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Gamma-hydroxybutyric acid (GHB) is a substance that is classified under two different categories by the United States Drug Enforcement Administration (DEA). GHB is produced in a legal form (trade name: Xyrem [sodium oxybate]) that is approved for the treatment of narcolepsy. Xyrem falls under the Schedule III controlled substance classification by the DEA. As a prescription medication, GHB can only be obtained when it is used under the supervision of a physician and with a written prescription.

GHB is also manufactured illicitly and used as a rave drug, a date rape drug, and as a fat burner. Illicit forms of GHB are classified by the DEA as belonging to the Schedule I category of controlled substances. Drugs classified under this category are not believed to have any useful medical applications, considered by the DEA not to be safe to use even when taken under the supervision of a physician, and illegal to obtain by anyone except with special permissions from the federal government.

The use of either form of GHB can lead to the development of physical dependence on the drug.

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GHB and Physical Dependence

GHB is a synthetic metabolite of the primary inhibitory neurotransmitter in the brain GABA (gamma-aminobutyric acid). GABA naturally functions to modulate the firing rates of neurons in the brain and spinal cord. GABA release in the central nervous system leads to a suppression of the firing rates of neurons in the brain and spinal cord; thus, it is an inhibitory neurotransmitter because it inhibits the activity of neurons. A side effect of GHB is feelings of sedation, mild euphoria, and a loss of inhibitions that can lead to individuals becoming more social or agreeable. Other side effects include amnesia, lethargy, and unconsciousness. These side effects have been exploited by predators and been central to its use as a date rape drug.

Chronic use of GHB in either its legal or illicit capacities can lead to the development of physical dependence. The withdrawal syndrome associated with discontinuing GHB has been compared to withdrawal from alcohol or benzodiazepines. Because people who use the legal form of GHB, Xyrem, take the drug in specific amounts and at specific periods, the severity of physical dependence that occurs is most often not as severe as the physical dependence that can occur in those who chronically abuse the drug. Chronic abusers of drugs typically take larger amounts, take it at more frequent intervals, and often use it in combination with other drugs such as alcohol. This can lead to far more severe manifestations of tolerance and withdrawal.

Research has identified that the withdrawal syndrome associated with discontinuing GHB occurs over three levels.

  • Mild withdrawal symptoms consist of insomnia, sweating, mild tremors, nausea, and vomiting.
  • People undergoing moderate withdrawal associated with GHB may experience the above symptoms as well as muscle cramps, irritability, restlessness, and bouts of anxiety.
  • People undergoing severe withdrawal from GHB may experience all of the above symptoms as well as high blood pressure, heartbeat irregularities, agitation, rhabdomyolysis (the breakdown of muscle fibers and their release into the bloodstream), delirium, psychosis, paranoia, and potential seizures.

Medicinal users of the drug are more likely to experience mild and sometimes moderate withdrawal syndromes, whereas abusers of GHB are more likely to experience moderate to severe withdrawal syndromes. The actual withdrawal syndrome that will appear in any individual is dependent on numerous factors that include the amount of the drug the person typically used, the length of time the person was using the drug, how often the person used the drug, whether they used the drug in conjunction with other drugs of abuse, and individual differences, such as body weight, metabolism, emotional makeup, etc.

The Withdrawal Timeline for GHB

The withdrawal syndrome associated with any drug occurs after a person has developed tolerance to the drug. Tolerance occurs as a result of using it on a regular basis. As the person continues to take the drug, their system adjusts its functioning to account for the drug being present in the body. The person’s system produces more hormones, neurotransmitters, etc., that account for many actions that are in opposition to the effects of the drug in an effort to maintain homeostasis or balance. The person then needs more of the drug to achieve the effects that were once experienced at lower doses. Eventually, some people find that after they have stopped using the drug and its levels in their system are depleted due to normal metabolic functions, they begin to experience negative effects because their system becomes unbalanced in favor of the adjustments made to account for the use of the drug (withdrawal symptoms). They need to keep using the drug to avoid these ill effects.

