GHB (gamma-hydroxybutyric-acid) is a drug that was initially synthesized in 1874 by Alexander Zaytsev, but its effects weren’t researched in humans until the 1960s. Upon administration to humans, it was discovered that GHB functions as a short-acting CNS depressant. GHB alters neurotransmission via binding to multiple receptor sites within the brain including: GHB receptors and GABA(B) receptors.
After binding to the aforementioned receptors, GHB acts as an agonist. Its agonism at GHB receptor sites facilitates an excitatory response, whereas agonism at GABA(B) receptor sites yields an inhibitory response. What’s more complex is that it also elicits a biphasic (dose-dependent) effect upon dopaminergic transmission. At low doses, it increases dopamine levels via GHB receptors, whereas at higher doses, it decreases dopamine via GABA(B).
As a result of its mechanism, GHB is considered an effective treatment for alcoholism, insomnia, narcolepsy, and in some cases, major depressive disorder. Though GHB is still used for narcolepsy under the brand name medication “Xyrem,” its usage for other conditions is unauthorized. For this reason, some unauthorized GHB users may discontinue treatment, but wonder how long it stays in their systems as to avoid failing a drug test.
How long does GHB stay in your system?
Assuming you’ve completely stopped using GHB, you may initially notice the emergence of unpleasant GHB withdrawal symptoms, especially if you were a chronic user. In other cases, you may not notice discontinuation symptoms, but may realize that certain side effects experienced whilst using GHB such as “brain fog,” continue to linger for days after your final dose. These lingering side effects may lead you to question whether any GHB is somehow still in your system.
To accurately determine how long GHB is likely to remain in your plasma after discontinuing treatment, it is necessary to know its elimination half-life. GHB is understood to have an elimination half-life within the range of 20 to 60 minutes when taken orally; this is extremely short-compared to most medications. By knowing its elimination half-life, we can estimate that it’ll take up to 1 hour (on average) for your body to eliminate 50% of an ingested GHB dose from plasma circulation.
With this information, we can estimate that it’ll take (on average) between 1.83 and 5.5 hours to eliminate 100% of the GHB from systemic circulation. This means that GHB should be out of your system within a few hours post-ingestion. However, just because GHB is out of your system within just 5.5 hours (on average), does not mean that your neurochemistry will have normalized and/or readjusted back to pre-GHB homeostasis.
It may take awhile for your neurochemistry to recalibrate itself to homeostatic functioning after GHB usage. During this recalibration phase, you may mistakenly believe that GHB is somehow still in systemic circulation. The reality is that while GHB was in your system, it induced a cascade of potent neurophysiological changes, but was rapidly eliminated.
After its elimination, you may not feel “normal” because your neurochemistry hasn’t readjusted itself back to homeostatic functioning. As a result of this altered neurochemical state, you’ll perhaps wrongfully perceive that GHB is still in your system. Just know that the GHB was likely eliminated within the first half-day (12 hours) post-ingestion and that your depersonalization is a lingering byproduct of the changes it made to your neurochemistry while it was in your system.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/4-Hydroxybutanoate
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/gamma-hydroxybutyrate.htm
Variables that influence how long GHB stays in your system
It is important to realize that not all GHB users will eliminate the drug from systemic circulation in the exact same amount of time. Some individuals will eliminate GHB from their plasma with extreme rapidity, while other may exhibit prolonged elimination, perhaps exceeding 6 hours. Differences in GHB elimination speeds stem from variables such as: individual attributes of the specific GHB user, dosage, and frequency of administration.
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Individual factors
Two individuals may simultaneously take an equipotent GHB dosage, yet one user may eliminate it from his/her plasma quicker than the other. The difference in elimination speed when administered at the same time, same dosage, and same potency (via the same routes) can best be explained by individual factors. These individual factors include things like a person’s age, body mass (water per kilogram of body weight), renal function, and sex.
Age: It is likely that GHB may exhibit a longer half-life among elderly individuals for a variety of reasons. Elderly individuals (over the age of 65) often experience diminishing renal and hepatic function, which may lead to less efficient GHB metabolism and elimination. However, since GHB is minimally metabolized via liver enzymes and is excreted chiefly via expiration (lungs), poorer renal/hepatic function among elderly is unlikely to have a clinically significant impact on its elimination half-life.
