This is an unofficial archive of PsychonautWiki as of 2025-08-11T15:14:44Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
Memantine is a moderate-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors.<ref>Parsons, C. G., Rammes, G., & Danysz, W. (2008). Pharmacodynamics of memantine: an update. Current neuropharmacology, 6(1), 55-78. - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645549/?report=classic</ref>
Memantine is a moderate-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors.<ref>{{cite journal | vauthors=((Rammes, G.)), ((Danysz, W.)), ((Parsons, C. G.)) | journal=Current Neuropharmacology | title=Pharmacodynamics of Memantine: An Update | volume=6 | issue=1 | pages=55–78 | date= March 2008 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2645549/ | issn=1570-159X | doi=10.2174/157015908783769671}}</ref>
NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “[[Visual_disconnection#Holes.2C_spaces_and_voids|hole]]”.
NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “[[Visual_disconnection#Holes.2C_spaces_and_voids|hole]]”.
Memantine acts as a non-competitive antagonist at the 5-HT<sub>3</sub> receptor, with a potency similar to that for the NMDA receptor.<ref>The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner. | https://www.ncbi.nlm.nih.gov/pubmed/11403963</ref>
Memantine acts as a non-competitive antagonist at the 5-HT<sub>3</sub> receptor, with a potency similar to that for the NMDA receptor.<ref>{{cite journal | vauthors=((Rammes, G.)), ((Rupprecht, R.)), ((Ferrari, U.)), ((Zieglgänsberger, W.)), ((Parsons, C. G.)) | journal=Neuroscience Letters | title=The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner | volume=306 | issue=1–2 | pages=81–84 | date=22 June 2001 | issn=0304-3940 | doi=10.1016/s0304-3940(01)01872-9}}</ref>
Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies possibly similar to the NMDA and 5-HT3 receptors, but this is difficult to ascertain with accuracy because of the rapid desensitization of nAChR responses.
Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies possibly similar to the NMDA and 5-HT3 receptors, but this is difficult to ascertain with accuracy because of the rapid desensitization of nAChR responses.
Alpha-7 nAChR upregulates quickly in response to antagonism, which could explain the cognitive-enhancing effects of chronic memantine treatment.<ref>Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons. | https://www.ncbi.nlm.nih.gov/pubmed/15522999</ref>
Alpha-7 nAChR upregulates quickly in response to antagonism, which could explain the cognitive-enhancing effects of chronic memantine treatment.<ref>{{cite journal | vauthors=((Aracava, Y.)), ((Pereira, E. F. R.)), ((Maelicke, A.)), ((Albuquerque, E. X.)) | journal=The Journal of Pharmacology and Experimental Therapeutics | title=Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons | volume=312 | issue=3 | pages=1195–1205 | date= March 2005 | issn=0022-3565 | doi=10.1124/jpet.104.077172}}</ref>
Memantine acts as an agonist at the dopamine D<sub>2</sub> receptor with equal or slightly higher affinity than to the NMDA receptors.<ref>Memantine agonist action at dopamine D2High receptors. | https://www.ncbi.nlm.nih.gov/pubmed/18000814</ref>
Memantine acts as an agonist at the dopamine D<sub>2</sub> receptor with equal or slightly higher affinity than to the NMDA receptors.<ref>{{cite journal | vauthors=((Seeman, P.)), ((Caruso, C.)), ((Lasaga, M.)) | journal=Synapse (New York, N.Y.) | title=Memantine agonist action at dopamine D2High receptors | volume=62 | issue=2 | pages=149–153 | date= February 2008 | issn=0887-4476 | doi=10.1002/syn.20472}}</ref>
====='''Sigmaergic (σ1 receptor)'''=====
====='''Sigmaergic (σ1 receptor)'''=====
It acts as an agonist at the σ1 receptor with a low K<sub>i</sub> of 2.6 µM.<ref>Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine. | https://www.ncbi.nlm.nih.gov/pubmed/15090047</ref> The effects of this activity are unclear (as the role of sigma receptors, in general, is not yet that well understood) and memantine is probably too weak at the sigma binding site to exhibit significant agonist effects, only exhibiting partial agonism or antagonism.
