At least to a certain extent.
Came across these on another forum in case you all havn't seen them. I'm sure you all know of/heard about Memantine's neuroprotective effects, but these three Spanish studies in rats highlight some specific neuroprotective properties that I was quite excited to read about/further verify. I wanted to share them.
I wish I knew the exact dosages they used or had the full texts.
Eur J Pharmacol. 2008 Jul 28;589(1-3):132-9. Epub 2008 May 20.
Memantine prevents the cognitive impairment induced by 3,4-methylenedioxymethamphetamine in rats.
Camarasa J, Marimˇn JM, Rodrigo T, Escubedo E, Pubill D.
Laboratory of Pharmacology and Pharmacognosy, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain. [email protected] <[email protected]>
Amphetamine abuse is an important risk factor for the development of cognitive impairment involving learning and memory. Since in previous studies we have demonstrated the effectiveness of alpha-7 nicotinic receptor antagonists in preventing the neurotoxicity induced by amphetamine derivatives, the present paper seeks to determine whether pre-treatment with memantine (MEM) (an antagonist of both nicotinic and NMDA receptors) counteracts the memory impairment induced by 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) administration in male Long Evans rats. In mice, MDMA and MEM induced a locomotor stimulant response but with a different profile. Moreover, MEM inhibited the rearing and thygmotaxis behaviour induced by MDMA. Non-spatial memory was tested in the object recognition test and the spatial learning and memory was tested in the Morris water maze. In our experimental conditions, rats receiving MEM pre-treatment recovered the ability to discriminate between the familiar and the novel object that had been abolished by MDMA treatment. Animals treated with MDMA showed impaired learning in the Morris water maze. Results of the probe trial demonstrated that MDMA-treated rats did not remember the location of the platform, but this memory impairment was also prevented by the MEM pre-treatment. Moreover, MEM alone improved the learning task. No differences were observed between the different groups as regards swim speed. In conclusion, MEM significantly improved the learning and memory impairment induced by MDMA and constitutes the first approach to the treatment of the long-term cognitive deficits found in ecstasy users.
PMID: 18582864 [PubMed - indexed for MEDLINE]
Edit: Just realized the experiment's conclusion in this was somewhat premature. They in the conclusion:
treatment of the long-term cognitive deficits
Not sure how they can conclude this would be a treatment for people who have used ecstasy many times in the past and experienced a cognitive deficit when they pre-treated the mice with Memantine before they ever even gave them MDMA.
They do, however, note that MEM did improve cognitive function alone, but that really shouldn't matter whether or not the user took MDMA many times in the past....unless (and this involves alot of Ex Dubio and mine's discussion way down below and some potential theories floating around the net about Memantine they are suggesting in the full text (which I have not read yet) that the cognitive deficit is due to a structural change in the alpha 7 nAChR such as downregulation or desensitization; if so, then perhaps Memantine's alpha 7 nAChR antagonism could fix or upregulate these receptors back to baseline levels and fix the cognitive deficit. However, I doubt they are suggesting this. And even then, its a somewhat unproven theory.
The Memantine could block some of the desired user effects of MDMA if co-administered with it although we don't know which ones in rats would translate into humans or how they would exactly.
Nonethless they do say that "MDMA and MEM induced a locomotor stimulant response but with a different profile" suggesting that the effects of MDMA were somehow changed or some of them were blocked/blunted. Additionally, Memantine has some stimulating effects of it's own due to its effected receptor profile and some of its specific potential dopamine receptor agonism (and the behavior has simply just been observed with rats treated with MEM alone). The abstract doesn't say what behaviors were observed in the MEM alone group; the full text may although I havn't had time to read it.
Neuropharmacology. 2008 Jun;54(8):1254-63. Epub 2008 Apr 9.
Memantine protects against amphetamine derivatives-induced neurotoxic damage in rodents.
Chipana C, Torres I, Camarasa J, Pubill D, Escubedo E.
Unitat de Farmacologia i Farmacogn˛sia, Facultat de FarmÓcia, Universitat de Barcelona, Avda Joan XXIII s/n, Zona Universitaria Pedralbes, 08028 Barcelona, Spain.
