Gabapentin is rumored to have been synthesized by chemists in the 1970s in attempt to develop an antispasmodic agent. After its synthesis, rights to gabapentin were acquired by Parke-Davis (a subsidiary of Pfizer) whereafter it underwent clinical trials that evaluated its safety and anticonvulsant efficacy in the treatment of seizures. Clinical trial data indicated that gabapentin was safe and effective as an anticonvulsant, and it went on to receive FDA approval in 1993 for the treatment of partial seizures, focal seizures, and mixed seizures.
In subsequent years, gabapentin underwent additional clinical trials and would attain FDA approval for the treatment of conditions such as: postherpetic neuralgia (2001), neuropathic pain (2002), and restless leg syndrome (2011). These days, gabapentin remains a widely-prescribed medication for the aforementioned FDA-approved indications, but has also gained off-label popularity for usage in numerous medical scenarios, including during opiate detoxification. Preliminary evidence indicates that gabapentin might effectively attenuate opiate withdrawal symptoms such as: body aches and pain, restlessness, and restless leg syndrome.
For this reason, a subset of patients undergoing opiate detoxification may receive an off-label prescription for gabapentin to help manage discontinuation symptoms. Numerous anecdotal accounts of patients who’ve successfully complete opiate withdrawal claim that gabapentin was of substantial therapeutic value throughout the detox process. That said, anyone planning on taking gabapentin to help manage opiate withdrawal symptoms should understand: its mechanism of action, the pros/cons associated with its usage, and scientific studies that’ve investigated its usefulness during opiate detoxification.
How Gabapentin May Help with Opiate Withdrawal (Symptom Management)
The primary way in which gabapentin may provide therapeutic value during opiate withdrawal is by reducing the severity of symptoms that emerge in the initial weeks or months of detoxification. By reducing the severity of debilitating opiate detoxification symptoms, individuals should have an easier time completing their withdrawal and refraining from future opiate administration. Nevertheless, it should be emphasized that the specific symptoms that gabapentin helps manage are often subject to individual variation.
In other words, certain individuals will claim that gabapentin just helps with their restlessness and/or restless leg syndrome, whereas others may report that it helps mostly with anxiety and depression. Another group of gabapentin recipients may note that gabapentin doesn’t reduce any of their opiate detoxification symptoms. Included below is a list of opiate withdrawal symptoms that might improve during opiate withdrawal as a result of gabapentin.
- Agitation: It’s common to experience severe bouts of agitation during opiate withdrawal. Agitation is characterized by internal restlessness, nervousness, or excitement whereby it becomes difficult to relax, sit still, and/or remain calm. Engaging in relaxation exercises and low grade physical activity (e.g. walking) can be helpful, however, these interventions may not adequately help certain individuals. Gabapentin seems to be a medication that increases inhibitory neurotransmission to reduce feelings of agitation. Furthermore, multiple preliminary studies indicate that gabapentin appears effective for the treatment of agitation.
- Anger: Another symptom that might emerge during opiate detoxification is anger. The anger that is experienced during opiate withdrawal can be mild, but is sometimes extreme and often accompanied by irritability. Explosive anger may increase risk of doing something you regret such as verbally attacking others who are trying to help, or possibly resorting to physical violence. It is possible that gabapentin might help mitigate some of the anger that occurs during opiate withdrawal. Gabapentin’s inhibitory effect can lower stress and may reduce negative emotions like anger in select individuals.
- Anxiety: During opiate withdrawal, many individuals report sudden onset of high anxiety and/or panic attacks. The anxiety and/or panic may be especially severe among those with a preexisting anxiety disorder (e.g. social phobia). Fortunately, anyone using gabapentin during the withdrawal process may be partially protected against a substantial anxiety spike. This is because gabapentin’s mechanism of action reduces excitatory neurotransmission and promotes sedation. Additionally, there are mounting data to support the off-label usage gabapentin for anxiety disorders.
- Cravings: Due to the potency of their intoxicating effects, physical dependence, and psychological dependence – opiates are among the most addictive drugs in the world. For this reason, among the most challenging aspects of opiate withdrawal involves resisting the powerful cravings that may surface. Cravings don’t usually occur in the earliest stages of withdrawal because the user feels extremely sick, however, they may surface within a month of detoxification. Case reports suggest that gabapentin might reduce cravings and/or urges to use opiates, thereby helping patients maintain detoxification.
- Depression: There are a few published studies suggesting that gabapentin may be of benefit when administered as an adjunct for the treatment of refractory depression. Based on these findings, it’s plausible that gabapentin might also attenuate depressive emotions that appear during opiate detoxification. If you find yourself extremely depressed during opiate detoxification, but receive a prescription for gabapentin, there’s a chance that it may facilitate modest mood enhancement. The degree of mood enhancement may be further enhanced if gabapentin is administered along with a first-line antidepressant.
