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  #1  
Old 03-24-08, 09:38 PM
barbarian barbarian is offline
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Memantine: The Solution to my Adderall Tolerance

To all that want to know more information on helping reduce and or fight tolerance to Adderall's anti-ADHD properties:

Remember that this testimony is only based on the first 2 weeks of adapting to my new medication cocktail: 300mg Seroquel; 300mg Lamictal; 20mg Adderall; 10mg Memantine. The difference here is that Memantine was added to the other three medications that I've taken since God knows when. It is quite possible that this solution is only temporary and might poop out eventually or rapidly, which seems to be the case when I find a "solution" to my amphetamine tolerance issue.

There has been a lot of hype regarding Memantine "preventing" and or "reversing" amphetamine tolerance. Although it may not completely eradicate amphetamine tolerance, it has surely helped with it from my experience. I can attest that this hype is definitely for a reason. In my case, when I started taking Memantine, its anti-tolerance properties didn't kick in until after the first week of taking it. But, then again that might not be accurate, as I stopped taking Adderall for a week whilst building up on Memantine for that week -- later to resume Adderall on the second week building up from 5mg of Memantine to 10mg.

I must say that ever since I started taking Memantine and resuming my Adderall beginning on the second week of my addition of Memantine, my attention has made almost a complete 180 -- from being very, very tolerant to Adderall and therefore getting barely any good results from it after prolonged use to a huge turnaround in terms of my concentration. I've taken week and 2-week breaks before from taking Adderall, and without Memantine I got maybe a day's worth of anti-ADHD effects when I resumed before completely pooping out; and these results were mediocre. Now with Memantine, I've gotten a solid week with 10 hours worth of anti-ADHD control...A SIGNIFICANT DIFFERENCE!

For example, I was and still am taking Adderall XR; before Memantine I was only getting maybe 3 hours worth of ADHD control after my medication vacation. These 3 hours worth of control only lasted about a day's -- and in rare cases -- or 2 day's worth of ADHD control. Combining Memantine along with the rest of my medication cocktail has made the difference. I'm very pleased with the results. For all of those worried about the amphetamine tolerance issue, I'd highly recommend discussing with your doctor about the possibility of being prescribed it for reducing amphetamine tolerance. From my experience, even without the Adderall, my attention and memory have significantly improved with the Memantine.

And ever since I've started Memantine, my alcoholism has dissipated. I was constantly increasing my dosage of Adderall and consuming large amounts of alcohol per week. It seemed as if I wasn't taking Bipolar meds because I was constantly manic presumably due to my increased consumption of alcohol and amphetamines. But now due to Memantine (at least in my honest opinion), I don't even feel like drinking. There are a few "bad" things with it, though...I have no sex drive whatsoever. I also consider myself to be non-creative whilst taking Memantine. But you know what, at least I'm catching up in school now and doing much, much better. I am still on the verge of failing, but I'm making a big comeback now that I'm able to concentrate. It is truly an amazing feeling.

But of course I'm no doctor. Perhaps my belief that Memantine is the reason for the improvement in my life is an illusion and is caused by something else. However, there is a strong correlation in terms of taking Memantine and resuming Adderall after a week's worth of a break that my life has made a complete turnaround. I am soooooooooooo happy now.

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Barbarian
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  #2  
Old 03-24-08, 10:01 PM
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Re: Memantine: The Solution to my Adderall Tolerance

Memantine is primarily used to treat Alzheimers...did your doc prescribe it to you off label for Adderall tolerance? Just curious

http://en.wikipedia.org/wiki/Memantine

Last edited by luvnlife79; 03-24-08 at 10:01 PM.. Reason: forgot link
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Old 03-24-08, 11:55 PM
adhdogwalker adhdogwalker is offline
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Re: Memantine: The Solution to my Adderall Tolerance

Interesting info. I'm going to do more research. I am on a similar cocktail to you except I keep having med problems so I had to reduce the Seroquel from 500 mg. to 200 due to elevated prolactin levels. I take 90-100 mg. Adderall XR & IR and just started Lamictal am on 50 mg. Usually the Adderall calms me down, even when I'm manic; however, it's not working at all right now. I feel like my brain has ceased to function (Seroquel helped a lot with my attention/organization). I'm not sure if it's because the meds aren't working very well right now because Mania Season has begun. I had a psychotic episode last week, then it ended and I'm swinging closer to mania every day. Last time this happened, I at least could think a bit and calm down for a part of every day thanks to the adderall. I am going to ask my psychiatrist about Memantine next time I see him.