Furthermore, certain medications taken by elderly individuals as a result of medical conditions may expedite the elimination of GHB. Some sources suggest that volume of GHB distribution lesser due to less water per kilogram among the elderly; this could also speed up its elimination. Among elderly patients taking GHB, elimination time will be largely determined based on their overall health, whether other medications are taken, water volume per kilogram, sex, and hepatic/renal function.
Some elderly individuals will likely eliminate GHB slower than younger adults based on certain age-related factors, while others may eliminate it quicker based on different age-related factors. If you are a younger adult in good health, you should eliminate GHB within the normative window of 2 to 6 hours post-ingestion.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19514965
Alcohol: Research suggests that co-administration of alcohol increases plasma concentrations of exogenous GHB and increases its elimination half-life by an average of 29%. Assuming a 29% increase in elimination half-life, we could expect the half-life range among users of GHB plus alcohol to fall within the range of 25.8 minutes and 1.29 hours. This would indicate that it may take up to 7.1 hours for an individual drinking alcohol to eliminate GHB from his/her system.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/16974199
Body mass + Fat (%): A person’s body mass and/or body fat percentage is known to affect the distribution of GHB in bodily fluids. GHB is a highly-hydrophilic substance, meaning it is soluble in water. Individuals with lower body fat tend to carry more water per kilogram of body weight – in part because they have less fat, but also because muscle tissue holds more water; those with less fat are more likely to have muscle.
As a result of the greater volume of water per kilogram among those with lower body fat, GHB is distributed more extensively throughout the body – leading to a longer window of retention. Among individuals who have a high percentage of body fat and/or are obese, the volume of GHB distribution will be lower due to less water per kilogram of body weight. This reduced distribution among those with high fat is may yield a slightly reduced elimination half-life.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/26074743
Food intake: Whether you ingested food prior to administering GHB may affect its absorption and ultimately how long it stays in your system. Specifically, research suggests that eating a high fat meal prior to administration of GHB will decrease its absorption by approximately 37%, reduce its peak plasma concentrations by 58%, and delay the time it takes to attain peak plasma concentrations from 45 minutes to 2 hours.
If you ate a high-fat meal prior to taking GHB, the absorption will be protracted, meaning GHB will make its way into your system later than usual. A layman would perceive this delayed absorption as GHB staying in his/her system for a longer duration. If we are referring to “system” as body, well then yes, this perception may be accurate. However, if by “system” we are referring to systemic plasma circulation, then this perception is inaccurate.
Delayed absorption simply means that there’s a lag between the time of ingestion and time in which it circulates in the plasma. Once GHB is circulating in the plasma, the total time it remains in circulation may be reduced after a high-fat meal as a result of decreased absorption. This means that if you ate fatty foods prior to GHB, expect it to remain in your body for a longer duration, but your plasma for a shorter one. Though the extent to which a high-fat meal affects elimination half-life of GHB is unclear, it likely has an influence.
- Source: https://books.google.com/books?id=BfdighlyGiwC
Hepatic function: Unlike most drugs that undergo extensive hepatic metabolism via various CYP450 isoenzymes, GHB is metabolized chiefly via non-hepatic pathways. A majority of GHB biotransformation is facilitated by the Krebs cycle (specifically via the enzyme GHB dehydrogenase). For this reason, it is unlikely that individuals with hepatic impairment will eliminate GHB at a significantly slower rate than those with normative hepatic function.
However, it is important to note that increases in GHB’s elimination half-life have been observed among those with hepatic impairment. In a study analyzing the pharmacokinetics of GHB among 16 patients with cirrhosis, it was discovered that hepatic impairment (as a result of the cirrhosis) increased elimination half-life by approximately 37 minutes. This implies that GHB may be retained for nearly 3.39 hours longer among those with hepatic impairment compared to those with normative hepatic function.
Metabolic rate: A person’s BMR (basal metabolic rate) could alter the pharmacokinetics of GHB such as its elimination half-life. Individuals with a high BMR are known to be burning more energy at rest. This increased energy expenditure at rest is associated with faster metabolism and elimination of exogenous drugs (e.g. GHB).
