Tramadol (brand name “Ultram”) is a synthetic drug approved by the FDA for the treatment of moderate to severe pain. It initially hit the market in 1995 as an immediate-release (IR) drug, and was since also engineered into an extended-release (ER) drug in 2005. Compared to many other pain medications, Tramadol is unique in that it elicits an array of effects across a spectrum of neurotransmitters.
It primarily acts as a mu-opioid receptor (MOR) agonist, thereby releasing both enkephalins and beta-endorphin to facilitate analgesic effects. Mu-receptor agonism is also understood to increase neurophysiological relaxation (which reduces anxiety) and enhance mood (often significantly). In addition, Tramadol increases serotonin (via SSRI/5-HT release) and antagonizes: NMDA, 5-HT2C, nAChRs, TRPV1, M1, and M3 receptors.
As a result of its complex mechanism of action, Tramadol is an appealing drug for the treatment of pain, as well as a multitude of off-label conditions. However, many users of the drug may dislike its side effects (e.g. itchiness, constipation, nausea), be wary of its long-term effects, and/or feel as if the drug has lost its efficacy (due to tolerance). For these reasons, some individuals have quit the drug, but wonder how long it’ll stay in their system after stopping.
How long does Tramadol stay in your system after stopping?
If you’ve stopped taking this drug, you’re likely in for a rollercoaster-ride of Tramadol withdrawal symptoms. Many of the discontinuation symptoms will be difficult to tolerate, especially if you’ve been taking the drug for a long-term. However, most people find solace in understanding that their body can detoxify itself once the Tramadol has fully left their system.
To understand how long Tramadol is likely to stay in your system after stopping, it is necessary to consider its elimination half-life. Elimination half-life is the average amount of time it takes for 50% of the drug to have been cleared from your system. Medical literature indicates that Tramadol’s elimination half-life is around 6.3 hours.
With this information we can estimate that upon complete cessation of Tramadol, it’ll stay in your system for approximately 1.44 days. Despite the fact that Tramadol should be out of your system within 48 hours after your last dose, it is necessary to consider that its primary metabolite “O-desmethyltramadol” (M1) has a longer half-life of 7.4 hours. For complete systemic elimination of Tramadol and its O-desmethyltramadol (M1) metabolite, it’ll take around 1.7 days.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/Tramadol
Variables that influence how long Tramadol stays in your system
Even though most people who’ve quit taking Tramadol should clear it, along with its metabolite (O-demethyltramadol), in less than 48 hours after their final dose – not everyone does. Some people take considerably longer than 2 days to fully excrete the drug, while others may excrete it in a substantially shorter duration. Variance in excretion speed are usually due to variables such as: individual factors, dosage, term of administration, and co-ingestion of other drugs.
If two individuals were to take a single 50 mg dose of Tramadol simultaneously, one person would likely excrete the drug quicker than the other. Perhaps one person would excrete the Tramadol substantially faster than the “norm,” or another individual may excrete it substantially slower than average. In any regard, individual factors such as: a person’s age, body mass/fat, genetics, and hepatic function can influence Tramadol’s pharmacokinetics – thereby affecting its excretion speed.
Age: It is hypothesized that the half-life of Tramadol may be increased among elderly patients compared to healthy adults. Elderly individuals often exhibit reduced hepatic blood flow and are taking other medications that may interfere with drug metabolism. Furthermore, elderly individuals may have other health problems and decreased physiologic efficiency as a result of old-age, resulting in slower excretion compared to younger adults.
Body mass + Body fat (%): It may be helpful to consider a person’s body mass when estimating how long Tramadol is likely to remain in their system. Usually, the greater a person’s body mass (height/weight) relative to the dosage of Tramadol they’ve taken – the quicker they’ll excrete the drug from their system. On the other hand, the lesser a person’s body mass in respect to the ingested Tramadol dose – the less efficiently it is likely to get metabolized and excreted.
Additionally, a person’s body fat percentage is also thought to influence detoxification speed. Individuals with a high body fat percentage may accumulate more Tramadol over time than people with a low body fat percentage, resulting in slower clearance. This is due to the fact that Tramadol is lipophilic, meaning it binds to fat stores and can “build-up” throughout the body.
