DXM (Dextromethorphan) is an antitussive agent comprised solely of a methylated dextrorotatory analogue of levorphanol, a semisynthetic non-opioid morphine derivative. It is classified as a “morphinan” drug and is an active ingredient within many over-the-counter (OTC) formulations utilized to treat allergies, coughing, influenza, and more. Examples of several popular over-the-counter formulations with DXM as an ingredient include: Vicks NyQuil/DayQuil, Mucinex DM, Robitussin, and more.
Despite its similar chemical structure to narcotics like morphine, DXM does not agonize the mu opioid receptor (MOR) and is therefore considered largely non-opioidergic. Instead, DXM and its pharmacologically active metabolite “dextrorphan” function as NMDA receptor antagonists. To a lesser extent it also agonizes sigma-1 and sigma-2 opioid receptors and antagonizes alpha-3/beta-4 nicotinic receptors. As a result of its pharmacodynamics, when utilized at a medically acceptable dose, DXM suppresses coughing.
When ingested at supratherapeutic doses DXM acts as a dissociative hallucinogen, hence its minor appeal among recreational drug users. That said, many DXM users (regardless of medicinal or recreational) may experience lingering unwanted side effects such as: brain fog, cognitive impairment, drug-induced psychosis, dissociation, and sedation. For this reason and others (such as fearing a drug test), DXM users may wonder how long it is likely to stay in their systems after ingestion.
How long does DXM stay in your system? (Dextromethorphan)
If you were a heavy, long-term user of DXM, you may experience DXM withdrawal symptoms upon discontinuation as your neurophysiology recalibrates itself to function without the drug. A majority of users will not experience any “withdrawals” simply because they used DXM as a short-term antitussive (to treat coughing). Still, even among short-term users, some side effects experienced while taking DXM may linger for days after the final dose.
This may lead individuals to question how long DXM stays in systemic circulation upon cessation. To determine how long DXM stays in your system, it is necessary to consider its elimination half-life within the range of 3 to 6 hours. This indicates that after you ingest DXM, it may take between 3 and 6 hours to eliminate 50% of the drug from systemic circulation.
Knowing its half-life, we can estimate that it’ll likely take between 16.5 and 33 hours to eliminate the drug from your system after stopping. Other sources suggest that among people with normal metabolism, dextromethorphan’s half-life is just 2 to 4 hours. Assuming this information is accurate, DXM may be cleared from a healthy adult’s system between 11 and 22 hours after stopping.
Due to the fact that DXM is extensively metabolized to form dextrorphan, it is also necessary to account for dextrorphan elimination. The half-life of dextrorphan ranges between 1.7 and 5.4 hours, meaning it’ll likely be out of your system between 9.35 and 29.7 hours of stopping; slightly quicker than the parent drug (dextromethorphan). Overall, you shouldn’t expect to retain DXM (dextromethorphan) nor its chief metabolite dextrorphan for longer than 2 days after your last dose.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/dextromethorphan
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7831698
Variables that influence how long DXM stays in your system
The half-life of DXM is thought to range between 3 and 6 hours, meaning some users may eliminate it from their systems in under 17 hours, whereas other users may take around 33 hours. Whether you are likely to eliminate DXM (and its dextrorphan metabolite) quickly or slowly from your system may be contingent upon certain variables. These variables that influence elimination speed include: individual attributes, dosage, term/frequency of administration, and co-administered drugs.
Two individuals could ingest an oral dose of 30 mg DXM, yet one user is likely to eliminate the drug (along with its dextrorphan metabolite) faster than the other individual. Differences in elimination speed are usually a result of individual factors. Examples of individual factors that can affect DXM’s half-life include: a user’s age, body mass, genetics, hepatic function, metabolic rate, and renal function.
Age: The clearance and elimination speed of various drugs are usually slower among the elderly (ages 65+) for a multitude of reasons. DXM is likely metabolized at a slower rate as a result of diminishing liver function associated with old age. This means that higher levels of DXM are likely to accumulate within the plasma as a result of prolonged metabolism.
