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Table of Contents

1. Dosage
2. Cognitive Effects
3. Plateaus
4. Toxicity and Harm Potential
5. Dependence and Abuse Potential
6. Overdose Risks
7. Dangerous Interactions
8. Legal Status

The Effects and Controversy Surrounding Dextromethorphan (DXM)

Introduction to DXM

Dextromethorphan (DXM), known colloquially as robo, dex, DM, and DXM, is categorized as a dissociative substance within the morphinan class. It serves as the primary active component in numerous over-the-counter (OTC) cold and cough medications. When consumed in doses surpassing approved medical recommendations, DXM induces dissociative effects akin to those produced by ketamine and phencyclidine (PCP). Its mechanism of action involves acting as a noncompetitive antagonist of the NMDA receptor.

Historical Background

DXM first surfaced in 1953 and obtained approval for use as a cough suppressant in the United States by 1958. Following its approval, it entered the market as an OTC medication under the brand name Romilar. However, as early as 1975, concerns regarding its widespread misuse prompted the voluntary removal of Romilar from the OTC market. In response, pharmaceutical companies introduced refined DXM products with additives intended to deter abuse, such as unpleasant-tasting ingredients.

Recreational Use Trends

Despite attempts to mitigate abuse, recreational use of DXM has persisted and is recognized as a growing phenomenon, particularly among adolescents attracted to its affordability and accessibility.

Subjective Effects

The subjective effects of DXM encompass a spectrum including dissociation, time distortion, bodily hallucinations, immersion enhancement, loss of motor control, euphoria, and ego dissolution. Users often liken low doses to an alcohol-like intoxication, while higher doses produce effects reminiscent of ketamine or PCP. Many users report experiencing a potent, uncomfortable body load accompanied by significant nausea.

Variability and Tolerability

Individual responses to DXM vary widely, likely influenced by genetic factors affecting metabolism. Consequently, some users find the DXM experience unpleasant, neutral, or dull, while others describe it as producing mystical-like psychedelic encounters.

Formulation Considerations

It's essential to note that DXM in freebase form, as found in products like Robocough RoboTablets, is approximately 27-37% more potent than its hydrobromide form due to a higher concentration of DXM by weight. Adjusting dosage calculations accordingly is crucial to avoid potential overdose.

Controversy and Safety Concerns

The toxicity of DXM in recreational doses remains a topic of controversy. While some evidence suggests that excessive use of NMDA antagonists like DXM may have neurotoxic effects, the exact risks are unclear. Numerous cases of DXM dependence and abuse have been documented, emphasizing the importance of employing harm reduction strategies when using this substance.

The Evolution of Dextromethorphan: A Historical Perspective

Origins and Development

The precursor to dextromethorphan (DXM), racemethorphan, was first documented in patent applications filed by Hoffmann-La Roche in 1946 (Swiss) and 1947 (US). Subsequently, a patent was granted in 1950. A breakthrough came in 1952 with the resolution of racemethorphan isomers using tartaric acid. DXM emerged as a result of successful testing in 1954, within research funded by the US Navy and CIA, exploring nonaddictive alternatives to codeine.

FDA Approval and Early Use

Formally approved by the FDA in 1958, DXM entered the market as an over-the-counter antitussive, providing a solution to some issues associated with codeine use, such as sedation and opiate dependence. Initially promising, DXM faced challenges akin to dissociative anesthetics like phencyclidine and ketamine, as it became linked with nonmedical usage.

Rise and Fall of Romilar

During the 1960s and 1970s, dextromethorphan gained popularity in tablet form under the brand name Romilar. However, its availability as an OTC tablet was short-lived. In 1973, due to a surge in sales driven by widespread misuse, Romilar tablets were discontinued and replaced with cough syrup formulations in an effort to curb abuse.

Internet Influence and Accessibility

The proliferation of internet access in the 1990s facilitated rapid dissemination of information about DXM. Online forums and discussion groups emerged, providing platforms for users to share experiences and procurement methods. By 1996, DXM hydrobromide (HBr) powder became available for bulk purchase from online retailers, enabling consumers to bypass syrup preparations.

Regulatory Responses

Concerns over DXM abuse led to regulatory interventions. Notably, as of January 1, 2012, California implemented restrictions on DXM sales to minors, requiring a doctor's prescription for purchase.

Deciphering the Chemistry and Pharmacology of Dextromethorphan (DXM)

Chemical Structure and Composition

Dextromethorphan belongs to the morphinan class and is characterized by its dextrorotatory molecular configuration. Structurally, it comprises a phenanthrene core structure fused with one aromatic ring (benzene) and two saturated rings (cyclohexane). Additionally, it features a saturated piperidine ring attached to specific positions (R9 and R13) of the core structure. Substituents include a methyl group at RN and a methoxy group at R3.