I read the wiki article and it said that it's being researched for opioid dependence, so maybe that's why it reduces your cravings for alcohol. I used to drink when manic before adderall but it eliminates all desire for alcohol.

Keep me posted on how this combo works out for you.
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Old 03-25-08, 12:10 AM
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Re: Memantine: The Solution to my Adderall Tolerance

I'm gonna ask my shrink about it too.
...I just take adderall tho
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Old 03-25-08, 02:21 AM
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Re: Memantine: The Solution to my Adderall Tolerance

Memantine is a NMDA antagonist. That's the mechanism by which it reverses /prevents further amphetamine tolerance.

but for those who don't want to pay $$ for a pharma.

Magnesium Citrate/Glycinate works the same exact way.. and its found in most good vitamin/whole food stores. 500mg ed

as for the OP.

... what is your diagnosis exactly? because this is the most bizarre "stack I've seen in a long time."


300mg Seroquel(quietapine); - atypical antipsychotic. the antithetical pharma to adderall. I have no idea why you would take this unless you were suffering from amphetamine psychosis (really high doses of adderall abuse). 300mg is too high of a dose to be used as a sleep aid. quietapine is most effective as a seditive in amounts below 125mg. I mean hell. just taking this cancels out any effect you would get from adderall at all.
it's an antagonist for damn near everything. the serotonin transporters, the dopamine transporters. long term use of seroquel = tardive dysknesia. (trust me. not a win)

300mg Lamictal; -mood stabilizer / anticonvulsant... ok.. hmm making more sense... you must have some kind of complex bipolar schizophrenic condition?
20mg Adderall; - we already know what this is.
10mg Memantine - NMDA antagonist and alzheimers treatment.

alrighty... I'd say first off the reason you don't feel much from the adderall is because of your seroquel.
your seroquel is anti dopamine. Honestly, I'm surprised you feel anything at all from it.
the memantine probably just helped to make the low amount of amphetamine you have more effective.

that's about it.
You want real results from your adderall treatment? and real cognitive improvement?
speak with your doctor ask him why you are on the seroquel. and if its possible to switch to something else and/or lower your dose by about half.
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Old 03-25-08, 02:31 AM
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Re: Memantine: The Solution to my Adderall Tolerance

Quote:
Originally Posted by variance View Post
Memantine is a NMDA antagonist. That's the mechanism by which it reverses /prevents further amphetamine tolerance.

but for those who don't want to pay $$ for a pharma.

Magnesium Citrate/Glycinate works the same exact way.. and its found in most good vitamin/whole food stores. 500mg ed
Source?
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Old 03-25-08, 01:05 PM
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Re: Memantine: The Solution to my Adderall Tolerance

when shopping for Magnesium, be sure to read the back of the bottle, most have Magnesium oxide which is not as effective (so I have heard.)

Quote:
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..Magnesium Citrate/Glycinate works the same exact way.. and its found in most good vitamin/whole food stores. 500mg ed
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Old 03-26-08, 03:08 PM
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Re: Memantine: The Solution to my Adderall Tolerance

Quote:
Originally Posted by despirit View Post
Source?
it's fairly well known that Mg is a NMDA antagonist

Magnesium ions (Mg2+) in cellular biology are usually in almost all senses opposite to Ca2+ ions, because they are bivalent too, but have greater electronegativity and thus hold on to water molecules stronger, preventing passage through the channel (even though magnesium is smaller). Thus Mg2+ ions block Ca2+ channels (NMDA channels) for example, etc.

http://en.wikipedia.org/wiki/Magnesi...annel_blockade
http://en.wikipedia.org/wiki/Magnesium_transport

Evidence with regards to the NMDA antagonist...

Quote:
Mechanisms of action of neuroprotectants in stroke.