- Fever: Some research suggests that gabapentin acts upon centers within the brain that are implicated in thermoregulation. Furthermore, a case report documented that gabapentin enhanced hypothermic episodes in a patient with hypothalamic dysfunction, suggestive of the fact that it may reduce body temperature. Based on these findings, it’s possible that gabapentin could modestly reduce fever or extreme spikes in body temperature during opiate detoxification.
- Headaches: A review of literature by Perloff, Berlin, Gillette, et al. (2016) suggests that gabapentin appears effective in the management of various types of headaches. Additionally, there’s some evidence supporting the idea that gabapentin could help patients cope with migraines. Throughout opiate withdrawal, some individuals may complain of ongoing headaches or migraines that don’t respond well to over-the-counter medications. Although gabapentin isn’t to treat opiate withdrawal-related headaches, it may turn out to be more effective than expected. (Source: https://www.ncbi.nlm.nih.gov/pubmed/26398728).
- Insomnia: Without pharmacological assistance, many individuals will struggle to cope with severe insomnia during opiate withdrawal. The insomnia may interfere with your ability to fall asleep at a desired time and/or stay asleep throughout the night. Insomnia can disrupt the circadian rhythm, which in turn could exacerbate opiate detoxification symptoms and/or prolong the recovery process. One potentially-useful pharmacological option for alleviation of withdrawal-related insomnia is gabapentin. Several studies have documented the efficacy of gabapentin for the treatment of insomnia. For this reason, it’s logical to speculate that a subset of individuals who receive gabapentin during opiate withdrawal may notice that it counteracts insomnia.
- Irritability: Although the research of gabapentin as an intervention for irritability is limited, there’s some evidence indicating that it might be effective. For example, a study by Hauer, Wical, and Charnas (2007) reported that gabapentin is capable of managing chronic unexplained irritability in pediatrics with neurological deficits. Considering these findings, it’s possible that gabapentin could help manage irritability that occurs among persons withdrawing from opiates. Many individuals mention that gabapentin makes them feel calmer, less anxious, and drastically decreases irritability. (Source: https://www.ncbi.nlm.nih.gov/pubmed/17272610).
- Mood swings: While detoxifying from opiates, some individuals will report disconcerting mood swings and/or emotional upheavals such that one moment you may feel angry, the next moment depressed, and the following an entirely different negative emotion. Although the mood swings should gradually diminish after several months of opiate abstinence, they may seem overwhelming in the early stages of withdrawal. Without pharmacological support, these mood swings might be of detriment to a person’s decision making and/or social relationships. As a result of its inhibitory effect upon neurotransmission, gabapentin may be useful in managing detox-related mood swings for a subset of individuals.
- Pain: Over a long-term of opiate usage, it is understood that neuroadaptation occurs whereby opioid receptors in the brain are subject to upregulation and tolerance is developed. In addition to receptor upregulation, some believe that long-term opioid usage impairs the body’s ability to manufacture endorphins and enkephalins. This combination of opioid receptor upregulation and potentially-reduced endorphin/enkephalin production sets the stage for increased pain sensitivity during opiate detoxification. Furthermore, in persons with chronic pain conditions, symptoms of pain experienced during detoxification are likely to be very intense not only from the increased pain sensitivity, but also due to the fact that an opiate is no longer treating their pain. Among those who experience pain while quitting opiates, it’s not a stretch to speculate that gabapentin might help. Not only is gabapentin approved by the FDA to treat neuropathic pain, but a study specifically reported that gabapentin increased pain threshold during opiate detoxification.
- Restlessness & RLS: Restlessness throughout the body, and more specifically, restless leg syndrome (RLS), are extremely common symptoms of opiate withdrawal. Unfortunately, the restlessness and RLS that emerge during opiate detoxification can be annoying, anxiety-provoking, and may interfere with sleep. That said, individuals who receive a prescription for gabapentin during opiate withdrawal are likely to notice that detoxification-related restlessness and RLS aren’t very severe. It is known that “gabapentin enacarbil,” a prodrug of gabapentin marketed under the brand Horizant, is FDA approved for the treatment of moderate-to-severe restless leg syndrome. Moreover, administration of gabapentin to opiate-dependent patients after a rapid detox protocol has been shown to attenuate restlessness and RLS.
- Sleep disturbances: During various stages of opioid withdrawal, it may seem impossible to get enough quality sleep. Various symptoms such as anxiety, insomnia, pain, and restlessness – can disturb sleep during opiate detoxification by interfering with sleep depth and total sleep time. The problem with low quality and/or inadequate sleep is that each can disrupt the circadian rhythm, ultimately exacerbating opiate withdrawal symptoms and prolonging the recovery process. Given the research indicating that gabapentin attenuates insomnia and enhance slow-wave sleep (SWS) in adults, it’s logical to assume that gabapentin might ameliorate sleep disturbances in a subset of individuals during opiate withdrawal.
- Spasms: It is known that during opiate detoxification, many individuals experience unwanted muscle spasms. The spasms may interfere with a person’s ability to stay focused at school and/or work, and might induce significant anxiety. Although spasms are generally disconcerting to patients undergoing opiate detoxification, most understand that they should gradually subside within a period of several months. That said, if you receive a prescription for gabapentin during detoxification, there’s a chance that it may help control muscle spasms. Research has documented successful usage of gabapentin for the treatment of hemifacial spasms, as well as violent painful spasms in persons with multiple sclerosis.
