Ketamine is a drug initially synthesized in the 1960s to be used as an anesthetic. It was approved by the FDA in 1970 and was utilized medically as anesthesia for soldiers during the Vietnam war. At the time, ketamine was considered a superior option to PCP (phencyclidine) due to its short duration of effect and reduced likelihood of adverse reactions.
It has since been discovered to elicit analgesic effects, and is sometimes utilized as a treatment for pain. More recently it has been discovered to act as a potent, fast-acting antidepressant, ameliorating depressive symptoms within hours of administration. In fact, many new antidepressants in the 2015 pipeline are modeled directly after ketamine (e.g. esketamine) to function as NMDA receptor antagonists.
Although ketamine has a variety of favorable properties when used as an anesthetic, analgesic, and/or antidepressant – it is not a utopian drug. Some ketamine users experience drug-induced psychosis, unpleasant psychotomimetic effects, and/or fail to attain therapeutic benefit following administration. If you have a bad experience with ketamine, you may cease usage only to wonder how long the drug stays in your system.
How long does Ketamine stay in your system?
Assuming you’ve completely stopped using this drug, you may experience some ketamine withdrawal symptoms if you were a regular (daily) user. In most cases, discontinuation effects may not be significant, but you may experience some lingering side effects from ketamine usage that you may want to stop. To determine whether any of the ketamine is still circulating throughout your plasma, it is necessary to examine its elimination half-life.
The elimination half-life of ketamine is reportedly 2.5 to 3 hours in adults and 1 to 2 hours in children. This means that if you are a healthy adult, you will have eliminated ketamine from your plasma between 13 hours 45 minutes and 16 hours 30 minutes (on average). In the event that a child was administered ketamine, the drug would be completely cleared from plasma within 11 hours post-administration (on average).
Although ketamine is metabolized to form metabolites such as norketamine and dehydronorketamine, these metabolites are known to exhibit shorter elimination half-lives than the parent drug (ketamine). Therefore you shouldn’t need to be concerned with whether various ketamine metabolites are circulating throughout your system for a longer duration than ketamine itself. Most users can expect to have excreted a majority of the drug within 24 hours of their last dosage, and completely from their body within several days thereafter.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/ketamine
Variables that influence how long Ketamine stays in your system
Despite the fact that most ketamine users will eliminate the drug from systemic circulation within 11 to 17 hours after their final dose, there is often variance in regards to precise elimination times. This variation in elimination speed is usually due to variables such as: individual attributes, dosage, term/frequency of administration, and co-administered drugs.
Two people may administer the same dosage of ketamine simultaneously, yet one may clear it from his/her system quicker than the other. The difference in clearance speed is usually a result of individual factors including: a person’s age, body mass, brain/spinal injuries, genetics, and hepatic function. When contemplating how long ketamine is likely to stay in your system, considering individual factors may be helpful.
Age: It is likely that a ketamine user’s age will influence how long the drug remains in their system. Elderly individuals (over the age of 65) are often unable to eliminate drugs with the same efficiency as younger adults. This is usually due to a number of reasons including: diminished hepatic function, decline in renal function, altered distribution, and decreased overall physiologic function.
Furthermore, elderly individuals may be dealing with another medical condition and taking medications that may prolong the elimination of ketamine. Though specific studies haven’t been conducted to assess the impact of age on ketamine elimination in humans, both the half-life and clearance rate are reduced among elderly rats. Based on this finding, it is logical to hypothesize a similar prolonged excretion among elderly humans.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24041212
Body mass + Fat (%): A person’s body mass relative to the dosage of ketamine they ingest may affect how long it stays in their system. In most cases, ketamine is administered within the range of 0.5 mg/lb to 2 mg/lb. Assuming a more massive individual is administered a total of 100 mg, whereas a smaller person is administered the same dosage, the more massive individual is likely to eliminate the drug quicker from his/her system.
Faster elimination should occur if the dosage is lesser in proportion to a person’s body mass. That said, the greater percentage of body fat an individual has, the longer they may retain ketamine. Ketamine is a lipophilic drug, meaning it is soluble in fat stores. Individuals with more body fat will have more fat stores, thereby allowing for greater accumulation of the drug – which could slow its elimination.
Brain/spinal cord injuries: Research has shown that ketamine metabolites have longer half-lives than the parent compound among individuals with brain and/or spinal cord injuries. If you’ve endured a brain or spinal cord injury and administer ketamine, its pharmacokinetic profile will adjust. The half-life of norketamine will increase to an average of 5.3 hours, whereas the concentrations of dehydronorketamine will elevate to approximately 6.9 hours.