Those with low BMRs are using up less energy at rest, and therefore may metabolize and eliminate exogenous substances like GHB at a slower rate. That said, it is important to consider that BMR is often related to body weight and individuals with a high body weight tend to have a lower BMR. This suggests that while a high metabolic rate may expedite the elimination of GHB, expedition may be offset by high body fat (due to decreased water volume per pound).
Renal function: Though kidneys don’t play a significant role in the excretion of GHB, it is still necessary to consider that renal impairment may prolong urinary excretion. A small percentage (~5%) of a GHB dose is excreted within urine after ingestion. Should an individual exhibit impaired renal function, it is possible that GHB (especially when administered at high doses), may accumulate in renal pathways.
The accumulation of GHB in renal pathways may lead to some of the drug getting reabsorbed and redistributed throughout the body – leading to a prolonged term of elimination. Although the increase in elimination half-life as a result of renal impairment may not be clinically significant, it may be prolonged to a slight extent, reflective upon the degree of impairment. Individuals with severe forms of impairment are likely to retain GHB for a longer duration than those with minor forms of impairment.
Sex: It is necessary to consider distributional differences of GHB between male and female users. Distribution of GHB tends to increase among males because men are known to carry a greater volume of water per kilogram (body weight) than females. GHB is hydrophilic, so it has an affinity for these water stores.
As a result, GHB is dispersed to a greater extent in the body of a male than that of a female, leading to a slightly prolonged elimination among men. Since females carry less water (volume) per kilogram (body weight) than males, the volume of GHB distribution will be reduced – leading to a faster elimination. Though overall body fat percentage likely influences GHB elimination to a greater extent than sex, it is still necessary to account for sex-based differences in water volume per kilogram when contemplating GHB’s elimination speed.
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Dosage (Potency)
The dosage of GHB that a person takes will likely affect how long it remains in systemic circulation post-ingestion. Individuals taking low doses of GHB are thought to eliminate the drug at a quicker rate than high-dose users because there’s a reduced amount of an exogenous substance for the body to process. In other words, lower doses results in decreased plasma concentrations, less extensive distribution, efficient metabolism, and more efficient elimination.
While individuals taking high doses of GHB will not “accumulate” the drug in bodily tissues, they may experience elevated plasma concentrations. In addition, an increased amount of GHB will necessitate metabolism and elimination. As a result of the heighted amount of GHB to be metabolized and eliminated, metabolism and elimination decrease in efficiency – possibly leading to longer systemic retention.
Research has shown that when a GHB dose is doubled from 4.5 grams to 9 grams, plasma concentrations increase by 3.7 fold. In the case of a GHB overdose (or supratherapeutic dose), it has been suggested that “zero order kinetics” should be assumed. This suggests that we should assume a standard amount of GHB to be eliminated per hour among those that ingested extremely high doses, contrary to first-order kinetics.
If you ingested an extremely high dose of GHB, it is likely that the time it takes to completely eliminate it from your system will be considerably longer than the average prolonged time of 5.5 hours. On the other hand, if you were to take just 0.5 grams of GHB, it is likely that you’d eliminate it in accordance with the commonly reported half-life of 20 to 60 minutes with total elimination occurring in the span of 1.83 to 5 hours. In summary, you should expect a faster elimination when taking a low dose than a high one.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/19653937
Note: A final note should be made regarding the potency of “liquid GHB” (commonly sold as a street drug). Unless you know the specific concentration of GHB (grams per milliliter) within the liquid formulation, it is impossible to accurately know the dosage. Hypothetically you could have two 6 ml formulations “liquid GHB,” yet one may be more diluted than the other – making it less potent. Generally the greater the concentration of GHB within a liquid formulation, the higher its viscosity.
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Frequency of administration (Chronic vs. Acute)
The frequency at which you administer GHB may affect how long it remains in your system upon cessation. The more frequently you ingest GHB, the greater the likelihood that you’ll have ingested a high dose in a short duration – compared to an infrequent user. As was discussed, the heightened dosage (especially over a short-term) may prolong elimination based on the fact that a greater total quantity of GHB will compromise the efficiency of metabolism and excretion.
