What can make you test positive for opiates?

WHAT CAUSES FALSE-POSITIVE URINE TOXICOLOGY SCREENS AND HOW CAN THEY BE DETECTED? – False-positive screens are the result of cross-reactivity to the antibody in EIA tests due to specific medications or direct binding to the antibody due to inadvertent ingestion of opiates (eg, poppy seeds).

Medications common to the inpatient setting (eg, quinolone antibiotics, rifampin) can also result in false-positives on opiate EIA testing.5 In addition, there are a wide variety of common medications (eg, verapamil, quetiapine, diphenhydramine, doxylamine) that are known to give false-positive results on methadone-specific EIA testing.6, 7 Poppy seeds can readily result in a positive finding in standard urine EIA testing; a product of the opium poppy, these seeds contain small amounts of codeine and morphine.

One study found morphine levels high enough to result in positive EIA testing after ingestion of 1 poppy seed muffin or 2 poppy seed bagels.8 This type of false-positive result is much less common in testing outside of clinical situations (eg, the workplace), wherein thresholds for a positive opiate screening are higher.9 A careful history for medications or food that can induce a false-positive result should be performed and, if present, GC-MS testing should be used to distinguish between the presence of true opiates and false-positive results.

A coincidental false-positive test could also result from the way in which lactate dehydrogenase and lactate interfere with assays for commonly abused substances such as opiates.10 Hence, urine from a patient who is at risk for lactic acidosis (eg, one with diabetes mellitus, liver disease, or a toxin ingestion) should undergo additional confirmatory testing.

The specific detection of heroin as separate from other opiates is facilitated by its unique metabolites. Heroin is a semisynthetic opiate that by virtue of its metabolism to morphine produces a positive result on standard EIA tests. Morphine is then further metabolized to morphine-3-glucuronide and morphine-6-glucuronide before excretion (primarily via the kidneys).

However, prior to its metabolism to morphine and subsequent glucuronidation, heroin is rapidly metabolized to 6-MAM. Because 6-MAM is the first product of heroin metabolism, no other compound produces this metabolite, and its presence is unequivocal confirmation of heroin usage. Importantly, 6-MAM is known to have a short half-life and is thought to be detectable by specified EIA or GC-MS only up to 12 hours after ingestion.11, 12 In situations in which a patient is taking a prescribed opiate as well as an illicit opiate, physicians must be especially careful when interpreting test results.

Opiate abuse by opiate-treated chronic pain patients is common 13 and can complicate interpretation of opiate testing. For example, since both codeine and heroin have morphine as a metabolite, mistaken accusations of morphine or heroin abuse may arise in patients prescribed codeine.

What can make you test positive for codeine?

Opiates, Screen and Confirmation, Urine (Codeine/Morphine) A qualitative urine test for opiates is performed in suspected overdose cases or as part of a drug of abuse program. The test is most sensitive for morphine and codeine, but other drugs will cross react in an immunoassay and give positive results (eg, hydrocodone, hydromorphone).

1. All presumptive positive assays should be confirmed, preferably by MS.
2. Morphine is a prescribed drug for pain relief, a metabolite of heroin, a metabolite of codeine, and a constituent of poppy seeds.
3. Its presence in urine, even after confirmation, must be interpreted very carefully.
4. Ingestion of poppy seeds (bagels, Danish) can cause positive opiate tests at a 300 ng/mL cutoff.1 The intake of heroin by the user can only be proved by the detection of 6-O-acetyl morphine.

Opiates in general are a group of drugs (commonly referred to as narcotics) that are used medically to relieve pain, but that also have a high potential for abuse. Morphine and codeine are found in the resin collected from the opium poppy. Other opiates are synthesized or manufactured (eg, heroin).

1. Opium appears as dark brown chunks or as a powder and is usually smoked or eaten.
2. Heroin can be a white or brownish powder that is usually dissolved in water and injected.
3. Opiates tend to relax the user.
4. When the opiates are injected, the user feels an immediate “rush.” Other initial and unpleasant effects include restlessness, nausea, and vomiting.

The user may go “on the nod,” going back and forth from feeling alert to drowsy. With very large doses, the user cannot be awakened, pupils become smaller, and the skin becomes cold, moist, and bluish in color. Furthermore, breathing slows down and death may occur.

What is the urine test for morphine?

MATERIALS AND METHODS – We reviewed the laboratory records of all urine samples sent for drug analysis over a period of 1 year at a tertiary-care de-addiction center. All cases with buprenorphine prescription for OST during this period were included in the study.

All the subjects were being treated as outpatients and were being administered the medication from the treatment center on a biweekly basis. At this center, urine samples sent for drug evaluation are screened for common drugs of abuse in the region as well as medications prescribed as OST from the center, which include heroin (detected as morphine), buprenorphine, dextropropoxyphene, and benzodiazepines.

A supervised urine sample (50 ml) is collected from patients coming for treatment at the de-addiction center. It is then sent to laboratory for analysis. A standardized modified hydrolysis method followed by thin-layer chromatography (TLC) is used for detection of drugs in the urine.

The detection limit for urinalysis in the laboratory is 0.5 μg/ml for morphine (heroin) and dextropropoxyphene, 0.2 μg/ml for benzodiazepines, and 1.0 μg/ml for buprenorphine. Data analysis was carried out using SPSS ® version 17. The pattern of prescription buprenorphine use and non-prescription opioid use was assessed using frequency distribution.

We used the chi-square test to compare non-prescription opioid use among those testing positive and negative for buprenorphine on urinalysis. Additionally, in order to assess the potential impact of the prescribed induction and maximum dose of buprenorphine on the findings, we carried out the independent-samples t test.

Which substance in urine drug testing is pathognomonic of heroin exposure?

6-MAM is pathognomonic for heroin use, detection time is 12-24 hours.

Is it possible to test positive for drugs?

What do the results mean? – If a drug test result is negative, it means that either:

• The drugs that were tested were not found in the sample.
• A very small amount of drugs were found, but not enough to be a positive test result for drugs.