- Tension: When opiates are discontinued after long-term use, it’s common for individuals to report substantial increases in muscle tension. The muscle tension occurring in opiate withdrawal may be extreme enough to cause pain and/or interfere with a person’s sleep. A potentially-effective way to alleviate muscle tension during opiate withdrawal is through the administration of gabapentin. Gabapentin inhibits excitatory neurotransmission and suppresses CNS activation to promote sedation and relaxation, thereby offsetting withdrawal-related tension.
- Tremor: In addition to the restlessness and muscle spasms that may occur during opiate detoxification, some individuals will experience tremor. Tremor is defined as rhythmic, uncontrollable movements of a particular body part. Those who detoxify from opiates end up with constant shakiness or quivering throughout their hands and/or feet are probably dealing with tremor. Although the intensity of tremor should diminish within several months of opiate detoxification, some individuals may wish to treat it with a medication. Those who receive gabapentin to help ease opiate withdrawal symptoms might find that it attenuates tremor.
How Gabapentin Works (Mechanisms of Action)
Although gabapentin has been utilized in medical settings since the early 1990s, the complete scope of its pharmacodynamic action remains unknown. Nonetheless, since its inception, researchers have pinpointed several neurobiological targets upon which gabapentin exerts an effect. Most evidence indicates that gabapentin functions primarily via blockade of voltage-gated calcium channels at alpha(2)delta (α2δ) subunits.
Gabapentin also appears to upregulate the synthesis of GABA through modulation of the enzymes glutamate decarboxylase (GAD) and branched-chain aminotransferase (BCAT). Other neurobiological targets of gabapentin’s action include: NMDA receptors, protein kinase C, proinflammatory cytokines – and possibly GABA(B) receptors. Included below is an explanation of each mechanism of gabapentin’s action as it may pertain to the therapeutic effects derived by individuals undergoing opiate withdrawal.
Voltage-gated calcium (Ca+) channels blocker: Within the brain, voltage-gated calcium channels regulate intraneuronal calcium (Ca+) influx as induced by membrane depolarization. Research suggests that normative voltage-gated calcium channel activity is critically important for the maintenance of healthy brain function, and when dysregulated, various neuropsychiatric conditions may occur including: ataxia, epilepsy migraine, and neuropathic pain. Nearly all research of gabapentin’s pharmacodynamics highlights the fact that it acts predominantly by blocking α2δ subunits of voltage-gated calcium channels (VGCCs).
Binding assays reveal that gabapentin exhibits highest affinity for α2δ-1 subunits followed by α2δ-2 subunits, yet also note that it has zero action upon α2δ-3 and α2δ-4 subunit isoforms. The α2δ subunits to which gabapentin binds and blocks can modulate activity within various types of voltage-gated calcium channels including: N-type, L-type, P-type, and Q-type. Some also speculate that gabapentin may act upon R-type channels, however, this hasn’t been confirmed.
- N-type: N-type voltage-gated calcium channels influence activity at presynaptic neurons and modulate neural events such as synaptogenesis and neurotransmission. Research suggests that gabapentin is a strong blocker of N-type calcium channels. Blockers of N-type calcium channels have been associated with reductions in neuropathic and intractable pain, and are hypothesized to be useful for the treatment of alcohol dependence. Blocking the N-type channel likely contributes to some degree of pain relief experienced during opiate withdrawal.
- L-type: L-type voltage-gated calcium channels influence excitation-contraction of skeletal muscles, cardiac muscles, and regulate the secretion of aldosterone within the adrenal cortex. Results from animal model studies suggest that gabapentin exhibits second highest affinity for L-type channels after N-type. It is known that L-type calcium channel blockers can reverse arrhythmia, lower blood pressure, and facilitate myorelaxation. Furthermore, work by Dogrul, Bilsky, Ossipov, et al. (2005) suggests that blockade of L-type calcium channels attenuates opioid-related sensory hypersensitivity and increases pain tolerance. Everything considered, gabapentin-induced blockade of L-type calcium channels may alleviate opiate detoxification symptoms such as: hypertension, irregular heartbeat, muscle pain, sensory hypersensitivity, and tension.
- P-type: P-type voltage-gated calcium channels function similar to N-type calcium channels such that they regulate the presynaptic release of neurotransmitters. It is also known that P-type calcium channels influence presynaptic release of neurotransmitters and neurohormones, and also regulate vesicle activity. To a lesser extent than its action on N-type and L-type channels, gabapentin also blocks P-type channels. Drugs that block P-type calcium channels have been documented as useful for the treatment of seizures. Some speculate the P-type channels might also influence blood pressure, heart rate, and pain. In brief, the P-type blockade provided by gabapentin during opiate detoxification may reduce the likelihood of seizures, tremor, pain, and high blood pressure.