It acts as an agonist at the σ1 receptor with a low K<sub>i</sub> of 2.6 µM.<ref>{{cite journal | vauthors=((Peeters, M.)), ((Romieu, P.)), ((Maurice, T.)), ((Su, T.-P.)), ((Maloteaux, J.-M.)), ((Hermans, E.)) | journal=The European Journal of Neuroscience | title=Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine | volume=19 | issue=8 | pages=2212–2220 | date= April 2004 | issn=0953-816X | doi=10.1111/j.0953-816X.2004.03297.x}}</ref> The effects of this activity are unclear (as the role of sigma receptors, in general, is not yet that well understood) and memantine is probably too weak at the sigma binding site to exhibit significant agonist effects, only exhibiting partial agonism or antagonism.
==Subjective effects==
==Subjective effects==
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
{{effects/base
{{effects/base
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*'''[[Effect::Stimulation]]''' - Memantine is mildly stimulating in comparison to other dissociatives such as [[ketamine]], [[MXE]], or [[DCK]].
*'''[[Effect::Stimulation]]''' - Memantine is mildly stimulating in comparison to other dissociatives such as [[ketamine]], [[MXE]], or [[DCK]].
*'''[[Effect::Spontaneous bodily sensations]]''' - The memantine "body high" is a sharp, pleasurable tingling sensation which has a location specific to the hands, feet, and head.
*'''[[Effect::Spontaneous bodily sensations]]''' - The memantine "body high" is a sharp, pleasurable tingling sensation which has a location specific to the hands, feet, and head.
*'''[[Effect::Stamina enhancement]]'''
*'''[[Effect::Bodily control enhancement]]'''
*'''[[Effect::Cough suppression]]'''
*'''[[Effect::Cough suppression]]'''
*'''[[Effect::Headache]]'''
*'''[[Effect::Appetite suppression]]'''
*'''[[Effect::Decreased libido]]'''
*'''[[Effect::Decreased libido]]'''
*'''[[Effect::Dizziness]]'''
*'''[[Effect::Orgasm suppression]]'''
*'''[[Effect::Dizziness]]''' - At high doses, this can result in strong and often pleasurable perceptions, when the eyes are closed, that one's body is rapidly spinning horizontally.
*'''[[Effect::Changes in felt gravity]]'''
*'''[[Effect::Gustatory suppression]]'''
*'''[[Effect::Gustatory suppression]]'''
*'''[[Effect::Increased heart rate]]'''
*'''[[Effect::Increased heart rate]]'''
*'''[[Effect::Nausea]]''' - High doses of memantine can sometimes result in nausea and vomiting.
*'''[[Effect::Nausea]]''' - High doses of memantine can sometimes result in nausea and vomiting.
*'''[[Effect::Nausea suppression]]''' - Although its interactions with dopamine and glutamate receptors are capable of causing nausea, memantine's 5-HT3 antagonism tends to result in a much lower likelihood that vomiting or gastrointestinal distress will occur when compared to other dissociatives, such as [[ketamine]] or [[DXM]].
*'''[[Effect::Constipation]]'''
*'''[[Effect::Pain relief]]'''
*'''[[Effect::Perception of bodily lightness]]''' - This creates the sensation that the body is floating and has become entirely weightless. This effect is oddly stimulating and encourages physical activities at low to moderate dosages by making the body feel light and effortless to move.
*'''[[Effect::Perception of bodily lightness]]''' - This creates the sensation that the body is floating and has become entirely weightless. This effect is oddly stimulating and encourages physical activities at low to moderate dosages by making the body feel light and effortless to move.
*'''[[Effect::Physical autonomy]]'''
*'''[[Effect::Physical autonomy]]'''
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*'''[[Effect::Tactile suppression]]''' - This partially to entirely suppresses one's own sense of touch, creating feelings of numbness within the extremities. It is responsible for the anesthetic properties of this substance.
*'''[[Effect::Tactile suppression]]''' - This partially to entirely suppresses one's own sense of touch, creating feelings of numbness within the extremities. It is responsible for the anesthetic properties of this substance.
*'''[[Effect::Motor control loss]]''' - A loss of gross and fine motor control alongside of balance and coordination is prevalent within memantine and becomes especially strong at higher dosages. This means that one should be sitting down before the onset unless they are experienced in case of falling over and injuring oneself.
*'''[[Effect::Motor control loss]]''' - A loss of gross and fine motor control alongside of balance and coordination is prevalent within memantine and becomes especially strong at higher dosages. This means that one should be sitting down before the onset unless they are experienced in case of falling over and injuring oneself.
