Codeine (3-methylmorphine) is an opioid medication commonly prescribed for the treatment of severe coughing (antitussive), mild to moderate pain (analgesic), and/or uncontrollable diarrhea (antidiarrheal). It is considered a natural form of methylated morphine and is the second-most significant alkaloid in opium, accounting for up to 3%. In the United States, codeine is typically manufactured in the formats of codeine sulfate or codeine phosphate.
Though the specifics of codeine’s pharmacodynamics are unknown, it is believed to elicit morphine-like effects; in part, these effects may stem from the fact that codeine is converted into morphine during its metabolism. Codeine primarily affects mu-receptors within the brain, exhibiting opioidergic effects (to a lesser extent than morphine). This mu-receptor stimulation leads users to feel euphoria, pleasure, physical relaxation, and pain relief.
The drug has a high propensity for abuse/dependence, especially when utilized recreationally; hence its classification as a Schedule II controlled-substance. Ongoing or chronic usage of codeine may impair physical/mental performance and yield an array of adverse effects (e.g. brain fog/coordination deficits/sedation/etc.). To avoid adverse deleterious effects of codeine (and pass mandatory drug tests), many individuals have stopped ingesting codeine and hope to completely clear it from their systems.
How long does Codeine stay in your system?
Just because a person stopped taking codeine recently does not necessarily mean that the drug will quickly clear from their system. There is a time gap between ingestion and (100%) complete excretion of codeine (and its metabolites). The elimination half-life of codeine is thought to range between 2.4 hours and 2.9 hours – with most sources suggesting half-life times closer to the 2.9 hour end of the half-life spectrum.
This indicates that for most individuals, 50% of the drug will have been excreted from the body in 2 hours and 54 minutes post-ingestion. To completely clear codeine from a person’s system, it will take approximately 15.97 hours (nearly 16 hours). Assuming someone metabolizes codeine at a faster rate (e.g. 2.4 hour half-life), the drug may be excreted sooner in 13.2 hours.
That said, various metabolites such as morphine-3-glucuronide, and especially codeine-6-glucuronide, may have longer half-lives than codeine itself. This means that in order to ensure complete systemic clearance of codeine and its metabolites, it may take up to 24 hours. After 24 hours, most individuals should not have any remnants of codeine (nor its metabolites) within their bodies.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/codeine
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1391681
Factors that influence how long Codeine stays in your system
It is necessary to understand that clearance rates of codeine are subject to slight individual variation based on a variety of factors. Individual factors such as a person’s age, body mass, genetics, and organ function can impact metabolism and clearance of codeine. In addition, the dosage of codeine ingested, frequency of administration, and whether a person is taking other drugs may affect excretion times.
Two individuals may take the same format of codeine, at the exact same time, and with the same dosage – yet one may metabolize and excrete the drug faster than the other. This could mean that one person eliminates the drug from their system up to 4 hours quicker than the other individual. Examples of individual factors to consider include: age, body size, food intake, liver/kidney health, and urinary pH.
Age: It is understood that the age of a codeine user can affect metabolism and excretion times. In general, the younger a person – the better their overall physiological health and the greater the blood flow to organs such as the liver and kidneys (both of which are involved in codeine metabolism). Furthermore, younger individuals aren’t usually taking other medications which could prolong codeine excretion times. Elderly individuals (ages 65 and up) may exhibit slower metabolism and excretion times of codeine compared to younger people.
Body height/weight/fat: A person’s body size (height/weight/fat) can influence how quickly a drug is absorbed and broken-down. Specifically, the larger a person is in proportion to the dosage of codeine that they ingest, the more likely they are to clear it at a quicker rate. The smaller an individual (height/weight/fat) relative to dosage of codeine ingested, the slower they will be to metabolize and excrete codeine.