- Q-type: Not much is known about voltage-gated Q-type calcium channels other than they have a high threshold for activation and are found within cerebellar granule cells. Within cerebellar granule cells, it is known that calcium influx influences things like: membrane potential, synaptic plasticity, apoptosis, and gene transcription. To a lesser extent than its blockade of P-type channels, gabapentin also blocks Q-type. It is unknown as to which specific symptoms of opiate withdrawal Q-type channel blockade might ameliorate.
- R-type: As of current, it is unknown as to whether R-type voltage-gated calcium channels are sufficiently blocked by gabapentin as to generate a noticeable therapeutic effect. R-type channels are located throughout the brain in regions such as the: amygdala, cortex, hippocampus, and striatum. Drugs that block R-type channels appear to exhibit anticonvulsant, antinociceptive, and mood stabilizing properties. Considering that the α2δ subunits upon which gabapentin binds are associated with R-type channels, its plausible a blockade of R-type channels might decrease pain, reduce likelihood of seizures, and help regulate mood – during opiate detoxification.
Overall, the blockade of voltage-gated calcium channels with gabapentin should inhibit excitatory transmission, decrease sympathetic tone, and regulate neural activity – the combination of which could significantly attenuate symptoms that emerge during opiate withdrawal, especially: seizures, tremor, rebound pain, hypertension, muscle tension, and restlessness. Preliminary evidence also suggests that a gabapentin-mediated blockade of calcium channels may prove therapeutically valuable for the management of: anxiety, headaches, insomnia, migraines, and sleep disturbances – all of which are experienced in opiate detox. Lastly, it’s reasonable to consider that aberrant calcium channel activity may be causally implicated in certain symptoms of opiate withdrawal, and that by administering gabapentin during withdrawal, calcium channel dysregulation maybe corrected whereby certain discontinuation symptoms subside.
GABA increases: Another mechanism by which gabapentin may alleviate the severity of opiate withdrawal symptoms involves increasing the concentration of GABA (gamma-aminobutyric-acid). Most acknowledge that GABA is the chief inhibitory neurotransmitter within the CNS and realize that deficient GABAergic signaling in certain regions of the brain is associated with anxiety, heightened arousal, and unremitting stress. Researchers have discovered that gabapentin promotes increases of GABA in various regions of the brain by modulating enzymes implicated in GABA synthesis, including: branched-chain aminotransferase (BCAT) and glutamic acid decarboxylase (GAD).
- Branched-chain aminotransferase (BCAT): Within the brain there are 2 distinct forms of branched-chain aminotransferase enzymes including: BCATm (a peripheral subtype associated with mitochondria) and BCATc (a cytosolic subtype associated with cerebral tissue). Studies suggest that gabapentin acts as a competitive inhibitor of BCATc due to its structural similarity to leucine. As an inhibitor of BCATc, it is thought that gabapentin inhibits the production of glutamate, but enhances the production of GABA.
- Glutamic acid decarboxylase (GAD): This is an enzyme that catalyzes the decarboxylation of glutamate to GABA and CO2. Studies suggest that the administration of gabapentin bolsters activity of the glutamic acid decarboxylase enzyme, whereby GABA production substantially increases. According to research by Fitzgerald and Carter (2011), greater activity of glutamic acid decarboxylase is associated with reduced physical pain, improved sleep, and stability of mood. This the benefits of increased glutamic acid decarboxylase activity are likely tied directly to increased GABA generation.
Human neuroimaging studies utilizing NMR spectroscopy confirm speculation that gabapentin promotes GABA synthesis. As a result of increased GABA synthesis, concentrations of GABA increase in various regions of the brain, but not within synapses, and furthermore, neither GABA(A) nor GABA(B) receptors are modified. Still, a non-synaptic increase in GABA plus nonvesicular release of GABA should not be dismissed as therapeutically insignificant for those undergoing opiate withdrawal.
During opiate withdrawal, it is understood GABAergic and glutamatergic transmission are likely subject to dysregulation. This is because the neuroadaptive changes that occurred from opioid administration involved crosstalk between mu-receptors, glutamate, and GABA. By increasing GABA synthesis and corresponding non-synaptic GABAergic signaling with gabapentin, it may be possible to derive anxiolytic, anticonvulsant, analgesic, and/or myorelaxant effects, thereby aiding management of symptoms such as anxiety, convulsions, pain, and muscle tension that may emerge during opiate detoxification.
Other mechanisms of Gabapentin’s action…
In addition to gabapentin’s primary action as a blocker of calcium channel subunits, and secondary action as a promoter of GABA synthesis, it interacts with a variety of other neurobiological targets including: NMDA receptors, protein kinase C, system L transporter receptors, and voltage-gated sodium channels. Additionally, there’s some evidence suggesting that gabapentin modulates proinflammatory cytokines and release of monoamines. Although these actions may be modest, they might make slight contributions to its therapeutic value in opiate withdrawal.
