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Table of Contents

1. Introduction
2. Chemistry and Pharmacology
   • Chemistry of Memantine
   • Pharmacological Profile
3. Dosage and Bioavailability
4. Physical Effects
   • Stimulating Nature
   • Spontaneous Bodily Sensations
   • Enhancement of Stamina and Bodily Control
   • Other Physical Effects
5. Visual Effects and Hallucinatory States
   • Visual Enhancement and Suppression
   • Distortions and Hallucinations
6. Cognitive Effects and Disconnective States
7. Toxicity, Tolerance, and Legal Status
   • Toxicity and Harm Potential
   • Tolerance and Addiction Potential
   • Dangerous Interactions
   • Legal Status
8. Conclusion

Understanding Memantine

Origin and Classification

Memantine, a dissociative substance belonging to the adamantane class, stands out for its long-lasting dissociative effects upon administration. Synthesized first by Eli Lilly and Company in 1968, its initial purpose was as a potential treatment for diabetes. While its recreational use remains relatively uncommon, memantine holds pharmacological ties to compounds such as PCP, ketamine, and DXM.

Pharmacological Action

Memantine operates as an NMDA receptor antagonist, binding to and inhibiting the signaling of excitatory receptors within the central nervous system. This mechanism induces a state referred to as "dissociative-anesthesia," characterized by a range of hallucinogenic attributes.

Applications of Memantine

Medical Usage

In the realm of medicine, memantine finds its primary application in the treatment of neurodegenerative conditions, particularly Alzheimer's disease. Its efficacy extends to mitigating cognitive decline associated with such ailments. Additionally, memantine has garnered attention as a nootropic due to its cognitive-enhancing effects.

Chemistry of Memantine

Memantine, also known as 3,5-dimethyladamantan-1-amine, represents a synthetic molecule classified as a substituted adamantane derivative. Its fundamental structure comprises adamantane, a diamondoid consisting of four interlocked cyclohexane rings arranged in a stable 3-dimensional lattice conformation. Within memantine's structure, methyl groups substitute carbon atoms at both R3 and R5 positions, while an amine substitution occurs at R1. Hence, its nomenclature reflects its structure: 3,5-dimethyladamantan-1-amine.

Pharmacological Profile

Glutamatergic (NMDA Receptor)

Memantine exhibits characteristics of a moderate-affinity voltage-dependent uncompetitive antagonist at glutamatergic NMDA receptors. These receptors facilitate the passage of electrical signals between neurons in the brain and spinal column. Memantine's action involves closing the NMDA receptors by blocking them, thereby disconnecting neurons. This disconnection results in sensations of numbness, impaired movement, and the renowned dissociative state colloquially termed the "hole."

Memantine stands out from other dissociatives due to its unique fast, voltage-dependent binding kinetics. These kinetics allow for functional ionic transmission through NMDA receptors unless a significant concentration of agonists is present. Consequently, memantine's pharmacodynamic profile at the NMDA receptor resembles that of endogenous magnesium more than other dissociatives. Moreover, its distinct pharmacology enables it to exert neuroprotective effects at doses that do not induce significant impairment, rendering it valuable in treating neurodegenerative disorders.

Serotonergic (5-HT3 Receptor)

At the 5-HT3 receptor, memantine acts as a non-competitive antagonist, exhibiting potency similar to its action at the NMDA receptor.

Cholinergic (Nicotinic Acetylcholine Receptor)

Memantine functions as a non-competitive antagonist at various neuronal nicotinic acetylcholine receptors (nAChRs). While its potency at these receptors may be comparable to its effects at the NMDA and 5-HT3 receptors, precise determination is challenging due to the rapid desensitization of nAChR responses. Notably, alpha-7 nAChR upregulates rapidly in response to antagonism, potentially explaining the cognitive-enhancing effects observed with chronic memantine treatment.

Dopaminergic (D2 Receptor)

Acting as an agonist at the dopamine D2 receptor, memantine exhibits affinity equal to or slightly higher than its affinity for NMDA receptors.

