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GHB Withdrawal & Detox Guide

Medically Reviewed By: Benjamin Caleb Williams RN, BA, CEN

Written By: Phillippe Greenough

Article Updated: 09/25/2020

Number of References: 18 Sources

GHB (gamma-hydroxybutyric acid/gamma-hydroxybutyrate) is a very powerful and highly addictive depressant and anesthetic drug. Capable of producing physical dependence within weeks of regular use, withdrawal is extremely unpleasant and potentially fatal. Our comprehensive guide outlines everything you need to know about GHB withdrawal, including the symptoms, timeline, specific effects on both the mind and body and more.

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What is GHB Withdrawal?

GHB withdrawal is very similar to the withdrawal syndromes of both alcohol and benzodiazepines. It is characterized by neurological hyperactivity which will manifest very severe physical and psychological withdrawal symptoms. Withdrawal from GHB will present two distinct phases of withdrawal symptoms; the acute and the post-acute phases. The acute phase is by far the most intense and can potentially be fatal, while the post-acute phase is less intense but much longer-lasting. Both phases are extremely uncomfortable, but the acute phase can be an absolute nightmare.

To paint the clearest possible picture of GHB withdrawal, let’s look at how exactly GHB works. GHB is a naturally occurring compound in the brain which is a derivative of the neurotransmitter GABA. The way that GHB works is through stimulating GABA and GHB receptors in the brain, in particular the GABA-β receptors as well as specific GHB receptors. Through stimulation of these receptors, GHB exerts its euphoric, depressive, and amnesiac effects. GABA is a major inhibitory neurotransmitter that acts to slow, dampen, and moderate a huge array of other nerve signals, and its effects are far-reaching. GHBs potent stimulation of GABA receptors will strongly affect someone’s state of mind and perceptions as well as physical processes such as breathing and heart rate.

Due to the intensity with which GHB stimulates GABA receptors, the brain will take steps to protect itself from damage. When neurotransmitter receptors are overstimulated they can be damaged or killed and this is known as excitotoxicity or neurotoxicity (depending on the receptor type). To avoid neurotoxic brain damage, the brain will reduce the number and the sensitivity of both GABA and GHB receptors which are activated by GHB through a process called downregulation.

Downregulation may begin to occur quite soon after someone has been using GHB regularly, sometimes as soon as a month or less. The most immediate effect of this is the development of tolerance. Tolerance is when someone needs more of the drug to produce the same effects as they experienced during previous use. This often leads to increased use and subsequently speeds up the process of downregulation. Further use will lead from tolerance to a physical dependence on GHB. This means someone will become physically and mentally unwell unless they use GHB.

Aside from the multifaceted effects on GABA and GHB receptors which are produced through prolonged GHB use, several other neurotransmitter systems are affected in an indirect manner. This includes dopamine, serotonin, and glutamate systems. The exact way these systems are affected is currently unclear, but levels of dopamine and glutamate become elevated in the nucleus accumbens and ventral tegmental area, parts of the limbic system or “reward center” of the brain which are known to play a large role in the development of drug addictions. Additionally, serotonin levels become increased during GHB use, subsequently leading to severe serotonin imbalances during GHB withdrawal.

Due to extensive downregulation, once an addict stops using GHB their body and brain will enter a hyperstimulated state and will not be able to calm or slow itself down. The normal dampening effects of GABA will not be enough to maintain balance, and this hyperactivity can result in an array of negative consequences including brain damage or death.

The Importance of Detox

Withdrawal from GHB can be fatal if it is left untreated, and GHB detox centers can provide a wide range of resources to ease this process. With trained professionals to provide medical monitoring, medications, and psychiatric care the withdrawal process can be undergone in the least dangerous and uncomfortable manner possible, and the symptoms of GHB withdrawal minimized. In addition, these centers can provide connections, therapies, and aftercare planning for continuing treatment and recovery after detox has been completed.