- NMDA receptor inhibitor: Gabapentin appears to inhibit activation of NMDA receptors in a concentration-dependent manner. Inhibition of NMDA receptors is understood to prevent overactivation of the receptor by excitatory neurotransmitters such as glutamate and glycine. This inhibitory effect is associated with an antinociceptive response whereby pain tolerance increases. It’s possible that inhibition of NMDA receptors by gabapentin prevents surges of physical pain experienced during opiate detoxification.
- Nitric oxide synthase (NOS): There’s evidence from in-vitro studies indicating that gabapentin increases neuronal nitric oxide synthase (nNOS) centrally and peripherally. Neuronal nitric oxide synthase is the enzyme implicated in the synthesis of nitric oxide by neurons and is involved in intraneuronal communication. Although it is unknown as to whether action as an inducer of neuronal nitric oxide synthase ameliorates certain opiate detoxification symptoms, it warrants consideration.
- Cytokine modulation: Another means by which gabapentin may facilitate therapeutic effects during opiate withdrawal is through modulation of cytokines. In animal research, gabapentin appears to significantly increase expression of interleukin-10 (an anti-inflammatory cytokine implicated in immunoregulation) plus simultaneously inhibits the expression of proinflammatory cytokines such as interleukin-1B and TNF-alpha. Assuming clinically-relevant doses of gabapentin modulate cytokines in humans similar to animal models, some might speculate a reduction in various opiate detoxification symptoms including: allodynia, pain, depression, and anxiety.
- Oxidative stress reduction: Research indicates that the administration of opiates like heroin to animal models significantly decreases total serum antioxidant capacity and downregulates central expression of antioxidant enzymes such as catalase, glutathione (GSH) peroxidase, and superoxide dismutase. Furthermore, post-opiate administration, markers of oxidative stress significantly increase such that damage is inflicted upon DNA, proteins, and lipids. The combination of high oxidative stress and low antioxidant expression can induce a host of deleterious neurophysiological effects during opiate withdrawal including: anxiety, depression, headache, inflammation, and pain. Gabapentin appears to upregulate glutathione (GSH) levels and attenuates markers of oxidative stress (e.g. malondialdehyde) in animals. Should gabapentin decrease oxidative stress in humans, this mechanism of its action may partially mitigate symptoms of opiate discontinuation.
- Substance P reduction: There’s reason to suspect gabapentin may alleviate symptoms of opiate detoxification through inhibition of substance P secretion. Substance P is a neuromodulator and neurotransmitter within the CNS that’s primarily implicated in inflammatory and pain responses. When released, substance P acts upon receptors to induce neurogenic inflammation and physical sensations of pain. Interestingly, mice devoid of the substance P receptor via knockout exhibit fewer physical symptoms of opiate withdrawal than those with normative substance P receptor expression. Not only might the gabapentin-mediated inhibition of substance P secretion reduce inflammation and pain during opiate detoxification, but it may also manage symptoms such as: nausea, mood swings, anxiety, and vomiting.
- Protein kinase C modulation: Protein kinase C (PKC) enzymes are involved in a host of neurobiological processes including central and peripheral nociception. Chronic opiate administration has been shown to increase the coupling of mu-opioid receptors (MOR) to pro-nociceptive PKC-dependent signaling pathways, possibly contributing to tolerance onset among long-term users. During opiate detoxification, an increase in physical sensations of pain may be related to abnormal signaling via protein kinase C. Animals with knockouts of protein kinase C subtypes (e.g. PKC-gamma) appear to exhibit less neuropathic pain. The administration of gabapentin appears to modulate protein kinase C expression. It is reasonable to speculate that protein kinase C modulation from gabapentin might improve aspects of opiate detoxification such as: pain, digestion, respiratory irregularities, and allodynia.
- Sodium (Na+) channel blocker: Although gabapentin’s primary action doesn’t involve modulation of voltage-gated sodium channels, research suggests that it decreases expression of Nav1.7 within dorsal root ganglion (DRG) neurons of animal models. As a result of decreased Nav1.7 expression, voltage-gated sodium channel currents are weakened. The weakening of voltage-gated sodium channel currents inhibits neuronal excitability and facilitates an analgesic-like response. Assuming gabapentin reduces Nav1.7 expression and corresponding sodium channel currents in humans, this may ameliorate detox-related symptoms such as pain and anxiety.
- System L transporter receptors: Some researchers believe that gabapentin might interact with an unknown receptor of the L-system amino acid transporter protein. Multiple studies have showcased that L-amino acids and gabapentin analogues inhibit binding of gabapentin to these receptors. It is thought that the L-system amino acid transporter protein might reduce the severity of many opiate withdrawal symptoms and prevent seizures from rapid detoxification.
- GABA(B) receptor agonism: Despite the fact that gabapentin was designed as a GABA-mimetic agent, most studies report that it doesn’t act upon GABA receptors. That said, there’s modest evidence indicating that gabapentin may function as a GABA(B) receptor agonist. Specifically, researchers reported that gabapentin preferentially agonizes GABAB1a subunits of glutamatergic heteroreceptors. It should be stated that GABA(B) receptors are widely distributed throughout the CNS, and since they are coupled with G-protein, the agonism of these receptors induces hyperpolarization whereby voltage-gated calcium channels are inhibited, and excitatory neurotransmission decreases. If GABA(B) receptors are agonized by gabapentin, this may reduce anxiety, muscle spasms, and restlessness during opiate detox.