If a drug test result is positive, it means that one or more drugs were found in amounts that suggest drug use or misuse. Positive tests require follow-up testing because they may be wrong (false positives). The follow-up test is usually a test that provides more accurate results. Learn more about laboratory tests, reference ranges, and understanding results,

Why does ibuprofen cause positive drug test?

OTCs – Determining what OTC products patients are taking is very important when using UDS testing, as some OTCs may cause false-positive results. Antihistamines, analgesics, cough suppressants, and heartburn medications have been shown to cause false-positives in studies and case reports.1-4 False-positive methadone levels have been documented with diphenhydramine 100 to 200 mg 2-4,14 and doxylamine intoxication.4,15 Additionally, doxylamine intoxication has produced false-positive opiate 14 and PCP 2 levels, and brompheniramine use may cause false-positive amphetamine 4 and LSD 3,9 levels.

1. Consider using second-generation antihistamines, as they have not been reported to cause false-positive UDS results.
2. Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been shown to interact with UDS immunoassays.
3. Both ibuprofen and naproxen have been documented to cause false-positive barbiturate 4 and cannabinoid 1-4 levels.

In addition, ibuprofen can cause a false-positive PCP level.1-2,4 Consider minimizing the use of NSAIDs in high-risk patients and recommending acetaminophen instead. The cough suppressant dextromethorphan may cause false-positive PCP 1,2,4 and opioid levels due to its metabolite’s similarity to the opioid agonist levorphanol.1,2 Furthermore, decongestants phenylephrine and pseudoephedrine have shown false-positive amphetamine levels due to similar structures.1,2 To prevent misinterpretations, consider limiting these medications in high-risk populations.

What would cause a false positive?

A false positive is when a drug test shows the presence of a medication or substance that you didn’t actually take. Multiple medications can cause false positive results. Some examples include NSAIDs, dextromethorphan, and some antidepressants.

What can cause a negative drug test?

Abstract – The terms ‘false-positive’ and ‘false-negative’ are widely used in discussions of urine drug test (UDT) results. These terms are inadequate because they are used in different ways by physicians and laboratory professionals and they are too narrow to encompass the larger universe of potentially misleading, inappropriate and unexpected drug test results.

This larger universe, while not solely comprised of technically ‘true’ or ‘false’ positive or negative test results, presents comparable interpretive challenges with corresponding clinical implications. In this review, we propose the terms ‘potentially inappropriate’ positive or negative test results in reference to UDT results that are ambiguous or unexpected and subject to misinterpretation.

Causes of potentially inappropriate positive UDT results include in vivo metabolic conversions of a drug, exposure to nonillicit sources of a drug and laboratory error. Causes of potentially inappropriate negative UDT results include limited assay specificity, absence of drug in the urine, presence of drug in the urine, but below established assay cutoff, specimen manipulation and laboratory error.

What drugs are tested in urine toxicology?

What are the types of drug tests? – There are several kinds of drug tests based on the biological sample they use and the types of drugs they detect. Different types of drug tests based on the sample used include:

Urine drug testing (UDT) : This is the most common drug test. It requires a sample of your urine (pee). Urine drug tests are most commonly used to detect alcohol, amphetamines, benzodiazepines, opiates/opioids, cocaine and marijuana (THC). Blood drug testing : Healthcare providers mainly use this type of test in emergencies. It’s also typically used to detect alcohol (ethanol) levels because it can provide a precise level. Hair follicle drug testing : A hair sample can provide information on substance use over time. Scalp hair has a detection window of three months, while slower-growing body hair has a detection window of up to 12 months. The results can vary based on the characteristics of each person’s hair. Hair testing can detect the use of cocaine, phencyclidine (PCP), amphetamines, opioids and 3,4-Methylenedioxymethamphetamine (MDMA). Breath drug testing : This is primarily used to detect recent alcohol consumption. The result is called a breath alcohol concentration (BrAC). Officials often use it to estimate a person’s blood alcohol content (BAC), However, BrAC can sometimes overestimate or underestimate the BAC. Recent research has focused on the potential use of breath testing for detecting cocaine, marijuana, benzodiazepines, amphetamines, opioids, methadone and buprenorphine. Sweat drug testing : Sweat testing involves wearing an absorbent pad on your skin that’s collected and tested after a certain amount of time. The results provide information on how much of a substance the person consumed over the entire time that they wore the pad. Sweat testing gives a detection window of hours to weeks.

Can you detect morphine?

How Long Can You Detect Morphine in a Drug Test? – There are many reasons why people might need to take a drug test. Two typical examples are for employment or legal reasons. Common testing methods are blood tests, urine tests, saliva tests, and hair tests.

How Long Does Morphine Stay in Your Blood – Blood tests – Up to three days after use. How Long Does Morphine Stay in Your Urine -Urine tests – Up to three days after use. How Long Does Morphine Stay in Your Saliva – Saliva tests – Up to four days after use. How Long Does Morphine Stay in Your Hair – Hair follicle tests – Up to ninety days after use.

Urine testing can sometimes produce a false positive drug test, especially when detecting opiates. This is rare, but it has been known to happen. Certain medications also cause interference with the testing process and show a false positive. Saliva tests and blood tests have a similar window for drug detection.

• This is because drugs found in saliva are on their way to the blood.
• Meanwhile, hair tests can identify morphine and other drugs for up to ninety days as the drugs that enter your bloodstream can transfer to your hair follicles.
• However, it is not a common testing method.
• Ultimately, trying to beat a test is risky at best.

If you have recently used drugs, you will likely be caught out. Failing drug testing can have several devastating consequences, but it doesn’t have to be this way. Help is available if you have lost control of your drug use.

What does a 12 panel drug test test for?

What Are 12-Panel Drug Screens? – The purpose of a 12-Panel Urinalysis Drug Screen is to determine whether you have illicit substances in your system. A typical 12-Panel Urinalysis Drug Screen tests for active components in 10 different substances, including amphetamines, barbiturates, benzodiazepines, cannabis, cocaine, methadone, methaqualone, opioids, phencyclidine, and propoxyphene.