Genetics: There is often genetic variation among codeine users that can affect the speed by which the drug is metabolized and excreted. Genes responsible for regulating CYP2D6 isoenzyme function (in the liver) may facilitate ultra-rapid or extremely poor metabolism of codeine. An ultra-rapid metabolizer may have different effects and possibly a faster excretion rate of codeine (and metabolites) when compared to a poor metabolizer.
Liver/kidney function: It is thought that individuals with liver (hepatic) impairment will not metabolize nor excrete codeine as quickly as those with healthy liver functionality. Since enzymes in the liver are responsible for a majority of codeines metabolism, a impairment will likely prolong clearance; the exact length will depend on severity of impairment and dosage ingested. In addition, since the kidneys aid in excretion of codeine, kidney (renal) impairment may also slow clearance rates.
Metabolic rate: The faster a person’s BMR (basal metabolic rate), the more likely they are to process and eliminate drugs from their system in an efficient manner. Someone with a slower BMR may experience a slower metabolism and excretion. Though metabolic rate doesn’t usually have a major impact on codeine clearance, it likely has a subtle one.
Urinary pH: Since a majority of codeine (and metabolites) is excreted through urine, it is speculated that excretion may be impacted by a person’s urinary pH. Individuals with a urinary pH of high alkalinity will likely excrete codeine at a slower rate compared to those with a urinary pH of high acidity. Alkaline urine prevents the drug from getting fully excreted and prompts reabsorption, thereby slowing elimination. Acidic urine prevents reabsorption of codeine and results in expedited clearance.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16819548
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22867045
Frequency of codeine ingestion
There are individuals that rarely use codeine (on an infrequent basis) and there are others who ingest codeine regularly (on a daily basis). The more frequently a person ingests codeine, the longer it is likely to take for a person to metabolize and excrete the drug. This is primarily due to the fact that frequent codeine users tend to accumulate more of the drug within their bodies from consecutive administration.
Think about it, a frequent codeine user may take their first dose in the morning, and before it is fully metabolized, may ingest a second dose. This second dose adds a greater total amount of codeine to circulate throughout their system, and further taxes the liver/kidneys to metabolize and excrete it. Since only so much codeine can be processed at a time, the rate of metabolism may slow and the drug won’t be excreted with maximal efficiency.
Additionally, frequent codeine users will likely have greater levels of codeine metabolites circulating throughout their system (and for a longer duration). Frequent users may also ingest codeine at later times in the day (e.g. afternoon/night), which is when the body’s metabolism tends to slow (especially at night). The slowing of the body’s metabolism at night can prolong codeine metabolism and excretion.
Therefore, if administered at a maximum 6 times per day, metabolism may take significantly longer than someone administering codeine just once per morning or once a week. Less frequent users will not accumulate as much codeine, and will be better at efficiently metabolizing the smaller amount that they do ingest.
Co-administration of drugs (Inducers vs. Inhibitors)
It is known that co-administration of other drugs (and over-the-counter supplements) could affect metabolism and clearance rates of codeine. Since codeine is chiefly metabolized by liver enzyme CYP2D6, drugs that alter CYP2D6 functioning (via induction or inhibition) will likely either expedite or prolong codeine clearance. CYP2D6 inducers are known to enhance metabolism and clearance of codeine and include substances such as: Dexamethasone and Rifampin.
On the other hand, CYP2D6 inhibitors impair metabolism and clearance of codeine. Examples of such CYP2D6 inhibitors include: Amiodarone, Celecoxib, Clomipramine, Diltiazem, Haldol, Perphenazine, and various SSRIs. If you happen to be taking either a CYP2D6 inducer or inhibitor, it is necessary to realize that this could affect the speed at which you are able to clear codeine from your system.
