Dextromethorphan

DXM

Psychoactive Class

Chemical Class

Dextromethorphan (DXM) is a morphinan-class dissociative commonly found in over-the-counter cough suppressants.¹² First approved by the FDA in 1957, it acts primarily as a prodrug, with most dissociative effects mediated by its metabolite dextrorphan through NMDA receptor antagonism. Despite its structural similarity to opioids like codeine, dextromethorphan lacks significant mu-opioid receptor activity.¹ Its widespread availability in household cold medicines has made it one of the most accessible dissociatives, contributing to its prevalence as a recreationally misused substance.³

Dosage & Duration

Dosage

Threshold75-75 mg

Light100-200 mg

Moderate200-400 mg

Strong300-600 mg

Heavy600-900 mg

Duration

Onset30-120 minutes

Come Up60-120 minutes

Peak3-6 hours

Offset2-4 hours

After Effects4-24 hours

Total8-12 hours

Half-life

3-30 hours

Subjective Effects

Effects vary widely by individual, dose, and context.

Physical

The subjective physical effects of DXM can be broken down into nine components all of which progressively intensify proportional to dosage.

Disconnection from tactile inputPhysical autonomy

Cognitive

The head space of DXM is often described as particularly impairing, disorientating and generally less clear headed in comparison to that of MXE and Ketamine.

Disconnection from consciousness Ego suppression, loss and death Time distortion Introspection Deja-Vu Removal of cultural filter Conceptual thinking Direct communication with the subconscious States of unity and interconnectedness

Visual

This substance does not enhance visual stimuli; instead it tends to degrade and decrease visual aptitude in a variety of ways.

Distortions

DXM exhibits a full array of dissociative distortions and alterations in visual perception.

Perspective distortions Environmental cubismEnvironmental orbismScenery slicing

Geometry

The visual geometry found within DXM can be described as intricate in complexity, fast in movement, soft in edges, rounded and angular in corners, large in size, immersive in presence and very brightly coloured in scheme when compared to that of MXE.

Hallucinatory States

At high dosages, DXM can produce a full range of high level hallucinatory states in a fashion that is less consistent and reproducible than that of many other commonly used psychedelics.

External hallucinations

Suppressions

Decreased visual acuity Suppression of pattern recognition Blurred vision Double vision

Auditory

The auditory effects of DXM are common in their occurrence and exhibit a range of effects.

Enhancements Suppression Distortions Hallucinations

Forked from Subjective Effect Documentation

by Josie KinsNovember 2012.

Reagent Testing

Loading reagent data

Expected colorimetric results are being prepared.

Pharmacology

Pharmacodynamics

Dextromethorphan functions primarily as a prodrug of its more potent metabolite dextrorphan, which mediates most of its dissociative effects through uncompetitive NMDA receptor antagonism at the PCP binding site.⁴ The parent compound also contributes directly through strong sigma-1 receptor agonism and serotonin transporter inhibition⁵, with sigma-1 activity potentially contributing to motor effects, tachycardia, and mydriasis. Dextromethorphan additionally acts as a negative allosteric modulator of nicotinic acetylcholine receptors, particularly α3β4 subtypes.⁶ Despite its morphinan structure, dextromethorphan lacks significant mu-opioid receptor activity and does not produce the analgesia, sedation, or respiratory depression typical of related opioid compounds. Published binding affinities vary considerably between studies, with reported values for sigma-1 ranging from 23 to 150 nM and SERT from 40 to over 2000 nM.

Pharmacokinetics

Dextromethorphan is rapidly absorbed from the gastrointestinal tract and undergoes extensive first-pass hepatic metabolism.⁴ The primary metabolic pathway involves O-demethylation via CYP2D6 to the active metabolite dextrorphan⁴, accounting for approximately 80% of dextrorphan formation. A secondary pathway involves N-demethylation via CYP3A4 to 3-methoxymorphinan⁴, which contributes over 90% of that metabolite's production. Both pathways converge on 3-hydroxymorphinan, with subsequent glucuronidation and sulfation. The elimination half-life varies substantially based on CYP2D6 activity, ranging from approximately 4 hours in extensive metabolizers to 13 hours or longer in poor metabolizers. Approximately 1 in 10 individuals of European descent exhibit reduced CYP2D6 activity.⁷ Brain concentrations of both dextromethorphan and dextrorphan substantially exceed serum levels.