Usually, you’ll visit a medical clinic or drug testing site and provide a urine sample. That sample will be sent to a laboratory to be tested for the components listed above. And, assuming none of those components are found in your system, a drug screen like this provides objective, scientific proof that you have abstained from drug use.

It’s important to know, however, that the detection time for each of these substances is different. Marijuana, for example, has the longest half-life of the substances checked for, and THC can be detectable in urine for a month or longer depending on the amount and frequency used.

It needs to be emphasized, however, that these time periods are estimates only. They depend on the specific type and quantity of drug used, the frequency of usage, any unique aspects of your health, and numerous other factors. THC, for example, can build up in the body’s fat cells and, as a result, be detectable for as many as three months for certain heavy, chronic users.

And, contrary to a somewhat common myth, simply drinking a large quantity of water cannot “flush” these components out of your system. At best, trying to “flush” your system like this will lead to a diluted sample, which will nevertheless be considered a failed test. In that circumstance, you’re adding even more time to how long you’ll be without the driving privileges that you need so much.

As you likely noticed, alcohol is technically not one of the substances testified for in the 12-Panel Drug Screen. That does not mean, however, that you want alcohol in your system when you take your drug screen. It’s important to remember that, ultimately, the Secretary of State is determining whether you have been sober for at least one year before your driving privileges are restored, not simply whether you passed the drug screen.

What meds can cause a false-positive for opioids?

Opioids – Although often used interchangeably, opiates and opioids refer to different classes of xenobiotics. Opiates are derivatives of the opium poppy (morphine and codeine). Opioids refers to a very broad class of drugs with opium-like effects (hydrocodone, oxycodone, propoxyphene, hydromorphone, fentanyl, methadone, propoxyphene, etc.).

Most urine drug screens are designed to detect opiates (namely morphine) and drugs metabolized to morphine by the human body (i.e., heroin) and often “miss” the majority of semi-synthetic and synthetic opioids; although, cross-reactivity does occur and is assay dependent. False-positive opiate tests have reportedly been caused by dextromethorphan, diphenhydramine, quinine, quinolones, rifampin, verapamil, and poppy seeds.4 In the hopes of testing for medical adherence, some urine drug screens specifically include methadone.

Of note, false positive methadone screens have been reported to be caused by quetiapine, doxylamine, olanzapine, diphenhydramine, and verapamil.16

What is a 10 point drug test?

Typical panels –

6-panel drug test: typically tests for Amphetamines/Methamphetamines, Barbiturates, Cocaine Metabolites, Marijuana Metabolites: Tetrahydrocannabinol (THC), Opiates (including Hydrocodone, Hydromorphone, Codeine, and Morphine) and Phencyclidine (PCP).7-panel drug test : often administered by companies or individuals concerned an employee might be abusing prescription drugs. Industries requiring alertness or the operation of heavy machinery, such as transportation and the DOT, may use the 7-panel test to gauge the presence of prescription drugs. These drugs, although legal, may impair a machine operator’s ability to do their job, or cause fatiguing side effects, particularly if abused. Standard 7-panel test : typically looks for marijuana, cocaine, opiates, PCP, amphetamines, benzodiazepines, & barbiturates.10-panel test : often administered to test employees in law enforcement and occupational medicine. Additionally, these 10-panel drug screens may examine if a person is violating the terms of probation. Many civil servants must pass a 10-panel test, particularly if their job entails dangerous work or the employee must ensure the safety of others. Standard 10-panel test : typically looks for cocaine, marijuana, PCP, amphetamines, opiates, benzodiazepines, barbiturates, methadone, propoxyphene, & Quaaludes.12-panel test: often administered as an extension to the 10-panel test. The 12-panel test looks for either the presence of extended opiates and prescription painkillers or traces of other controlled substances if that poses a dangerous threat to the workplace. Standard 12-panel test: looks for cocaine, marijuana, PCP, amphetamines, opiates, benzodiazepines, barbiturates, methadone, propoxyphene, Quaaludes, Ecstasy/MDA, & Oxycodone/Percoset.

Curious about other Mobile Health numbered drug panel combinations for employer drug testing, from 6-panel drug tests to 12-panel tests? Interested in knowing what comprises an 8-panel test ? Click here for typically tested panel variations in the list format.

Will you test positive for opiates after Narcan?

Abstract – Study objective: To determine whether the excreted metabolites of naloxone hydrochloride cause positive urine toxicologic screens for opiates. Design: Prospective, randomized, double-blinded human protocol. Setting: Urban Level I military emergency department.

1. Participants: Fourteen adult volunteers who took no routine medications, were not pregnant, had no known sensitivity to naloxone, and who were negative for a pretest urine and serum toxicologic screen.
2. Interventions: We administered either 2 or 4 mg IV naloxone to 14 subjects.
3. Urine drug screening was obtained before administration and at 60 minutes, 6 hours, and 48 hours after administration.

Results: All urine drug screens using the enzyme-multiplied immunoassay technique were negative for opiates at both dosage levels. The sample size of 14 yielded a power of more than,99 to detect the difference between positive and negative samples. Conclusion: Although the metabolites of naloxone hydrochloride are similar in structure to oxymorphone and are excreted in human urine for several days, naloxone was not associated with a positive enzymatic urine screen for opiates.

Can a drug test go wrong?

Drug screenings can be scary for everyone, especially if you have concerns about your employment. False-positive results can happen, even with no fault of your own. There are a number of prescription and over-the-counter medications, supplements and foods that can lead to a false positive.

Can a negative drug test be wrong?

Interpreting Test Results – Many drugs are rapidly metabolized into active or inactive metabolites. Drug testing is dependent on detecting these metabolites. Opioids and benzodiazepines include multiple drugs with overlapping metabolic pathways, which can make interpretation of screening results difficult ( and ), False-positive results can occur from cross-reactivity of commonly used medications with the assay. This a particular concern with immunoassays. lists common medications that can cause false-positive results on urine drug testing. Negative results are particularly difficult to interpret, especially when a patient is receiving long-term opioid therapy and the physician expects a positive result.