To a lesser extent, codeine is metabolized by CYP3A4 enzymes, therefore drugs that act as inducers/inhibitors of CYP3A4 may also affect clearance rates. Examples of CYP3A4 inducers include: Carbamezepine, Dexamethasone, Glucocorticoids, and Progesterone. Examples of CYP3A4 inhibitors include: Aminodarone, Cannabinoids, Danazol. Realize that drugs affecting CYP2D6 will likely have a greater impact on clearance than agents affecting CYP3A4.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1811505
Dosage (High vs. Low)
The dosage at which codeine is administered may affect how long it stays in your system. The higher the dosage of codeine a person ingests, the greater the toll on the individual’s physiology – specifically the liver and kidneys to metabolize and excrete it. Those taking lower doses of codeine will likely be able to efficiently metabolize (via liver) and excrete (via kidneys) the drug; there is a reduced physiological burden at lower doses.
When utilized for the treatment of chronic pain, codeine may be prescribed between 15 mg and 60 mg to be taken once every 4 hours “as necessary.” The maximum dosage of codeine to be ingested in 24 hours (1 day) is considered 360 mg. Since dosages greater than 60 mg aren’t associated with any additional improvements in pain (and are likely to trigger adverse effects), most people take doses under 60 mg.
The more codeine a person ingests on a regular basis, the more likely the drug (and various metabolites) will accumulate within their system. Therefore individuals on higher doses (especially relative to body mass) can slow clearance rates. The lower the dose of codeine you took, the faster your body should be able to metabolize and excrete it.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8934303
Codeine: Absorption, Metabolism, Excretion (Details)
Codeine is commonly considered a prodrug due to the fact that it is inactive until metabolized. Following ingestion, codeine is rapidly absorbed by the gastrointestinal tract and processed by the portal vein within the liver. Plasma concentrations of codeine peak approximately 1 hour after ingestion, and the drug is distributed at an estimated 3 liters/kg to 6 liters/kg. Only 7% to 25% of codeine binds to plasma proteins, and it is unlikely to accumulate in bodily tissues.
Within the liver, codeine is metabolized by a variety of enzymes including: CYP2D6, CYP3A4, and UGT2B7. Approximately 70%-80% of a codeine dose is converted by UGT2B7/UGT2B4 via conjugation with glucuronic acid to the metabolite “codeine-6-glucuronide” (C6G). CYP2D6 is responsible for converting 5%-10% of codeine to morphine via O-demthylation.
CYP3A4 facilitates conversion of 10%-15% codeine into norcodeine via N-demethylation. The morphine and codeine-6-glucuronide (C6G) are thought to elicit a majority of codeine’s analgesic effects via action upon mu-opioid receptors. Both morphine and norcodeine are subject to additional metabolism via conjugation with glucuronic acid, forming: (60%) morphine-3-glucuronide (M3G) and (5%-10%) morphine-6-glucuronide (M6G).
After codeine is metabolized by the liver, an estimated 90% of the drug is excreted via the kidneys within 24 hours of ingestion. Up to 10% of the excreted codeine is unchanged, whereas the remaining consists of metabolites: (70%) codeine-6-glucuornide (C6G), 10% norcodeine, 10% morphine, 4% normorphine, and 1% hydrocodone. A small percentage of the drug is also excreted via feces.
Since the average elimination half-life is 2.9 hours, the codeine should be fully excreted from a person’s body within 16 hours. Though half-lives of various codeine metabolites could exceed 2.9 hours, they should have been fully eliminated from the body within 24 hours.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/codeine
- Source: http://www.ncbi.nlm.nih.gov/pubmed/1391681
- Source: https://www.pharmgkb.org/pathway/PA146123006
Types of Codeine Drug Tests
There are a variety of ways in which a person could be drug-tested for codeine. While the most common way to test for codeine is via a urine sample, other ways to determine whether someone has used codeine include: saliva tests, hair tests, and blood tests. Most users are concerned with urine tests (due to their popularity) and hair tests (due to their longer window of detection).
Urine tests: Most standard drug tests require collection of a fresh urine sample. Urine tests for codeine are considered less invasive than blood tests and provide a longer window to detect codeine and various metabolites. To test positive for codeine on a urine test (in accordance with SAMHSA-5 standards), you’d need to have at least 2000 ng/ml of opioids in your system; this high cutoff is set to avoid false-positives.