Research studies and clinical observations have resulted in the development of an overall timeline associated with withdrawal from GHB. The actual withdrawal timeline that any single person experiences will vary depending on the previous aforementioned factors.

  • Most people experience an acute withdrawal period that begins hours to one day after they discontinue the drug. Individuals with more severe manifestations of abuse will experience the acute phase earlier. Symptoms that occur in the acute phase are most often anxiety, sweating, increased blood pressure, irregular heartbeat, mild confusion, nausea, and/or vomiting.
  • Symptoms of withdrawal peak within 1-6 days after discontinuation of the drug and then begin to decrease in their severity. In this phase, individuals often experience problems with insomnia, loss of appetite, anxiety and mood issues, and milder manifestations of the above symptoms.
  • About one week to 10 days after discontinuation of GHB, the symptom profile should have significantly decreased. Individuals may still experience mild issues with mood, jitteriness, unpleasantness, etc.

Those who undergo more severe manifestations of withdrawal will begin to experience these more severe symptoms early in the course of withdrawal, typically within the first week. Cravings to use GHB can occur at any stage.

The potential to develop seizures is highest in the initial and middle stages of withdrawal and decreases over time, although it is certainly possible for an individual to suffer seizures in any phase of the withdrawal process. Seizures are potentially fatal. Because there is a potential for a person to experience seizures and psychotic issues including delirium, it is not safe for anyone who uses GHB to attempt to discontinue the drug without being under the supervision of a physician.

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Discontinuing GHB Use and Withdrawal Management

People who are attempting to discontinue their use of GHB should get involved in a withdrawal management or medical detox program that is supervised by a physician. The physician can use medications to control withdrawal symptoms and eliminate the potential to develop seizures during withdrawal.

Benzodiazepines like Valium (diazepam) are commonly prescribed to control withdrawal symptoms from drugs like GHB or alcohol. These drugs are prescribed on a tapering schedule such that an initial dosage that controls potential symptoms is established. The dose is then slowly tapered down at intervals over the course of the withdrawal management period to allow the person to be weaned off the drug. In addition, the following medications may be used:

  • Antihypertensive medications to control any issues with high blood pressure or irregular heartbeat
  • The muscle relaxant baclofen to control cravings and issues with irritability and tension
  • Gabapentin (brand name Neurontin) to assist with the withdrawal process
  • Other medications to address specific issues, such as headache, nausea, etc.

The use of a physician-assisted withdrawal management program is strongly recommended due to the potential dangers associated with the development of seizures and/or delirium that can occur in individuals who are trying to discontinue GHB. In addition, the potential for relapse during the withdrawal period is significantly reduced when a formal medical detox program is used. Relapse during withdrawal can be another potential danger associated with early recovery because individuals undergoing withdrawal from GHB can become disoriented, emotionally distraught, and desperate.

An overdose of GHB can be potentially fatal due to its central nervous system depressant effects. Thus, for most individuals, initial inpatient admission in the early stages of withdrawal management is recommended in order for the physician to monitor the person’s progress, address any issues or emergencies, and ensure that the person is on the road to recovery before they are left to function on their own.

GHB is highly toxic, and individuals can overdose on the drug very easily, even in small amounts.

Simply going through a medical detox program is not a justifiable program of recovery for abuse of any drug, including GHB. Because individuals who abuse drugs often have numerous co-occurring problems, are susceptible to relapse at any stage in their recovery, and require very strong support, the completion of a physician-assisted withdrawal management program is only the very beginning of recovery from a substance abuse issue.

Any person who has abused GHB should become involved in a long-term treatment program following the completion of detox. The long-term treatment program should include medical management of issues (use of medications and medical consultations), substance use disorder therapy, support group participation, and any other interventions identified as helpful in the assessment phase of the program. Participation in a substance use disorder treatment should continue for years following detox, and for many individuals, some form of participation in treatment will continue for the rest of their lives.