True-negative results occur when a patient is not taking the medication as prescribed and there is no drug present in the urine sample, or when the drug is metabolized so rapidly that the metabolites are eliminated before they can be detected. False-negative results occur when a drug or metabolite is present at such low levels that it is not detected.

Confirmatory testing is essential to distinguish a true negative from a false negative. Contaminants can also interfere with the immunoassay’s ability to detect the presence of drugs. The use of heroin with concurrent prescription opioids is also a cause for concern. Although both substances will give a positive result for opioids, the presence of 6-monoacetylmorphine indicates heroin use. This metabolite has a short half-life, however, with a window of detection in urine of approximately two to eight hours.

What drug test is most accurate?

Blood tests. They may be more intrusive than other methods, but blood tests are well-regarded as accurate and comprehensive. Hair tests and sweat tests can be particularly poor when it comes to accuracy. External contact with a drug or even the smoke from a drug can throw a false positive.

What does a drug screen detect?

Types of Drug Tests – Drug tests vary, depending on what types of drugs are being tested for and what types of specimens are being collected. Urine, hair, saliva (oral fluid), or sweat samples can be used as test specimens. In federally regulated programs, only urine samples are collected, although the Secretary of Health and Human Service has released guidelines for the inclusion of oral fluid specimens.

Pre-employment: You can make passing a drug test a condition of employment. With this approach, all job candidates will receive drug testing prior to being hired. Annual Physical Tests: You can test your employees for alcohol and other drug use as part of an annual physical examination. Be sure to inform employees that drug-testing will be part of the exam. Failure to provide prior notification is a violation of the employee’s constitutional rights. For-cause and Reasonable Suspicion Tests: You may decide to test employees who show discernible signs of being unfit for duty (for-cause testing), or who have a documented pattern of unsafe work behavior (reasonable suspicion testing.) These kinds of tests help to protect the safety and wellbeing of the employee and other coworkers. Post-accident Tests: Testing employees who were involved in a workplace accident or unsafe practices can help determine whether alcohol or other drug use was a contributing factor to the incident. Post-treatment Tests: Testing employees who return to work after completing a rehabilitation program can encourage them to remain drug-free. Random Tests: Tests using an unpredictable selection process are the most effective for deterring illicit drug use.

What happens if a drug test comes back positive?

What Is Tested & How – A urine test is the most common method of testing. A urinalysis will reveal the presence of a drug in the system even after drug effects have worn off, although the length of time varies by drug. For example, marijuana can be detected in urine from anywhere to a few days up to a full month, depending on a number of individual factors such as the amount of body fat in a person, or how much of the drug was used.

Some employers will conduct their own onsite drug testing. “These tests provide only a non-negative result and cannot confirm a positive result,” Pederson noted. “A non-negative result with this test would require an additional confirmatory test at a qualified collection center.” The hair testing method detects drug use over the longest window of time, sometimes up to three months for a drug like marijuana, Pederson said.

“The drug gets incorporated into the hair follicle and will show up when the hair is tested.” Once a sample of hair or urine is collected, the sample is analyzed at a certified laboratory. If the test results in a positive reading, meaning there is drug residue in the body, the results are forwarded to a medical review officer, who reviews the results and looks for any possible valid medical explanation for the results.

“As a medical review officer, I would review a patient’s medical history. If the individual has a valid medical explanation for the result, this can be sorted out and the test will be reported as negative.” Dr. Pederson said. Although the test may be reported as negative, the medication may still inhibit an individual’s job safety or performance.

This is another aspect of drug testing that requires the expertise of a certified MRO. “If someone is prescribed a narcotic, and driving is part of their job, this may be passed on to the employer as a negative test with potential safety concerns for the employer to consider,” Dr.

How long will ibuprofen show up on a drug test?

Can Advil make you test positive on a drug test? – Ibuprofen can stay in your system for up to 24 hours, depending on the dose. As a result, it is possible that ibuprofen, which is the active ingredient in Advil, could cause a false positive on a drug test. However, it is unlikely that this would happen as most drug tests are designed to detect recreational drugs, not over-the-counter medications.

Can ibuprofen cause false positive on drug test?

OTCs – Determining what OTC products patients are taking is very important when using UDS testing, as some OTCs may cause false-positive results. Antihistamines, analgesics, cough suppressants, and heartburn medications have been shown to cause false-positives in studies and case reports.1-4 False-positive methadone levels have been documented with diphenhydramine 100 to 200 mg 2-4,14 and doxylamine intoxication.4,15 Additionally, doxylamine intoxication has produced false-positive opiate 14 and PCP 2 levels, and brompheniramine use may cause false-positive amphetamine 4 and LSD 3,9 levels.

Consider using second-generation antihistamines, as they have not been reported to cause false-positive UDS results. Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been shown to interact with UDS immunoassays. Both ibuprofen and naproxen have been documented to cause false-positive barbiturate 4 and cannabinoid 1-4 levels.

In addition, ibuprofen can cause a false-positive PCP level.1-2,4 Consider minimizing the use of NSAIDs in high-risk patients and recommending acetaminophen instead. The cough suppressant dextromethorphan may cause false-positive PCP 1,2,4 and opioid levels due to its metabolite’s similarity to the opioid agonist levorphanol.1,2 Furthermore, decongestants phenylephrine and pseudoephedrine have shown false-positive amphetamine levels due to similar structures.1,2 To prevent misinterpretations, consider limiting these medications in high-risk populations.

Can ibuprofen cause a false positive for Benzos?

Abstract – Anecdotal and uncontrolled studies have suggested that nonsteroidal anti-inflammatory drugs produce false-positive results in immunoassay urine tests for some drugs of abuse. This study was performed in 60 volunteers who took ibuprofen as either a single 400-mg dose, or 200 mg three times a day, or 400 mg three times a day, and in 42 patients taking ibuprofen, naproxyn, or fenoprofen in therapeutic regimens for more than 30 days.