Based on these averages, we can estimate that it’ll take around 1.21 days to eliminate norketamine, whereas it’ll take around 1.58 days to eliminate dehydronorketamine metabolites. Usually the greater the severity of the injuries, the longer it’ll take to clear these metabolites from your system. This is much different than in a non-injured person in which the metabolites are systemically cleared more rapidly than the parent drug (ketamine).
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12538370
Genetics: Your genetic expression can have an impact on how quickly ketamine is cleared from your system, as well as the number of adverse effects you experience while taking it. Research suggests that the CYP2B6*6 allele decreases steady-state clearance of ketamine, meaning if you have this gene, it’ll stay in your system for a longer duration than usual. That said, CYP2B6 enzymes aren’t responsible for the majority of hepatic metabolism of ketamine.
The drug undergoes N-demethylation primarily via the CYP3A4 isoenzyme within the liver. CYP3A4 isoenzyme function is regulated by the CYP3A4 gene, and therefore it is necessary to consider the role of the CYP3A4 gene in ketamine’s pharmacokinetics. Although polymorphisms of CYP3A4 genes that would affect ketamine’s metabolism are uncommon, a poor CYP3A4 metabolizer as a result of certain alleles may exhibit a prolonged elimination half-life of ketamine and/or its metabolites.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25702819
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12065445
Hydration: It is thought that the majority of ketamine is excreted within urine as metabolites. As a result of this urinary excretion, it is possible that the degree to which someone is hydrated while using ketamine may have a slight impact on its excretion speed. Individuals that are well-hydrated tend to exhibit increased urinary flow rates, which in turn facilitate faster excretion of various drugs (and metabolites).
If you’ve been well-hydrated while taking ketamine, you may eliminate ketamine (and its metabolites) more efficiently than if you were dehydrated. A person who’s dehydrated will have a decreased urinary flow rate, and as a result, less of the drug will get eliminated in a short period of time. Despite a slight impact of hydration on ketamine excretion, it is unlikely to be clinically significant.
Hepatic/Renal function: It is likely that hepatic impairment prolongs the elimination of ketamine, possibly a significant extent in certain cases. Usually the degree of impairment dictates the extent to which drug elimination is prolonged. Individuals with severe hepatic impairment will likely exhibit poor functioning of CYP450 isoenzymes (e.g. CYP3A4, CYP2B6, CYP2C9), thereby leading to decreased metabolism, slowed metabolism, and elevated plasma concentrations of the drug.
This inevitably leads to a significantly longer term of elimination, perhaps exceeding 2 days. In addition, an individual with renal impairment may also excrete ketamine at a slower rate than those with normative renal function. This is due to the fact that since the kidneys are impaired, they are unable to efficiently excrete the drug, which results in accumulation of ketamine (and metabolites) – leading to reabsorption and recirculation prior to excretion. Research in rabbits indicates that elimination half-life increases by nearly 2 hours among those with renal impairment; whether this also applies to humans isn’t well understood.
- Source: http://www.medsafe.govt.nz/profs/datasheet/k/ketamineinf.pdf
- Source: http://www.ncbi.nlm.nih.gov/pubmed/4029219
Metabolic rate: A person’s basal metabolic rate (BMR) is known to affect how quickly various drugs are metabolized. It is possible that those with a high BMR metabolize and eliminate ketamine slightly quicker from their systems than individuals with a low BMR. A high BMR indicates that the body is burning more energy in a resting state, and therefore may be faster to process certain exogenous substances like ketamine. A very low BMR may prolong the drug’s elimination due to slowed physiologic processes.
Generally the greater the dosage of ketamine you take (especially relative to your body weight), the longer you should expect it to remain in your system. A person who administers 200 mg of intravenous ketamine will likely take longer to eliminate the drug from his/her system than someone who administers just 50 mg. This is due to the fact that when you ingest a higher dosage, more of the drug needs to be metabolized, distributed, and excreted.
High doses result in slower metabolism due to the fact that they may overwhelm hepatic enzymes CYP3A4, CYP2B6, and CYP2C9. The efficiency of these enzymes decreases when larger doses are ingested. In addition, once a larger dose is metabolized, it yields a greater quantity of metabolites plus a greater amount of unchanged ketamine that is distributed throughout the body.