Genetics: It is necessary to understand that genetic variants, particularly of genes responsible for influencing hepatic enzymes, can affect the pharmacokinetics of Tramadol. Since the drug is chiefly metabolized by CYP2D6 isoenzymes to form O-desmethyltramadol – variants of CYP2D6 alleles may affect both clearance speed and elimination half-life. Variation in other enzymes CYP3A4 and CYP2B6 may also impact how long Tramadol stays in your system, but to a lesser extent than CYP2D6.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12191703
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17570739
Food intake + Hydration: If you took your last dose of Tramadol with food, it could’ve affected its time of absorption. A large meal along with Tramadol is thought to delay its absorption because the body is simultaneously working to breakdown food. Delayed absorption means that it may take your body slightly longer to eliminate the drug because it wasn’t absorbed as quickly.
This is not to suggest that the food affects elimination half-life; this should remain unaffected. In addition to food intake possibly delaying absorption, intake of fluids may expedite excretion. Significant fluid intake is thought to boost urinary flow rate, which is known to enhance clearance speed.
Hepatic + Renal function: Tramadol is extensively metabolized by enzymes within the liver and processed by the kidneys prior to excretion. Should an individual exhibit hepatic impairment, the elimination half-life of Tramadol may increase. In other words, it may take longer for the liver to “break down” the drug and its metabolites as a result of its impaired function.
This may result in heightened levels of Tramadol circulating throughout the body, taking longer to eliminate. To a lesser extent, a person’s renal function will also affect excretion of Tramadol. Someone with suboptimal kidney performance may excrete the drug at a slower rate (with less efficiency) compared to those with normative renal function.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/14650359
Metabolic rate: A person’s basal metabolic rate (BMR) may influence the duration over which Tramadol remains in systemic circulation following your last dose. Specifically, those with high BMRs often metabolize and excrete drugs (and other exogenous substances) faster than individuals with low BMRs. A high BMR indicates that a person is burning more energy at rest, which also often leads to more efficient drug metabolism and excretion.
A high BMR is also often associated with less total body fat for Tramadol binding and accumulation. As a result, those with higher BMRs may excrete the drug quicker than those with low BMRs. That said, the extent to which metabolic rate affects elimination half-life of Tramadol isn’t fully elucidated.
Urinary pH: Most of a Tramadol dose is eliminated via urinary excretion in the form of metabolites. Some research suggests that urinary drug clearance is often influenced by the pH of a person’s urine. Specifically, the greater the alkalinity of a person’s urine, the longer they’re likely to retain drug metabolites prior to excretion.
Alkaline urine may promote reabsorption of Tramadol metabolites by the kidneys, resulting in recirculation throughout the system. For this reason, half-life could be extensively increased among individuals on a highly alkaline diet. On the other hand, those with acidic urine are thought to excrete metabolites of Tramadol with efficiency and inhibit the possibility of reabsorption and recirculation.
Dosage (Low vs. High)
The dosage of Tramadol that a person takes can influence how long it remains in their system. Higher doses place greater burden on hepatic isoenzymes for metabolism, as well as get converted into an increased number of metabolites prior to excretion. Therefore a person taking a higher dose of the drug (e.g. 300 mg per 24 hours) will metabolize the drug at a slower speed (due to the increased amount) and more metabolites will necessitate clearance – compared to a low dose user.
In addition to slower metabolism and excretion speed, high dosages yield greater accumulation of Tramadol (and metabolites) in body fats/tissues. A study with horses noted that when 10 mg/kg doses were administered, a greater amount of the drug’s “M2” (N-desmethyltramadol) accumulated compared to 5 mg/kg doses. Although these findings don’t necessarily apply to humans, the possibility of increased accumulation with dosing makes logical sense – and shouldn’t be dismissed.
Another study reported that among those who’ve overdosed on Tramadol, the mean half-life of the drug increases to 9.24 hours (compared to its average of 6.3 hours). Researchers noted that the degree to which half-life increased was “dose-dependent” among those who overdosed. In other words, the highest overdoses were associated with the longest half-lives compared to the lowest overdoses. This supports the idea that ingested dose directly influences Tramadol’s half-life – especially at supratherapeutic levels.
- Source: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348403/
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24180699
Term of Administration
Both the frequency by which someone administers Tramadol, as well as the duration of the term over which it is administered can affect how long it is likely to stay in their system. Someone taking immediate-release (IR) Tramadol on an “as-needed,” intermittent basis will likely excrete the drug quicker than an individual taking extended-release (ER) Tramadol once daily. Since most Tramadol users take the 24-hour “ER” format, term of administration typically has a greater influence on excretion than frequency of usage.