In addition, distribution of various drugs such as DXM is often altered among elderly (compared to younger adults) due to altered concentrations of plasma proteins. If also considering decreased renal function, as well as the fact that elderly individuals are likely to be taking (other) drugs and/or have health conditions that interfere with efficient elimination of DXM – we can surmise a longer elimination half-life. If you are a healthy, young adult, elimination of DXM should be much quicker than that of an elderly individual.
Body mass + Fat (%): A person’s body mass and/or body fat percentage may alter the pharmacokinetics of DXM, especially when administered consistently over a long-term. Usually the greater a person’s body mass relative to the dosage of a drug administered, the quicker they are likely to excrete it – especially if it is a single dose. Larger individuals taking a “standard” dose (or one that isn’t increased to reflect their above-average weight) are equipped with a bigger system for efficient elimination.
However, it is important to also consider that DXM is lipophilic and may accumulate in fat stores throughout the body of a larger individual when administered over a long-term. This increased accumulation within fat stores suggests that retention may increase and elimination may take longer than usual. Conversely, if you have a low body fat percentage, DXM shouldn’t accumulate to a significant extent and faster elimination is likely.
Genetics: Perhaps the biggest factor to consider in regards to how long DXM will stay in your system are your genetics. The expression of alleles of your CYP2D6 gene will determine how long a DXM dose is likely to stay in your system. The CYP2D6 gene predicts the function of CYP2D6 isoenzymes in your liver.
If a genetic analysis (e.g. Genesight) reveals that you are a poor CYP2D6 metabolizer, you’ll likely retain DXM for a much longer duration than average. About 3% to 10% of the population are poor CYP2D6 metabolizers and may exhibit an elimination half-life of 19.1 hours. This indicates that it’ll take 4.38 days to fully clear DXM from the system of a poor metabolizer; this is nearly 3 days longer than average.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8841152
Hepatic function: DXM is known to be extensively metabolized by isoenzymes (namely CYP2D6) within the liver. For this reason, any individual with hepatic impairment may exhibit poorer function of CYP2D6 isoenzymes and may retain DXM for a longer duration. Suboptimal function of CYP2D6 as a result of hepatic impairment will likely increase plasma concentrations of DXM and prolong systemic retention.
The degree of an individual’s hepatic impairment will likely influence how long DXM stays in his/her system. The greater the severity of the impairment, the longer DXM will likely be retained, whereas in cases of minor impairment, increases in half-life may not be clinically significant. It is important to realize that hepatic function doesn’t affect DXM’s half-life to the same extent as CYP2D6 polymorphisms, however, it still has an impact on systemic retention.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/2789923
Metabolic rate: It is possible that a person’s BMR (basal metabolic rate) affects how long DXM stays in their system. Individuals with a high BMR are known to be utilizing more energy stores in a resting state, whereas people with a low BMR are using up less energy stores during rest. For this reason, many speculate that the higher an individual’s BMR, the quicker they are likely to metabolize and excrete an exogenous drug such as DXM.
Someone with a low BMR, on the other hand, may metabolize and excrete DXM (and other exogenous drugs) at a slower pace. There is some evidence from hyperthyroid and hypothyroid individuals that supports the impact of BMR on elimination half-lives of drugs. That said, the degree to which a high or low BMR among those with normative thyroid function affects DXM elimination isn’t well understood.
Renal function: Since a majority of DXM is processed by the kidneys and excreted via urine, impairment of renal function may compromise efficiency of DXM metabolite excretion. As a result of this compromised metabolite excretion, they may accumulate within the kidneys, sometimes to a considerable extent. Upon accumulation of DXM metabolites, some may be likely to get reabsorbed and recirculate throughout the body – leading to slower elimination.
The extent to which accumulation occurs is likely related to the degree of renal impairment. Someone with severe forms of renal impairment may experience a noticeable increase in DXM half-life, whereas an individual with minor impairment may not notice a significant difference in elimination half-life. That said, anyone with suboptimal renal function is likely to retain DXM metabolites for slightly longer than if their kidneys were healthy.
Dosage (High vs. Low)
The dosage of DXM that a person ingests will likely influence how long it remains in systemic circulation. Though elimination times are usually similar among users taking low-level medicinal dosages, elimination times may be considerably longer among those taking supratherapeutic or recreational doses. The increase in elimination half-life of DXM among those taking abnormally high doses is likely influenced by several factors.