Since ketamine is lipophilic, it is thought to accumulate in fat stores throughout the body. When more of the drug is circulating throughout the body (as a result of a high dose), we could surmise that more would likely accumulate in fat stores – leading to prolonged elimination. In addition, a greater number of metabolites formed as a result of a higher dose will also decrease the efficiency by which the kidneys are able to excrete the drug via urine.
A heightened number of metabolites means that a greater percentage are likely to get reabsorbed and recirculated prior to renal elimination. Therefore you could expect the drug to stay in your body for longer duration if you ingested a high dose. If you took a low dose of ketamine, its metabolism will be efficient, its accumulation will be reduced, and its excretion will be faster.
Frequency of Administration
The term over which you’ve been taking ketamine, as well as the frequency at which you use it are likely to affect how long it stays in your system. If you are a long-term, high-frequency user of ketamine, you’re more likely to have reached steady state concentrations of the drug in your system. In addition, a long-term frequent user will have likely accumulated a greater amount of the drug within various fat stores throughout the body, and will usually administer higher doses than short-term users.
Higher doses are used among long-term users due to the fact that individuals become tolerant to the effects of lower doses when regularly administered, especially over an extended term. That said, a short-term/infrequent ketamine user is unlikely to have built up any sort of tolerance, nor reached maximal concentrations of ketamine (and its metabolites) throughout their body. If you consider yourself an extremely short-term user or have only used ketamine a single time, you can expect elimination to be quicker than a long-term user.
If you are a short-term user, but are using ketamine at a high frequency rate (e.g. several times throughout the day), it is likely to accumulate to a more significant extent than a one-time user. For this reason, even though you may have used the drug for a short-term, the highly frequent ingestion is likely to prolong its elimination from your system. The bottom line is that the less frequent you use ketamine, and the shorter the term over which you’ve been using it, the faster you’re likely to eliminate it.
Co-administered drugs (CYP3A4 inhibitors)
Taking a drug that affects various CYP450 (cytochrome P450) enzymes within the liver may affect how long ketamine stays in your system. Specifically, the enzyme CYP3A4 is responsible for the majority of ketamine metabolism via N-demethylation. Therefore any simultaneously administered exogenous substance that either disrupts or enhances the function of CYP3A4 enzymes will respectively prolong or expedite excretion of ketamine (and metabolites).
Substances known as CYP3A4 inhibitors are known to interfere with the metabolism of ketamine by downregulating CYP3A4 function. Should you have taken a CYP3A4 inhibitor along with ketamine, the drug will metabolize at a slower rate than usual, and ultimately remain in your system for a longer duration. Examples of CYP3A4 inhibitors include: Cobicistat, Indinavir, Itraconazole, Ketoconazole, Nefazodone, Nelfinavir, Ritonavir, Telithromycin, and Tlarithromycin.
On the other hand, research suggests that if you’re taking a CYP3A4 inducer, or an agent known to enhance enzymatic function of CYP3A4, you’ll metabolize and eliminate the drug at a faster rate. Examples of some CYP3A4 inducers include: Butalbital, Carbamazepine, Glucocorticoids, Modafinil, Oxcarbazepine, Phenobarbital, Phenytoin, Quercetin, Rifabutin, Rifampicin, and St. John’s wort. Understand that the potency of CYP3A4 inhibition or induction may be subject to variation based on the particular agent administered, as well as its dosage.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21508826
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12065445
Ketamine: Absorption, Metabolism, Excretion (Details)
Following parenteral (intravenous) administration, ketamine is rapidly absorbed and plasma concentrations peak at around 0.75 g/ml approximately 1 hour post-administration. An estimated 20% to 50% of ketamine binds to plasma proteins and is distributed at a volume of 1 to 3 L/kg throughout the body. High concentrations of ketamine are thought to appear within fat stores, the liver, lungs, and brain – whereas low concentrations appear within heart, muscle tissue, and plasma.
After administration, ketamine is subject to extensive hepatic metabolism via various CYP450 isoenzymes including: CYP3A4, CYP2B6, and CYP2C9. CYP3A4 facilitates a majority of the metabolism via N-demethylation to form the pharmacologically active metabolite “norketamine” – which has approximately 16% the potency of ketamine. Norketamine is subject to additional dehydrogenation to form the secondary metabolite, dehydronorketamine.