Of the 510 urines collected from 102 individuals during these dosage regimens, two gave false-positive tests for cannabinoid by enzyme-mediated immunoassay (EMIA), one after 1200 mg of ibuprofen in three divided doses for one day and one in a patient taking naproxyn on a chronic basis; none was falsely positive for benzodiazepines.

Two urines were false-positive for barbiturates by fluorescence polarization immunoassay (FPIA), one in a patient taking ibuprofen and one in a patient taking naproxyn. These data, collected prospectively, demonstrate the small likelihood of a false-positive immunoassay test result for cannabinoids, benzodiazepines, or barbiturates after the acute or chronic ingestion of ibuprofen, or after the chronic ingestion of naproxyn or fenoprofen.

Do opioids reduce test?

Long-term Opioids Linked to Hypogonadism and the Role of Testosterone Supplementation Therapy Opioids play a pivotal role in managing chronic pain with increasing prescription rates over the last few years. Hence, it is crucial to focus on the adverse effects of narcotics, and one of the lesser-known side effects is hypogonadism. Opioids act on the hypothalamus, pituitary, and directly on the gonads affecting serum testosterone levels. Narcotic-induced androgen insufficiency contributes to sexual dysfunction, infertility, hyperalgesia, and involving various body functions overall, affecting the quality of life. Opioid-induced hypogonadism is very challenging to diagnose for the clinicians, as the patients often under-report the symptoms. There are no established guidelines to analyze androgen insufficiency and dealing with their manifestations successfully. We did a substantial search in PubMed and Google Scholar, using various combinations of keywords to collect data to evaluate the impacts of opioids on serum testosterone levels. This study aims to highlight the clinical significance of opioid-induced androgen deficiency and the diagnostic techniques to recognize and credible treatment alternatives, including testosterone replacement therapy. Health care providers should screen the patients routinely for the signs and symptoms and monitor them often for the hormonal changes to select the patients cautiously for testosterone replacement therapy. Keywords: testosterone, chronic pain, hypogonadism, narcotics, opioids, opioid-induced hypogonadism, testosterone replacement therapy Recent evidence suggests that as many as 39 million (12% of the population) people in the United States of America (USA) have chronic pain, Opioids have been commonly prescribed for both acute and chronic pain over the past 15 years in the USA, They play an essential role in the disappointment of other non-opioid analgesics, either alone or in combination, As narcotics are the mainstay of pharmacotherapy in chronic pain and palliative therapy, there is an increase in drug-related complications, significantly affecting the patients’ quality of life, It is essential to follow specific standard guidelines before prescribing narcotics to forestall overtreatment and to monitor them continuously, Before considering opioids as an option, it is imperative to comprehend the risks and benefits of opioid therapy. Narcotics-related adverse effects are receptor-mediated and hence inseparable. Factors like sex, race, and age can also impact the development of side effects. The risk is more noteworthy with higher doses, yet even with lower doses, side effects can still happen on patients who take it for more than 30 days, Short-term opioids-related adverse effects mostly involve the gastrointestinal and the central nervous system, producing nausea, vomiting, constipation, sedation, and respiratory depression. Long-term adverse effects are addiction, dependence, and tolerance. A lesser-known yet one of the common side effects is narcotics suppressing the gonadal function in both genders ranging from 21% to 86%, Opioid-induced hypogonadism is often under-reported and, consequently, underdiagnosed because of low clinician awareness, The impact on the hypothalamic-pituitary-gonadal axis is immediate, and the hormonal changes are dose-related, The most widely recognized symptom of narcotic-induced androgen deficiency is sexual dysfunction affecting 76% of males and 64% of females among long-term opioids users, In males, androgen deficiency leads to sexual dysfunction, fatigue, hot flushes, and night sweats. In females, lower levels of estradiol and progesterone lead to oligomenorrhea, amenorrhea, anovulation, and infertility, Narcotics can reduce the serum testosterone levels by acting on the hypothalamus-pituitary axis, thereby suppressing the release of gonadotrophins, Low testosterone levels can affect pain control leading to hyperalgesia, mood impairment, fatigue, and depression. Opioids have a significant impact on bones affecting bone density leading to osteoporosis, which is a metabolic sequela of hypogonadism, Few management alternatives have been attempted to treat the side effects, including reducing the dose of opioids, discontinuing the opioids, opioid rotation, symptomatic management, switching the route of administration, and considering other pain relief options. In patients who develop hypogonadism symptoms, supplementation with testosterone improves sexual dysfunction and enhances pain sensitivity and quality of life. However, the effectiveness of these strategies is not yet apparent, and we need additional imminent prospective trials and further research to determine the best treatment strategy, From this narrative review, we aim to summarize the underlying mechanism by which opioids affect the testosterone levels, discuss their clinical significance, compare the results from previous studies, and finally make an inference on whether testosterone supplementation can improve the symptoms. We additionally attempted to give clinical guidelines to analyze and prescribe a treatment convention to reestablish testosterone’s typical physiological levels. This study will likewise assist with making awareness among the physicians, which will prompt better guiding of the patients. Methods We did an extensive data search from PubMed and Google Scholar using various combinations of the medical subject headings (MeSH) keywords and regular keywords “opioids”, “chronic pain”, “opioid-induced hypogonadism”, “testosterone replacement therapy”. We limited the search to include the studies published in English, with available full articles and conducted on humans. We excluded animal studies, non-English studies, case reports, and editorials. We analyzed all the relevant studies to yield more data, applying no time limitations. We aimed our search at identifying the data which focused on the pathophysiology of opioids, the diagnostic tests, and testosterone supplementation. Discussion Opioids’ Effects on the Hypothalamic-pituitary-gonadal (HPG) Axis In normal physiological status, the pulsatile