Firstly, high dosages tax enzymes in the liver to a greater extent than lower doses. This means that CYP2D6 isoenzymes will need to work harder among high dose users because there’s a greater quantity of DXM to metabolize. As a result of the increased CYP2D6 isoenzyme workload, the efficiency of metabolism is likely to plummet, leading to increased plasma levels and protracted systemic retention of DXM.
It is the increased hepatic burden that is partly responsible for a significant increase in half-life among those that may have attempted to “overdose” with DXM. Additionally, at high doses, a greater level of DXM metabolites such as dextrorphan circulate throughout the body. This means that high dose users may essentially accumulate more metabolites than lower dose users – further prolonging elimination.
Finally, it is necessary to consider that renal excretion may be less efficient among high dose users. The heightened level of DXM metabolites as generated by a high dose may accumulate in renal pathways and some of these metabolites may be reabsorbed and recirculated throughout the user’s system, leading to slower-than-average excretion. It is the combination of less efficient hepatic metabolism, propensity of metabolite accumulation, and compromised renal excretion – that may extend half-life among high dose users.
Frequency of administration (Acute vs. Chronic)
The more frequently you use DXM, the more likely you are to ingest a high cumulative daily dosage. Someone using DXM several times per day at 20 mg will ingest a cumulative daily total of 60 mg per day. An individual using DXM just once per day at 30 mg will have only ingested half the dosage of the first hypothetical user, resulting in quicker systemic elimination as a result of a lower total dose.
Among frequent users, each successively administered dosage adds to the previous dose within the system. Frequent DXM users may ingest a second or third dose before their first dose was fully metabolized and/or excreted. This means that the DXM and its metabolites may accumulate within the plasma of a frequent user to a greater extent than they would have in an infrequent user.
Infrequent DXM users are less likely to ingest large doses in a short-duration, allowing the body to fully excrete metabolites from the previous dosage before another is introduced. It should also be noted that frequent users may build up a tolerance to the effects of DXM, requiring dosage increases to derive the same therapeutic (or recreational) effect that was attained when they initially began using DXM (at lower doses). Therefore frequent users of DXM will have a propensity to retain the drug in their systems for a longer duration than infrequent users.
Co-administered drugs (CYP2D6)
If you’ve taken DXM along with another drug, it is important to consider how the other drug may affect DXM’s metabolism. Since DXM is metabolized by CYP2D6 isoenzymes within the liver, any co-administered drug that interferes with or enhances the enzymatic function of CYP2D6 is likely to affect how long DXM stays in your system. Drugs classified as “CYP2D6 inhibitors” are known to interfere with CYP2D6 isoenzyme function.
Examples of CYP2D6 inhibitors include: Bupropion, Cinacalcet, Fluoxetine, Paroxetine, Quinidine, and Ritonavir. Should you have taken any of the aforementioned agents, you’ll likely metabolize DXM poorer than usual, leading to increases in plasma concentrations and a prolonged elimination. Contrarily, if you’ve taken a drug classified as a “CYP2D6 inducer,” your CYP2D6 isoenzyme function may have been bolstered.
Bolstering of CYP2D6 isoenzyme function leads to faster, more efficient metabolism of DXM. Examples of CYP2D6 inducers include: Dexamethasone, Glutethimide, and Rifampicin. Taking any of these agents along with DXM should lead to quicker-than-average systemic excretion. Keep in mind that the degree of respective CYP2D6 inhibition/induction may be contingent upon the potency of the specific drug, as well as the dosage at which it was administered.
DXM: Absorption, Metabolism, Excretion (Details)
Following oral administration of DXM (dextromethorphan), it is rapidly absorbed via the gastrointestinal (GI) tract. Peak plasma concentrations are attained in approximately 2.5 hours post-ingestion and the drug is widely distributed throughout the body. After absorption, DXM is subject to extensive first-pass hepatic metabolism.
Hepatic metabolism is chiefly facilitated by CYP2D6 isoenzymes (cytochrome P450 2D6), converting dextromethorphan (via demethylation) to its prominent pharmacologically active metabolite “dextrorphan.” Since the CYP2D6 isoenzyme is highly polymorphic, elimination half-life of DXM and “dextrorphan” metabolite formation is subject to interindividual variation. Approximately 84% of the population are considered CYP2D6 “fast metabolizers,” meaning they quickly metabolize DXM and form normal levels of dextrorphan metabolites.