Lyden P, Wahlgren NG.
University of California San Diego Medical Center, San Diego, CA 92103-8466, USA.
During cerebral ischemia, there is excessive activity of excitatory amino acids, especially glutamate. Activation of glutamate receptors leads to a marked increase in intracellular calcium, which in turn leads to activation of intracellular enzymes and neuronal death--the so-called excitotoxic cascade. The calcium antagonist nimodipine, which acts at L-type calcium channels, was tested for a putative neuroprotectant effect in patients with acute ischemic stroke, but no beneficial effect was demonstrated. Glutamate receptors are attractive targets for neuroprotectant drugs because glutamate plays a central role in the excitotoxic cascade. Clinical trials of NMDA (N-methyl-D-aspartate) antagonists have been disappointing, however, and psychiatric side effects seem to be a general problem with this class of drug. Another strategy proposed for interfering with NMDA receptor function is the infusion of magnesium. The NMDA receptor is normally blocked by magnesium ions and will only respond to glutamate when this magnesium-induced block is removed on depolarization. A large clinical trial to investigate possible neuroprotection by magnesium is underway. The NMDA receptor also has a glycine-binding site and a polyamine-binding site, and the cation channel will only open in response to glutamate if glycine and polyamines are already bound to these obligatory modulatory sites. Gavestinel is selective for the glycine-binding site, and eliprodil for the polyamine site, but large international clinical trials have failed to find any beneficial effects in patients with acute ischemic stroke. Neurotoxic free radicals are also generated during cerebral ischemia. Laboratory stroke models suggest that free radical scavengers might be effective neuroprotectants. One of these, NXY-059, was effective in several animal studies, and preliminary studies in human subjects show that plasma concentrations that are neuroprotective in animal models can be achieved and are well tolerated. Lubeluzole interferes with the glutamate-induced neuronal damage mediated through the formation of nitric oxide. However, a meta-analysis of all clinical trials of lubeluzole was unable to detect a neuroprotectant effect of the drug. There is now some evidence that, in addition to necrosis, some neurons die as a result of apoptosis after cerebral ischemia. Several drugs that interfere with the apoptosis cascade, for example, caspase inhibitors, are under investigation. Clomethiazole ('ZENDRA'; a trademark, the property of the AstraZeneca group of companies) is also undergoing a second large clinical trial in patients with major ischemic strokes. This drug's mechanism of action is not completely clear, but it is known to activate a nonbenzodiazepine site on the GABA(A) (gamma-aminobutyric acid) receptor. This causes increased chloride conductance and hyperpolarization. In vitro clomethiazole inhibits ischemia-induced glutamate efflux from cerebral neurons. The first large controlled trial showed it to be well tolerated and suggested a clinically significant effect in patients with deficits of a major stroke.
Quote:
NMDA receptor complex blockade by oral administration of magnesium: comparison with MK-801.

Decollogne S, Tomas A, Lecerf C, Adamowicz E, Seman M.
Institut de Recherche Preclinique (IRPC), Le Plessis-Robinson, France.
The ion channel of the N-methyl-D-aspartate (NMDA) receptor complex is subject to a voltage-dependent regulation by Mg2+ cations. Under physiological conditions, this channel is supposed to be blocked by a high concentration of magnesium in extracellular fluids. A single dose of magnesium organic salts (i.e., aspartate, pyroglutamate, and lactate) given orally to normal mice rapidly increases the plasma Mg2+ level and reveals a significant dose-dependent antagonist effect of magnesium on the latency of NMDA-induced convulsions; this effect is similar to that seen after administration of the dizocilpine (MK-801) channel blocker. An anticonvulsant effect of Mg2+ treatment is also observed with strychnine-induced convulsions but not with bicuculline-, picrotoxin-, or pentylenetetrazol-induced convulsions. In the forced swimming test, Mg2+ salts reduce the immobility time in a way similar to imipramine and thus resemble the antidepressant-like activity of MK-801. This activity is masked at high doses of magnesium by a myorelaxant effect that is comparable to MK-801-induced ataxia. Potentiation of yohimbine fatal toxicity is another test commonly used to evaluate putative antidepressant drugs. Administration of Mg2+ salts, like administration of imipramine strongly potentiates yohimbine lethality in contrast to MK-801, which is only poorly active in this test. Neither Mg2+ nor MK-801 treatment can prevent reserpine-induced hypothermia. These data demonstrate that oral administration of magnesium to normal animals can antagonize NMDA-mediated responses and lead to antidepressant-like effects that are comparable to those of MK-801. This important regulatory role of Mg2+ in the central nervous system needs further investigation to evaluate the potential therapeutic advantages of magnesium supplementation in psychiatric disorders.
Evidence for Mg/Ca levels changing in amphetamine treatment. In Vivo.
Quote:
Effect of dextroamphetamine and methylphenidate on calcium and magnesium concentration in hyperactive boys.