Someone that took Tramadol ER for just 2 days is unlikely to have reached steady state concentrations of the drug throughout their bloodstream. It is estimated that steady state levels are attained after approximately 4 days of administration. For this reason, if someone used the “ER” format for less than 4 days, they probably will excrete it faster than someone who’s been taking it for over 4 days.
Some speculate that the drug continues to accumulate within the body, specifically the tissues even after reaching a steady state within the bloodstream. Tissue accumulation may occur to a greater extent in a long-term user compared to short-term user. Research in horses and humans shows that Tramadol and its metabolites accumulate to a greater extent when administered over a long-term compared to a short-term (or single-dose).
It should also be mentioned that many long-term users are taking higher doses of Tramadol than short-term users (resulting from tolerance associated with long-term treatment). In this case, not only would the long-term of administration have resulted in greater Tramadol (and metabolite accumulation), but the upward titration in dosing would’ve as well. In short, if you are a single-dose or short-term Tramadol user, you’ll probably excrete the drug faster than a long-term user.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/7517823
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24180699
Co-ingestion of other drugs
If you’re taking other drugs along with Tramadol, its pharmacokinetics may be altered. Since Tramadol is metabolized primarily by CYP2D6 to form its most prominent metabolite “O-desmethyltramadol” (M1), any drugs interacting with the functionality of CYP2D6 isoenzymes could influence its elimination half-life. Drugs known as CYP2D6 inhibitors interfere with CYP2D6 function, resulting in less efficient metabolism and impaired clearance.
Examples of some CYP2D6 inhibitors include: Cinacalcet, Paxil, Prozac, Quinidine, Ritonavir, and Wellbutrin. On the other hand, drugs that induce or enhance function of CYP2D6 are thought to reduce metabolism and excretion times. Examples of CYP2D6 inducers that may expedite the formation of O-desmethyltramadol include: Dexamethasone and Rifampicin.
To a lesser extent, enzymes such as CYP2B6 and CYP3A4 aid in the conversion of Tramadol to form the less notable metabolite N-desmethyltramadol (M2). Therefore taking a CYP2B6 inhibitor (e.g. Curcumin, Orphenadrine, ThioTEPA, Ticlopidine) or CYP3A4 inhibitor (e.g. Indinavir, Nelfinavir, Ritonavir, Saquinavir) – could slow the formation of M2. On the other hand, a CYP2B6 inducer (e.g. Carbamazepine, Phenobarbital, Phenytoin, Rifampicin) or CYP3A4 inducer (Carbamazepine, Phenobarbital, Phenytoin, Modafinil, St. John’s wort) may expedite the formation of M2 (N-desmethyltramadol).
Tramadol (Ultram): Absorption, Metabolism, Excretion (Details)
Following administration of Tramadol, it is extensively absorbed by the gastrointestinal (GI) tract. The bioavailability of a 100 mg oral dose is estimated to be 75% and peak plasma concentrations of Tramadol (and its O-desmethyl metabolite) appear 1.5 to 3 hours post-administration in healthy adults. The drug is then distributed throughout the body and approximately 20% of a dose binds to plasma proteins.
Steady state concentrations are attained within 2 days of administration of the immediate release (IR) format, whereas 4 days are required to reach a steady state with the extended-release (ER) format. As a result of its lipophilic properties, Tramadol is known to accumulate within bodily tissues; the accumulation increases over time and with higher doses. After the drug is absorbed by the gastrointestinal tract, it is metabolized extensively within the liver.
The major metabolic pathways that convert Tramadol to metabolites include O-demethylation, N-demethylation, glucuronidation, and suflation. CYP2D6 enzymes are known to play a major role in the O-demethylation process, converting Tramadol to “O-desmethyltramadol” (M1). N-demethylation is spurred by CYP2B6 and CYP3A4 enzymes, converting Tramadol to the less prominent metabolite, “N-desmethyltramadol” (M2).
Both O-desmethyl and N-desmethyl metabolites undergo secondary metabolism to form: N, N-didesmethytramadol (M3) and N,O-didesmethyltramadol (M5), followed by N, N,O-tridesmethyltramadol (M3). Hepatic glucuronidation is facilitated by UGT2B7 and UGT1A8 enzymes. Tramadol and all of its metabolites are then processed by the kidneys for urinary excretion.