We hypothesize that 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH) interact with alpha-7 nicotinic receptors (nAChR). Here we examine whether memantine (MEM), an antagonist of NMDAR and alpha-7 nAChR, prevents MDMA and METH neurotoxicity. MEM prevented both serotonergic injury induced by MDMA in rat and dopaminergic lesion by METH in mice. MEM has a better protective effect in front of MDMA- and METH-induced neurotoxicity than methyllycaconitine (MLA), a specific alpha-7 nAChR antagonist. The double antagonism that MEM exerts on NMDA receptor and on alpha-7 nAChR, probably contributes to its effectiveness. MEM inhibited reactive oxygen species production induced by MDMA or METH in synaptosomes. This effect was not modified by NMDA receptor antagonists, but reversed by alpha-7 nAChR agonist (PNU 282987), demonstrating a preventive effect of MEM as a result of it blocking alpha-7 nAChR. In synaptosomes, MDMA decreased 5-HT uptake by about 40%. This decrease was prevented by MEM and by MLA but enhanced by PNU 282987. A similar pattern was observed when we measured the dopamine transport inhibited by METH. The inhibition of both transporters by amphetamine derivatives seems to be regulated by the calcium incorporation after activation of alpha-7 nAChR. MDMA competitively displaces [(3)H]MLA from rat brain membranes. MEM and METH also displace [(3)H]MLA with non-competitive displacement profiles that fit a two-site model. We conclude that MEM prevents MDMA and METH effects in rodents. MEM may offer neuroprotection against neurotoxicity induced by MDMA and METH by preventing the deleterious effects of these amphetamine derivatives on their respective transporters.
PMID: 18455739 [PubMed - indexed for MEDLINE]
Neurotoxicology. 2008 Jan;29(1):179-83. Epub 2007 Sep 22.
Memantine prevents MDMA-induced neurotoxicity.
Chipana C, Camarasa J, Pubill D, Escubedo E.
Unitat de Farmacologia i Farmacogn˛sia, Facultat de FarmÓcia, Nucli Universitari de Pedralbes, Universitat de Barcelona, Av. Joan XXIII s/n, 08028 Barcelona, Spain.
MDMA (ecstasy) is an illicit drug causing long-term neurotoxicity. Previous studies demonstrated the interaction of MDMA with alpha-7 nicotinic acetylcholine receptor (nAChR) in mouse brain membranes and the involvement of alpha-7 nicotinic acetylcholine receptors (nAChR) in dopaminergic neurotoxicity induced by MDMA in mice. The aim of the present study was to investigate the utility of memantine (MEM), an alpha-7 nAChR antagonist used for treatment of Alzheimer's disease patients, to prevent neurotoxicity induced by MDMA in rats and the oxidative effect of this amphetamine derivative in mice striatal synaptosomes. In isolated mouse striatal synaptosomes (an in vitro model of MDMA neurotoxicity of dopaminergic origin), MDMA (50 microM)-induced reactive oxygen species (ROS) production that was fully inhibited by MEM (0.3 microM). This effect of MEM was fully prevented by PNU 282987 (0.5 microM), a specific agonist of alpha-7 nAChR. The preventive effect of MEM on this oxidative effect can be attributed to a direct antagonism between MDMA (acting probably as agonist) and MEM (acting as antagonist) at the alpha-7 nAChR. In Dark Agouti rats (an in vivo model of MDMA neurotoxicity of serotonergic origin), a single dose of MDMA (18 mg/kg) induced persistent hyperthermia, which was not affected by MEM pre-treatment. [(3)H]Paroxetine binding (a marker of serotonergic injury) was measured in the hippocampus of animals killed at 24h and 7 days after treatment. MDMA induced a significant reduction in [(3)H]paroxetine binding sites at both times of sacrifice that was fully prevented by pre-treatment with MEM. Since previous studies demonstrate that increased glutamate activity is not involved in the neurotoxic action of MDMA, it can be concluded that the effectiveness of MEM against MDMA-induced neurotoxicity would be the result of blockade of alpha-7 nAChR, although an indirect mechanism based on the interplay among the various neurotransmission systems leading to an increase in basal acetylcholine release should also be taken into account.
PMID: 17980434 [PubMed - indexed for MEDLINE]
Wonder if the neuroprotective effect of Memantine blocks some of the beneficial affects of these drugs though. Personally, I have found on at least one or two occasions that taking 20mg Memantine about an hour before taking 40mg Adderall IR does tend to blunt the effects somewhat, although they are still noticeable; however, take into account that this was not a very controlled observation by me as I don't feel I have had enough experience combining these two medications.
I do remember Medieval saying something about that though.
Edit: (yes this is repeating what I said in at post way below) Got full text of these now. Have not read through them yet. If anyone else would like help in getting them, PM me. I may be able to provide some assistance