Codeine and its metabolites will become detectable within urine within several hours of ingestion, and remain detectable for between 1 and 2 days. Unless an individual took an extremely large dosage of codeine and/or suffers from hepatic/renal impairment – a urine test should not detect codeine after 24 hours. An estimated 90% of the codeine (and its metabolites) will have been excreted via the urine within 16 hours, making it extremely unlikely to test positive for codeine on a urine test after 1 day.
Research has shown that when urine samples are analyzed with EMIT (enzyme multiplied immunoassay technique) or GC/MS (gas chromatography/mass spectrometry), codeine (and metabolites) can be detected between 22 to 52 hours post-ingestion. Detection times in urine are generally longer when a greater dosage was ingested.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7762943
Hair tests: Another less common way to test whether someone had ingested codeine is via a hair test. A hair test involves plucking hair follicles (usually from a person’s head) and sending them to a laboratory for analysis. Research has shown that codeine can be detected in the proximal 1 cm of a hair sample after just 30 minutes of an orally administered 120 mg dose.
In other words, individuals taking high doses may test positive for codeine in a hair sample within just the most recent outgrowth of 1 cm. In distal hair segments, it will take codeine longer to appear (sometimes up to 3 weeks) following an oral 120 mg dose. It has been found to remain detectable for up to 10 weeks (70 days), making hair testing the best option to determine long-term codeine usage.
Various codeine metabolites such as morphine and glucuronides may not be detectable in hair samples. Furthermore, it is thought that hair color can impact the ability to detect codeine in human hair. Individuals with black hair (and to a lesser extent brown hair) are most likely to test positive compared to those with blonde or red hair.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8839662
- Source: http://www.ncbi.nlm.nih.gov/pubmed/14670132
Saliva tests: It is known that saliva concentrations of codeine tend to correlate well to plasma concentrations of codeine. Since saliva testing is relatively quick, and less invasive than a blood draw or urine sample, it may be a preferred testing modality in certain circumstances. For example, if a law enforcement agent suspects that an individual may have illicitly ingested codeine – it may be most convenient to collect a sample of oral fluid (saliva) for analysis.
Concentrations of codeine in saliva are thought to peak between 30 minutes and 2 hours of administration, ranging from 19 ng/ml to 74 ng/ml (~46 ng/ml). A saliva test may detect codeine within just 15 minutes of ingestion, and for over 24 hours following ingestion. That said, saliva codeine concentrations drop significantly after several hours and other substances in salivary fluid may interfere with test results.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/10517550
- Source: http://www.ncbi.nlm.nih.gov/pubmed/9541855
- Source: http://www.ncbi.nlm.nih.gov/pubmed/6834790
Blood tests: Due to the compressed window of detection for codeine in the bloodstream, as well as the invasive nature of blood tests, blood-based assessments are seldom preferred. A blood test may be used among individuals that are hospitalized for a suspected overdose and/or drug-related complications. Upon hospitalization, a blood sample may be collected and rapidly analyzed to determine whether the patient had ingested codeine.
Codeine can be detected in the bloodstream within just minutes of ingestion and its levels peak within 1-2 hours after administration. Since codeine has a half-life of 2.9 hours, the drug won’t remain detectable for long within the blood. Most blood tests will only detect codeine within 16 hours of ingestion.
Who is usually tested for Codeine?
Since codeine (and its metabolites) can be detected on standard SAMHSA-5 drug tests, many people are subject to codeine testing. This includes: athletes (professional and collegiate), drug rehabilitation patients, employees (current and prospective), military members, and possibly even some students. Should an individual fail (i.e. test positive) for opioids, it could result in harsh penalization.
Athletes: To ensure that athletes aren’t ingesting illicit substances and/or performance enhancing agents, they are commonly tested for drugs. Should an athlete have recently ingested codeine, he/she may test positive for opioids, resulting in a temporary suspension or permanent ban from their respective sport. For this reason, it is uncommon for an athlete to regularly use codeine.