Sigmaergic (σ1 Receptor)

Memantine serves as an agonist at the σ1 receptor, with a low Ki of 2.6 µM. However, the precise effects of this activity remain unclear, given the limited understanding of sigma receptors in general. Memantine's binding at the sigma site may not be potent enough to elicit significant agonist effects, potentially manifesting as partial agonism or antagonism.

Subjective Effects

(Note: The following subjective effects are based on anecdotal reports and analyses from the Subjective Effect Index (SEI) and PsychonautWiki contributors. As such, they should be interpreted with caution. Additionally, the occurrence of these effects may vary unpredictably, with higher doses increasing the likelihood. Furthermore, higher doses may lead to adverse effects, including addiction, severe injury, or fatality.)

Navigating Memantine Dosage and Bioavailability

Dosage Guidelines

Threshold

The threshold dose for memantine is reported to be 10 mg. This represents the minimum amount required to elicit any discernible effects.

Light Dose

A light dose of memantine typically ranges from 30 to 70 mg. At this dosage level, users may experience mild effects without significant impairment.

Common Dose

A common dose falls within the range of 70 to 110 mg. Users can anticipate experiencing more pronounced effects at this dosage level.

Strong Dose

A strong dose of memantine ranges from 110 to 170 mg. At this level, users may encounter intense effects, potentially leading to profound dissociation and altered perception.

Heavy Dose

Doses exceeding 170 mg are considered heavy. Such doses can induce extreme dissociation and significantly alter consciousness. Users should approach these doses with caution due to the potential for intense and prolonged effects.

Bioavailability

Memantine exhibits a bioavailability ranging from 41% to 63%. This indicates the proportion of the administered dose that enters systemic circulation and is available to produce pharmacological effects. Variability in bioavailability can influence the intensity and duration of memantine's effects, emphasizing the importance of considering individual response and metabolism when determining dosage.

Understanding the Physical Effects of Memantine

Stimulating Nature

Memantine exhibits mild stimulation compared to other dissociatives like ketamine, MXE, or DCK. While it falls short of the intense stimulation induced by PCP and its derivatives, it offers a noticeable boost in energy and alertness.

Spontaneous Bodily Sensations

A distinctive feature of memantine is its "body high," characterized by sharp, pleasurable tingling sensations localized in the hands, feet, and head. This sensation adds to the overall experience, contributing to a sense of physical well-being.

Enhancement of Stamina and Bodily Control

Users often report enhanced stamina and improved bodily control under the influence of memantine. These effects can promote engagement in physical activities and contribute to a heightened sense of physical capability.

Other Physical Effects

• Cough Suppression: Memantine demonstrates cough-suppressing properties, providing relief from respiratory discomfort.
• Appetite Suppression: Users may experience a decrease in appetite while under the influence of memantine.
• Decreased Libido and Orgasm Suppression: Memantine can reduce sexual desire and delay or inhibit orgasm.
• Dizziness: At higher doses, memantine may induce strong and often pleasurable sensations of spinning, especially when the eyes are closed.
• Changes in Felt Gravity: Users may perceive alterations in their sense of gravity.
• Nausea: High doses of memantine can lead to nausea and vomiting, although its 5-HT3 antagonism reduces the likelihood compared to other dissociatives.
• Constipation: Memantine can cause constipation, affecting gastrointestinal function.
• Pain Relief: Some users report pain-relieving effects attributed to memantine.
• Perception of Bodily Lightness: Memantine creates a sensation of weightlessness, encouraging physical activities.
• Physical Euphoria: Memantine can induce feelings of pleasure and bliss, ranging from mild to intense.
• Tactile Suppression: Users may experience partial to complete suppression of touch sensation, resulting in numbness.
• Motor Control Loss: Memantine can impair gross and fine motor control, balance, and coordination, particularly at higher doses.
• Difficulty Urinating: Like other NMDA antagonists, memantine can cause urinary difficulties, including numbing or painful sensations in the bladder and urinary tract.

Visual Effects and Hallucinatory States

Visual Enhancement and Suppression

Memantine may enhance visual acuity and color perception while also causing acuity suppression, blurring vision. Users may also experience double vision, frame rate suppression, and difficulty recognizing patterns.