Pharmacological Mechanisms

The precise pharmacology of DXM remains incompletely understood. In vitro studies suggest its primary mode of action involves antagonism of N-methyl-D-aspartate (NMDA) receptors, which are crucial for glutamate-mediated excitatory neurotransmission in the central nervous system. This mechanism parallels those of ketamine and phencyclidine (PCP).

Interestingly, DXM acts as a prodrug for its metabolite dextrorphan, which serves as the actual mediator of its dissociative effects. Additional pharmacological actions include nonselective serotonin reuptake inhibition, alpha-3 beta-4 nicotinic receptor antagonism, and sigma-1 receptor agonism.

Physiological Effects and Metabolism

At elevated doses, DXM induces physiological responses such as increased blood pressure and heart rate, along with heightened plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone. Unlike typical μ-opioid agonists, DXM exhibits minimal affinity for these receptors.

Metabolically, DXM undergoes O-demethylation to form dextrorphan, primarily mediated by the CYP2D6 enzyme. Additionally, it is N-demethylated into 3-methoxymorphinan by the CYP3A4 enzyme. Both dextrorphan and 3-methoxymorphinan further metabolize into 3-hydroxymorphinan. Genetic variations in metabolism significantly influence the DXM experience, with poor metabolizers exhibiting altered pharmacokinetics.

Understanding Dextrorphan

Dextrorphan, a metabolite of DXM, plays a pivotal role in its psychoactive effects. It exhibits enhanced potency as an NMDA receptor antagonist compared to DXM and demonstrates reduced activity as a serotonin reuptake inhibitor. Dextrorphan also interacts with nicotinic and sigma-1 receptors, albeit to a lesser extent than DXM.

Exploration of 3-Methoxymorphinan and 3-Hydroxymorphinan

3-Methoxymorphinan, another DXM metabolite, arises from N-demethylation and possesses local anesthetic properties. Conversely, 3-hydroxymorphinan, formed via O-demethylation and metabolization of dextrorphan, exhibits neuroprotective and neurotrophic effects.

Conclusion: Insights into DXM's Effects

The multifaceted pharmacological actions of DXM and its metabolites contribute to a wide array of subjective effects, ranging from bodily sensations to hallucinatory states. Understanding the chemical and physiological underpinnings provides crucial insights into DXM's mechanisms of action and potential therapeutic applications.

Understanding Dextromethorphan Dosage

Threshold Dose

The threshold dose for dextromethorphan (DXM) is typically around 75 milligrams. At this level, users may begin to perceive subtle effects, although they may not be fully pronounced.

Light Dosage Range

A light dose of DXM typically falls within the range of 100 to 200 milligrams. At this level, users may experience mild effects, such as slight euphoria or changes in perception.

Common Dosage Range

The common dosage range for DXM spans from 200 to 400 milligrams. Within this range, users often experience more pronounced effects, including dissociation, time distortion, and alterations in sensory perception.

Strong Dosage Range

A strong dose of DXM ranges from 400 to 700 milligrams. At this level, users may encounter intense dissociative effects, significant alterations in perception, and profound changes in consciousness.

Heavy Dosage

Dosages exceeding 700 milligrams are considered heavy. At this level, users may experience extremely potent dissociative effects, profound alterations in perception and cognition, and a heightened risk of adverse reactions.

Exploring the Cognitive and Sensory Effects of Dextromethorphan (DXM)