release of gonadotrophin-releasing hormone (GnRH) from the hypothalamus stimulates the pituitary to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). LH acts on the testes (Leydig cells) and ovaries (theca cells) to produce testosterone, Testosterone is aromatized to estradiol, which is also derived through the peripheral conversion of oestrone. Oestrone is secreted directly from the adrenal glands and also through the aromatization of androstenedione, a product of testosterone, FSH acts on Sertoli cells to produce sex hormone-binding globulin (SHBG) and inhibin. FSH also supports the production and maturation of sperm cells and stimulates the development of ovarian follicles. The sex hormones and inhibin have a negative feedback mechanism on LH, FSH, and GnRH, Narcotics act directly on the hypothalamus through its receptors guanine nucleotide-binding protein (G-protein)-coupled mu-opioid peptide (MOP) receptors and inhibit the pulsatile release of GnRH, which blocks the release of LH and FSH from the pituitary, affecting the production of testosterone or estrogen from the gonads. Moreover, narcotics also act directly on the pituitary gland to suppress the release of gonadotropins, They also increase prolactin levels, which can inhibit the secretion of GnRH and cause low testosterone levels, Ragni et al. showed that there was significantly lower LH, FSH, testosterone, and high prolactin levels (12.3 +/- 10.5 vs.5.9 +/-2.5 ng/ml, P 15 ng/ml, Their study also implied that hyperprolactinemia is not associated with any particular type of opioid but can be related to environmental stress factors and the social conditions seen in heroin addicts. Prolactin suppresses the pulsatile release of GnRH and acts directly on the pituitary affecting LH secretion, leading to lower levels of sex hormones, Patients with high prolactin present with galactorrhea, painful gynecomastia, infertility, and irregularities with menstrual cycles. Opioids negatively affect the release of corticotrophin-releasing hormone (CRH) and vasopressin at the hypothalamus. Low CRH down-regulates the adrenocorticotrophic hormone (ACTH) secretion leading to decreased levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEAS), DHEAS is a sensitive marker of opioid-induced adrenal deficiency, the precursor of testosterone in the adrenal gland, Lower levels of dehydroepiandrosterone sulfate (DHEAS) can add to fatigue, weakness, depression, and sexual dysfunction. Rhodin et al. have noted lower levels of DHEAS (1.56 mol/L vs.2.71 mol/L; P < 0.05) and higher levels of prolactin (25.1 g/L vs.8.88 g/L) (P < 0.001 ) in females on opioids when compared to the controls, Reduced levels of DHEAS in female patients on opioids clearly explain hypoadrenalism caused by opioids, which leads to low adrenal androgen production, DHEAS replacement therapy helps in improving sexual dysfunction and fatigue in patients with low DHEAS levels. Opioids can reduce the production of sperm, testicular interstitial fluid, and testosterone by acting directly on the gonads through the MOP receptors. It also has some detrimental effects on semen parameters like affecting the sperm count (oligozoospermia), morphology (teratozoospermia), forward motility (asthenospermia), semen volume (hypospermia), and sperm concentration, In the study population, asthenospermia was reported in all cases of opioid users, and hypospermia and teratozoospermia to a lesser extent, In chronic opioid users, when compared to healthy adults, a reduction in the sperm concentration (22 million vs.66 million/dl; P = 0.004), reduced activity of superoxide dismutase and catalase, and an increase in the fragmentation of deoxyribonucleic acid (DNA) (36% vs.27%) were noted, The study proved the association between the opioid doses and impaired semen parameters with the group on high doses had a high percentage of sperm DNA damage and diminished semen parameters. Narcotics have a significant effect on semen parameters like quality, antioxidant capacity, sperm function, and DNA integrity. Opioid-induced hypogonadism is both through its central and peripheral effects, as summarized in Figure below. Opioids effects on the hypothalamic-pituitary-gonadal (HPG) axis GnRH: gonadotropin-releasing hormone; CRH: corticotropin-releasing hormone; LH: luteinizing hormone; FSH: follicle-stimulating hormone; ACTH: adrenocorticotropic hormone; DHEAS: dehydroepiandrosterone sulfate According to Roberts et al., after administering intrathecal opioids, the testosterone levels reduced significantly from 7.7 +/- 1.1 nmol/I at baseline to 2.0 +/- 0.7, 2.8 +/- 0.5, 4.0 +/- 0.9 nmol/L at 1, 4, and 12 weeks, respectively (P < 0.0001), LH and FSH were in the normal physiological range and not increased, explaining central hypogonadism. This study explains the suppression of the HPG axis with opioids through its receptors, without an increase in LH describing a central effect. Daniell demonstrated that among men on oral opioids, 89% showed reduced levels of free testosterone, dihydrotestosterone, estradiol, LH, and FSH (P < 0.0001), and 87% reported erectile dysfunction and reduced libido, Daniell also proved that in opioid-consuming postmenopausal women, independent of BMI and age, average values of LH and FSH were 70% to 73% lower than the control group (P < 0.001), with median values of 4.1 and 32.5 mIU/ml for LH and 7.1 and 71.0 mIU/ml for FSH, Rhodin et al. found in their study on female patients on opioids that the mean estradiol value was 208 pmol/L vs.510 pmol/L (P < 0.05), DHEAS levels were 40.6 vs.65.3 mg/l, the LH peak was 17.6 IE/L vs.38.3 IE/L (P < 0.01), and the baseline FSH was 25.7 IE/L vs.60.7 IE/L (P < 0.05) compared to the controls,The data supports that opioid-induced hypogonadism is through the suppression of the HPG axis along with ovarian and adrenal androgen production explaining both central and peripheral effects. Moreover, the effect of opioids on the HPG axis gets accentuated due to various other factors like age, chronic pain, comorbidities like anxiety, and drug therapies like chemotherapy, which can influence the hormonal levels, Hence the diagnosis of opioid-induced hypogonadism is very challenging. There are guidelines to initially screen the patients on opioids with ADAM (androgen deficiency in aging males) questionnaire, and if this is positive, then follow up with measuring serum testosterone levels is recommended, Once the diagnosis is suspected, we need to measure total testosterone, free testosterone, estradiol, LH, FSH, sex hormone-binding globulin, DHEAS, an evaluation of adrenal function, and always collaborate the care with an endocrinologist to confirm the diagnosis. There are no particular guidelines or recommendations to diagnose hypogonadism in women other than measuring estradiol in addition to testosterone, LH, FSH, DHEAS, and bone density to guide treatment, Clinical Significance of Low Testosterone Testosterone, more than