How to Find a GHB Detox Center

Symptoms of GHB Withdrawal

The acute phase of withdrawal is by far the most severe and is considered a “medical emergency” by medical professionals. During the acute withdrawal phase, the risks for brain damage and/or death are real and someone is likely to be suffering from psychosis or delirium. Medical attention is absolutely required if someone is to make it through acute withdrawal. This phase may begin as soon as a couple of hours or less after the last time someone used GHB, as it has an extremely short half-life of between 30 and 60 minutes.

Some of the symptoms of GHB withdrawal include:

  • Delirium and Confusion
  • Hallucinations (visual, auditory, tactile, or a combination)
  • Psychosis and Paranoid Delusions
  • Seizures
  • Tremors and Shaking
  • Rhabdomyolysis (muscle tissue breaking down and entering the blood)
  • Hyper/Hypothermia (high or low body temperature)
  • Hypertension (high blood pressure)
  • Tachycardia (rapid heart rate)
  • Insomnia
  • Nausea, Vomiting, and Diarrhea
  • Extreme Anxiety
  • Agitation and Irritability
  • Diaphoresis (excessive sweating)

Acute withdrawal is a very scary, intense, and dangerous experience but with medical help, the symptoms can be reduced and managed. One of the characteristics of GHB withdrawal that differentiates it from withdrawal from other drugs is the quickness of onset. It is possible to experience minor withdrawal symptoms within 30 minutes of the last dose, but it is more common for symptoms to appear after 2 to 4 hours of abstinence. These symptoms are extremely uncomfortable, potentially fatal, and quite long-lasting often taking around 1 to 2 weeks to fully subside.

Post-Acute GHB Withdrawal

This phase is much less severe, but it is still very unpleasant. While the physical symptoms may have resolved, there are still multiple psychological symptoms that may persist for quite some time. The most common post-acute withdrawal symptom is anxiety. Most anti-anxiety medications work in a very similar way as GHB, so dependence and tolerance to GHB will act to increase global anxiety and social anxiety in particular. These symptoms will begin very intense and slowly dissipate over the next few months.

Some of the most common symptoms of post-acute withdrawal from GHB are:

  • Increased Anxiety
  • Cravings for GHB
  • Depression

There have been relatively few controlled studies done on the long term withdrawal symptoms of GHB in humans. This phase of GHB withdrawal is not very well understood at present. The above symptoms are the common course of post-acute withdrawal, although not necessarily unique to GHB withdrawal.

While these symptoms are much less dangerous from a physical standpoint, they are unpleasant and very persistent. Issues with anxiety and depression are bad enough on their own, but these issues may also worsen cravings for GHB. This time is very sensitive and critical for someone trying to recover from GHB addiction, and professional medical help is often recommended to help reduce these symptoms.

GHB Withdrawal Timeline

Withdrawal from GHB often begins soon after the last time someone used the drug. On average, symptoms will begin between 30 minutes to 4 hours after the last use and escalate in intensity over the first few days. Since GHB has a very short half-life, these symptoms will appear soon, but this should not give the impression that the symptoms are short-lived. The typical timeline for acute withdrawal is between 1 and 2 weeks, while post-acute withdrawal may last for several months.

First Week

The first week of GHB withdrawal will be the most dangerous and intense by far. Within hours of the last use of GHB, symptoms will begin to appear. The most common initial symptoms include intense sweating, tremors, rapid heart rate, and elevated blood pressure. Anxiety and irritability will emerge early and persist throughout the entire acute phase of withdrawal, possibly persisting for several weeks. Soon after these symptoms appear, they may be joined by tactile hallucinations such as strange feelings or sensation in the limbs or extremities. Body temperature may begin to rise or lower, accompanied by the tactile hallucinations transforming into a feeling of the skin burning or freezing. Around 48-72 hours after these symptoms begin, they will reach peak intensity. Additionally, the appearance of delirium usually occurs during this timeframe as well and it may be very long-lasting, or even appear to resolve before reemerging. This may or may not include paranoid delusions, but will certainly include profound confusion and disorientation in both time and space. The symptoms of GHB withdrawal typically reach their peak intensity around the fourth day after they have begun and will begin a gradual decline from this point onwards.