*'''[[Effect::Difficulty urinating]]''' - As with other NMDA antagonists, memantine is capable of causing both acute and chronic difficulties with urination, and may produce a numbing or painful sensation in the bladder and/or urinary tract in some users, especially with frequent usage of high dosages.
}}
}}
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*'''[[Effect::Acuity enhancement]]'''
*'''[[Effect::Acuity enhancement]]'''
*'''[[Effect::Colour enhancement]]'''
*'''[[Effect::Colour enhancement]]'''
*'''[[Effect::Optical sliding]]'''
====Suppression====
====Suppression====
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====Distortions====
====Distortions====
*'''[[Effect:Depth perception distortions]]'''
*'''[[Effect::Symmetrical texture repetition]]'''
*'''[[Effect::After images]]'''
*'''[[Effect::Brightness alteration]]'''
*'''[[Effect::Drifting]]'''
*'''[[Effect::Visual haze]]'''
*'''[[Effect::Depth perception distortions]]'''
*'''[[Effect::Perspective distortion]]'''
*'''[[Effect::Perspective distortion]]'''
*'''[[Effect::Environmental cubism]]'''
*'''[[Effect::Environmental cubism]]'''
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====[[Effect::Geometry]]====
====[[Effect::Geometry]]====
The visual geometry produced by memantine can be described as dark but sharp when compared to that of [[ketamine]] or [[DXM]]. It is unknown to what level the geometry memantine extends to. Memantine can be described as simplistic in complexity, abstract in style, synthetic in feel, structured in organization, dimly lit in lighting, multicoloured in scheme, flat in shading, soft in edges, both small and large in size, slow in speed, smooth in motion, equal in rounded and angular corners, immersive, in-depth, and progressive in intensity.
The visual geometry produced by memantine can be described as dark but sharp when compared to that of [[ketamine]] or [[DXM]]. It is unknown to what level the geometry memantine extends to. Memantine can be described as simplistic in complexity, abstract in style, synthetic in feel, structured in organization, dimly lit in lighting, multicoloured in scheme, flat in shading, soft in edges, both small and large in size, slow in speed, smooth in motion, equal in rounded and angular corners, immersive, in-depth, and progressive in intensity.
====Hallucinatory states====
Higher doses of memantine can produce a full range of high level hallucinatory states.These effects include:
*'''[[Effect::Machinescapes]]'''
*'''[[Effect::Internal hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - This effect can be comprehensively described through its [[Internal_hallucinations#Variations|variations]] as delirious in believability, fixed in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style.
*'''[[Effect::External hallucination]]''' (''[[effect::autonomous entities]]'') Even though this effect exists, it's not deliriant and believable unlike other [[dissociative]] and [[deliriant]] substances.
}}
}}
|{{effects/cognitive|
|{{effects/cognitive|
The cognitive effects of memantine is said to be more clear-headed but less euphoric when compared to [[ketamine]] or [[MXE]].
The cognitive effects of memantine is said to be more clear-headed but less euphoric when compared to [[ketamine]] or [[MXE]].
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*'''[[Effect::Creativity enhancement]]'''
*'''[[Effect::Creativity enhancement]]'''
*'''[[Effect::Depersonalization]]'''
*'''[[Effect::Depersonalization]]'''
*'''[[Effect::Déjà vu]]'''
*'''[[Effect::Derealization]]'''
*'''[[Effect::Derealization]]'''
*'''[[Effect::Disinhibition]]'''
*'''[[Effect::Disinhibition]]'''
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*'''[[Effect::Feelings of impending doom]]'''
*'''[[Effect::Feelings of impending doom]]'''
*'''[[Effect::Immersion enhancement]]'''
*'''[[Effect::Immersion enhancement]]'''
*'''[[Effect::Increased music appreciation]]'''
*'''[[Effect::Introspection]]'''
*'''[[Effect::Introspection]]'''
*'''[[Effect::Mania]]'''
*'''[[Effect::Mania]]'''
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*'''[[Effect::Thought deceleration]]
*'''[[Effect::Thought deceleration]]
*'''[[Effect::Time distortion]]'''
*'''[[Effect::Time distortion]]'''
*'''[[Effect::Motivation enhancement]]'''
}}
}}
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}}
}}
===Experience reports===
===Experience reports===
There are currently no anecdotal reports which describe the effects of this compound within our [[experience index]]. Additional experience reports can be found here:
Anecdotal reports which describe the effects of this compound within our [[experience index]] include:
{{Further|Research chemicals#Toxicity and harm potential}}
{{Further|Responsible use#Hallucinogens}}
The toxicity and long-term health effects of recreational memantine use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]], although up to 400mg has been tolerated.<ref>http://www.drugbank.ca/drugs/DB01043</ref> This is because memantine has very little history of recreational human usage.