In other words, frequent users may be administering a second dose prior to the systemic elimination of an initial dose – perhaps facilitating prolonged GHB retention. Furthermore, it is necessary to speculate that frequent users are likely to have built up a tolerance to lower doses of GHB as a result of chronic administration. This tolerance may prompt frequent users to increase the dosage of GHB to derive the same therapeutic effects that they’re no longer able to attain from lower doses.
An infrequent GHB user is able to clear an initial dose of GHB from his/her system before an additional dose is taken; this is because there’s a greater time gap (possibly days or weeks) between ingestions. Additionally, an infrequent user is unlikely to have built up tolerance to the effects of GHB, and as a result, is more likely to take a low dose – leading to faster elimination. For these reasons, it would be likely that a frequent (chronic) GHB user would exhibit a prolonged elimination half-life compared to an infrequent (single-dose) user.
GHB: Absorption, Metabolism, Excretion (Details)
Following oral administration of GHB, the drug is rapidly absorbed via the gastrointestinal (GI) tract. Its absorption is influenced partially by dosage in that an increase in dosage prolongs the time it takes to attain maximum plasma concentrations. Additionally, taking GHB along with a high fat meal is known to decrease absorption, prolong time it takes to reach peak plasma concentrations, and reduce overall peak plasma concentrations.
Taking GHB on an empty stomach is known to expedite absorption, decrease the time it takes to reach peak plasma concentrations, and increase peak plasma concentrations. After absorption, GHB crosses the blood-brain barrier and is distributed throughout the brain, cerebrospinal fluid, liver, and kidneys. It binds at various receptor sites within the brain and is distributed with the highest concentration in the basal ganglia.
Studies suggest that metabolism of GHB is facilitated primarily by pathways of the Krebs (tricarboxylic acid) cycle. Specifically the enzyme GHB dehydrogenase (a cytosolic NADP+-linked enzyme) acts as a catalyst to convert GHB to succinic semialdehyde (SSA), which is further converted to succinate (via the succinic semialdehyde dehydrogenase enzyme). Upon its conversion to succinic acid, it enters the Krebs (tricarboxylic acid) cycle where it is metabolized to carbon dioxide and water.
Alpha-ketoglutarate also catalyzes the conversion of GHB to succinic semialdehyde via a transhydrogenase (mitochondrial oxidoreductase enzyme). Beta-oxidation is also responsible for secondary metabolism of GHB via 3,4-dihydroxybutyrate to carbon dioxide and water. No pharmacologically active metabolites of GHB have been discovered.
Once the GHB has been fully metabolized to carbon dioxide, it is “eliminated” mainly via expiration. Less than 5% of a GHB is excreted unchanged within urine when collected 6 to 8 hours post-ingestion and fecal excretion is considered negligible. The half-life of 20 to 60 minutes indicates that nearly 100% of a GHB dose should be eliminated from systemic circulation within 6 hours of ingestion.
- Source: https://pubchem.ncbi.nlm.nih.gov/compound/4-Hydroxybutanoate
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/gamma-hydroxybutyrate.htm
Types of GHB Drug Tests
Many individuals are worried that they’ll fail a drug test after taking GHB. However, in the majority of cases, drug tests for GHB will not be administered. Standard drug tests (e.g. SAMHSA-5), and even more extensive screenings do not typically assess for GHB unless specifically requested. Even in the rare case that an individual is subject to GHB testing, he/she is unlikely to test positive due to its rapid elimination half-life. Listed below are some specific ways in which a person can be tested for GHB.
Urine tests: The NHSTA (National Highway Traffic Safety Administration) reports that peak concentrations of GHB appear within the urine after 4 hours of administration. Due to the fact that only 5% of a GHB dose is eliminated via urine and its half-life is short, GHB becomes undetectable between 10 and 12 hours post-ingestion. In the urine sample of a non-GHB user, endogenous GHB concentrations can be detected at approximately 7 mg/L.
Exogenously ingested GHB will spike urinary levels to exceed 10 mg/L, hence the reason 10 mg/L is commonly used as a threshold or “cutoff” to detect abuse. That said, there is evidence that following the collection of urine samples, GHB levels can spontaneously increase in storage, thereby skewing the results. This spontaneous increase may make it difficult to interpret whether someone truly ingested exogenous GHB.