Additional hydroxylation of the cyclohexone ring, conjugation with glucuronic acid, and dehydration of hydroxylated metabolites occurs prior to urinary excretion. Ketamine is thought to be eliminated from the system in a biphasic or triphasic pattern. The initial phase of elimination is thought to exhibit a 15 minute elimination half-life, whereas the secondary phase of elimination may occur between 2 and 4 hours post-administration.
This indicates that it could take up to 22 hours for complete plasma elimination of ketamine, but most likely will take just under 14 hours (on average). An estimated 90% of ketamine is processed by the kidneys and excreted via urine, whereas 3-5% is excreted via feces. Of the 90-95% that is eliminated via urine, only 2-4% is of unchanged ketamine – the majority is of metabolites such as norketamine and dehydronorketamine.
- Source: http://www.medsafe.govt.nz/Profs/Datasheet/k/ketalar100mginj.pdf
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/ketamine
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12065445
Types of Ketamine Drug Tests
After administration of ketamine, it is possible to determine whether any of the drug (or its metabolites) are still in your system via a drug test. Although the drug will have cleared your plasma within 1 to 3 days, is metabolites will remain detectable for awhile thereafter. Keep in mind that the standard SAMHSA-5 panel doesn’t aim to detect ketamine, but a ketamine-specific test is well equipped to detect norketamine and dehydronorketamine metabolites.
Urine tests: The most common type of test to determine whether someone has ingested ketamine is via collection of a fresh urine sample. The sample is then sent to a laboratory for a urinalysis which reports levels of various metabolites such as norketamine and dehydronorketamine. Since urinary excretion of unchanged ketamine is relatively low, ketamine isn’t generally a preferred biomarker on urinalyses.
By utilizing techniques such as gas chromatography/mass spectrometry (GC/MS), it is possible to detect norketamine within a urine sample for up to 14 days after ketamine administration. Research in monkeys found that norketamine could remain detectable for up to 31 days after ketamine administration. Detection limits are generally set at 5ng/mL, making the metabolites detectable among heavy users for 1-2 weeks after their last dose.
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/ketamine.htm
- Source: http://www.ncbi.nlm.nih.gov/pubmed/11599604
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16105264
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15842758
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26447937
Hair tests: It is possible to detect ketamine by collecting a sample of hair follicles from a prospective user’s head. The sample of hair follicles can then be sent to a laboratory for analysis, which will determine levels of ketamine and its metabolite norketamine (and sometimes dehydronorketamine). Researchers have proposed that these tests should utilize a cutoff threshold of 0.5 ng/mg for ketamine and 0.1 ng/mg norketamine in a hair sample; concentrations above these limits indicate repeated exposure to ketamine.
Hair tests may be advantageous over urine tests in that they may provide a longer window of detection of up to several months after ketamine ingestion. One study determined that the amount of ketamine within hair samples correlates directly to the frequency of use/abuse. Concentrations of ketamine and norketamine are easiest to detect in hair, whereas the metabolite dehydronorketamine is only likely to appear among high dose users.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25616219
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16105255
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16844332
Saliva tests: Oral fluid (saliva) samples can be collected to determine whether an individual has recently ingested ketamine. Various devices such as the OratectXP Oral Fluid Drug Screen Device are being engineered to rapidly detect ketamine in an oral fluid sample. It is thought that these devices would be useful for law enforcement agents to pinpoint the specific drug responsible for an individual’s intoxication.
The cutoff for ketamine detection in oral fluid devices like the OratectXP is set at 15 ng/ml. Currently the accuracy of such devices are approximately 94%, and as a result, they may be utilized more often in the future – especially as accuracy increases at lower thresholds. Furthermore, collection of an oral fluid sample and analysis in a laboratory via liquid chromatography/mass spectrometry (LC/MS) is highly accurate – and may be used to confirm results from a device like the OratectXP.
That said, ketamine is unlikely to remain in your saliva for an extensive term after administration. For this reason, it is likely that saliva tests would be reserved for assessing intoxication solely on the day of intoxication – rather than several days thereafter.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/22417838
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17046188
Blood tests: A blood test is seldom utilized to determine levels of ketamine due to the fact that it is invasive and offers a smaller window of detection compared to urine tests. For this reason, most individuals subject to a ketamine test will be assessed with a urine sample. Ketamine is thought to get eliminated from the plasma within 24 hours of administration.