Schmidt ME, Kruesi MJ, Elia J, Borcherding BG, Elin RJ, Hosseini JM, McFarlin KE, Hamburger S.
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892, USA.
Levels of calcium in plasma, red blood cells, and mononuclear blood cells, levels of calcium in plasma, and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind, placebo-controlled study of methylphenidate and dextroamphetamine in hyperactive boys. Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment, and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition. There was no change in magnesium levels in red blood cells or mononuclear blood cells. These measures were obtained 30 minutes before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m., 11:00 a.m., and noon on the last day of each 3-week phase. Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug x time interaction. Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy, the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use.
as I said earlier in another thread. Memantine and the other non-selective NMDA inhibitors are potentially better alternatives. The problem is aquiriing them legally and the price. The gray area is ordering it from a international pharmacy online (drugbuyers.com for legit ones) as they are not scheduled pharmaceuticals. there would be no huge inquisition with importing a personal amount. still the psychiatric side-effects as noted above are a factor and you should talk to your doctor about it.
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Old 03-26-08, 05:44 PM
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Re: Memantine: The Solution to my Adderall Tolerance

Quote:
Originally Posted by variance
Evidence for Mg/Ca levels changing in amphetamine treatment. In Vivo.
Quote:
Effect of dextroamphetamine and methylphenidate on calcium and magnesium concentration in hyperactive boys.

Schmidt ME, Kruesi MJ, Elia J, Borcherding BG, Elin RJ, Hosseini JM, McFarlin KE, Hamburger S.
Section on Clinical Pharmacology, National Institute of Mental Health, Bethesda, MD 20892, USA.
Levels of calcium in plasma, red blood cells, and mononuclear blood cells, levels of calcium in plasma, and the plasma calcium-to-magnesium ratio were measured at baseline and after 3 weeks of each drug phase of a double-blind, placebo-controlled study of methylphenidate and dextroamphetamine in hyperactive boys. Levels of magnesium in plasma were significantly higher after 3 weeks of dextroamphetamine treatment, and the calcium-to-magnesium ratio was significantly lower after 3 weeks of either drug compared with the baseline or placebo condition. There was no change in magnesium levels in red blood cells or mononuclear blood cells. These measures were obtained 30 minutes before the morning dose and at 9 a.m., 9:30 a.m., 10:30 a.m., 11:00 a.m., and noon on the last day of each 3-week phase. Analysis of variance revealed a drug effect on plasma magnesium and on the calcium-to-magnesium ratio but no drug x time interaction. Although these changes were not correlated with the time course of acute symptomatic response to stimulant therapy, the decrease in the ratio may be relevant to side effects and treatment resistance associated with stimulant use.
Thanks for the sources. I was aware that Magnesium was an NMDA antagonist and I've seen threads on the bluelight forums that suggest that an NMDA antagonist could prevent tolerance to amphetamines. I haven't seen any studies on this, however.

I agree that Magnesium supplementation may help alleviate some side affects, but I don't see anything talking about tolerance in particular. Am I missing something?
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Old 03-26-08, 09:30 PM
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Re: Memantine: The Solution to my Adderall Tolerance

Quote:
Originally Posted by despirit View Post
Thanks for the sources. I was aware that Magnesium was an NMDA antagonist and I've seen threads on the bluelight forums that suggest that an NMDA antagonist could prevent tolerance to amphetamines. I haven't seen any studies on this, however.

I agree that Magnesium supplementation may help alleviate some side affects, but I don't see anything talking about tolerance in particular. Am I missing something?
Forgive me, I ASSumed you were looking for sources with regards to Mg being a NMDA antagonist...

I'll might have attributed the Magnesium tolerance reduction/prevention to something I read about NMDA antagonists in general rather than Magnesium itself...in which I'll have to restate my claim that Mg due to its role as a nmda antagonist may prevent/reduce tolerance and there is evidence demonstrating its neuroprotective qualities with amphetamine.


I wasn't able to find anything specific on Mg and Amphetamine Tolerance (no funding for it I guess) but plenty on Pharma NMDA antagonists and tolerance reduction / increasing sensitivity... but then again I only had time to hit up pubmed. Haven't had the time to do a particularly thorough search.