A urine test is usually non-invasive, easy to administer, and provides a detection window up to 10 hours. That said, if a reasonable amount of time had elapsed between GHB ingestion and collection of a urine sample, detecting exogenous GHB usage will be difficult and/or impossible. Twelve hours seems to be the upper limit of GHB detection in a urine sample.
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/gamma-hydroxybutyrate.htm
- Source: http://www.ncbi.nlm.nih.gov/pubmed/17030106
- Source: http://www.ncbi.nlm.nih.gov/pubmed/15538955
Blood tests: Perhaps the most common way to determine whether someone is intoxicated with GHB is to collect a blood sample. Though blood tests are relatively invasive, they generally provide the most accurate information in regards to degree of GHB intoxication. Since GHB concentrations are known to peak within the plasma in approximately 20 to 45 minutes post-ingestion, a blood test must be conducted as soon as possible after suspected ingestion.
Some sources suggest that following a single dose, GHB may remain detectable in the blood or plasma for between 6 and 8 hours – depending on the user. Endogenous concentrations of GHB in the bloodstream are usually below 1 mg/L, whereas after exogenous GHB ingestion, levels are generally within the range of 20 mg/L and 500 mg/L – depending on the dosage ingested and amount of elapsed time between ingestion and blood sample collection.
- Source: http://www.nhtsa.gov/people/injury/research/job185drugs/gamma-hydroxybutyrate.htm
Saliva tests: A way to determine whether someone has ingested GHB is by administering a saliva (oral fluid) assessment. An oral fluid test is capable of detecting exogenous ingestion of GHB for up to 6 hours post-ingestion. Though the detection time of GHB in oral fluid is less than its detection time in urine, an oral fluid sample may be collected to bolster the credibility of a urinalysis.
Should an individual test positive for GHB on both a saliva and urine test, it’s likely that they ingested exogenous GHB and/or are intoxicated. Concentrations of salivary GHB peak within 10 minutes of administration, meaning the drug is rapidly detectable in oral fluid after ingestion. In most GHB users, salivary concentrations are back within the normal range (of a non-user) after several hours post-ingestion.
Non-GHB users generally exhibit 0.15 to 3.33 mg/L within oral fluid, as evidenced by gas chromatography/mass spectrometry (GC/MS). Therefore it is likely that exogenously ingested GHB would increase concentrations within oral fluid above 3.33 mg/L.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/21439150
Hair tests: If an accurate hair test were developed to detect exogenous ingestion of GHB, it would perhaps be favorable over other assessments for numerous reasons. Hair tests are relatively non-invasive, yet are able to portray drug ingestion over an extended period. Furthermore, GHB may remain detectable for over a month on a hair sample, making a hair sample preferred for its extended window of detection.
Researchers have been working to establish some sort of criteria for GHB hair testing, but results are relatively unreliable and subject to potential inaccuracies. Therefore most reports suggest proceeding with caution when interpreting the levels of GHB in follicle samples. Some research has demonstrated that liquid extraction followed by HPLC (high-performance liquid chromatography) can distinguish GHB users from non-GHB users based on segmental analyses of hair follicles.
In one case, hair samples were collected from a female victim of a GHB-induced sexual assault. It was determined that increases of GHB concentrations to levels of 2.4 ng/mg were apparent in hair follicle segments of the victim – indicating that exogenous GHB had been ingested. This is significantly more than standard segments which are likely to contain 0.6 ng/mg to 0.8 ng/mg.
- Source: http://www.ncbi.nlm.nih.gov/pubmed/25433016
- Source: http://www.ncbi.nlm.nih.gov/pubmed/24947196
- Source: http://www.ncbi.nlm.nih.gov/pubmed/14670136
- Source: http://www.ncbi.nlm.nih.gov/pubmed/12570228
Who may be tested for GHB?
Though GHB is a “Schedule I” controlled-substance, its usage is relatively uncommon and its window of detection is considered extremely short. For this reason, it is uncommon to test individuals for the presence of GHB (and metabolites). However, an individual may be tested for GHB in the event that they are a criminal, rehabilitation patient, were hospitalized (from an overdose), and/or were victims of a criminal act (e.g. date-rape).