Cognitive Effects

• Analysis Suppression: DXM can suppress analytical thinking processes.
• Anxiety Suppression or Anxiety: While DXM typically suppresses anxiety, it can also induce it, especially at heavy dosages.
• Conceptual Thinking: DXM may alter conceptual thinking patterns.
• Confusion: Users may experience confusion, particularly at higher doses.
• Cognitive Euphoria: While cognitive euphoria is common, it may occasionally manifest as cognitive dysphoria.
• Cognitive Fatigue: DXM may induce cognitive fatigue.
• Creativity Enhancement: Some users report enhanced creativity while under the influence of DXM.
• Decreased Libido: DXM can decrease libido.
• Déjà Vu: Users may experience sensations of déjà vu.
• Delusion: Delusional thinking can occur, especially at higher doses.
• Depersonalization: DXM may induce feelings of depersonalization.
• Derealization: Users may experience derealization, perceiving the external world as unreal.
• Disinhibition: DXM can lead to disinhibited behavior, even at moderate dosages.
• Ego Inflation: Users may experience an inflated sense of ego.
• Dream Potentiation: DXM may potentiate dreams.
• Emotion Enhancement: While not as consistent as with other hallucinogens, DXM can enhance emotions.
• Empathy, Affection, and Sociability Enhancement: DXM may enhance feelings of empathy and sociability, akin to entactogens like MDMA.
• Immersion Enhancement: DXM can enhance immersion in activities or experiences.
• Increased Sense of Humor: Users may experience an increased sense of humor, especially at lower dosages.
• Increased Music Appreciation: Music appreciation can be greatly intensified on DXM.
• Memory Suppression: DXM may suppress memory formation.
• Ego Death: DXM can induce a sense of ego dissolution.
• Amnesia: Users may experience partial or complete memory loss, especially with higher doses.
• Focus Suppression: DXM can suppress focus and concentration.
• Motivation Suppression: Users may experience reduced motivation.
• Novelty Enhancement: DXM can enhance perceptions of novelty.
• Personal Bias Suppression: DXM may suppress personal biases, though less prominently than other hallucinogens.
• Personal Meaning Enhancement: DXM may enhance the personal significance of experiences, especially at lower dosages.
• Thought Deceleration: DXM can slow down thought processes.
• Time Distortion: Users often experience time dilation, with minutes feeling like hours.
• Sleepiness: DXM can induce feelings of drowsiness.

Auditory Effects

• Auditory Enhancement: DXM may enhance auditory perception.
• Auditory Suppression: Conversely, DXM can suppress auditory sensations.
• Auditory Distortion: Users may experience distorted auditory perceptions.
• Auditory Hallucination: Auditory hallucinations can occur on DXM.

Disconnective Effects

• Cognitive Disconnection: DXM may induce feelings of cognitive disconnection.
• Physical Disconnection: Users may feel physically disconnected, though less intensely than with ketamine or PCP.
• Visual Disconnection: DXM can induce visual disconnection, akin to the "K-hole" experienced with ketamine.

Multi-sensory Effects

• Synaesthesia: DXM may induce synaesthetic experiences, though they are rare and non-reproducible.

Transpersonal Effects

• Spirituality Enhancement: DXM can enhance feelings of spirituality.
• Existential Self-Realization: Users may experience profound insights into existential themes.
• Unity and Interconnectedness: DXM can foster feelings of unity and interconnectedness.

Afterglow

• Euphoric Afterglow: Following the experience, users may feel euphoric, rejuvenated, and relaxed.
• Cognitive Aftereffects: The afterglow may involve reduced anxiety, increased sensory appreciation, and mild feelings of derealization or depersonalization.

Understanding the Plateaus of Dextromethorphan (DXM) Use

First Plateau (1.5 - 2.5 mg/kg)

• Description: The first plateau is characterized by mild effects, often likened to feeling "drunk."
• Effects: Cognitive euphoria, increased music appreciation, time distortion, pupil dilation, and stimulation are common.
• Intensity: Not very intense compared to higher plateaus.

Second Plateau (2.5 - 7.5 mg/kg)

• Description: Many users consider the second plateau to be the most recreational.
• Effects: More sedating than stimulating, with intensified euphoria and visual disconnection.
• Additional Effects: Wakefulness, physical euphoria, spatial disorientation, perception of bodily lightness, frame rate suppression, and enhanced music appreciation.
• Music Enhancement: Music is often greatly enhanced at this plateau, described as rich, clear, and amplified.

Third Plateau (7.5 - 15 mg/kg)

• Description: The third plateau is significantly more intense than the second.
• Effects: Includes dissociation, sedation, memory suppression, auditory and internal hallucinations, cognitive dysphoria, euphoria, anxiety, and delusions.
• Visuals: Closed eye visuals (CEVs) are common, consisting of darker colored geometric patterns and landscapes.
• Introspective: Often reported as extremely introspective, inspiring users to improve their lives.
• Afterglow: Tiring but accompanied by a mood boost for days or weeks afterward.

Fourth Plateau (15 - 20 mg/kg)

• Description: The fourth plateau includes external hallucinations and complete dissociation.
• Effects: Intensified effects of the third plateau, with greater intensity and risk.
• Risk: Doses in this range are dangerous with a high risk of injury and overdose.

Fifth Plateau (Plateau Sigma)

• Description: Plateau Sigma is often unintentional and highly unpleasant.
• Method: Achieved by redosing, resulting in delirious hallucinations, dysphoria, delirium, psychosis, and anxiety.
• Risk: High potential for serotonin syndrome and neurotoxicity, strongly advised against.

Understanding Toxicity and Harm Potential of DXM

Lack of Scientific Research

• Unknown Toxic Dosage: The toxicity and long-term health effects of recreational DXM use in humans have not been scientifically studied, and the exact toxic dosage remains unknown.