being considered a sex hormone, has different roles in various body systems' metabolic functions. The hormone's significant anabolic effects include increasing the muscle mass, exercise tolerance, maturation of bone, and linear growth, It has a substantial influence on general health, mood, and wellbeing through its actions on the cognitive centers in the brain, Various factors like aging, lack of physical activity, excess distribution of body fat tissue, smoking, and even medical conditions like diabetes mellitus, hepatic dysfunction, hypothyroidism, obesity, serum albumin, and sex hormone-binding globulin (SHBG) levels can influence the level of testosterone, Low testosterone levels are associated with dyslipidemia, weight gain, glucose intolerance, poor tissue healing, mood changes, depression, fatigue, anxiety in both sexes, Low testosterone levels are associated with osteopenia and osteoporosis and increase the risk of osteoporotic fractures by 50-60%, Opioids affect bone metabolism by directly acting on the osteoblasts and indirectly through the suppression of testosterone, which reduces bone mineral density leading to osteoporosis. Few studies prove the association of low androgen levels with a high incidence of coronary heart diseases (CHD) and reveal that serum testosterone levels are inversely related to deaths with CHD, The relationship between the low testosterone levels and CHD can be explained by the fact that it can influence serum high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol levels, The prevalence of hypogonadism is significantly different between men and women, depending on the route of opioid therapy. With long-term oral opioids, women have a lower prevalence than men, but with intrathecal opioids, the prevalence of androgen deficiency is higher in both genders, In a study among chronic pain patients using intrathecal opioids, reduced libido and potency were reported in 96% of men with lower levels of testosterone and free androgen index (FAI = testosterone/SHBG) (P < 0.001), and 69% of women presented with decreased libido, irregularities in the menstrual cycles, and anovulation with lower levels of LH, FSH, estrogen, and progesterone, In women, long-term opioids affect the hormonal levels of LH, FSH, testosterone, and progesterone, which has a significant impact on their menstrual cycles, In addition to irregularities in their menstrual cycles, the inhibition of adrenal androgens and ovarian sex hormones can also cause anovulation, reduced fertility, depression, and osteoporosis, Daniell has reported that among women on long-term intrathecal opioids, 70% had amenorrhea (P < 0.05), 30% presented with irregularities in the menstrual cycles, and 84% reported sexual dysfunction along with fatigue, depression, and increased risk of osteoporotic fractures before age 60 (P < 0.05),In men, the most significant symptoms are erectile dysfunction, reduced ejaculatory volume, problems with achieving orgasm, decreased libido, and infertility. Still, fatigue, depression, less body hair, breast pain, gynecomastia, shrinking testes, reduced muscle mass, low concentration, mood disturbance, night sweats, and hot flushes can also be noted, Opioids can lead to the endocrine changes immediately as early as four hours, and it is easily reversible once discontinued within 24 hours, Patients on higher doses of narcotics have an increased impact on testosterone levels. For an increase of 10 mg in the methadone dose, a reduction of 0.97 ng/dl (P = 0.003) in the testosterone levels was noted, The study explains the inverse relationship between the methadone dose and the testosterone levels (CI -0.003, -0.000, P < 0.018), Data suggests that when the daily morphine dose exceeds 100-200 mg equivalents, we could expect significant effects on the endocrine changes, Long-acting opioids have a significant association with hypogonadism as they cause GnRH suppression. Rubinstein et al. proved that compared to men on short-acting opioids (SAO) (34%), men on long-acting opioids (LAO) (74%) after controlling for the BMI and daily dose, showed a significant rate of hypogonadism (odds ratio of 4.78, 95% CI 1.51-1.5.07, P = 0.008), Both LAO and SAO can cause the acute suppression of GnRH when they reach the threshold serum levels. The more significant suppression of GnRH with LAO is due to the fact that LAO achieve more stable serum levels, whereas SAO varies throughout the day, When opioid-induced hypogonadism is suspected, obtaining a thorough history before measuring the serum testosterone levels is of paramount importance. Testosterone levels peak in men in the mornings but fluctuate during the daytime; hence the diagnosis should be based on multiple measurements than a single reading, Role of Testosterone Supplementation Narcotic-induced androgen deficiency should be managed initially with conservative measures like diet and lifestyle modifications. When these traditional measures fail, consider other options like reducing the dose, switching to a different opioid, or switching to a non-opioid analgesics like non-steroidal anti-inflammatory drugs (NSAIDs) and the hormonal replacement therapy. Patients develop the classic symptoms of hypogonadism with testosterone levels lower than 300 ng/dl, However, in most cases, the serum androgen levels are variable; therefore, evaluating the patients based on their signs and symptoms is essential. Hence, we should diagnose the patients based on both the clinical assessment of symptoms and the laboratory parameters, It is even more critical to decide when to start the androgen supplementation therapy and who can get benefit from such treatment. When considering the testosterone replacement therapy, careful attention to exclude the patients with breast or prostate cancer, high prostate-specific antigen (PSA) levels, hematocrit > 50%, untreated obstructive sleep apnea, and poorly controlled heart failure, Moreover, the risks of hypercalcemia, polycythemia, and lipid abnormalities should also be considered, The target range of testosterone levels is between 400-700 ng/dl for men and women 20-80 ng/dl, Each laboratory will have its cut-off values, but a range of 280-800 ng/dl is recommended, The main aim of replacement therapy is to maintain the normal serum levels of testosterone between the intervals of administration. For women, hormonal replacement therapy (HRT) may include the administration of estrogen and progestin or oral contraceptives to improve the symptoms. DHEAS (50 mg daily), a precursor of testosterone, can be used as a hormonal supplement, but it is not a standardized therapy, HRT for women hence includes various doses of estrogens and progestins with a significant risk for breast cancer and cardiovascular diseases. Though various testosterone preparations are available for the replacement therapy in men, it should be chosen based on the cost, patient choice, and the burden of the