Research suggests that 60% of a Tramadol dose appears as metabolites within urine, whereas 30% appears as unchanged Tramadol. Based on the half-life of Tramadol at 6.3 hours, and its primary “M1” metabolite (O-desmethyltramadol) at 7.4 hours, both should be completely excreted within 2 days of ingestion.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/Tramadol
- Source: https://www.pharmgkb.org/pathway/PA165946349
Types of Tramadol Drug Tests
Though Tramadol will not be detected on a standard (SAMHSA-5 panel) drug screening, it is certainly detectable with an advanced panel screening. For example, a toxicology screening specifically engineered to detect prescription drugs is likely to detect Tramadol. Types of tests include: urine tests, hair tests, saliva tests – and in rare cases, blood tests.
Urine tests: A urine test involves collecting a fresh urine sample from a prospective Tramadol user. Upon collection of this sample, it is sent to a laboratory and analyzed with gas chromatography/mass spectrometry (GC/MS) to detect unchanged Tramadol, but mostly its metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2). Research shows that Tramadol (and metabolites) appear in urine within 2 hours of ingestion.
Furthermore, Tramadol (and metabolites) remain detectable for up to 40 hours after administration at the threshold of 12.5 pg. Assuming you excrete Tramadol at an average rate, it should be out of your urine within 2 days (48 hours) of ingestion. That said, it is necessary to realize that when administered at high (supratherapeutic doses), especially over a long-term, detection windows may be extended for an additional day or two.
It is also necessary to note that Tramadol is capable of triggering a false-positive on a PCP (phencyclidine) urine screening. Although a false-positive for PCP on a urine test after Tramadol ingestion isn’t common, it may occur. This is something to be aware of if you’ve never used PCP, but test positive for it because of your Tramadol prescription.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/8237385
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21924518
Hair tests: Hair testing is generally administered to complement urine testing, but may be used as a standalone drug test modality. A hair test typically involves collecting a sample of follicles from a person’s head and sending them to a laboratory for analysis. Most of the follicles will need to be at least 3 cm in length, and the longer each one is, the easier it’ll be to detect long-term Tramadol ingestion.
After the follicles are collected, they are often analyzed with a technique called liquid chromatography/mass spectrometry (LC/MS). This technique will reveal the amount of Tramadol, O-desmethyltramadol (ODMT), and N-desmethyltramadol (NDMT) that someone has ingested. The accuracy of a hair test is nearly perfect and listed in some publications as between 90 and 110%, with recovery values of the drug exceeding 90%.
Research has shown that in cases of Tramadol abuse, concentrations of unchanged Tramadol and its ODMT/NDMT metabolites are high, within the range of 0.22-1.18 ng/mg of hair. Someone using Tramadol with proper medical care will only exhibit 0.07-0.80 ng/mg of hair – substantially less than abusers. Due to their high level of accuracy, minimal invasiveness, and long detection window (spanning months after ingestion), hair tests are an appealing way to detect Tramadol.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25459945
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23519701
- Source: http://www.ncbi.nlm.nih.gov/pubmed/23127661
Saliva tests: Collecting an oral fluid sample (of saliva) from a person’s mouth can also reveal whether they’ve used Tramadol. Following collection of an oral fluid sample, it is then sent to a laboratory and analyzed with gas chromatography/mass spectrometry (GC/MS). This “GC/MS” technique is able to determine whether any Tramadol or metabolites (M1/M2) remain in a person’s system.
Research shows that following Tramadol administration, up to 87.7% can be detected in salivary fluid. The drug is thought to initially become detectable within less than an hour of ingestion, and may remain detectable for over 24 hours. Though saliva samples are convenient and may be improved upon in the future, they provide a shorter window of detection than urine testing.
A new testing modality called “Exhaled Breath” (EB) has emerged as well. This is less invasive than collecting salivary fluid from a prospective user. It involves utilizing a breathalyzer-like device formatted to detect prescription drugs in the breath of a user. Research shows that Tramadol and its metabolites appear within “exhaled breath” for 8 to 24 hours after administration.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26388171
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17194631
Blood tests: A blood test can be used to detect Tramadol quickly after ingestion. It is thought that blood testing detects Tramadol more quickly than any other modality. However, blood testing is inconvenient in the fact that it is invasive and only offers a short window to detect Tramadol after administration. Following ingestion, the drug should appear within the bloodstream for about an hour, but may not remain detectable for 24 hours post-ingestion.
In most cases, blood tests are used in scientific research and for hospitalized patients. Those in the hospital as a result of a suspected Tramadol overdose may have blood drawn to determine the exact serum levels. Urine tests and hair tests are less invasive and provide longer detection windows than blood tests, hence are preferred.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21735309
Who could get tested for Tramadol?
