Medication used to treat Alzheimer's disease Memantine, sold under the brand name Namenda among others, is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth. Common side effects include headache, constipation, sleepiness, and dizziness. Severe

How long does Memantine last?

The total duration of Memantine via oral is 18 hours to 36 hours. Onset typically occurs within 30 minutes to 3 hours. Peak effects last 3 hours to 12 hours.

Memantine — SubstanceWiki

SubstanceWiki

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How It Feels

The most remarkable thing about Memantine is how long you must wait for it to speak. You take it and nothing happens. An hour passes. Two. You check whether you remembered to actually swallow the tablet. Three hours in, a faint, almost sub-perceptual shift begins to register — not a feeling, exactly, but the absence of a feeling, as though a thin layer of emotional static that you had never consciously noticed has been quietly switched off. The world looks the same. It sounds the same. But something in the way you relate to it has changed by a single, barely detectable degree.

Over the next several hours — and the timeline here is measured in hours the way most dissociatives measure minutes — the dissociation builds with geological patience. It never reaches the depths of ketamine or the architectural grandeur of MXE. Instead, it establishes a subtle, pervasive flatness: emotions are not eliminated but reduced, as though they are arriving through a compressor that clips the peaks and fills the valleys. You feel neither happy nor sad, neither anxious nor calm — just present, in a neutral, observational way that is almost robotic. Physical sensation is mildly dulled; the body feels slightly distant, as though enclosed in a thin, invisible membrane. Sound is unchanged but feels less engaging, less capable of provoking emotional response.

The peak, if it can be called that, is a broad plateau that may span six to twelve hours. It is remarkably undramatic. You can function normally — work, converse, navigate the world — but everything has a faint unreality to it, a sense of watching your own life on a screen that is slightly too far away. Closed-eye visuals are minimal or absent. Music sounds technically correct but emotionally flat, as though the performers are competent but uninspired. There is no euphoria, no insight, no sense of profundity. The compound simply removes a layer of engagement from experience and leaves you to observe what remains.

The return to baseline is almost imperceptible and extraordinarily slow. Twenty-four hours later you may still feel slightly off — not impaired, but flattened, as though the world has not quite regained its full color depth. Forty-eight hours and you are probably back, though it is difficult to pinpoint the exact moment when baseline returned. The experience leaves behind no afterglow, no residual insight, no sense of having been anywhere. It is the dissociative equivalent of watching paint dry — undeniably an alteration of consciousness, but one that challenges the very notion that alteration is inherently interesting.

Subjective Effects

The effects listed below are based on the Subjective Effect Index (SEI), an open research literature based on anecdotal reports and personal analyses. They should be viewed with a healthy degree of skepticism. 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.

Physical Effects

Physical(14)

Appetite suppression— A distinct decrease in hunger and desire to eat, ranging from reduced interest in food to complete d...
Changes in felt gravity— A distortion of one's proprioceptive sense of gravity in which the perceived direction of gravitatio...
Constipation— A slowing or cessation of bowel movements resulting in difficulty passing stool, commonly caused by ...
Cough suppression— A decreased desire and need to cough, medically known as antitussive action, which can also allow in...
Dizziness— A sensation of spinning, swaying, or lightheadedness that impairs balance and spatial orientation, o...
Headache— A painful sensation of pressure, throbbing, or aching in the head that can range from a dull backgro...
Increased heart rate— A noticeable acceleration of heartbeat that can range from a subtle awareness of one's pulse to a fo...
Motor control loss— A distinct decrease in the ability to control one's physical body with precision, balance, and coord...
Nausea— An uncomfortable sensation of queasiness and stomach discomfort that may or may not lead to vomiting...
Pain relief— A suppression of negative physical sensations such as aches and pains, ranging from dulled awareness...
Physical disconnection— A perceptual distancing from one's own physical body that ranges from a subtle sense of numbness or ...
Physical euphoria— An intensely pleasurable bodily sensation that can manifest as waves of warmth, tingling electricity...
Respiratory depression— A dangerous slowing and shallowing of breathing that can progress from barely noticeable reductions ...
Stimulation— A state of heightened physical and mental energy characterized by increased wakefulness, elevated mo...

Tactile(1)

Tactile suppression— A progressive decrease in the ability to feel physical touch, ranging from mild numbness to complete...

Cognitive & Perceptual Effects

Visual(14)

After images— A visual phenomenon in which a faint, ghostly imprint of a previously viewed image persists in the v...
Brightness alteration— Perceived increase or decrease in environmental brightness beyond actual illumination levels, common...
Colour enhancement— An intensification of the brightness, vividness, and saturation of colors in the external environmen...
Depth perception distortions— Alterations in how the distance of objects within the visual field is perceived, causing layers of s...
Double vision— The visual experience of seeing a single object as two separate, overlapping images, similar to cros...
Drifting— The visual experience of perceiving stationary objects, textures, and surfaces as appearing to flow,...