Drug rehabilitation patients: Individuals at drug rehabilitation facilities are often drug-tested to ensure that they’ve remained sober. Standard tests such as the SAMHSA-5 and even more extensive testing panels are commonly administered to rehab patients. Should a rehab client test positive for codeine (or opioids), they may require a longer stay in rehab and more coaching.
Employees: Many employees are subject to random and/or mandatory drug testing. These drug tests commonly assess for the presence of opioids and will detect codeine. Should an employee test positive for codeine, the individual may lose his/her job. In addition, prospective employees may be denied a job if they test positive for codeine.
Military personnel: Those enlisted in the U.S. military are regularly tested for ingestion of drugs. Opioids like codeine are easily detected on a urine test. Should a military member have ingested opioids, he/she may be delisted and sent packing without compensation for his/her services. Therefore it is uncommon for those in the military to ingest codeine without an authorized prescription.
Students: These days more schools are starting to drug-test their students. This testing is typically conducted to determine whether a student may be ingesting substances like codeine on an illicit or unauthorized (non-medicinal) basis. Should opioids get detected in a student, he/she may be suspended and mandated to a drug rehabilitation facility or troubled-youth program.
Tips to clear Codeine from your system
There are several ways in which a person may be able to expedite the clearance of codeine from their system. Tricks to clear codeine at a quicker rate may involve: manipulating urinary pH and possibly utilizing enzymatic “inducers” to speed up drug metabolism. Keep in mind that none of these clearance tips have been medically verified. Always consult a medical professional if considering any of the tips below.
- Discontinue codeine: Though discontinuation of codeine isn’t some special trick to expedite clearance, those who don’t stop using the drug should not expect it to be efficiently cleared from their body. Some people think they can get away with using the drug at low doses and/or with less frequency and still fully detoxify. If you want to operate fully sober (without codeine in your system), you’ll need to completely stop using.
- Enzymatic “inducers”: There are a variety of drugs and supplements that can enhance the metabolism of codeine, possibly leading to a quicker clearance speed. Substances that induce activity of CYP2D6, CYP3A4, and other liver-based enzymes may reduce total excretion time. Understand that enzymatic inducers should never be ingested without medical consent – as they may have contraindications with codeine and/or other substances that you’re taking.
- Manipulate urinary pH: A person’s urinary pH is known to affect excretion rates of drugs (likely including codeine). Strategically increasing the acidity of your urine will likely lead to faster overall clearance, especially if your urine is of high alkalinity. The degree to which clearance is likely related to the level of acidity.
- Hydration/Diet/Supplements: Staying hydrated, eating a healthy diet, and taking supplements may be helpful when attempting to detoxify. Hydration ensures that your body will excrete a normative amount of codeine in your urine, whereas dehydration may slow the process. A healthy diet will ensure that your body has the nutrients it needs to run properly. Supplements may support liver and/or kidney function – leading to optimal clearance times.
- Regular exercise: Getting a bit of daily exercise (especially in the form of cardio) can ramp up metabolism, improve blood flow/circulation to certain regions, and should aid in drug clearance. Though the degree to which exercise will speed up codeine clearance isn’t known, it may help. If anything, exercise can help your body produce natural endorphins that replace the effect of codeine.
Have you failed a drug test because of Codeine?
If you’ve been drug-tested and ended up failing the test because you ingested codeine, share your experience in the comments section below. Discuss how much codeine you took, the type of drug test administered, as well as the amount of time between codeine administration and testing. Mention whether the test detected “codeine” or other metabolites such as morphine and codeine-6-glucuronide (C6G).
On the other hand, if you were able to pass a drug test following ingestion of codeine, discuss why you think you passed the test. Realize that in most cases, codeine will have cleared from a person’s system within 24 hours post-ingestion. Nearly everyone should be able to pass a drug test if administered 48 hours post-codeine ingestion.