Gabapentin, most commonly known by the brand name Neurontin, is a medication that was initially manufactured as an analog to the neurotransmitter gamma aminobutyric acid (GABA). GABA is an inhibitory neurotransmitter, meaning that its release results in the decreases in the rates of firing of other neurons. GABA is the major inhibitory neurotransmitter in the central nervous system, and its presence allows for fine-tuning of the actions in the brain and spinal cord as well as suppression of continued neuronal firing that could be potentially damaging to the cells. Research into the mechanism of action of gabapentin indicates that it does not act on the same neurotransmitter receptors as GABA. Research is ongoing regarding the actual mechanism of action associated with gabapentin.
Gabapentin is not listed as a controlled substance by the United States Drug Enforcement Administration (DEA), but it does require a prescription in order to be obtained legally. This status indicates that the DEA considers gabapentin a drug that does not have a significant potential for abuse or for the development of physical dependence in individuals who use it. This has led to the drug being freely prescribed for a number of conditions. Individuals may develop tolerance to the drug, resulting in physicians prescribing dosage increases seemingly without much concern; however, this lack of concern may not be warranted.
Medicinal Uses of Gabapentin
Gabapentin is available in a capsule, tablet, or liquid form. FDA-approved uses for gabapentin include:
- As a pain treatment: Gabapentin is approved for the treatment of neuropathic pain associated with the development of shingles; this fo5rm of pain is tactically termed postherapeutic neuralgia.
- As a seizure treatment for those over 12: Gabapentin is approved for the treatment of seizures (partial seizures) in adults over the age of 12. It is considered to be an adjunctive therapy, meaning that it is an additional form of intervention that can be added to existing treatments to increase their effectiveness.
- For seizure control in children: Gabapentin is also approved as an adjunctive therapy for seizure control in children under the age of 12 (3-12).
The dosages recommended for gabapentin vary depending on the age of the individual, with young children and elderly individuals expected to respond to lower doses; lower doses are also used as a safety procedure for these demographics. Even though physicians often increase the dosage of gabapentin for patients who begin to develop tolerance to the drug, the FDA reports that there is a ceiling to the effectiveness of the drug, and its increased effectiveness for treating neuropathic pain has not been demonstrated at extremely high doses (over 1800 mg).
Gabapentin also has some other medicinal uses that have not been formally endorsed by the FDA.
- Gabapentin may be prescribed for the treatment of other types of pain, including pain that is often associated with diabetes (peripheral neuropathy).
- Some research has indicated that gabapentin can be useful as an adjunctive treatment for individuals with bipolar disorder who suffer from anxiety. Gabapentin appears to address the anxiety but does not appear to directly address issues with mania and depression.
- Gabapentin appears to be effective in the treatment of restless leg syndrome.
- Gabapentin is frequently used to assist individuals recovering from substance use disorders. The medication appears to be effective in the control of withdrawal symptoms from a number of different substances of abuse.
Often these additional uses (off-label uses) of gabapentin are associated with the use of higher doses than recommended for the treatment of pain or seizures. There is quite a bit of research suggesting that gabapentin is efficacious for these above conditions and a number of isolated studies suggesting it may be useful in the treatment of other conditions. Though the drug is prescribed for the above uses, it has not formally been approved by the FDA for these uses.
Gabapentin as a Withdrawal Management Medication
A number of research studies have suggested that gabapentin has significant utility for individuals who are experiencing withdrawal symptoms from a number of different substances. Gabapentin appears to be most efficacious in reducing cravings during withdrawal, managing some of the symptoms of withdrawal, and managing other symptoms, such as pain.
Research has suggested that gabapentin can be useful as a withdrawal management intervention for:
- Withdrawal from alcohol, where it is useful in the control of potential seizures and other symptoms, such as anxiety
- Withdrawal from benzodiazepines, where it is efficacious for potential seizure control, cravings, anxiety, and other symptoms
- Opiate withdrawal, where it is efficacious in the control of some general symptoms, such as nausea and anxiety, and in reducing cravings
- Withdrawal from cannabis, where it is often useful in reducing cravings and general symptoms of irritability, malaise, headache, and even some cognitive issues
In the majority of these studies, it appears that gabapentin’s use as a withdrawal management medication is primarily as an adjunctive treatment, meaning that it is added to other treatments to increase the overall effectiveness of the intervention. Other isolated studies have suggested that gabapentin may be useful as an adjunctive medication for withdrawal from some other substances, particularly in managing issues with anxiety and with cravings, such as for individuals with stimulant use disorders (e.g., Ritalin, cocaine, methylphenidate, etc.), although the results of this research are mixed.