Still evidence is fairly conclusive that NMDA antagonists play a neuroprotective role and reduce tolerance/increase sensitivity to amphetamines.

Quote:
Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801.

Karler R, Calder LD, Chaudhry IA, Turkanis SA.
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132.
"Reverse tolerance" was produced in rats and mice by repeated exposure to either cocaine or amphetamine. The locomotorstimulant effect was studied in mice; stereotypy and convulsions in rats. MK-801, the NMDA antagonist, blocked the development of "reverse tolerance" to all three effects. In contrast, haloperidol selectively blocked "reverse tolerance" to cocaine-induced stereotypy but not to convulsions. The data suggest that the glutamate system participates in the mechanism of "reverse tolerance" to the dopaminergic effects of cocaine and amphetamine, as well as to the convulsant effect of cocaine.
PMID: 2671566 [PubMed - indexed for MEDLINE]
Not NMDA related... tolerance related and interesting.
oxytocin is a fascinating hormone/neurotransmitter

Quote:
Role of oxytocin in the neuroadaptation to drugs of abuse.

Sarnyai Z, Kovács GL.
Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, Belmont, MA 02178, USA.
Oxytocin (OXT), a neurohypophyseal hormone, has a wide range of behavioral effects outside its classic peripheral endocrine functions. OXT involvement in adaptive central nervous system processes has been demonstrated as an inhibitory, amnestic action on learning and memory in different paradigms. Because adaptation and learning are likely to be involved in the neural events leading to drug tolerance and dependence, the question logically arose whether OXT is able to influence the development of tolerance of and dependence on abused drugs. In this review, we summarize our results on the effects of OXT on opiate (including morphine, heroin, and the endogenous opiates beta-endorphin and enkephalin) tolerance and dependence, heroin self-administration, psychostimulant-induced behavioral changes, and behavioral tolerance and sensitization. The sites and mechanisms of action and the possible physiological role of OXT are also discussed. In the first part of this review the effects of exogenously administered OXT on both the acute and chronic behavioral effects of opiates and psychostimulants have been summarized. OXT inhibited the development of tolerance to morphine, heroin, beta-endorphin, and enkephalin, OXT also inhibited the development of cross-tolerance between the predominantly mu-agonist heroin and the predominantly delta-agonist enkephalin in mice. Naloxone-precipitated morphine withdrawal syndrome was also attenuated by OXT. Heroin self-administration was decreased by OXT administration in heroin-tolerant rats. OXT inhibited cocaine-induced exploratory activity, locomotor hyperactivity, and stereotyped behavior in rats and in mice. Behavioral tolerance to cocaine was also attenuated by OXT. On the contrary, OXT stimulated the development of behavioral sensitization to cocaine. OXT did not alter the stereotyped behavior induced by amphetamine. In the second series of experiments, the sites of action of OXT on drug-related behavior were investigated. Intracerebro-ventricular (ICV) and intracerebral (IC) administration of an OXT-receptor antagonist inhibited the effects of peripherally administered OXT on morphine tolerance, heroin self-administration, and cocaine-induced sniffing behavior. This suggests the central, intracerebral location of OXT target sites. Local IC microinjection of OXT in physiological doses into the posterior olfactory nucleus, tuberculum olfactorium, nucleus accumbens, central amygdaloid nucleus, and the hippocampus inhibited the development of tolerance to and dependence on morphine as well as cocaine-induced sniffing behavior and tolerance to cocaine. The physiological role of endogenous OXT in acute morphine tolerance has also been demonstrated, since OXT antiserum (ICV) and OXT-receptor antagonist (injected into the basal forebrain structures) potentiated the development of morphine tolerance. Finally, we investigated the possible mechanisms of action of OXT on drug related behavior. Both morphine tolerance and dependence, and cocaine administration, increased dopamine utilization in the mesencephalon and in the nucleus accumbens, respectively. OXT treatment decreased the alpha-methylparatyrosine-induced dopamine utilization in the mesencephalon and in the nucleus accumbens-septal complex. Chronic OXT treatment decreased the number of apparent binding sites of dopamine in the basal forebrain area. It also inhibited a cocaine-induced increase in dopamine utilization in the nucleus accumbens, but not in the striatum. In light of this information, it appears that OXT inhibits the development of opiate tolerance, dependence, and self-administration as well as the acute behavioral actions of and chronic tolerance to cocaine. This suggests the possible role of this neuropeptide in the regulation of drug abuse. Therefore, OXT may act as a neuromodulator on dopaminergic neurotransmission in limbic-basal forebrain structures to regulate adaptive CNS processes leading to drug addiction.
PMID: 9210215 [PubMed - indexed for MEDLINE]
Quote:
Effects of blockade of NMDA receptors and NO synthase on the expression of associative and non-associative sensitization to effects of cocaine.