Pharmacology

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.

The toxicity and long-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. -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-all dissociatives, meaning that after the consumption of memantine all dissociatives will have a reduced effect.

Memantine has very limited information on drug combinations and should therefore be treated with extreme caution when combined with other drugs.

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.
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-onlymedicine).
United States:** Memantine is only available through a prescription.
China:** Memantine is a prescription drug.
Responsible use
Hallucinogen
Dissociative
Ketamine
Memantine (Wikipedia)
Memantine (Erowid Vault)
Memantine (Isomer Design)
Memantine (Drugs.com)
Memantine (Drugs-Forum)
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

Detection Methods

Standard Drug Panel Inclusion

Memantine is NOT included on any standard drug screening panel. It is an NMDA receptor antagonist prescribed for moderate to severe Alzheimer's disease and is not classified as a substance of abuse. No immunoassay-based detection method targets memantine. Standard 5-panel, 10-panel, and extended panels will not detect this compound. Memantine does not cross-react with PCP, ketamine, or any other dissociative immunoassay.

Urine Detection

Memantine is primarily excreted unchanged in the urine, with approximately 48 percent of a dose recovered as parent compound. The exceptionally long half-life of 60 to 80 hours results in extended urine detection windows of 7 to 14 days after a single dose. In patients on chronic memantine therapy, urinary detection may persist for 2 to 3 weeks after discontinuation. The high proportion of unchanged drug in urine facilitates detection when specifically targeted by LC-MS/MS methods.

Blood and Serum Detection

Blood detection windows extend to 5 to 10 days due to the long half-life. Therapeutic plasma concentrations range from 70 to 150 ng/mL at steady state. Blood testing for memantine is available through clinical laboratories performing therapeutic drug monitoring, though this is rarely performed in practice.

Hair Follicle Detection

No validated hair testing methods have been specifically developed for memantine in forensic contexts. The compound's basic, lipophilic nature suggests adequate hair incorporation.

Confirmatory Methods

LC-MS/MS is the preferred confirmatory method, providing excellent sensitivity and specificity. GC-MS with derivatization is also applicable. The adamantane ring structure produces characteristic mass spectral fragmentation patterns that facilitate identification.

Reagent Testing

No reagent testing protocols exist for memantine. Standard harm reduction reagents do not produce diagnostic reactions with adamantane derivatives. Pharmaceutical-grade memantine is widely available and does not require reagent verification.