Second Week

The beginning of the second week of GHB withdrawal is often much less severe than the first week, however, it is still may be extremely unpleasant. While the worst of the hallucinations and cardiovascular symptoms may have subsided, anxiety and insomnia may still be prominent. In addition, someone may expect delirium to persist to some degree early into the second week in some cases. Symptoms of delirium are inconsistent during GHB withdrawal, and often emerge early, but may also have a delayed onset. Furthermore, delirium may come and go over the first two weeks, which is a unique feature of GHB withdrawal compared to other drug withdrawal syndromes. Usually, by the end of the second week, these symptoms will have resolved for the most part, with only lingering vestiges possibly remaining by the fourteenth day after GHB withdrawal began.

Third Week

There is quite a bit of variability in the individual experience of GHB withdrawal, with reports of acute withdrawal symptoms lasting between 2 to 15 days. On average, the beginning of week three will mark the end of acute withdrawal, and a probable transition into post-acute withdrawal. This may exhibit symptoms of elevated anxiety, depression, irritability, continued insomnia, and intense cravings. This is often the time of greatest relapse risk, as the worst of the symptoms are gone, yet someone feels mentally drained and depressed with a strong feeling that more GHB will “fix” their state of mind and give them relief. It is highly recommended to enter counseling or therapy at this time if someone has not already done so.

Fourth Week and Onwards

Again, with so little clear data on GHB withdrawal, the course of post-acute symptoms may vary greatly. The symptoms of anxiety, depression, and cravings can be expected to last for some time still. Insomnia may also remain an issue, but over the counter sleep aids may be helpful by this point. Symptoms of social anxiety may become more prominent at this time, as people are often re-entering the world at three or four weeks after GHB cessation. The brain is able to restore the imbalances produced through heavy GHB use, but this must be given time. It is a slow process and even though it is uncomfortable, the symptoms should decrease gradually over the next few weeks.

What Happens to the Body During GHB Withdrawal?

GHB addiction can produce profound neurotransmitter imbalances which will result in severe physical effects during withdrawal. These physical symptoms are potentially life-threatening and while not always fatal, they may result in brain damage if left untreated. While GHB works primarily through GABA and GHB specific receptor interactions, this produces secondary and tertiary effects in a variety of other neurotransmitter systems throughout the brain. The greatest effect is on the cardiovascular system, motor function, and digestion. Some of these effects include:

-Cardiovascular Effects

The most immediate effect of GHB withdrawal is on heart rate and blood pressure. With GABA being a major inhibitory neurotransmitter, the downregulation produced through chronic GHB use results in an amplification of signals to the heart during withdrawal. This probably has to do with GABA being unable to moderate norepinephrine secretion during acute withdrawal. Norepinephrine is both a neurotransmitter as well as a hormone in the blood and is an overseer of adrenaline levels in the body. Adrenaline is a major contributor to the fight-or-flight response and is bulk released in dangerous situations to increase survivability (such as when facing a predator). Norepinephrine overproduction leads to increased levels of adrenaline, subsequently constricting blood vessels which increase blood pressure as well as increasing heart rate and heart muscle contractility.

-Motor Effects

GHB withdrawal produces some very severe effects with regard to motor control. The most immediate and obvious effect is the emergence of tremors and shaking. This is due to a combination of GABA and glutamate disruptions which are produced through GHB use, and subsequent withdrawal. Glutamate is a major excitatory neurotransmitter, and increased levels lead to general nervous system hyperactivity, both within and outside the brain. This may also result in involuntary muscle spasms, hyperactive reflexes such as the startle response, and in severe cases may produce grand mal (now known as tonic-clonic) seizures. These symptoms may be managed with medications, but they present very real dangers, both in themselves as well as complications which may arise from unexpectedly having a seizure such as when driving a car. It is also possible to suffer brain damage from simply experiencing the seizure itself, so doing risky activities is not a requirement for seizure-induced injury or complications.