• Anecdotal Evidence: Anecdotal evidence suggests that trying DXM at low to moderate doses sparingly may not lead to negative health effects. However, waiting periods between doses are recommended to minimize potential damage to organs such as the kidneys, heart, and liver due to the presence of toxic chemicals in the bloodstream after DXM use.

• Long-Term Effects: Chronic users have reported issues with memory, attention, and mood persisting for months after stopping usage. Although no neurotoxic effects have been observed in animals, repeated administration during adolescence has been shown to impair learning in adulthood.

Dependence and Abuse Potential

• Dependence: DXM can lead to dependence with chronic use and has moderate abuse potential. Cravings and withdrawal effects may occur if usage is suddenly stopped.

• Withdrawal Symptoms: Users may experience withdrawal symptoms such as fatigue, apathy, flashbacks, constipation, insomnia, nightmares, inability to feel pleasure, impaired memory, attention deficit, decreased libido, panic attacks, tremors, yellowing of the skin, hives, and muscle pain.

• Tolerance Development: Tolerance to DXM develops with prolonged use, requiring larger doses to achieve the same effects. Cross-tolerance with other dissociatives occurs.

• Permanent Tolerance: Some users report irreversible tolerance to DXM after a certain number of doses, potentially indicating neurotoxicity.

Overdose Risks

• Threshold for Overdose: Anecdotal evidence suggests significant risk of overdose at doses of roughly 15mg/kg to 20mg/kg, leading to delusions, hallucinations, psychosis, confusion, panic attacks, sedation, severe balance issues, increased heart rate, nystagmus, amnesia, respiratory depression, dangerously high fever, and seizures.

• Serotonin Syndrome: Extremely high and repeated doses may lead to serotonin syndrome, with symptoms including hyperthermia, autonomic dysfunction, altered mental status, and neuromuscular abnormalities.

• Medical Attention: Severe overdose cases may require medical attention to prevent life-threatening complications such as extremely elevated heart rate and blood pressure, urinary retention, rhabdomyolysis, seizures, and brain cell death.

Dangerous Interactions

• Combination Risks: DXM can interact dangerously with various substances, including benzodiazepines, cannabis, DOx, 25x-NBOMe, amphetamines, cocaine, MAOIs, SSRIs, opioids, and more, potentially leading to serotonin syndrome, respiratory depression, seizures, or other severe health problems.

Legal Status

• Availability: DXM is available over the counter or by prescription in most countries, with age restrictions in some regions. Legal status varies by country, with some countries regulating it as a controlled substance due to its potential for abuse and associated risks.

Frequently Asked Questions (FAQ)

Q: What are the recommended dosage ranges for DXM use?

A: Dosages vary depending on the desired effects. Threshold doses start around 75mg, with light doses ranging from 100 to 200mg, common doses from 200 to 400mg, strong doses from 400 to 700mg, and heavy doses at 700mg and above.

Q: What cognitive effects can DXM produce?

A: DXM can cause a range of cognitive effects, including analysis suppression, anxiety suppression, confusion, cognitive euphoria or dysphoria, creativity enhancement, decreased libido, déjà vu, delusion, depersonalization, derealization, disinhibition, ego inflation, dream potentiation, emotion enhancement, empathy enhancement, immersion enhancement, and more.

Q: What are the different plateaus associated with DXM use?

A: DXM users often categorize their experiences into five "plateaus." These include the first plateau, second plateau, third plateau, fourth plateau, and the fifth plateau, also known as "Plateau Sigma."

Q: Is DXM safe to use?

A: The safety of DXM use is not well-studied, and its long-term health effects remain unclear. Anecdotal evidence suggests that low to moderate doses used sparingly may not lead to negative health effects, but chronic use can result in dependence, withdrawal symptoms, and potential organ damage.

Q: What are the risks of DXM overdose?

A: DXM overdose can lead to a wide range of effects, including delusions, hallucinations, psychosis, confusion, panic attacks, sedation, balance issues, increased heart rate, respiratory depression, fever, seizures, and potentially life-threatening complications.

Q: Are there any dangerous interactions with DXM?

A: Yes, DXM can interact dangerously with various substances, including benzodiazepines, cannabis, DOx, 25x-NBOMe, amphetamines, cocaine, MAOIs, SSRIs, opioids, and more, potentially leading to serotonin syndrome, respiratory depression, seizures, or other severe health problems.

Q: What is the legal status of DXM?

A: DXM is available over the counter or by prescription in most countries, with age restrictions in some regions. Legal status varies by country, with some countries regulating it as a controlled substance due to its potential for abuse and associated risks.