Roughly 6.8% of the population are considered CYP2D6 “intermediate metabolizers,” meaning they are likely to retain DXM in their systems for nearly double the time of fast metabolizers. Finally up to 10% of the population are considered CYP2D6 “poor metabolizers,” indicating that they may retain DXM in their systems for a considerably longer duration than fast metabolizers and that less dextrorphan metabolites will be formed in the process.
To a minor extent, CYP450 enzymes other than CYP2D6 play a role in the metabolism of DXM. Specifically, CYP3A4 and CYP3A5 isoenzymes are thought to make minor contributions to DXM metabolism, converting dextromethorphan to 3-methoxymorphinan and 3-hydroxymorphinan metabolites. In fast metabolizers, DXM should be expected to exhibit a half-life of 3 to 6 hours, suggesting that it will have been eliminated from the plasma in under 33 hours.
However, among poor metabolizers, DXM’s half-life may increase to ~19.1 hours, suggesting that it may stay in a user’s system for nearly 4.5 days after their final dose. After DXM is metabolized and distributed, levels in the plasma decline and its metabolites are processed by the kidneys for urinary excretion. The percentage of unchanged parent drug (DXM) and metabolites that appear within urine is determined by CYP2D6 phenotype.
A fast metabolizer (CYP2D6) will excrete mostly dextrorphan metabolites within urine and a small amount of unchanged DXM. A poor metabolizer (CYP2D6) will mostly excrete unchanged DXM within urine and minimal (perhaps zero) dextrorphan metabolites. A majority of the drug is excreted within the first 24 hours after dosing via urine, and only 0.1% is excreted via feces.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/dextromethorphan
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/dextromethorphan.htm
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8841152
Types of DXM Drug Tests
Most people shouldn’t be worried about a drug test for “DXM” unless they have a history of abusing it. DXM isn’t assessed for on standard drug tests (e.g. SAMHSA-5) and is unlikely to be assessed for on more advanced panels. Since DXM is unlikely to stay in your system for longer than 48 hours, its detectability is considered low. Only in rare cases of DXM abuse could it trigger false-positives for PCP or opioids.
Urine tests: Assuming someone wanted to determine whether DXM and its metabolites were in your system, they could conduct a urine screening. This would involve collecting a fresh sample of urine and analyzing it with liquid-chromatography/mass-spectrometry (LC/MS) to determine levels of DXM and metabolites (e.g. dextrorphan). If levels of DXM and/or metabolites exceeded a certain threshold, it would be known as to whether you abused or ingested an exceptionally large dose of DXM.
That said, there will be some differences on a urinalysis dependent upon the individual DXM user. Users that are poor CYP2D6 metabolizers will excrete greater concentrations of DXM unchanged, whereas fast CYP2D6 metabolizers will excrete greater concentrations of DXM metabolites such as dextrorphan. Since poorer metabolizers are likely to retain the DXM for a longer duration than faster metabolizers, window of detection in a urine screening may be contingent upon CYP2D6 phenotype.
A majority of people are fast metabolizers and therefore will have excreted most DXM metabolites within 24 hours of their final dose. In some cases it could take up to 48 hours for complete urinary excretion. It would be unlikely to detect high levels of DXM metabolites after 3 days of cessation unless it was abused and/or used by a poor metabolizer. No one should really expect DXM to remain in his/her system after a week of sobriety.
Blood tests: It is known that peak plasma concentrations of DXM are attained in approximately 2.5 hours post-ingestion. This means that if a blood test to detect DXM were administered, it would be most accurate within 2 and 3 hours of the drug ingestion. To a certain extent, a blood test would be able to detect DXM for up to 24 hours after ingestion, but its window of detection would be shorter than a urinary screening.
Since blood tests are considered highly-invasive and only offer a short window of detection, they are seldom utilized outside of hospitalizations and scientific research. If a drug screening for DXM were devised, urinary testing would be preferred. However, results from a blood test would provide more accurate data regarding plasma concentrations of DXM and in determining CYP2D6 phenotype.