-Gastrointestinal Effects

While fairly minor compared to the other physical symptoms of GHB withdrawal, gastrointestinal distress is very common. While the exact mechanism is unclear, it is known that there is a large number of GABA-β receptors all throughout the gastrointestinal tract, from the stomach all the way to the end of the line. These receptors play a role in slowing and calming neurological activity in the enteric nervous system, thereby promoting healthy digestion and functional gut regulation. Additionally, serotonin is known to play a huge role in the intestines as around 95% of the serotonin in the body is found in the gut and enteric nervous system. While in the brain serotonin acts as a mood regulator, in the gut it acts to manage intestinal muscle contractions and, similar to GABA-β, helps slow and moderate healthy digestion. Disruptions in both of these systems can frequently result in nausea, stomach cramps, and diarrhea.

Psychological Effects of GHB Withdrawal

The physical symptoms of GHB withdrawal can be dangerous and unpleasant, for sure, but the psychological symptoms are frequently the reason that people relapse and return to using GHB use. These symptoms can be intense as well as very long-lived, typically taking weeks or months to fully resolve. Additionally, the psychological symptoms of acute withdrawal such as delirium and psychosis can be a terrifying experience. Some of the most common psychological symptoms include:

-Delirium and Psychosis

Even though these symptoms are not directly dangerous, they are certainly unpleasant and may indirectly lead to dangerous or fatal situations. The massive disruptions in GABA, and subsequently glutamate, systems can produce multiple symptoms, including psychosis and/or delirium. These symptoms are distinct, but they arise from the same imbalances and can easily compound each other. Increases in glutamate levels or glutamate sensitivity may result in hyperactive and disorganized thinking as well as a disconnection from reality, while a lack of inhibitory GABA can lead to further amplification of these hyperactive and dissociative symptoms. Delirium may be characterized by profound confusion regarding time, place, and someone’s particular situation while psychosis can exhibit an altered perception of reality. When combined, this complex of symptoms can result in aggressive or violent outbursts, a general combative mindset, or attempts to escape from those who are trying to help. Additionally, psychosis-induced perceptual distortion can lead to self-harm, either intentional or otherwise, for example, someone thinking they can fly and jumping out of a window.

-Increased Anxiety

Anxiety is by far the most common symptom experienced during withdrawal from GHB. Almost every known anti-anxiety medication works by interacting with the GABA system in the brain, similarly to the way GHB works. Through chronic GHB use and subsequent withdrawal, a GHB user will experience what is known as “rebound anxiety” which is a very intense form of anxiety which resembles a very prolonged panic attack. While these symptoms will eventually resolve over time, the first few days or weeks will exhibit extremely intense anxiety at all times, with a particular spike in social anxiety.

-Cravings For GHB

Cravings for GHB is probably the longest-lasting symptom from GHB withdrawal. This may persist for many months and maybe most intense in the few weeks immediately after GHB use is discontinued. GHB has some interesting interactions with dopamine, a major excitatory neurotransmitter. While small amounts of GHB use will reduce the levels of dopamine in the brain, once a certain threshold is passed it will actually increase dopamine levels in specific areas of the limbic system. The limbic system is a known contributor to addictions of all kinds and is thought to be responsible for the experience of drug cravings. GHB induced changes in the limbic system will produce very strong connections between “feeling good” and GHB use. The strong linkage between feeling good and GHB use will manifest as very strong cravings for GHB, with an addict feeling that their only chance for relief is through continued GHB use. The risk for GHB relapse is highest immediately after discharge from treatment, and cravings are certainly a large contributor to GHB relapses.

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What Factors Influence the Intensity of Withdrawal?