The toxicity and long-term health effects of recreational memantine use do not seem to have been studied in any scientific context and the [[Toxicity::exact toxic dosage is unknown]], although up to 400mg has been tolerated.<ref>{{Citation | title=Memantine | url=https://go.drugbank.com/drugs/DB01043}}</ref> This is because memantine has very little history of recreational human usage.
Anecdotal evidence from people who have tried memantine within the community suggests that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.
Anecdotal evidence from people who have tried memantine within the community suggests that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). [https://www.google.com/ Independent research] should always be done to ensure that a combination of two or more substances is safe before consumption.
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*'''Australia:''' Memantine is S4, meaning it is available only with a prescription.{{citation needed}}
*'''Australia:''' Memantine is S4, meaning it is available only with a prescription.{{citation needed}}
*'''Germany:''' Memantine is a prescription medicine, according to Anlage 1 AMVV.<ref>https://www.gesetze-im-internet.de/amvv/BJNR363210005.html</ref>
*'''France:''' Memantine is a restricted prescription medicine<ref>{{Citation | title=Groupe générique - MEMANTINE (CHLORHYDRATE DE) 10 mg - EBIXA 10 mg, comprimé pelliculé - AXURA 10 mg, comprimé pelliculé - Base de données publique des médicaments | url=https://base-donnees-publique.medicaments.gouv.fr/afficheGroupeGene.php?idGrp=1119}}</ref>.
*'''Germany:''' Memantine is a prescription medicine, according to Anlage 1 AMVV.<ref>{{Citation | title=AMVV - Verordnung über die Verschreibungspflicht von Arzneimitteln | url=https://www.gesetze-im-internet.de/amvv/BJNR363210005.html}}</ref>
*'''Russia''': Memantine is only available through a prescription.{{citation needed}}
*'''Russia''': Memantine is only available through a prescription.{{citation needed}}
*'''Switzerland''': Memantine is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a prescription.{{citation needed}}
*'''Switzerland''': Memantine is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a prescription.{{citation needed}}
*'''United Kingdom:''' Memantine is a POM ('''p'''rescription-'''o'''nly '''m'''edicine).{{citation needed}}
*'''United Kingdom:''' Memantine is a POM ('''p'''rescription-'''o'''nly '''m'''edicine).{{citation needed}}
*'''United States:''' Memantine is only available through a prescription.{{citation needed}}
*'''United States:''' Memantine is only available through a prescription.{{citation needed}}
*'''China:''' Memantine is a prescription drug.{{citation needed}}
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Memantine is a dissociativesubstance of the adamantane class that produces long-lived dissociative effects when administered. It is a derivative of amantadine and is pharmacologically related to compounds like PCP, ketamine, and DXM, although its recreational use is comparatively rare.
Memantine was first synthesized by Eli Lilly and Company in 1968 as a potential agent to treat diabetes.[citation needed]
Memantine is classified as an NMDA receptor antagonist. This means it binds to and blocks the signaling of excitatory receptors in the central nervous system. These compounds induce a state known as "dissociative-anesthesia," which has a number of hallucinogenic attributes.
In medicine, memantine is used primarily in humans in the treatment of neurodegenerative diseases like Alzheimer's disease. It also has seen use as a nootropic for its cognitive-enhancing effects.
Memantine, or 3,5-dimethyladamantan-1-amine, is a man-made molecule classified as a substituted adamantane derivative. Its core structure is adamantane, a diamondoid of four interlocked cyclohexane rings in a stable 3-dimensional lattice conformation. Memantine is substituted with a methyl carbon at both R3 and R5; it contains an amine substitution at R1. Its name is derived from its structure; 3,5-dimethyladamantan-1-amine.