- Monoaminergic modulation: Gabapentin is capable of modulating central and peripheral release of monoamines. Research suggests that gabapentin inhibits dopamine release in certain regions of the brain (e.g. caudate nucleus), yet induces norepinephrine secretion within the locus coeruleus and throughout the spinal cord. The release of norepinephrine is understood to generate analgesic effects through activation of alpha-2 adrenoreceptors and G-protein-coupled potassium channels. Moreover, gabapentin appears to elevate serum concentrations of whole blood serotonin in humans without affecting melatonin – likely as a result of its action upon blood platelets. The totality of gabapentin-mediated monoaminergic modulation may attenuate opiate withdrawal symptoms such as muscle pain, insomnia, anxiety, and/or depression.
Note: The extent to which each of the aforestated [hypothetical] mechanisms of gabapentin’s action attenuates opiate discontinuation symptoms remains unclear. It’s possible that certain mechanisms yield greater symptomatic reduction during detox than others, yet also possible that the value of each mechanism is subject to individual variation. For example, someone with high oxidative stress may derive marked benefit from the antioxidant effect of gabapentin, whereas another individual with high inflammation may derive greater benefit from cytokine modulation.
Benefits of Using Gabapentin for Opiate Withdrawal (Possibilities)
Included below is a list of potential benefits to be attained from utilizing gabapentin during opiate discontinuation. Arguably the most substantial benefit to be derived from gabapentin during detoxification is that it may prove efficacious in attenuating the severity of discontinuation symptoms, thereby allowing individuals to completely detoxify from a potent opioid. Other potentially favorable aspects associated with administration of gabapentin during opiate detoxification might include its: adjunct efficacy, ability to treat comorbid conditions, low abuse potential, affordable cost, and tolerability.
- Adjunct option: During opiate detoxification, it is common for patients to receive multiple pharmaceutical medications, each of which is intended to mitigate specific detox-related symptoms. In some cases, medications will be prescribed to target a specific symptom of detoxification, whereas in others, they may be prescribed to synergistically attenuate a particularly overwhelming symptom (e.g. rebound pain). In any regard, when taking multiple medications, it is important to ensure that they won’t cause a potentially-dangerous interaction effect. Research suggests that properly-dosed gabapentin can be safely administered as an adjunct to other medications during detox, including: buprenorphine, clonidine, methadone, naltrexone, and tramadol. Moreover, it is reasonable to suspect that administering gabapentin plus another medication will yield synergistic benefit such that the relief attained from the combination (gabapentin plus another drug) will outweigh the symptomatic reduction from either agent as a standalone.
- As-needed: Although most professionals recommend that gabapentin be administered 3 times per day in even dosages, some individuals report therapeutic benefit from administration of gabapentin on an “as-needed” basis. It is possible that a subset of individuals undergoing opiate detoxification might prefer to take gabapentin “as-needed,” only when symptoms are at peak severity, rather than several times throughout the day. One reason patients may prefer “as-needed” dosing is that they won’t feel under the influence of gabapentin for an entire day. Other advantages associated with “as-needed” dosing may include: fewer side effects, slower tolerance onset, and a milder withdrawal from gabapentin.
- Comorbid conditions: It is known that gabapentin has the potential to mitigate a host of opiate withdrawal symptoms such as: rebound pain, restlessness, and restless leg syndrome (RLS). That said, the therapeutic potential of gabapentin is not limited solely to the management of opiate detoxification symptoms. Gabapentin may also help manage medical comorbidities among patients with opioid dependence such as: neuropathic pain and seizures – each of which it is FDA-approved to treat. Other neuropsychiatric conditions that may respond well to gabapentin include: anxiety, bipolar disorder, headache, insomnia, and migraine.
- Evidence-based: Although gabapentin is not FDA-approved for the management of opiate withdrawal symptoms, its usage during detoxification is supported by preliminary evidence. For example, a controlled trial comprised of 60 patients undergoing heroin withdrawal discovered that gabapentin significantly attenuated detoxification symptoms in the first 5 days of heroin discontinuation – compared to a placebo. What’s more, nearly all other proof-of-concept trials and case reports have reported alleviation of opioid detoxification symptoms resulting from administration of gabapentin. The available evidence strongly favors the idea that gabapentin provides therapeutic value during opiate detoxification for a subset of patients.
- Few contraindications: Since gabapentin isn’t subject to extensive hepatic metabolism, it is not associated with pharmacokinetic interactions. Furthermore, it appears as though medical contraindications with gabapentin are limited. Examples of conditions contraindicated with gabapentin include: hypersensitivity and/or allergy to gabapentin itself, renal impairment, and pregnancy. The fact that gabapentin has few contraindications makes it a preferred option over drugs with a greater number of contraindications.