Interactions

Substance	Status	Note
Acetylfentanyl	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Buprenorphine	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Codeine	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Desomorphine	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Dextropropoxyphene	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Dihydrocodeine	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Ethylmorphine	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Fentanyl	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Heroin	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Hydrocodone	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Hydromorphone	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Kratom	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Methadone	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Morphine	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Naloxone	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
O-Desmethyltramadol	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Oxycodone	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Oxymorphone	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
Pethidine	Dangerous	Both cause respiratory depression and unconsciousness; vomiting while dissociated risks aspiration
1,4-Butanediol	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
2-Fluorodeschloroketamine	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
2M2B	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
3-Cl-PCP	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
3-HO-PCE	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
3-HO-PCP	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
3-MeO-PCE	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
3-MeO-PCMo	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
3-MeO-PCP	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
4-MeO-PCP	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
5F-AKB48	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
5F-PB-22	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
AB-FUBINACA	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
Alcohol	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Alprazolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Anandamide	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
APICA	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
Atropa belladonna	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Baclofen	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Benzodiazepines	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Benzydamine	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Cake	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Cannabidiol	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
Cannabis	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
Carisoprodol	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Clonazepam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Clonazolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Clonidine	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Datura	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Deschloroetizolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Deschloroketamine	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Dextromethorphan	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Diazepam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Diclazepam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Diphenhydramine	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Diphenidine	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Ephenidine	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Eszopiclone	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Etizolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
F-Phenibut	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Flualprazolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Flubromazepam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Flubromazolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Flunitrazepam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Flunitrazolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Gabapentin	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Gaboxadol	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
GBL	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
GHB	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Grayanotoxin	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
HXE	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Inhalants	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
JWH-018	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
JWH-073	Caution	Cannabis can intensify dissociation and increase confusion and disorientation
Ketamine	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Lorazepam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Mephenaqualone	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Methaqualone	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Methoxetamine	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Methoxphenidine	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Metizolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Midazolam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Mirtazapine	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
MXiPr	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Myristicin	Caution	Unpredictable compounding of hallucinogenic effects with anticholinergic delirium
Nicotine	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Nifoxipam	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Nitrous	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
O-PCE	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
PCE	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
PCP	Caution	Compounding dissociative effects can cause confusion, mania, and loss of motor control
Pentobarbital	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
Phenobarbital	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
SAMe	Caution	Both cause CNS depression; increased risk of vomiting, unconsciousness, and respiratory depression
1,3-Butanediol	Low Risk & Synergy	Produces unique synergistic effects; often combined
1B-LSD	Low Risk & Synergy	Produces unique synergistic effects; often combined
1cP-AL-LAD	Low Risk & Synergy	Produces unique synergistic effects; often combined
1cP-LSD	Low Risk & Synergy	Produces unique synergistic effects; often combined
1cP-MiPLA	Low Risk & Synergy	Produces unique synergistic effects; often combined
1P-ETH-LAD	Low Risk & Synergy	Produces unique synergistic effects; often combined
1P-LSD	Low Risk & Synergy	Produces unique synergistic effects; often combined
1V-LSD	Low Risk & Synergy	Produces unique synergistic effects; often combined
2,5-DMA	Low Risk & Synergy	Produces unique synergistic effects; often combined
25B-NBOH	Low Risk & Synergy	Produces unique synergistic effects; often combined
25B-NBOMe	Low Risk & Synergy	Produces unique synergistic effects; often combined
25C-NBOH	Low Risk & Synergy	Produces unique synergistic effects; often combined
25C-NBOMe	Low Risk & Synergy	Produces unique synergistic effects; often combined
25D-NBOMe	Low Risk & Synergy	Produces unique synergistic effects; often combined
25E-NBOH	Low Risk & Synergy	Produces unique synergistic effects; often combined
25I-NBOH	Low Risk & Synergy	Produces unique synergistic effects; often combined
25I-NBOMe	Low Risk & Synergy	Produces unique synergistic effects; often combined
25N-NBOMe	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-B	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-B-FLY	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-C	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-D	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-E	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-H	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-I	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-P	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-T	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-T-2	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-T-21	Low Risk & Synergy	Produces unique synergistic effects; often combined
2C-T-7	Low Risk & Synergy	Produces unique synergistic effects; often combined
3C-E	Low Risk & Synergy	Produces unique synergistic effects; often combined
3C-P	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-AcO-DET	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-AcO-DiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-AcO-DMT	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-AcO-MET	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-AcO-MiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-HO-DET	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-HO-DiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-HO-DPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-HO-EPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-HO-MET	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-HO-MiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
4-HO-MPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
5-MeO-DALT	Low Risk & Synergy	Produces unique synergistic effects; often combined
5-MeO-DiBF	Low Risk & Synergy	Produces unique synergistic effects; often combined
5-MeO-DiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
5-MeO-DMT	Low Risk & Synergy	Produces unique synergistic effects; often combined
5-MeO-MiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
6-APB	Low Risk & Synergy	Produces unique synergistic effects; often combined
AL-LAD	Low Risk & Synergy	Produces unique synergistic effects; often combined
ALD-52	Low Risk & Synergy	Produces unique synergistic effects; often combined
Allylescaline	Low Risk & Synergy	Produces unique synergistic effects; often combined
Ayahuasca	Low Risk & Synergy	Produces unique synergistic effects; often combined
Bromo-DragonFLY	Low Risk & Synergy	Produces unique synergistic effects; often combined
Bufotenin	Low Risk & Synergy	Produces unique synergistic effects; often combined
DET	Low Risk & Synergy	Produces unique synergistic effects; often combined
DiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
DMT	Low Risk & Synergy	Produces unique synergistic effects; often combined
DOB	Low Risk & Synergy	Produces unique synergistic effects; often combined
DOC	Low Risk & Synergy	Produces unique synergistic effects; often combined
DOI	Low Risk & Synergy	Produces unique synergistic effects; often combined
DOM	Low Risk & Synergy	Produces unique synergistic effects; often combined
DPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
Efavirenz	Low Risk & Synergy	Produces unique synergistic effects; often combined
EPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
Escaline	Low Risk & Synergy	Produces unique synergistic effects; often combined
ETH-LAD	Low Risk & Synergy	Produces unique synergistic effects; often combined
Ibogaine	Low Risk & Synergy	Produces unique synergistic effects; often combined
LAE-32	Low Risk & Synergy	Produces unique synergistic effects; often combined
LSA	Low Risk & Synergy	Produces unique synergistic effects; often combined
LSD	Low Risk & Synergy	Produces unique synergistic effects; often combined
LSM-775	Low Risk & Synergy	Produces unique synergistic effects; often combined
LSZ	Low Risk & Synergy	Produces unique synergistic effects; often combined
MDA	Low Risk & Synergy	Produces unique synergistic effects; often combined
Mescaline	Low Risk & Synergy	Produces unique synergistic effects; often combined
MET	Low Risk & Synergy	Produces unique synergistic effects; often combined
Methallylescaline	Low Risk & Synergy	Produces unique synergistic effects; often combined
MiPLA	Low Risk & Synergy	Produces unique synergistic effects; often combined
MiPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
MPT	Low Risk & Synergy	Produces unique synergistic effects; often combined
PARGY-LAD	Low Risk & Synergy	Produces unique synergistic effects; often combined
PRO-LAD	Low Risk & Synergy	Produces unique synergistic effects; often combined
Psilocybin Mushrooms	Low Risk & Synergy	Produces unique synergistic effects; often combined