Memantine is a moderate-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors.[2]
NMDA receptors allow for electrical signals to pass between neurons in the brain and spinal column; for the signals to pass, the receptor must be open. Dissociatives close the NMDA receptors by blocking them. This disconnection of neurons leads to loss of feeling, difficulty moving, and eventually the famous “hole”.
Memantine is distinct from most other dissociatives due to its fast, voltage-dependent binding kinetics that allow for functional ionic transmission through the NMDA receptors unless in the presence of a large enough concentration of agonists, causing memantine to be more similar in pharmacodynamical profile at the NMDA receptor to endogenous magnesium than to other dissociatives. Memantine's unique pharmacological profile allows it to elicit neuroprotective properties at doses that lack strong amounts of impairment, making it useful in the treatment of neurodegenerative disorders.
Serotonergic (5-HT3 receptor)
Memantine acts as a non-competitive antagonist at the 5-HT3 receptor, with a potency similar to that for the NMDA receptor.[3]
Cholinergic (nicotinic acetylcholine receptor)
Memantine acts as a non-competitive antagonist at different neuronal nicotinic acetylcholine receptors (nAChRs) at potencies possibly similar to the NMDA and 5-HT3 receptors, but this is difficult to ascertain with accuracy because of the rapid desensitization of nAChR responses.
Alpha-7 nAChR upregulates quickly in response to antagonism, which could explain the cognitive-enhancing effects of chronic memantine treatment.[4]
Dopaminergic (D2 receptor)
Memantine acts as an agonist at the dopamine D2 receptor with equal or slightly higher affinity than to the NMDA receptors.[5]
Sigmaergic (σ1 receptor)
It acts as an agonist at the σ1 receptor with a low Ki of 2.6 µM.[6] The effects of this activity are unclear (as the role of sigma receptors, in general, is not yet that well understood) and memantine is probably too weak at the sigma binding site to exhibit significant agonist effects, only exhibiting partial agonism or antagonism.
Subjective effects
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWikicontributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
Physical effects
Memantine is more stimulating than ketamine or MXE but less so than PCP and its derivatives.
Stimulation - Memantine is mildly stimulating in comparison to other dissociatives such as ketamine, MXE, or DCK.
Spontaneous bodily sensations - The memantine "body high" is a sharp, pleasurable tingling sensation which has a location specific to the hands, feet, and head.
Dizziness - At high doses, this can result in strong and often pleasurable perceptions, when the eyes are closed, that one's body is rapidly spinning horizontally.
Nausea - High doses of memantine can sometimes result in nausea and vomiting.
Nausea suppression - Although its interactions with dopamine and glutamate receptors are capable of causing nausea, memantine's 5-HT3 antagonism tends to result in a much lower likelihood that vomiting or gastrointestinal distress will occur when compared to other dissociatives, such as ketamine or DXM.
Perception of bodily lightness - This creates the sensation that the body is floating and has become entirely weightless. This effect is oddly stimulating and encourages physical activities at low to moderate dosages by making the body feel light and effortless to move.
Physical euphoria - This results in feelings which range from mild pleasure to powerful, all-encompassing bliss.
Tactile suppression - This partially to entirely suppresses one's own sense of touch, creating feelings of numbness within the extremities. It is responsible for the anesthetic properties of this substance.
Motor control loss - A loss of gross and fine motor control alongside of balance and coordination is prevalent within memantine and becomes especially strong at higher dosages. This means that one should be sitting down before the onset unless they are experienced in case of falling over and injuring oneself.
Difficulty urinating - As with other NMDA antagonists, memantine is capable of causing both acute and chronic difficulties with urination, and may produce a numbing or painful sensation in the bladder and/or urinary tract in some users, especially with frequent usage of high dosages.
Pattern recognition suppression - This effect generally occurs at higher doses and makes the user unable to recognize and interpret perceivable visual data.
The visual geometry produced by memantine can be described as dark but sharp when compared to that of ketamine or DXM. It is unknown to what level the geometry memantine extends to. Memantine can be described as simplistic in complexity, abstract in style, synthetic in feel, structured in organization, dimly lit in lighting, multicoloured in scheme, flat in shading, soft in edges, both small and large in size, slow in speed, smooth in motion, equal in rounded and angular corners, immersive, in-depth, and progressive in intensity.