Hair tests: It is possible to detect DXM within the hair follicles of users, especially in proximal segments. Hair tests aren’t commonly employed to detect DXM simply due to the fact that it is not considered an illicit drug – it is available over-the-counter. However, scientists have determined that hair testing reveals DXM in the follicles of both humans and rats.
A hair test involves collecting a sample of follicles and sending it to a laboratory for analysis with gas chromatography/mass spectrometry (GC/MS) or liquid chromatography/mass spectrometry (LC/MS). These techniques will reveal how much DXM was likely in a user’s system and will determine whether the drug was used consistently and/or abused over an extended term. An advantage associated with hair testing for DXM compared to other modalities is its window of detection that may exceed 1 month post-final dose.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21311876
Saliva tests: In the future, it is likely that we will be able to collect a saliva sample (oral fluid) and determine whether any DXM (or other drugs) are in that person’s system. Since DXM is not illicit, it is unclear as to whether it will be a chemical included in salivary screening of future drug detection devices. That said, if we were able to swab the saliva of an intoxicated individual and rapidly determine if DXM was in his/her system – this would assist law enforcement agents.
An advantage of saliva testing over other modalities is that it is relatively non-invasive and is quick. A drawback associated with saliva testing for DXM is that it may be subject to inaccurate results. It may also provide a shorter window of detection when compared to urinary and/or hair screenings.
Tips to clear DXM from your system
If you’ve used DXM and are worried that it may have accumulated in your system, there are some tips you could consider to expedite its elimination. Keep in mind that none of these tips have been medically verified, they are based on speculation. Prior to acting upon any of the tips listed below, be sure to confirm safety and alleged efficacy with a medical professional.
- Activated charcoal: Supplementation with activated charcoal is great for general detoxification, but also effective for eliminating unmetabolized compounds from your system. If you took a large dose of DXM and/or are worried that high levels may be saturating within your liver, administration of activated charcoal will likely help. Activated charcoal has a negative electric charge, allowing it to bind to chemicals (and toxins) via adsorption – thereby eliminating them as quickly as possible from your system. This supplement may be of most benefit to CYP2D6 poor metabolizers.
- Calcium-D-Glucarate: If you took DXM, you’ll likely excrete a majority of the drug within 1 to 2 days of ingestion in your urine. Urinary excretion is facilitated by various pathways within your kidneys. If various pathways are clogged with toxins and chemicals, it may be of benefit to supplement with calcium-d-glucarate. This supplement acts as a beta-glucuronidase inhibitor which forces toxins out of detoxification pathways.
- CYP2D6 induction: To eliminate DXM as quickly as possible, concomitant ingestion of a CYP2D6 inducer is likely to speed things up. CYP2D6 inducers enhance isoenzyme function of CYP2D6, increasing the speed and degree of DXM metabolism. Rather than lingering in your liver for an extended duration, a CYP2D6 inducer will force the drug to be metabolized. A CYP2D6 inducer may be of greatest benefit to those with poor CYP2D6 function.
- Hydration: Hydration is understood to affect urinary flow rate, which in turn can affect renal excretion of drugs. If you want to ensure that DXM and/or its metabolites are eliminated with efficiency from your kidneys, you may want to drink plenty of water (as to remain hydrated). Obviously don’t overhydrate, but drink enough to ensure optimal renal excretion.
- Exercise: Getting some daily exercise may be beneficial if you used DXM over a long-term (or at a high dose). Long-term users may have accumulated more of the DXM within fat tissues and/or stores throughout the body than short-term users. By getting some daily exercise to burn some fat stores, you may force DXM out of your body at a quicker rate.
How long has DXM stayed in your system after stopping?
If you’ve taken DXM, share a comment regarding how long you believe it stayed in your system after your final dose. Do you believe that it lingered for a longer duration than usual such as over 48 hours? Or do you believe that you were able to eliminate DXM (and dextrorphan) from your body in a shorter period?
Support your speculation with data such as: CYP2D6 function, high/low dose usage, short/long-term of administration, co-administered drugs, etc. Understand that most individuals should eliminate DXM and its metabolites from systemic circulation within 1.38 days after their final dose. However, those with poor CYP2D6 metabolism may take 4 to 5 days to completely eliminate DXM from their systems.