Grönig M, Atalla A, Kuschinsky K.
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Ketzerbach 63, DE-35032 Marburg, Germany.
After repeated administration of psychostimulant drugs, a sensitization rather than a tolerance to the behavioral effects can be observed. In our own previous studies, it was shown that both blockade of NMDA glutamate receptors and inhibition of NO synthase selectively inhibited the expression of associative but not non-associative sensitization to D-amphetamine. The present experiments were performed in order to study whether a similar selective inhibition of expression of associative sensitization to cocaine can be observed after blockade of NMDA receptors by MK-801 or inhibition of NO synthase by L-NAME. MK-801 as well as L-NAME inhibited the locomotor activity in acutely cocaine-treated rats. Both drugs did not prevent the sensitization either in the associative or the non-associative group. The results suggest that the acute locomotor effects of cocaine were inhibited by both drugs whereas both the non-associative and the associative sensitization to locomotor effects were not inhibited by blockade of NMDA receptors or inhibition of NO synthase. Accordingly, the expression of neither type of sensitization to cocaine was inhibited by any of these drugs. Copyright (c) 2006 S. Karger AG, Basel.
PMID: 16837778 [PubMed - indexed for MEDLINE]
Quote:
Calcium channel antagonists suppress cross-tolerance to the anxiogenic effects of D-amphetamine and nicotine in the mouse elevated plus maze test.

Biala G, Kruk M.
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4 Staszica Street, 20-081 Lublin, Poland. grazyna.biala@am.lublin.pl
The purpose of the current experiments was to examine the anxiety-related effects of repeated amphetamine and nicotine administration using the mouse elevated plus maze (EPM). d-amphetamine was administered daily for 8 days (2 mg/kg, i.p.). On the 9th day, mice were challenged with amphetamine (2 mg/kg, i.p.) or nicotine (0.1 mg/kg, s.c.), and were tested 30 min after this last injection. Additionally, a distinct group of mice was pretreated with nicotine (0.1 mg/kg, s.c., 6 days). These mice were subjected to nicotine (0.1 mg/kg, s.c.) or amphetamine (2 mg/kg, i.p.) challenge on the seventh day to see if full crossover effects developed after the pretreatment of both psychostimulant drugs. Moreover, the L-type voltage-dependent calcium channel antagonists nimodipine (5 and 10 mg/kg, i.p.), flunarizine (5 and 10 mg/kg, i.p.), verapamil (5 and 10 mg/kg, i.p.) and diltiazem (5 and 10 mg/kg, i.p.) were injected prior to each injection of chronic d-amphetamine or nicotine. We observed cross-tolerance to the anxiogenic effects of d-amphetamine and nicotine that was blunted by a pretreatment with calcium channel blockers. Overall our findings imply that similar neural calcium-dependent mechanisms are involved in the anxiety-related responses to chronic amphetamine and nicotine injections. As anxiety seems to be an important factor for the development of psychostimulant dependence, the L-type VDCC antagonists can offer an interesting approach for the pharmacotherapy of addiction, including amphetamine and/or nicotine dependence.
More of the same:
Quote:
Amphetamine-induced anxiety-related behavior in animal models.


Biała G, Kruk M. Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Staszica 4, PL 20-081 Lublin, Poland. grazyna.biala@am.lublin.pl.
The purpose of this study was to examine the anxiety-related effects of acute and repeated amphetamine administration using the elevated plus maze (EPM) and light/dark box tests in mice. D-amphetamine (2 mg/kg ip, 30 min after injection) had a significant anxiogenic effect only in the EPM test, as shown by specific decreases in the percentage of time spent in the open arms as well as in the percentage of open arm entries. Tolerance to this anxiogenic action developed after 8 days of daily d-amphetamine administration (2 mg/kg, ip). An anxiolytic effect was observed after the ninth injection, i.e. there were specific increases in the percentage of time spent in the open arms and in the percentage of open arm entries. L-type voltage-dependent calcium channel antagonists: nimodipine (5, 10 and 20 mg/kg, ip), flunarizine (5, 10 and 20 mg/kg, ip), verapamil (5, 10 and 20 mg/kg, ip), and diltiazem (5, 10 and 20 mg/kg, ip) were also injected prior to an acute low dose of d-amphetamine or to each injection of subchronic d-amphetamine. Our results revealed that calcium channel blockers dose-dependently attenuated both an anxiogenic effect of d-amphetamine and the development of tolerance to this effect. Our results suggest that neural calcium-dependent mechanisms are involved in the anxiety-related responses to acute and subchronic amphetamine injection that may lead to addiction relapse in human users.
Quote:
Comparative effects of NO-synthase inhibitor and NMDA antagonist on generation of nitric oxide and release of amino acids and acetylcholine in the rat brain elicited by amphetamine neurotoxicity.

