions.

Maybe taking it 12+ hours afterwards would still work, given the long duration of methamphetamine. My post served as an explanation of the study's findings in case it was difficult to understand. Their time-frames were shorter because they had to ensure the preservation of the chemicals in the rat's brains for analysis.

~ vaya

 

[runlikell]

Sunlight. Good ole' Vitamin D seems to be helpful.

Here's the study that brought this to my attention: http://www.ncbi.nlm.nih.gov/pubmed/17105922

Calcitriol protects against the dopamine- and serotonin-depleting effects of neurotoxic doses of methamphetamine.
Cass WA, Smith MP, Peters LE.
Source
Department of Anatomy and Neurobiology, MN-225 Chandler Medical Center, University of KY, Lexington, KY 40536-0298, USA. [email protected]
Abstract
Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in brain dopamine (DA) and serotonin (5-HT) content. Calcitriol, the active metabolite of vitamin D, has potent effects on brain cells, both in vitro and in vivo, including the ability to upregulate trophic factors and protect against various lesions. The present experiments were designed to examine the ability of calcitriol to protect against METH-induced reductions in striatal and nucleus accumbens levels of DA and 5-HT. Male Fischer-344 rats were administered vehicle or calcitriol (1 microg/kg, s.c.) once a day for eight consecutive days. After the seventh day of treatment the animals were given METH (5 mg/kg, s.c.) or saline four times in 1 day at 2-h intervals. Seven days later the striata and accumbens were harvested from the animals for high-performance liquid chromatography (HPLC) analysis of monoamines and metabolites. In animals treated with vehicle and METH, there were significant reductions in DA, 5-HT, and their metabolites in both the striatum and accumbens. In animals treated with calcitriol and METH, the magnitude of the METH-induced reductions in DA, 5-HT, and metabolites was substantially and significantly attenuated. The calcitriol treatments did not reduce the hyperthermia associated with multiple injections of METH, indicating that the neuroprotective effects of calcitriol are not due to the prevention of increases in body temperature. These results suggest that calcitriol can provide significant protection against the DA- and 5-HT-depleting effects of neurotoxic doses of METH.

 

[Vaya]

These results suggest that calcitriol can provide significant protection against the DA- and 5-HT-depleting effects of neurotoxic doses of METH.

Way cool contribution to this discussion, runlikell! :D

~ vaya

Afterthought: Do therapeutic sunlights that mimic the effect of natural sunlight for depressed patients also release Vitamin D, and subsequently calcitriol, in the human brain?

 

[runlikell]

Afterthought: Do therapeutic sunlights that mimic the effect of natural sunlight for depressed patients also release Vitamin D, and subsequently calcitriol, in the human brain?

I don't think so. Sunlight causes responses through multiple pathways with different results. When UV radiation hits the skin, it triggers the release of a chemical which goes through a chain reaction that results in viatmin d. When the blue wavelength of sunlight hits the eyes, it triggers the release of serotonin in the brain. Light boxes are meant to mimic the latter, but not the former.

Just take a supplement. It (vit d) has so many beneficial effects and is deficient in so many people that its going to help regardless of whether one uses meth.

 

[Amu]

Vaya, another reason desoxyn toxicity is rare is because the chance of hyperthermia with such doses is MUCH less than it is with recreational doses. Personally I've experienced and read about worse effects from marijuana on attention/memory/learning than from long-term stimulant use. Ironic since marijuana is often obsessed over by a certain loud group of drug users that consider it to be somehow special and consider users of other drugs to be somehow misguided.

Dysphoric, none of any of this should be taken as medical advice on what to do to prevent neurotoxicity. I'm sure you know this already but you brought up certain things in your post that made me want to confirm this. As for the harms, you would be replacing your last dose of methamphetamine with the dexmethylphenidate, so I don't think there will be any increased risk of heart problems, you're basically reducing your meth intake and proportionately adding a small dose of d-MPH at the end.

 

[Vaya]

Sunbathing & Decapitation

I don't think so. Sunlight causes responses through multiple pathways with different results. When UV radiation hits the skin, it triggers the release of a chemical which goes through a chain reaction that results in viatmin d. When the blue wavelength of sunlight hits the eyes, it triggers the release of serotonin in the brain. Light boxes are meant to mimic the latter, but not the former.

Just take a supplement. It (vit d) has so many beneficial effects and is deficient in so many people that its going to help regardless of whether one uses meth.