- Criminal suspects: In some cases, a criminal may be tested for GHB if it was thought to have been ingested. Should a criminal get caught with GHB in their system, he/she may face harsh legal penalization. Penalization may be more significant if GHB was unlawfully administered to an unknowing victim.
- Drug rehab patients: Individuals in rehabilitation with a past history of GHB usage and/or abuse may be subject to GHB testing. In this case, rehabilitation personnel may schedule regular testing for GHB to determine whether the drug has been ingested. Should an individual test positive for high levels of GHB, he/she may require additional time in rehabilitation.
- Hospital patients: Anyone that has overdosed (whether intentionally or unintentionally) may be blood-tested for the presence of GHB. If GHB is detected on a blood test, medical professionals will attempt to determine the level of exposure and do what they can to mitigate its deleterious effects.
- Intoxicated drivers: A driver that appears intoxicated may be subject to a battery of drug/alcohol tests. A law enforcement agent may conduct extensive testing to determine whether the individual had ingested alcohol and/or prescription drugs. If the individual passes a standard drug test, it is possible that he/she will be subject to GHB testing.
- Victims of a crime: Anyone that has been drugged against their will (such as in the case of “date rape”) may be tested for GHB. The exact level of GHB in the victim’s system will be recorded for legal purposes. This will help the victim build a strong case against a criminal.
Tips to clear GHB from your system
If you ingested GHB, there’s not really much that can be done to clear it from your system in a faster period of time. If you take GHB and immediately regret it, obviously you’ll want to ingest activated charcoal as soon as possible and contact emergency medical services. Eating fatty foods may also decrease GHB absorption and lead to faster plasma elimination.
That said, before you consider implementing any of the suggestions below, discuss their safety and alleged efficacy with a medical professional. Also realize that compared to other drugs, there aren’t really many tricks to expedite elimination of GHB. GHB is eliminated quickly on its own (usually in under 6 hours). For this reason, there isn’t usually a need to speed up the elimination process.
- Activated charcoal: If a person administers an unintentionally high dose of GHB, it is plausible that activated charcoal may provide benefit. Activated charcoal is known to bind to exogenous drugs and toxins via adsorption. It is likely that if ingested immediately after GHB, activated charcoal could promote faster detoxification by limiting the amount of absorbed/circulating GHB. (Source: http://www.ncbi.nlm.nih.gov/pubmed/23017433).
- Calcium-D-Glucarate: A small percentage of GHB is eliminated via urine, most reports suggest under 5%. If your goal is to eliminate the 5% that gets excreted via urine as quickly as possible, you could consider the supplement known as calcium-d-glucarate. This supplement acts as a beta-glucuronidase inhibitor, which clears detoxification pathways and promotes efficient renal excretion of drugs.
- Avoid alcohol: Individuals that drink alcohol along with GHB are not only putting their lives at risk (combining multiple CNS depressants can be fatal), but they’ll retain the GHB for a longer duration than usual. Studies show that alcohol increases the half-life of GHB by up to 29%. This means that it could take over 7 hours to eliminate GHB from systemic circulation if you had a drink with it.
- Fatty foods: If you eat fatty foods along with GHB, it will promote slower absorption, but likely faster plasma elimination. This is due to the fact that fatty foods decrease peak plasma concentrations of GHB, resulting in a lower systemically circulating quantity of the drug. As a result, you may be more likely to eliminate it faster because less will have been absorbed.
How long has GHB stayed in your system after stopping?
If you’ve taken GHB and believe it stayed in your system for a long duration after stopping, share a comment mentioning why. To help support your hypothesis that you retained GHB stayed in your system for a long duration after ingestion, mention factors that may have increased its elimination half-life such as: co-ingested alcohol, large GHB doses, low body fat percentage, etc. If you believe that you were able to rapidly clear GHB from your system, mention some factors that may have facilitated rapid elimination.
Understand that most single-dose GHB users will have completely eliminated it from systemic circulation within 6 hours of their final dose. In rare cases will the elimination period extend beyond 6 hours. For this reason, it is illogical to assume that GHB is somehow still in your system after 24 hours post-ingestion. With the passing of a full day, complete excretion of this hydrophilic drug will have occurred.