Bashkatova V, Kraus MM, Vanin A, Hornick A, Prast H.
Institute of Pharmacology, Russian Academy of Medical Sciences, 125315, Moscow, Russia. bashkatovav@yahoo.com
The aim of this study was to clarify the role of nitric oxide (NO) and lipid peroxidation (LPO) processes as well as the contribution of various neurotransmitters in pathophysiological mechanisms of neurotoxicity induced by amphetamine (AMPH). NO level was determined directly in brain tissues using electron paramagnetic resonance spectroscopy technique. The content of the products of lipid peroxidation (LPO) was measured spectrophotometrically as thiobarbituric acid reactive species (TBARS). The output of neurotransmitter amino acids (glutamate, aspartate, and GABA) and acetylcholine (ACH) was monitored in nucleus accumbens (NAc) by push-pull technique with HPLC detection. Repeated, systemic application of AMPH elevated striatal and cortical NO generation and LPO production. Moreover, administration of AMPH led to a marked and long-lasting increase of ACH release. Surprisingly, while glutamate output was not affected, aspartate release was enhanced 30 to 50 min after each AMPH injection. The release rate of GABA was also elevated. The selective NO-synthase inhibitor 7-nitroindazole (7-NI) was highly effective in abating the rise in the neurotransmitter release induced by the AMPH. The NOS inhibitor also abolished the increase of NO generation produced by AMPH, but did not influence the intensity of LPO elicited by the AMPH administration. Pretreatment with the noncompetitive NMDA receptor antagonist dizocilpine (MK-801) completely prevented increase of NO generation and TBARS formation induced by multiple doses of AMPH. Dizocilpine also abolished the effect of the psychostimulant drug on the release of neurotransmitters ACH, glutamate, aspartate, and GABA in the NAc. Our findings suggest a key role of NO in AMPH-induced transmitter release, but not in the formation of LPO products. It appears that AMPH enhances release of ACH and neurotransmitter amino acids through increased NO synthesis and induces neurotoxicity via NO and also by NO-independent LPO.
PMID: 15542720 [PubMed - indexed for MEDLINE]


I'll find some regarding tolerance.

as for that one site...
Bluelight is a interesting place to find some interesting claims, unintended effects of pharmas, anecdotal evidence, and drug/medical studies that are usually obscure and hard to find. and there are some actual legit academics there, unfortunately they are all drowned out loudly by the nature of the site and the objective of the majority of the people there. (extreme hedonism and experiments with very little concern for their health.).

I can see the appeal of it.. but I've always been more about objective quality of life/efficiency improvements and life extension via nutrition, supplements, exercise and pharmaceuticals. still a interesting resource
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Old 03-27-08, 12:15 AM
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Re: Memantine: The Solution to my Adderall Tolerance

Interesting, I'm all about subjective quality of life/aesthetic/psychological improvements while stile caring a great deal about life extension and nutrition, suppliments, exercise, and pharmaceuticals.
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Old 03-27-08, 12:40 PM
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Re: Memantine: The Solution to my Adderall Tolerance

In reference to:
Quote:
Blockade of "reverse tolerance" to cocaine and amphetamine by MK-801.

