|Common names||Memantine, Memaxa, Ebixa, Namenda, Namenda XR, Namzaric (with donepezil, both extended-release)|
|Routes of Administration|
|Summary sheet: Memantine|
Memantine is a dissociative substance 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.
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.
Glutamatergic (NMDA receptor)
Memantine is a moderate-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors. 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.
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.
Dopaminergic (D2 receptor)
Memantine acts as an agonist at the dopamine D2 receptor with equal or slightly higher affinity than to the NMDA receptors.
Sigmaergic (σ1 receptor)
It acts as an agonist at the σ1 receptor with a low Ki of 2.6 µM. 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.
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 PsychonautWiki contributors. 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 ☠.
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.
- Stamina enhancement
- Bodily control enhancement
- Cough suppression
- Appetite suppression
- Decreased libido
- Orgasm suppression
- 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.
- Changes in felt gravity
- Gustatory suppression
- Increased heart rate
- 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.
- Pain relief
- 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 autonomy
- 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.
- Acuity suppression - In other words, this effect is the blurring or muddling of vision.
- Double vision - This component is prevalent at moderate to heavy doses and makes reading impossible unless the user closes one eye.
- Frame rate suppression
- Pattern recognition suppression - This effect generally occurs at higher doses and makes the user unable to recognize and interpret perceivable visual data.
- Symmetrical texture repetition
- After images
- Brightness alteration
- Visual haze
- Depth perception distortions
- Perspective distortion
- Environmental cubism
- Environmental orbism
- Scenery slicing
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.
Higher doses of memantine can produce a full range of high level hallucinatory states.These effects include:
- Internal hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - This effect can be comprehensively described through its variations as delirious in believability, fixed in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style.
- External hallucination (autonomous entities) Even though this affect exists, it's not deliriant and believable unlike other dissociative and deliriant substances.
The cognitive effects of memantine is said to be more clear-headed but less euphoric when compared to ketamine or MXE.
- Analysis suppression
- Anxiety suppression
- Cognitive euphoria
- Conceptual thinking
- Creativity enhancement
- Déjà vu
- Dream suppression
- Feelings of impending doom
- Immersion enhancement
- Memory suppression
- Personal meaning enhancement
- Thought deceleration
- Time distortion
- Physical disconnection
- 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.
- Cognitive disconnection
Anecdotal reports which describe the effects of this compound within our experience index include:
Additional experience reports can be found here:
Toxicity and harm potential
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. 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 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.
- 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.
This legality section is a stub.
As such, it may contain incomplete or wrong information. You can help by expanding it.
- Australia: Memantine is S4, meaning it is available only with a prescription.
- France: Memantine is a restricted prescription medicine.
- Germany: Memantine is a prescription medicine, according to Anlage 1 AMVV.
- Russia: Memantine is only available through a prescription.
- Switzerland: Memantine is listed as a "Abgabekategorie B" pharmaceutical, which generally requires a prescription.
- United Kingdom: Memantine is a POM (prescription-only medicine).
- United States: Memantine is only available through a prescription.
- 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
- 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
- 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
- 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
- Memantine agonist action at dopamine D2High receptors. | https://www.ncbi.nlm.nih.gov/pubmed/18000814
- Involvement of the sigma 1 receptor in the modulation of dopaminergic transmission by amantadine. | https://www.ncbi.nlm.nih.gov/pubmed/15090047