treatment, Oral preparations are a good option when it is introduced first because of good compliance among patients. However, they have a major risk of hepatotoxicity due to its first-pass metabolism through the liver. The intramuscular preparations (75-100 mg once every week or 150-200 mg every two weeks) are the most cost-effective, But they can make the testosterone reach the supraphysiological levels after administration and then suddenly drop to sub-physiological levels before the next administration, Mood swings, acne, and injection site pain are few reported side effects. It is imperative to monitor the patients with hematocrit as there is a greater risk of polycythemia in the first few months after starting the therapy, Transdermal preparations available in the form of patches and creams are also effective. The most recommended one is 1% hydroalcoholic gel (50-100 mg of testosterone every day), which can dry fast with good bioavailability, In older patients, the gel formulations are the first choice as it can be rapidly reversed if any adverse effects develop. But there is a possibility for secondary transfer through skin-skin contact and can increase the serum testosterone levels. Transdermal patches (delivers 5-10 mg of testosterone over 24 hours) can be applied every night but should be observed for any allergic reaction, Testosterone pellets are available for subcutaneous injections in different doses at an interval of 3-6 months, We should measure the baseline levels of free testosterone, total testosterone, LH, FSH, prolactin, prostate-specific antigen, and complete blood count before starting the therapy. The labs should be repeated after 3-6 months after starting the therapy, then every 3-12 months after that as needed, We should also monitor them with complete blood count, liver function tests, coagulation studies, serum calcium, and lipid profile along with a dual-energy x-ray absorptiometry scanning (repeat after one or two years) during the therapy, Testosterone replacement therapy (TRT) has significant risks of stimulating the growth of the prostate gland, gynecomastia, priapism, male pattern baldness, abuse potential, low HDL (high-density lipoproteins), oligospermia, and azoospermia, In a double-blinded study of 41 men with total testosterone < 12 nmol/l ( testosterone injections three times in six months vs. placebo injections), TRT has improved the median serum total testosterone levels from 6.8 nmol/l (5.0; 9.3) to 12.3 nmol/l (7.0; 19.9) (P < 0.001 vs. placebo), increased lean body mass 3.6 kg (2.3; 5.0) (TRT) vs.0.1 kg (-2.1; 1.5) (placebo) and lowered the total body fat -1.2 kg (-3.1; 0.7) vs.1.2 kg ( 0.9; 2.5) both P < 0.003, without much improvement in pain perception, There was no significant change with pain perception, though TRT has shown improvement in body composition like improving the lean body mass and lowering the body fat. Low testosterone is associated with increased pain sensitivity as it interferes with opioid analgesia, and it can be reversed with testosterone supplementation therapy (TST). A retrospective pilot analysis examined the effect of testosterone supplementation therapy on chronic pain based on the Numerical Rating Scale (NRS), daily morphine (MED) equivalent dose, and the impact of TST on the hypogonadal symptoms measured with the International Index of Erectile Function (IIEF-5) and Androgen Deficiency in Aging Males (ADAM), Raheem et al. have shown that there was an increase in the median testosterone by 262.5 ng/dl (P < 0.05) with an improvement of hypogonadal symptoms (ADAM and IIEF-5 scores) like improving the sexual desire, erectile function, body composition, and quality of life (P < 0.05) in TST group, The data also proves the improvement in the Numerical Pain Rating Scale (NRS) (P = 0.02) and reduction in the daily morphine equivalent (MED) (P < 0.05) in testosterone supplemental therapy (TST) group vs. non-TST group, TST has a significant role in reducing the opioid dose requirement and improving the pain perception and hypogonadal symptoms. In a randomized study of 53 female patients with acquired immunodeficiency syndrome (AIDS) wasting syndrome with low serum androgen levels, transdermal testosterone improved the serum testosterone levels in a dose-dependent manner (P < 0.0001), caused weight gain ( amounting to 4% increase of initial weight) (P = 0.041) and increased the fat-free mass to a greater extent, improved the quality of life in terms of general physical health, emotional wellbeing, energy and social function (P= 0.024) and improved the pain score evaluated based on the pain item on 36 items short-form health survey (SF-36) (P= 0.059), These studies have demonstrated that TST has improved the pain perception and serum androgen levels along with significant improvement in the quality of life in terms of improving the energy level, physical and mental wellbeing. In this comprehensive literature review, we did not include any methodological quality assessment criteria. As well, we did not assess a specified population group based on their age or ethnicity. Opioid-induced hypogonadism is a lesser-known but highly prevalent adverse effect in patients on long-term opioid therapy. Narcotics have both central and peripheral effects causing reduced serum testosterone levels. The clinicians should look for these lesser known adverse consequences and assess them clinically based on their signs and symptoms. Testosterone replacement therapy is a viable option for managing symptomatic males, and we recommend collaborative care with an endocrinologist for the best outcome. Careful patient selection and close monitoring during therapy are the prerequisites for a successful therapy. We need further studies to provide us more details on the prevalence of opioid-induced hypogonadism and proper guidelines on diagnosis and treatment. We thank Dr. Hassan Tohid for his guidance throughout writing this paper and editorial assistance. The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus. The authors have declared that no competing interests exist.1. The future of pain research, education, and treatment: a summary of the IOM report "Relieving pain in America: A blueprint for transforming prevention, care, education, and research". Steglitz J, Buscemi J, Ferguson MJ. Transl Behav Med.2012; 2 :6–8.2. Prevention of opioid abuse in chronic non-cancer pain: an algorithmic, evidence based approach. 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How long will ibuprofen show up on a drug test?

Can Advil make you test positive on a drug test? – Ibuprofen can stay in your system for up to 24 hours, depending on the dose. As a result, it is possible that ibuprofen, which is the active ingredient in Advil, could cause a false positive on a drug test. However, it is unlikely that this would happen as most drug tests are designed to detect recreational drugs, not over-the-counter medications.