Interactions

Dangerous

Highest risk

These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.

AlcoholAMTGHB/GBLLithiumMAOIsMDMAMephedroneOpioidsPCPSSRIsTramadol

Unsafe

Avoid

There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.

2C-T-x compounds5-MeO-xxT tryptaminesAmphetaminesCocaineDiphenhydramineDOx compoundsMXENBOMe compoundsPregabalin

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

BenzodiazepinesCaffeine

TripSit

Tolerance

Full Tolerance

Tolerance develops with prolonged and repeated use, though the rate varies considerably between individuals. Unlike classical psychedelics, DXM can be used on consecutive days without immediate dramatic tolerance buildup, though regular long-term use will produce tolerance. Some users report an irreversible, permanent tolerance that develops over extended periods of heavy use, potentially correlating with cumulative lifetime doses. Anecdotal reports suggest a threshold around 50 uses after which the characteristic effects may be permanently diminished, though the mechanism remains unclear.

Baseline Reset

1-2 weeks

Half Tolerance

3-7 days

Cross Tolerance

Dissociatives (all NMDA receptor antagonists)

Harm Potential

Addiction & Dependence

Psychological

Low

Psychological addiction is uncommon but documented.⁸ Some users develop craving and emotional dependence with regular use, finding it difficult to stop.⁸ DXM is considered less addictive than opioid-based cough suppressants like codeine, though it is classified as habit-forming.

Physical

Low

Physical dependence is not well-established.⁸ Long-term regular users report withdrawal symptoms similar to antidepressant discontinuation syndrome, including disturbances in sleep, senses, movement, mood, and cognition.⁸ Some users report a 1-2 week hangover period after stopping regular use. Life-threatening withdrawal has not been documented.⁸

Toxicity

Central Nervous System

Chronic heavy use over extended periods may cause cognitive deficits including impaired episodic memory, learning difficulties, and abnormalities in visual processing and abstract language comprehension;⁸ the theory that DXM causes Olney's lesions (brain vacuolization) remains inconclusive in humans, and oral administration in rats did not produce such lesions.⁹

Cardiovascular

Acute increases in systolic and diastolic blood pressure along with increased heart rate occur at high doses;⁸ serious cardiovascular events are primarily associated with overdose or products containing stimulant adulterants.

Urinary System

Urinary retention becomes increasingly likely at higher doses and may result in complete inability to urinate at very high doses; this is an acute effect during intoxication rather than chronic damage.

Psychosis Risk

Psychotic symptoms including delusions, paranoia, and detachment from reality occur at high doses, particularly at third plateau and above.⁸ Plateau sigma (extended high-dose sessions) carries high risk of delirium and psychosis. Extended heavy use over days or weeks may cause lasting delusional, paranoid, and psychotic ideation persisting for weeks, months, or longer after cessation.⁸

Seizure Risk

Seizures have been reported in overdose scenarios.¹¹ Many reported seizure cases involve adulterants such as chlorpheniramine maleate rather than DXM itself.⁸ States of agitation with epileptic episodes may occur at very high doses.

History & Culture

Discovery and Development

The racemic parent compound racemethorphan was first described in patent applications by Hoffmann-La Roche in Switzerland and the United States in 1946 and 1947, respectively, with a patent granted in 1950. Resolution of the two isomers using tartaric acid was published in 1952. Dextromethorphan…

Trip Reports

Legality

By Country

United StatesNot scheduledUnscheduled

Controlled Substances Act (21 U.S.C. § 811(g)(2))^99100101

At the federal level, the Controlled Substances Act does not include dextromethorphan in any schedule, so DXM itself is not subject to the Act’s controlled-substance controls. FDA’s OTC Monograph M012 includes dextromethorphan and dextromethorphan hydrobromide for eligible nonprescription cold and cough products; FDA product requirements and separate state retail restrictions remain distinct from federal CSA scheduling.

By state

Across the 50 states, D.C., and the permanent territories, dextromethorphan is federally unscheduled under the Controlled Substances Act. Most states treat it consistently with federal law as an ordinary over-the-counter medicine, though a number of states impose their own age-of-sale restrictions, possession limits, or other controls that diverge from the federal position.

Alaska