History

Main article: Discovery and development of memantine and related compounds Memantine was first synthesized, patented, and described by Eli Lilly and Company in 1963 as an anti-diabetic agent, but it was ineffective at lowering blood sugar. By 1972, it was discovered to have central nervous system (CNS) activity, and was developed by Merz for treatment of neurological diseases, such as Parkinson's disease. Memantine was first studied in the treatment of Alzheimer's disease in 1986. The drug was first marketed for dementia in 1989 in Germany under the name Axura.

It was not discovered to act as an NMDA receptor antagonist until 1989, after clinical trials had initiated. Prior to this, it was theorized to directly and/or indirectly modulate the dopaminergic, noradrenergic, and serotonergic systems. However, these actions were later realized to occur at 100-fold higher concentrations than those achieved therapeutically and hence are unlikely to be involved in its effects.

In the United States, some CNS activities were discovered at Children's Hospital of Boston in 1990, and Children's licensed patents covering uses of memantine outside the field of ophthalmology to Neurobiological Technologies (NTI) in 1995. In 1998, NTI amended its agreement with Children's to allow Merz to take over development.

In 2000, Merz partnered with Forest to develop the drug for Alzheimer's disease in the United States under the brand name Namenda. In 2000, Merz partnered with Suntory for the Japanese market and with Lundbeck for other markets including Europe; the drug was originally marketed by Lundbeck under the name Ebixa. Memantine was approved in the European Union in 2002 and in the United States in 2003.

Sales of the drug reached $1.8 billion for 2014. The cost of Namenda was $269 to $489 a month in 2012.

In February 2014, as the July 2015 patent expiration for memantine neared, Actavis, which had acquired Forest, announced that it was launching an extended release (XR) form of memantine that could be taken once a day instead of twice a day as needed with the then-current "immediate release" (IR) version, and that it intended to stop selling the IR version in August 2014 and withdraw the marketing authorization. This is a tactic to thwart generic competition called product hopping. However the supply of the XR version ran short, so Actavis extended the deadline until the fall. In September 2014 the attorney general of New York, Eric Schneiderman, filed a lawsuit to compel Actavis to keep selling the IR version on the basis of antitrust law.

In December 2014, a judge granted New York State its request and issued an injunction, preventing Actavis from withdrawing the IR version until generic versions could launch. Actavis appealed and in May a panel of the Second Circuit Court of Appeals upheld the injunction, and in June Actavis asked that its case be heard by the full Second Circuit panel. In August 2015, Actavis' request was denied.

Toxicity & Safety

Further information: 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 exact toxic dosage is unknown, although up to 400mg has been tolerated. This is because memantine has very little history of recreational human usage.

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 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.

Addiction Potential

unknown

Overdose Information

Overdose on Memantine can range from unpleasant to life-threatening depending on the dose, route, and whether other substances are involved.

Signs of overdose: Severe nystagmus, complete unresponsiveness, vomiting (aspiration risk while unconscious), severely depressed breathing, seizures, extremely elevated heart rate or blood pressure.

Critical dangers:

Respiratory depression: Particularly when combined with other depressants
Aspiration: Loss of protective reflexes combined with nausea creates choking risk
Hyperthermia or hypothermia: Impaired thermoregulation at high doses

Emergency response: Place the person in the recovery position. Monitor breathing. Call emergency services if breathing is slow, shallow, or irregular; if the person is unresponsive to stimulation; or if seizures occur. Be honest with medical personnel about what was consumed — they are there to help, not to judge.

Dangerous Interactions

The combinations listed below may be life-threatening. Independent research should always be conducted to ensure safety when combining substances.

AcetylfentanylDangerous