- Low abuse potential: Unlike pregabalin (the successor to gabapentin), gabapentin is not formally classified as a controlled substance. As a result of its uncontrolled status, most consider the abuse potential of gabapentin to be low or nonexistent. Due to the low abuse potential of gabapentin, some medical professionals may prefer the usage of gabapentin during opiate detoxification to drugs like benzodiazepines. The last thing a professional should want is to replace an addiction to opioids with an addiction to benzodiazepines (or another controlled substance). Utilizing effective agents during detoxification with low potential for abuse is critical for the wellbeing and future of the patient.
- Low cost: Another benefit associated with utilizing gabapentin during opiate detoxification is that, as a generic drug, it is relatively inexpensive. Many new medications cost hundreds of dollars for just a 30-day supply of pills. By comparison, a total of 90 capsules of gabapentin can be purchased within an average price range of $10 to $16 – most would consider this extremely affordable. For those with minimalistic and/or poor health insurance, paying a small out-of-pocket expense to attain gabapentin shouldn’t be a big deal.
- Monotherapeutic potential: Most individuals who discontinue illicit opiates (e.g. heroin) generally transition to some sort of an opioid replacement therapy (e.g. buprenorphine) to avoid a severe detox. Some hypothesize that high-dose gabapentin could prove useful as a monotherapeutic opioid replacement therapy. Although gabapentin does not stimulate the mu-receptor, it may attenuate detox-related symptoms enough for patients to fully transition off of opioidergic agents, including buprenorphine. It is not farfetched to assume that a subset of patients might exhibit remission of opioid dependence with gabapentin monotherapy.
- Slow tolerance onset: When administered regularly over an extended duration, nearly every neuropsychiatric medication induces some degree of tolerance. That said, some medications induce tolerance at a faster rate than others. For example, patients can become tolerant to low dosages of benzodiazepines within a short-duration of several weeks. Once tolerance is developed, not only are the medications tougher to discontinue, but the therapeutic effects that they provide diminish unless the dosage is increased. Fortunately, most patients won’t rapidly develop tolerance to the effects of gabapentin – making it a more sustainable intervention over a longer duration.
- Tolerability: Studies investigating the therapeutic potential of gabapentin during opiate detoxification report that it’s well-tolerated and unlikely to induce unwanted side effects and/or provoke adverse reactions. In the event that gabapentin side effects occur, they are generally mild and can be managed with dosage adjustments. Since tolerability is not generally a major issue during gabapentin treatment, gabapentin may serve as a viable alternative to medications with harsher side effect profiles.
Drawbacks of Using Gabapentin for Opiate Withdrawal (Possibilities)
Despite potential benefits to be attained from administering gabapentin during opiate detoxification, there are numerous potential drawbacks that warrant contemplation. Perhaps the most significant drawback associated with administering gabapentin for the management of opiate detoxification is that it might be ineffective, ultimately leaving certain patients to suffer rather than attenuating severe detoxification-related symptoms. Other possible drawbacks associated with using gabapentin during opiate detox include: abuse potential, cognitive deficits, off-label status, side effects, and withdrawal symptoms upon discontinuation.
- Adverse reactions: If a patient undergoing opiate detoxification works closely with a medical professional and adheres to treatment recommendations, likelihood of an adverse reaction should be extremely low. Although adverse reactions are uncommon, they can still occur in a small percentage of gabapentin users. Examples of adverse reactions to gabapentin include: depression, renal toxicity, slurred speech, and suicidal thoughts. In animal model research, gabapentin increased the formation of adenocarcinomas, leading some to suspect that gabapentin could induce something similar in humans. Anyone who experiences an adverse reaction may dislike the fact that it further complicates the detoxification process and/or exacerbates opiate withdrawal-related symptoms.
- Abuse potential: Despite the fact that it is not a controlled substance, a subset of persons may abuse and/or use gabapentin recreationally to experience an allegedly pleasurable intoxication (i.e. “high”). Many medical professionals remain largely unaware of gabapentin abuse because it is never suspected. After all, why would a professional suspect that an uncontrolled substance is being abused by his/her patients? The truth is that gabapentin is sometimes taken in large doses to attain an intoxicating effect or “high.” Since a subset of persons undergoing opiate detoxification may have addictive, impulsive, and/or high-risk personalities, the abuse potential of gabapentin may make it an unfavorable intervention during opiate detoxification.
- Cognitive impairment: A noticeable side effect that can occur while taking gabapentin for opiate withdrawal is cognitive impairment. Anyone who regularly performs cognitively-demanding tasks in either academic or occupational settings may notice a deterioration of performance after initiation of gabapentin treatment. You may report experiencing “brain fog” and aspects of executive function such as: attention, organization of thoughts, memorization, and recall – may be subject to impairment while using gabapentin. Though the top priority for those undergoing opiate detoxification will be to completely detoxify from opiates, there may be alternative options to gabapentin (e.g. clonidine) that could manage detox-related symptoms without provoking cognitive impairment.