Hallucinatory states
Higher doses of memantine can produce a full range of high level hallucinatory states.These effects include:
Visual disconnection - This eventually results in memantine's equivalent to the ketamine "k-hole" or, more specifically, holes, spaces and voids alongside structures. However, many users may find it difficult or at least uncomfortable to reach this state due to the high dose required and associated side effects.
The toxicity and long-term health effects of recreational memantine use do not seem to have been studied in any scientific context and the exact toxic dosage is unknown, although up to 400mg has been tolerated.[7] This is because memantine has very little history of recreational human usage.
Anecdotal evidence from people who have tried memantine within the community suggests that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed). Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
Tolerance and addiction potential
The dependence potential for memantine is unknown. However, due to its long duration and long onset, users are discouraged to redose, meaning it is unlikely users will develop an addiction.
Memantine presents cross-tolerance with [[Cross-tolerance::all dissociatives]], meaning that after the consumption of memantine all dissociatives will have a reduced effect.
Dangerous interactions
Memantine has very limited information on drug combinations and should therefore be treated with extreme caution when combined with other drugs.
Warning:Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).
Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.
Stimulants - Both stimulants and dissociatives carry the risk of adverse psychological reactions like anxiety, mania, delusions and psychosis and these risks are exacerbated when the two substances are combined.
Depressants - Because both depress the respiratory system, this combination can result in an increased risk of suddenly falling unconscious, vomiting and choking to death from the resulting suffocation. If nausea or vomiting occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Other interactions
Cannabis - Cannabis is reported to increase the effects of memantine.
Nicotine - Anecdotal reports suggest an interaction between tobacco and memantine.
Opioids - Memantine is reported to increase the effects, prevent build up and in some cases reverse tolerance to opioids.
Stimulants - Memantine is reported to increase the effects, prevent build up and in some cases reverse tolerance to stimulants.
Alcohol - Memantine is reported to increase the effects, prevent build up and, in some cases, reverse tolerance to alcohol.
Lipton, S. A. (2006). Paradigm shift in neuroprotection by NMDA receptor blockade: Memantine and beyond. Nature Reviews Drug Discovery, 5(2), 160. https://doi.org/10.1038/nrd1958
Morris, H., & Wallach, J. (2014). From PCP to MXE: A comprehensive review of the non-medical use of dissociative drugs. Drug Testing and Analysis, 6(7–8), 614–632. https://doi.org/10.1002/dta.1620
References
↑Lee, S.-H., Kim, S.-H., Noh, Y.-H., Choi, B.-M., Noh, G.-J., Park, W.-D., Kim, E.-J., Cho, I.-H., Bae, C.-S. (February 2016). "Pharmacokinetics of Memantine after a Single and Multiple Dose of Oral and Patch Administration in Rats". Basic & Clinical Pharmacology & Toxicology. 118 (2): 122–127. doi:10.1111/bcpt.12479. ISSN1742-7843.
↑Rammes, G., Rupprecht, R., Ferrari, U., Zieglgänsberger, W., Parsons, C. G. (22 June 2001). "The N-methyl-D-aspartate receptor channel blockers memantine, MRZ 2/579 and other amino-alkyl-cyclohexanes antagonise 5-HT(3) receptor currents in cultured HEK-293 and N1E-115 cell systems in a non-competitive manner". Neuroscience Letters. 306 (1–2): 81–84. doi:10.1016/s0304-3940(01)01872-9. ISSN0304-3940.
↑Aracava, Y., Pereira, E. F. R., Maelicke, A., Albuquerque, E. X. (March 2005). "Memantine blocks alpha7* nicotinic acetylcholine receptors more potently than n-methyl-D-aspartate receptors in rat hippocampal neurons". The Journal of Pharmacology and Experimental Therapeutics. 312 (3): 1195–1205. doi:10.1124/jpet.104.077172. ISSN0022-3565.
↑Seeman, P., Caruso, C., Lasaga, M. (February 2008). "Memantine agonist action at dopamine D2High receptors". Synapse (New York, N.Y.). 62 (2): 149–153. doi:10.1002/syn.20472. ISSN0887-4476.
↑Peeters, M., Romieu, P., Maurice, T., Su, T.-P., Maloteaux, J.-M., Hermans, E. (April 2004). "Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine". The European Journal of Neuroscience. 19 (8): 2212–2220. doi:10.1111/j.0953-816X.2004.03297.x. ISSN0953-816X.
