Memantine as a neuroprotective, memory enhancing agent, and potentially effective adjunct to amphetamine, methylphenidate, and MDMA usage. Pharmakeus Follow Apr 23, 2015 · 6 min read

Memantine is an adamantane-amine structured uncompetitive NMDA antagonist that is approved for treatment for dementias such as moderate-to-severe Alzheimer’s disease. It has shown limited effectiveness in slowing the cognitive decline that occurs with the terribly degenerative disease of dementia. A disease that one will certainly die from and die with. However, memantine is an interesting substance in that it can be used for neuroprotective, nootropic, and tolerance reducing agent. Here is a sketch of some of the uses of memantine — I would spend more time writing a more in depth review but there are much more interesting and effective supplements and adjuncts for MDMA/Amphetamine protection that can certainly be discussed extensively if you ask me.

Before I continue here is the most comprehensive review of memantine that is probably publically accessible. If you are interested I recommend reading/skimming this:

Corroboration:

From Neuropharmacology, 1999

N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential in numerous CNS disorders ranging from acute neurodegeneration (e.g. stroke and trauma), chronic neurodegeneration (e.g. Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, ALS) to symptomatic treatment (e.g. epilepsy, Parkinson’s disease, drug dependence, depression, anxiety and chronic pain). However, many NMDA receptor antagonists also produce highly undesirable side effects at doses within their putative therapeutic range

See wikipedia for further links.

Hamilton Morris briefly discusses memantine in his extensive review of Non-medical use of Dissociatives:

Memantine substitutes for PCP or (+)-MK-801 in rats and monkeys drug discrimination paradigms. Full substitution occurred at relatively high doses that generally cause a reduction in re- s ponse rate. Likewise intravenous memantine an d amantadine serve a s a positive reinforcers in rhesus monkeys trained to self-administer PCP. [151] Isolated reports have been posted to websites s uch as www.erowid.org and the coun ter-culture magazine The Entheogen Review of human use at supra-therapeutic doses to induce dissociative effects, with users describing 100 mg oral doses of memantine and oral doses of amantadine in excess of 2 g. [152–154] Results from clinical studies support these reports of dissociative activity. [155,156] While many users described the effects as positive, neither compound has been widely used as a dissociative likely due to the long duration of action (over 40 h). Factors that may limit abuse-liability are discussed in greater detail in the future perspectives section. Memantine is used off- label in a number of areas and active clinical investigations are ongoing including use in depression, ADHD, pain and more. [157] Therapeutic doses (~10 mg) of memantine induced a mild altered state with cognitive stimulation and altered thought patterns with some parallels to low dose arylcyclohexylamines…

Assortment of studies and abstracts — a mildly delectable, multicourse menu based on the delights and dishonors of memantine:

Memantine prevents MDMA-induced neurotoxicity (Neurotoxicology, Volume 29, Issue 1, January 2008, Pages 179–183)

Abstract

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 μM)-induced reactive oxygen species (ROS) production that was fully inhibited by MEM (0.3 μM). This effect of MEM was fully prevented by PNU 282987 (0.5 μM), 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. [3H]Paroxetine binding (a marker of serotonergic injury) was measured in the hippocampus of animals killed at 24 h and 7 days after treatment. MDMA induced a significant reduction in [3H]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.

Memantine (3,5-Dimethyladamantan-1-amine)

Memantine Pharmacological Targets (see drugbank for more info):

It mainly acts as an uncompetitive antagonist of NMDA (3A, 2A and 2B [links to UniProt {Universal Protein Resource}] 5HT3a antagonist (weak affinity) Alpha-7-nicotinic cholinergic antagonist Dopamine (D2) agonist

Abstract The neurotransmitter glutamate activates several classes of metabotropic receptor and three major types of ionotropic receptor — α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate and N-methyl-d-aspartate (NMDA). The involvement of glutamate mediated neurotoxicity in the pathogenesis of Alzheimer’s disease (AD) is finding increasing scientific acceptance. Central to this hypothesis is the assumption that glutamate receptors, in particular of the NMDA type, are overactivated in a tonic rather than a phasic manner. Such continuous, mild, chronic activation ultimately leads to neuronal damage/death. Additionally, impairment of synaptic plasticity (learning) may result not only from neuronal damage per se but may also be a direct consequence of this continuous, non-contingent NMDA receptor activation. Complete NMDA receptor blockade has also been shown to impair neuronal plasticity, thus, both hypo- and hyperactivity of theglutamatergic system leads to dysfunction. Memantine received marketing authorization from the EMEA (European Medicines Agency) for the treatment of moderate to severe AD in Europe and was subsequently also approved by the FDA (Food and Drug Administration) for use in the same indication in the USA. Memantine is a moderate affinity, uncompetitive NMDA receptor antagonist with strong voltage-dependency and fast kinetics. This review summarizes existing hypotheses on the mechanism of action (MOA) of memantine in an attempt to understand how the accepted interaction with NMDA receptors could allow memantine to provide both neuroprotection and reverse deficits in learning/memory by the same MOA.

An additional dissociative study concerning the noble gas Xenon and N2O:

Nitrous Oxide and Xenon Prevent Amphetamine-Induced Carrier-Mediated Dopamine Release in a Memantine-Like Fashion and Protect Against Behavioral Sensitization

Background

Amphetamine administration induces stimulation-independent dopamine release in the nucleus accumbens(NAcc) through reverse dopamine transport, a critical neurochemical event involved in its psychostimulant action, and furthermore decreases stimulation-dependent vesicular dopamine release. These effects may involve possible indirect glutamatergic mechanisms.

Methods

We investigated the effects of nitrous oxide and xenon, which possess antagonistic action at the N-methyl-D-aspartate (NMDA) receptor, on brain slices ex vivo on amphetamine-induced changes in carrier-mediated and KCl-evoked dopamine release in the NAcc, and in vivo on amphetamine-induced locomotor sensitization.

Results

Like the low-affinity NMDA receptor antagonist memantine, but not the prototypical compound MK-801, nitrous oxide and xenon at appropriate concentrations blocked both the increase in carrier-mediated dopamine release and locomotor sensitization produced by amphetamine.

Conclusions

In contrast to what has generally been found using prototypical NMDA receptor antagonists, these data regarding the effect of memantine, nitrous oxide, and xenon support the hypothesis that activation of certain NMDA receptors (possibly those containing the NR1a/NR2D subunit) in the NAcc is involved in the amphetamine-induced increase in carrier-mediated dopamine release and the development of behavioral sensitization to amphetamine. Nitrous oxide, xenon, and memantine may be of therapeutic interest for treating drug dependence.

Memantine has many anecdotal reports throughout bluelight, longecity, reddit et al… reddit search query for memantine here.

Reported to help with issues as various as:

Tinnitus (helping or curing) Anxiety (moderate-severe) headaches opioid tolerance / dependence / withdrawal GABAergic upregulation [I am skeptical] tolerance to a variety of racetams, nootropics, stimulants (amphetamine, methylphenidate and such and such) enhancement of memory, recall, general cognition (although the famed maxim still holds the dose makes the poison. Memantine b mn kk,

Ceretropic is a reliable source for memantine.