Most individuals will not be tested for Tramadol unless a law enforcement agent suspects that they’re intoxicated on a prescription drug. Certain professions such as: truckers, pilots, and those operating heavy machinery may get screened randomly for prescription drugs like Tramadol. Other individuals such as: military personnel, rehab patients, and criminals may also be subject to random prescription drug screenings.
- Athletes: It is extremely unlikely that an athlete would use Tramadol without authorized medical permission. It is also rare that an athlete would be subject to extensive drug panels for prescription drugs like Tramadol. That said, should a collegiate, professional, or Olympic athlete get caught with Tramadol in his/her system – they may be penalized or banned from competition.
- Criminals: Law enforcement agents often find that criminals ingest any drugs they can obtain, regardless of whether they’re prescriptions. Since ingestion of Tramadol at high doses elicits an opioidergic intoxication, this may be appealing to criminals. Should a law enforcement agent suspect that a criminal has taken Tramadol (or used the drug in a crime), that person may be subject to testing and punished if they test positive.
- Employees: Many employers require that their employees maintain a state of alertness, vigilance, and focus on the job. Lack of concentration could result in the death of a fellow employee, damaged equipment, or other injuries. For this reason, various jobs such as: truck drivers, pilots, and those operating heavy machinery – may be tested for Tramadol (and other prescription CNS depressants).
- Military personnel: On occasion, the military may test their personnel for prescription drug usage. This testing helps determine whether any individual administered drugs on an unauthorized basis. Additionally, since Tramadol is a depressant, it may increase likelihood of errors in combat and training. Any military members that test positive for Tramadol without medical approval may be delisted and/or penalized.
- Rehab patients: Individuals in rehab may be prescribed Tramadol to help them cope with chronic pain and/or transition off of more potent medications. That said, most individuals in rehab are attempting to kick the habit of all drugs and live a sober lifestyle. Since rehabilitation professionals know that patients may attempt to abuse drugs (even prescriptions), they may issue random drug tests capable of detecting Tramadol.
How to get Tramadol out of your system
Most people want to know what they can do to fully clear Tramadol from their system as soon as possible. Below are some tips that may prove beneficial for expediting the clearance of Tramadol and its metabolites from your body after stopping. Prior to implementation of any of these suggestions, always verify their safety and hypothetical efficacy with a medical professional.
- Complete cessation: Permanently stopping Tramadol can be tough, especially if you’ve been taking it for a long-term. However, complete cessation is required if you want to fully excrete the drug from your body. Realize that the sooner you cease usage of Tramadol, the quicker you can expect it to be excreted.
- Burn body fat: Tramadol is a lipophilic drug, meaning it’ll bind to fat stores throughout your body. If you have a high percentage of body fat, Tramadol may have accumulated to a significant extent within your system. Burning body fat will help purge your fat stores of the accumulated Tramadol, thereby speeding up detoxification.
- Maintain hydration: Most of a Tramadol dose is metabolized within the liver, processed by the kidneys, and eliminated via urine. Maintaining hydration ensures that your urinary flow rate is high. A high urinary flow rate is associated with faster clearance speed and excretion of various drugs, especially those that are eliminated principally via urine. Drink plenty of water to ensure that your urinary flow rate is optimal.
- Acidify urine: In addition to increasing urinary flow rate with hydration, you may want to acidify your urine. Individuals with a high urinary pH (alkaline urine) tend to excrete drugs slower than those with a low urinary pH (acidic urine). You can enhance the acidity of your urine by eating foods such as meats, grains, cranberries, etc. Don’t go overboard with the acidification though as this could result in acidosis.
- Activated charcoal: To ensure that no unmetabolized Tramadol or its metabolites are floating around within your system, you may want to take activated charcoal. I recommend activated charcoal as being among the best supplements for antidepressant withdrawal. It essentially binds to any toxic remnants within your gut and ensures that they’re eliminated from your body.
How long has Tramadol stayed in your system after stopping?
If you’ve fully stopped taking Tramadol, share a comment in regards to how long you believe it stayed in your system. Do you believe that you excreted the drug quicker or slower than average? To help others get an ideal of how long Tramadol may have stayed in your system after cessation, share factors that may affect its excretion time including: your age, dosage, and term of administration.
Understand that in general, most people will excrete Tramadol in less than a day-and-a-half (1.5 days) and its principal “M1” metabolite (O-desmethyltramadol) in less than 2 days (48 hours) after their final dose. If you are concerned that the drug will linger in your bodily tissues for longer than 2 days, you could consider using some sort of detoxification protocol. However, in most cases, your body will be more than capable of detoxifying itself.