The DEA currently maintains the position that gabapentin is not a controlled substance and therefore is not considered to be a potential drug of abuse. This stance may be modified slightly in the future based on evidence gathered after the initial research trials that resulted in gabapentin’s approval by the FDA. The first line of evidence that may suggest that gabapentin has some potential for abuse and for the development of physical dependence is the DEA’s classification of the drug Lyrica (pregabalin), a drug that is very similar in structure to gabapentin. The DEA classifies Lyrica as a Schedule V controlled substance, indicating that it has some potential for the development of abuse and physical dependence.
These research reports are preliminary, and further controlled research needs to be completed in order to determine any actual potential abuse associated gabapentin. It appears that the psychoactive effects associated with the abuse and misuse of gabapentin are context dependent and vary according to expectations. However, it is often observed that the psychoactive effects of any substance of abuse will vary to some extent depending on the individual’s expectations and beliefs. Thus, there is an initial concern that gabapentin may be a potential drug of abuse by some researchers, and this concern is backed up by some research. However, gabapentin is obviously not a major drug of abuse in the same category as alcohol, narcotic medications, cocaine, etc.
The next line of evidence comes from several documented case studies in the research literature of instances of gabapentin abuse.
- A report in the American Journal on Addictions published in 2004 documented the abuse of gabapentin by a number of inmates. These inmates all had pre-existing substance use disorders (mostly stimulant use disorders as a result of cocaine abuse) and were grinding up and snorting gabapentin in their cells. All of the inmates reported getting some type of euphoric effects from this practice.
- In 2012, a letter in the British Journal of General Practice expressed concern for the rising number of individuals using gabapentin in the UK and its abuse. Its abuse was associated with psychoactive effects similar to those produced by cannabis.
- Information from a study reported in the European Addiction Research Journalsuggested that opiate users were using gabapentin drugs to cut drugs like heroin or to enhance the effects of methadone abuse.
Physical Dependence on Gabapentin
Even though the DEA’s status regarding gabapentin indicates that it is not believed that the drug produces physical dependence in those who use it, there are scattered clinical reports of individuals developing physical dependence on the drug. One of the initial reports involved an elderly individual who used gabapentin as an adjunctive treatment for her bipolar disorder and developed a mild syndrome of physical dependence as a result of this use.
Other case studies have suggested that gabapentin use and abuse do result in a mild syndrome of physical dependence and even delirium; however, it appears that most of these cases are associated with very high doses of the drug. Based on these reports, it appears that the symptoms of withdrawal from gabapentin that are associated with the development of physical dependence are relatively mild in most cases.
Withdrawal symptoms include:
- Gastrointestinal effects that appear mostly to consist of nausea, vomiting, and abdominal cramps or pain
- Effects on the peripheral nervous system that include the development of muscle spasms, sweating, and irregular or increased heart rate
- Cognitive/emotional effects that include the potential to develop issues with irritability, anxiety, and delirium (disorientation and confusion; rare cases of catatonia (being frozen in a specific position)
- Seizures upon discontinuation of the drug for those who use it to control seizures
- Potential suicidality (rare)
Because both the abuse of gabapentin and the documentation of withdrawal symptoms are scattered in the research and do not appear to be the general rule, there are some potential risk factors that may be associated with developing withdrawal symptoms from gabapentin.
Risk factors associated might include:
- Regular uses of gabapentin in doses far above the maximum level of its effectiveness as recognized by the FDA
- Regular use of gabapentin by individuals who have a formal diagnosis of a mental health disorder
- Use of gabapentin with illicit drugs, such as cocaine or opiates
- Use of gabapentin in a manner that is not consistent with its intended and prescribed use, such as grinding up pills and snorting the powder, injecting the powder after combining it with water, etc.
- Abrupt discontinuation of the drug
- Individual variations in metabolism and emotional adjustment
Because most of the cases associated with the development of withdrawal symptoms as a result of discontinuation of gabapentin appear to have occurred in individuals who have taken extremely high doses of the drug and then suddenly stopped use, it is imperative that gabapentin only be used under the supervision of a physician and according to its prescribed uses. Discontinuation of the drug should be performed under a physician’s supervision and according to a tapering schedule.
A tapering schedule is a typical approach to discontinuing use of a drug that may produce withdrawal symptoms. The physician slowly decreases the dosage of the drug given to the patient at specified intervals to slowly wean the person off the drug. This allows the individual’s system to slowly adjust to decreasing doses of the drug. It is an extremely effective approach to managing withdrawal from a number of drugs, including benzodiazepines.