Eye-opening! (no pun intended LOL)
My gratitude goes to you for sharing that bit about the multiple pathways - I own a lightbox (from the early '90s, it's as big as a suitcase and could light illuminate the entire floor of a house!) and definitely knew of its effect on serotonin... What you say makes sense though, since I've only ever been instructed to look indirectly at it, not sunbathe in front of it %)

Vaya, another reason desoxyn toxicity is rare is because the chance of hyperthermia with such doses is MUCH less than it is with recreational doses.

Yeah for sure, I've given this a lot of thought recently and come to the conclusion, with yours and negrogesic's help in the other thread, that I'm really not risking much with the prescriptions I take and at the dosages that I take them. You've both helped, you substantially so.

Dysphoric, none of any of this should be taken as medical advice on what to do to prevent neurotoxicity. I'm sure you know this already but you brought up certain things in your post that made me want to confirm this.

I feel I ought to mention this again, too; that is, that I'm certainly not advocating the idea of a human attempting to replicate a decrease in stimulant toxicity based on six decapitated rats It's made for a pretty interesting conversation, though, no?

Be well,

~ vaya

 

[runlikell]

Aside from neurotoxoicity, all stimulants cause vasoconstriction, decreasing bloodflow to the brain (and the rest of the body).

Looking at the fact that the increase in blood flow that occurs from exercise is what makes it such a healthy activity for the brain, one can from there easily see what engaging in activities which have an opposite effect on bloodflow to the brain might potentially mean in terms of brain health. Taking that into account, it seems hard to justify long long-term regular stimulant usage--at least for me, as someone who strives ultimately for optimal mental well-being. Yet, I still find them too... well, stimulating, too give up entirely

 

[Amu]

Aside from neurotoxoicity, all stimulants cause vasoconstriction, decreasing bloodflow to the brain (and the rest of the body).

Looking at the fact that the increase in blood flow that occurs from exercise is what makes it such a healthy activity for the brain, one can from there easily see what engaging in activities which have an opposite effect on bloodflow to the brain might potentially mean in terms of brain health. Taking that into account, it seems hard to justify long long-term regular stimulant usage--at least for me, as someone who strives ultimately for optimal mental well-being. Yet, I still find them too... well, stimulating, too give up entirely

Any neurotoxicity estimates would take into account the factor of vasoconstriction, and no, stimulants across the board are not harmful to brain health in low doses, methylphenidate for example has quite a body of evidence for it's benefits, same with caffeine.

 

[atrollappears]

My regimen:

-Reasonable dose of magnesium to prevent the excitotoxic side of amphetamine neurotoxicity, I usually supplement to 100% DV of chelated magnesium. I say reasonable because supposedly too much Mg can act as a Ca agonist, which would make Mg supplementation useless and exacerbate neurotoxicity. (High doses of magnesium exacerbate MPTP neurotoxicity; MPTP toxicity is different in some ways from amphetamine's though)
-Alpha lipoic acid, since it's a good antioxidant, and might help your brain recover too (doses of 800 mg alpha lipoic acid plus 2g [I think] of acetyl-L-carnitine improve working memory by 20% with regular administration). I don't take this with oral amphetamine, because the acidity will hinder absorption, but I take it daily.
-Acetyl-L-carnitine, same reasons as above, although it's not acidic. This one has been shown in studies to attenuate amph neurotoxicity.
-Vitamin C (buffered, time release). Vitamin C also has been shown to protect against amphetamine (and MDMA) neurotoxicity. Buffered so it doesn't hinder absorption, time release because it's metabolized so fast.
-Vitamin D, because it's an antioxidant
-Selenium (as selenomethionine), since it's an effective antioxidant and has been shown to protect against amph neurotoxicity
-A cigarette, since tobacco smoke also protects against amphetamine neurotoxicity
-Citicoline, since it's neuroprotective/neurotrophic, and a cholinergic agent like nicotine. (I know some of you will think "Well aren't there MAOIs in tobacco smoke?" However, nicotine administered alone protects from MPTP neurotoxicity.) So, I speculate that it helps protect from/repair damage. It also helps with focus, but I wouldn't take it for a fun amphetamine high for that very reason.
-Alpha GPC, another cholinergic agent, just for the hell of it.

Also, I avoid caffeine, because it exacerbates amph neurotoxicity. However, while not consuming amphetamine, I regularly consume caffeine, because caffeine *tolerance* is protective.