Distortions and Hallucinations

Memantine-induced visual distortions include symmetrical texture repetition, afterimages, brightness alteration, drifting, visual haze, and distortions in depth perception and perspective. Hallucinatory states at higher doses can lead to experiences like machinescapes and internal hallucinations, characterized by autonomous entities, sceneries, and landscapes.

Cognitive Effects and Disconnective States

Memantine's cognitive effects include clear-headedness, amnesia, anxiety suppression, cognitive euphoria, conceptual thinking, creativity enhancement, depersonalization, and time distortion. Disconnective effects manifest as physical, visual, and cognitive disconnection, potentially leading to profound dissociative states akin to the "k-hole."

Toxicity, Tolerance, and Legal Status

Toxicity and Harm Potential

The long-term health effects and toxic dosage of recreational memantine use remain largely unknown. Limited data suggest tolerability up to 400 mg, but caution is advised due to the substance's sparse recreational history.

Tolerance and Addiction Potential

Memantine's dependence potential and addiction risk are unclear. However, its long duration and onset discourage redosing, mitigating the likelihood of addiction. Cross-tolerance with other dissociatives reduces their effectiveness after memantine use.

Dangerous Interactions

Combining memantine with other substances, particularly stimulants or depressants, poses risks of adverse psychological reactions, respiratory depression, and overdose. Users should exercise extreme caution and conduct thorough research before combining memantine with other drugs.

Other Interactions

• Cannabis: Cannabis may potentiate the effects of memantine.
• Nicotine: Anecdotal reports suggest an interaction between tobacco and memantine.
• Opioids and Stimulants: Memantine may enhance, prevent tolerance buildup, or reverse tolerance to opioids and stimulants.
• Alcohol: Memantine may increase the effects, prevent tolerance buildup, or reverse tolerance to alcohol.

Legal Status (Continued)

• Australia: Memantine is classified as Schedule 4, available only with a prescription.
• France: Memantine is a restricted prescription medicine.
• Germany: Memantine is prescription-only, regulated under Anlage 1 AMVV.
• Russia: Memantine requires a prescription for access.
• Switzerland: Memantine is categorized as a "Abgabekategorie B" pharmaceutical, generally requiring a prescription.
• United Kingdom: Memantine is a prescription-only medicine.
• United States: Memantine is available only with a prescription.

Conclusion

Memantine offers a complex array of physical, visual, and cognitive effects, with potential for both therapeutic and recreational use. However, its precise mechanisms, toxicity profile, and interactions require further study. Users should approach memantine with caution, adhere to dosage guidelines, and consider legal regulations and potential interactions before use.

Frequently Asked Questions (FAQ)

1. What is memantine?

Memantine is a man-made molecule classified as a substituted adamantane derivative. It acts as an NMDA receptor antagonist and is used primarily in medicine for the treatment of neurodegenerative diseases like Alzheimer's.

2. What are the physical effects of memantine?

Memantine can induce a range of physical effects including stimulation, spontaneous bodily sensations, enhancement of stamina and bodily control, cough suppression, appetite suppression, decreased libido, dizziness, changes in felt gravity, increased heart rate, nausea, constipation, pain relief, and more.

3. What are the visual effects of memantine?

Visual effects of memantine include enhancement and suppression of vision, distortions, hallucinations, and alterations in perception such as symmetrical texture repetition, afterimages, brightness alteration, drifting, visual haze, and distortions in depth perception and perspective.

4. Is memantine addictive?

The addiction potential of memantine is unclear. Its long duration and onset discourage redosing, but users should be cautious and avoid excessive use.

5. What are the legal implications of memantine?

The legal status of memantine varies by country, ranging from prescription-only to restricted availability. Users should adhere to local regulations and seek medical guidance when considering memantine use.

6. Are there any dangerous interactions with memantine?

Combining memantine with other substances, particularly stimulants or depressants, poses risks of adverse reactions and overdose. Users should exercise caution and conduct thorough research before combining memantine with other drugs.