Karler R, Calder LD, Chaudhry IA, Turkanis SA.
Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132.
"Reverse tolerance" was produced in rats and mice by repeated exposure to either cocaine or amphetamine. The locomotorstimulant effect was studied in mice; stereotypy and convulsions in rats. MK-801, the NMDA antagonist, blocked the development of "reverse tolerance" to all three effects. In contrast, haloperidol selectively blocked "reverse tolerance" to cocaine-induced stereotypy but not to convulsions. The data suggest that the glutamate system participates in the mechanism of "reverse tolerance" to the dopaminergic effects of cocaine and amphetamine, as well as to the convulsant effect of cocaine.
PMID: 2671566 [PubMed - indexed for MEDLINE]
I found these two abstracts on PubMed:
Quote:
Chronic amphetamine: tolerance and reverse tolerance reflect different behavioral actions of the drug.

Leith NJ, Kuczenski R.
Chronic administration of amphetamine (AMPH) has been reported to produce tolerance to the drug's behavioral effects in some paradigms (self-stimulation, discriminative stimulus, self-administration) and an enhanced effect or reverse tolerance when other behaviors are monitored (locomotor activity, stereotypy). The present study investigated whether the two phenomena are, in fact, related to the particular behavior monitored or reflect the marked differences in the injection regimens (1X vs. 3X daily injections) used to produce the phenomena. The effects of chronic AMPH administered once or three times daily on AMPH facilitation of self-stimulation responding and on the locomotor stimulant and stereotypy-producing effects of the drug were assessed. Regardless of the injection regimen used, chronic AMPH resulted in an enhancement of the locomotor stimulant effects of the drug as well as a more rapid onset and greater intensity of the stereotypy produced. In the self-stimulation paradigm, only the 3X daily regimen significantly reduced the effectiveness of a challenge dose of AMPH (tolerance), although the 1X regimen produced effects that were qualitatively similar but quantitatively less. Perhaps behavioral tasks in which tolerance develops reflect the mood-altering properties of the drug in humans whereas a process similar to reverse tolerance may underlie the increased susceptibility to psychoses elicited by the drug with repeated use.
PMID: 7291243 [PubMed - indexed for MEDLINE]
Quote:
Characteristics of "reverse tolerance" to amphetamine-induced locomotor stimulation in mice.
Chaudhry IA, Turkanis SA, Karler R.

Department of Pharmacology, University of Utah School of Medicine, Salt Lake City 84132.

The characteristics of chronically administered amphetamine on the locomotor and anticonvulsant effects were studied in adult CF-1 mice. The influence of dose of the drug and interdose interval on the development of "reverse tolerance" to the locomotor stimulation was investigated, in addition to the selectivity of the response and the persistence of the change in pharmacodynamics. Once-daily treatment with 6 mg/kg amphetamine for 4 weeks resulted in a 2-3 fold increase in locomotor activity. The increase in responsiveness, however, was limited to the first period of 2 weeks and there was no subsequent change in pharmacodynamics during the last 2 weeks of treatment. After 36 days of withdrawal, the response had not returned to that of control, illustrating the persistence of the effect. The results of varying the interdose interval indicated that "reverse tolerance" occurred even when the interval was as long as 14 days. These results represent additional evidence of the persistence of the phenomenon. Selectivity of the changes in the CNS was illustrated by the cross-reactivity with a motor-stimulant dose of cocaine but not with that of morphine. Selectivity was also demonstrated by the failure of "reverse tolerance" to develop to the anticonvulsant effects of amphetamine, which also appear to be mediated dopaminergically.

PMID: 3216957 [PubMed - indexed for MEDLINE]
I'm having a hard time wrapping my brain around what "reverse tolerance" or "sensitization" is, or how it applies to human models specifically. It seems like it's qualitatively different than normal "tolerance" though.
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Old 03-27-08, 12:47 PM
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Re: Memantine: The Solution to my Adderall Tolerance

This thread prompted me to speak to my physician about this possibility, I just returned from his office where there was a conveniently placed tissue holder with this drug listed on it as Namenda® and he thought it was an interesting prospect and said he would do some research on it before he felt comfortable prescribing it. I referred him to your post here so he could see your experience, he knows of this board and thinks it is a great resource for us. (He also has ADHD) Excellent information...
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Old 03-27-08, 11:26 PM
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Re: Memantine: The Solution to my Adderall Tolerance

I think anything that increases potency will increase your tolerance. The only thing I can imagine making someone less tolerant would be taking less or making it somehow less potent.
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Old 03-28-08, 01:29 AM
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Re: Memantine: The Solution to my Adderall Tolerance

I remember on an aspergers site a person mentioned they had some great results from memantine.

http://www.wrongplanet.net/postt24213.html
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