As a result of this fast elimination, it remains difficult to detect via collection of a blood sample. A blood test may be utilized in scientific research to confirm plasma concentrations of the drug and/or among hospitalized patients. Additionally, a blood test is effective when collected the day of ketamine administration, but detectability of ketamine (and metabolites) in the bloodstream diminishes with each passing day.
Who may be tested for Ketamine?
Most individuals are unlikely to be tested for ketamine unless they have been known to abuse it in the past. As was mentioned, ketamine is not assessed for on standardized drug panels like the SAMHSA-5. However, if you are a criminal, in rehabilitation, and/or are in the military – you may be held to higher standards and could be assessed with an advanced drug screening.
- Criminals: Criminals have been known to administer ketamine to themselves, as well as use it on others as a “date rape” drug. For this reason, law enforcement agents may testing criminals and/or victims of various crimes to determine whether ketamine has been ingested. If a criminal is caught having ingested ketamine, they may face harsh legal consequences.
- Drug rehab clients: Individuals in drug rehabilitation may look to ingest any illicit drug with the intent of intoxication. For this reason, patients that are suspected to have ingested ketamine may be screened for its presence. If they end up testing positive for ketamine (or its metabolites), they may require additional time in the rehab clinic.
- Employees: Though most employers do not test for ketamine, some may administer advanced drug tests on suspicion that their employee may be using illicit drugs. Various occupations such as pilots, truck drivers, and/or those involving the operation of heavy machinery may endanger lives of others should they ingest ketamine prior to work. As a result, some individuals may be subject to a urinalysis for ketamine.
- Military personnel: It is possible that certain members of the military may be subject to extensive drug panels. If someone is suspected to have used a drug like ketamine, it may impair their performance and result in increased likelihood of injuries/deaths/equipment damage. For this reason, military may administer an advanced drug panel if they suspect that you’ve ingested ketamine.
Tips to clear Ketamine from your system
If your goal is to clear ketamine from your system as quickly as possible, there may be some tricks you can consider implementing. Keep in mind that prior to implementing any of these suggestions, it is necessary to confirm safety and alleged efficacy with a medical professional. Also realize that certain suggestions may provide greater benefit to some ketamine users compared to others.
- Discontinuation: The first step to completely detoxify and get ketamine out of your system is to stop using it. The sooner you stop using ketamine, the quicker you can expect to excrete it from your body. Unfortunately many people continue using the drug intermittently and fail to realize that it may accumulate in fat stores with each additional usage, resulting in slower elimination.
- Exercise: Since ketamine is lipophilic and can accumulate within bodily tissue, including fats – it may be necessary to burn some of your body fat via exercise. Burning this fat will essentially flush out ketamine that was previously stored in fat deposits throughout your body. Although exercise may not make a huge difference in excretion speed, it is likely to facilitate a faster detoxification.
- Activated charcoal: If you took ketamine and want to get it out of your system quickly, you could consider taking activated charcoal as a supplement. Activated charcoal has a charge opposite to most drugs, allowing it to adsorb unmetabolized ketamine, as well as various endotoxins lingering in your body. This may be worth taking if your goal is to completely detoxify after using ketamine.
- Calcium-D-Glucarate: Another supplement you may want to consider taking for detox purposses is that of calcium-d-glucarate, which essentially flushes out toxins stored in renal detoxification pathways. It does this by inhibiting beta-glucuronidase, thereby allowing ketamine (and its metabolites) to get eliminated as efficiently as possible.
- CYP3A4 inducers: Taking ketamine along with a CYP3A4 inducer will expedite its metabolism and elimination. If you concurrently administered a CYP3A4 inducer, you’ll enhance the function of CYP3A4 enzymes within your liver, leading to faster metabolism. If the ketamine has already been absorbed and fully metabolized, a CYP3A4 inducer likely won’t do you much good.
How long has Ketamine stayed in your system after stopping?
If you use ketamine regularly and/or recently stopped using ketamine, share a comment regarding how long you believe it stayed in your system Do you think that you were able to eliminate it quickly (e.g. under 14 hours) after administration? Or do you think that you eliminated it at a slower rate (e.g. up to 20 hours)?
Mention any factors that you believe may have influenced how long it stayed in your system such as: usage of other drugs (e.g. CYP3A4 inhibitors), hepatic/renal impairment, or usage at supratherapeutic dosages. Understand that most users will eliminate the drug from their system in under 24 hours, but the drug and metabolites remain detectable in urine and hair for weeks after your last dose with advanced drug screenings (e.g. GC/MS).