GHB withdrawal symptoms can vary quite a bit between individuals, both in symptom intensity and duration. There is certainly an element of control with some of these factors such as GHB use habits, but some of these are out of someone’s control such as genetics. These differences in withdrawal symptoms may affect both the intensity as well as the very presence of certain symptoms. Very light or infrequent GHB users may not experience delirium, psychosis, or seizures and the likelihood of these particular symptoms is dependent upon both the amounts of GHB someone used and the duration of their use.

Some of the greatest contributors of GHB withdrawal intensity and duration include:

  • Amount of GHB someone used
  • Length of time that someone used GHB
  • A genetic predisposition for addiction
  • Co-occurring mental health issues (particularly congenital GABA dysregulation conditions)

The largest contributing factors to the intensity and duration of GHB withdrawal are certainly the amounts of GHB someone used and the duration of use. The amounts of GHB used will directly impact the degree of downregulation which the brain undergoes. This greater the degree of downregulation, the greater the intensity of GHB withdrawal symptoms will be. As for the duration of use, this may affect the intensity of withdrawal symptoms, but it absolutely affects the duration of the withdrawal symptoms. The longer the brain has operated after undergoing downregulation, the more “fixed” these neurotransmitter changes become, and subsequently the longer these changes will take to reverse. This could prolong the duration of both phases of GHB withdrawal.

Genetics play a very large role in someone’s propensity towards addiction and indirectly may play a role in the GHB withdrawal symptoms someone experiences. While this is a very tangential influence, it is an influence nonetheless. While anyone is capable of becoming physically dependent on a drug, if someone has a genetic predisposition it may take less of the drug to produce dependence. The exact reasons for this are currently unclear, but it may have to do with neuroplasticity and genetically carried neuroadaptive potential. This means that someone with a heavy family history of addiction may become addicted to a drug more quickly and with lower total amounts used than someone with no family history of addiction. The end result is that the brain of someone with a genetic predisposition for addiction may undergo greater downregulation at an earlier time than someone with no such disposition, with greater downregulation translating to a more intense GHB withdrawal experience.

Preexisting mental health issues may also affect the symptoms of GHB withdrawal. For example, if someone were to suffer from epilepsy, schizophrenia, or bipolar disorder then they would be much more likely to experience seizures and psychosis during acute withdrawal. Likewise, if someone suffered from anxiety or depression then these withdrawal symptoms would be greatly amplified due to their preexisting neurotransmitter imbalance which led to these conditions in the first place. These symptoms may also increase the incidence of cravings as well as making the cravings more appealing, thus increasing the chances of relapse.

GHB Withdrawal Treatment

Since GHB withdrawal is considered a medical emergency, it is crucial for someone to seek treatment if they expect to undergo withdrawal. The acute phase can be mentally crippling and may even be fatal if it is left untreated. Additionally, the prolonged symptoms of GHB withdrawal are thought to pose a massive risk of relapse, so receiving treatment is doubly important. There is a wide range of medications, therapies, and supportive practices that are extremely helpful in treating GHB withdrawal.

The first step towards GHB withdrawal treatment will be to enter a GHB detox center. These centers specialize in the safe and effective treatment of GHB withdrawal, as well as offering referrals to further treatment and continuing care services. This could be a major aid in successfully overcoming an addiction to GHB.

-Medications

There are currently no FDA approved medications for the treatment of GHB withdrawal, however, there are many medications that have been used successfully for this application. The standard practice is to treat individual symptoms as they emerge, and this can be done reliably and effectively with a variety of medication classes. Certain medications may be used exclusively to treat acute withdrawal symptoms, while others may be used only for prolonged GHB withdrawal symptoms withdrawal.

Some of the medications most commonly used to treat withdrawal include:

  • Antidepressants
  • Anti-Anxiety Medications
  • GABA/Glutamate Agents
  • Certain Blood Pressure Medications

Due to the variability of symptoms between individuals, the exact medications used may differ between people. These are just a few medication classes that are commonly used, but there are many others that may be beneficial. Some of these, such as antipsychotics, may only be used if psychosis or delirium emerge as symptoms but are otherwise not applicable. Entering a GHB withdrawal treatment center will allow someone to discuss their medical and GHB use history with medical professionals and figure out which medications may offer the greatest relief.

