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'''Memantine''' is a [[psychoactive substance]] of the [[Chemical class::adamantane]] chemical class that produces long-lived [[Psychoactive class::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''' is a [[dissociative]] [[psychoactive substance|substance]] of the [[Chemical class::adamantane]] chemical class that produces long-lived [[Psychoactive class::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 was first synthesized by Eli Lilly and Company in 1968 as a potential agent to treat diabetes.{{citation needed}}
It may contain incorrect information, particularly with respect to dosage, duration, subjective effects, toxicity and other risks. It may also not meet PW style and grammar standards.
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 chemical 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.
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.
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 physical sensations - The memantine "body high" is a sharp, pleasurable tingling sensation which has a location specific to the hands, feet, and head.
Nausea - High doses of memantine can sometimes result in nausea and vomiting.
Perception of decreased weight - 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.
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.
Cognitive effects
The cognitive effects of memantine is said to be more clear-headed but less euphoric when compared to ketamine or MXE.
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.[3] 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.
"[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] & "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - 25x compounds are highly stimulating and physically straining. Combinations with Memantine should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
"[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
"[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
"[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
"[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Memantine may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
"[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Tramadol is known to lower the seizure threshold[4] and combinations with stimulants may further increase this risk.
Other interactions
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.
↑Talaie, H.; Panahandeh, R.; Fayaznouri, M. R.; Asadi, Z.; Abdollahi, M. (2009). "Dose-independent occurrence of seizure with tramadol". Journal of Medical Toxicology. 5 (2): 63–67. doi:10.1007/BF03161089. eISSN1937-6995. ISSN1556-9039. OCLC163567183.