-Therapies

Due to the intense psychological symptoms of GHB withdrawal, therapies have been found very effective for symptoms reduction in both phases of withdrawal. The intense anxiety someone experiences will benefit from a therapeutic approach and learning how to deal with cravings in a healthy, constructive way will be critical if someone hopes to achieve lasting recovery from GHB addiction.

Some of the therapies most commonly used to treat GHB withdrawal include:

  • Behavioral Therapies
  • Group and Individual Counseling
  • Relapse Prevention and Coping Skills Development
  • Addiction Education
  • Mindfulness Practices

These are just a few therapies that have been found effective, but each person may find certain therapies more effective than others. Managing the anxiety, depression, and cravings is usually the biggest challenge in early treatment from GHB withdrawal, and these therapies may offer great relief and hope to those in this situation. Relapse is quite common within the first few weeks after ceasing GHB use and these treatments may reduce the likelihood of relapse and increase the chances of successful recovery.

Treatment for GHB withdrawal symptoms is a necessity if someone is to complete the process safely and with the best chance of success. GHB detox centers will be able to provide the most effective medications, therapeutic techniques, and continuing care services for someone in need of GHB withdrawal treatment.

References For This Article

  1. 1 Neurocritical Care: Baclofen and Gamma-Hydroxybutyrate Withdrawal
  2. 2 Trials: Improving GHB Withdrawal with Baclofen - Study Protocol for A Feasibility Study for A Randomised Controlled Trial
  3. 3 Journal of the Formosan Medical Association: Clinical Management of Gamma-Hydroxybutyrate (GHB) Withdrawal Delirium with CIWA-Ar Protocol
  4. 4 Neptune Clinical Guidance: Guidance on the Clinical Management of Acute and Chronic Harms of Club Drugs and Novel Psychoactive Substances
  5. 5 Psychiatria Danubina: Inpatient Management of GHB/GBL Withdrawal
  6. 6 Medical Journal of Australia: Severe GHB Withdrawal Delirium Managed with Dexmedetomidine
  7. 7 Current Neuropharmacology: GHB Pharmacology and Toxicology - Acute Intoxication, Concentrations in Blood and Urine in Forensic Cases and Treatment of the Withdrawal Syndrome
  8. 8 Journal of Advanced Pharmaceutical Technology & Research: GHB Acid - A Rage or Reprieve
  9. 9 Neuropsychobiology: The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance - A Review
  10. 10 World Health Organization: Pre-Review of Gamma-Hydroxybutyric Acid (GHB)
  11. 11 Journal of Analytical Toxicology: A Reference Range for Endogenous Gamma-Hydroxybutyrate in Urine by Gas Chromatography-Mass Spectrometry
  12. 12 Annals of Emergency Medicine: Gamma-Hydroxybutyrate Withdrawal Syndrome
  13. 13 Journal of Addiction Medicine: Inpatient Gamma-Hydroxybutyrate Detoxification - A Case Report Describing Day-to-day Therapeutic Management
  14. 14 CNS Drug Reviews: A Review of Pharmacology of NCS-382, a Putative Antagonist of γ-Hydroxybutyric Acid (GHB) Receptor
  15. 15 Toxicology In Vitro: Toxicologic/Transport Properties of NCS-382, a γHydroxybutyrate (GHB) Receptor Ligand, in Neuronal and Epithelial Cells - Therapeutic Implications for SSADH Deficiency, a GABA Metabolic Disorder
  16. 16 Frontiers in Pharmacology: A Gut Feeling About GABA - Focus on GABA-β Receptors
  17. 17 Canadian Society of Intestinal Research: Irritable Bowel Syndrome (IBS) and Serotonin
  18. 18 Schizophrenia Bulletin: Altered Cortical Expression of GABA-Related Genes in Schizophrenia - Illness Progression vs Developmental Disturbance

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