- Impaired motor skills: During opiate detoxification, most individuals will take some time off of work for rest and recovery, however, others may be eager to get back to work and/or run some errands to take their mind off of detoxification-related symptoms. Unfortunately, if gabapentin is used during the detoxification process, it may impair motor skills and coordination, whereby it becomes dangerous to operate a motor vehicle or heavy machinery. Anyone operating a motor vehicle or machinery during detoxification may put themselves and others at increased risk for accident-related injury and/or death. In general, the higher the dosage of gabapentin administered, the more substantial the motor impairment. The inability to operate a motor vehicle and/or machinery may be perceived as another drawback of using gabapentin during detox.
- Ineffective: As of current, several preliminary trials reported that gabapentin was no more effective than a placebo control in reducing symptoms of opiate withdrawal. Considering these findings, some might suspect that gabapentin is relatively useless and/or a poor pharmacological intervention during opiate detoxification. That said, even if gabapentin appeared effective for managing symptoms of opiate withdrawal, it is unlikely to help every patient – some may derive zero benefit from its particular pharmacodynamics. Since opiate withdrawal symptoms are often intense, most patients will want to stick with FDA-approved interventions supported by strong evidence – rather than test an unproven, possibly ineffective intervention like gabapentin.
- Interactions: Although gabapentin does not interact with other substances pharmacokinetically, it may interact pharmacodynamically. Gabapentin is understood to decrease CNS activity through modulation of voltage-gated ion channels and GABAergic transmission. When CNS activity decreases from gabapentin, any co-administered substances that simultaneously suppress CNS activity could provoke dangerous interaction effects. Since many individuals undergoing opioid detoxification utilize multi-drug protocols to cope with symptoms, dosing mistakes and/or lack of adherence to gabapentin dosing guidelines could induce respiratory depression, possibly leading to death. Examples of various substances that might interact with gabapentin include: alcohol, antihistamines, barbiturates, benzodiazepines, nonbenzodiazepines, and opioids.
- Intoxication: As was already mentioned, gabapentin is sometimes abused by patients seeking some sort of intoxication. Since a subset of patients undergoing opioid detoxification likely have a history of drug abuse and/or misuse, it’s possible that these individuals may misuse gabapentin by administering supratherapeutic doses. Administration of supratherapeutic doses to attain an intoxicating “high” during opioid withdrawal can be dangerous and might end up replacing an addiction to opioids with gabapentin. Moreover, other individuals may take gabapentin at normative dosages to help ease opiate discontinuation symptoms, yet might experience an unwanted state of intoxication.
- Long-term effects: Medications prescribed to patients during opiate detoxification are often extremely helpful when opiate withdrawal symptoms are at their peak. That said, some patients continue taking medications for a much longer duration than originally planned. In certain cases, patients may remain medicated with gabapentin for months after the acute stages of detoxification for the management of “PAWS” (Post Acute Withdrawal Syndrome). Others may continue using gabapentin because they fear that without it, they may relapse and reinstate illicit opioid usage. Although gabapentin can be safely administered over a long duration, some patients may experience unwanted or deleterious long-term neurophysiological effects if regularly administered for years.
- Off-label: Because gabapentin is not officially approved by the FDA for the management of opiate withdrawal symptoms, prescribing it to patients during detoxification is considered “off-label.” Due to the off-label status of gabapentin among persons undergoing opiate detoxification, it will be difficult to attain – even if it really helps mitigate detox-related symptoms. Other medications with stronger scientific support for usage during opiate detoxification will necessitate testing before a gabapentin prescription is considered. In fact, some professionals may not even consider gabapentin as a potential intervention during opiate detox.
- Side effects: Although gabapentin may help manage opiate discontinuation symptoms, it is not devoid of side effects. Common side effects resulting from gabapentin administration include: ataxia, blurred vision, drowsiness, edema, fatigue, fever, irritability, sedation, sexual dysfunction, tremor, and xerostomia. It’s possible that some of the side effects from gabapentin may overlap with and/or potentiate the symptoms of opiate detoxification, ultimately making the detoxification process more difficult and complicated. Certain individuals may find gabapentin’s side effects to be overwhelming and may prefer to administer a different medication.
- Superior options: While emerging data suggests that gabapentin may effectively attenuate opiate detoxification symptoms, stronger data is needed before gabapentin can be considered a viable first-line detox therapy. Knowing that gabapentin is of questionable therapeutic value during opiate withdrawal, it becomes obvious that there are superior, scientifically-tested interventions. Examples of medications that are regarded as effective in managing opiate detoxification include: buprenorphine, methadone, and naltrexone. Until stronger evidence from large, randomized controlled trials supports the therapeutic value of gabapentin during opiate detoxification – it should be considered an inferior option to rigorously-tested strategies.
- Tolerance onset: Though patients using gabapentin to help manage opiate withdrawal are unlikely to develop tolerance if the drug is discontinued within several months of detoxification, some may continue using it for a longer duration and become tolerant to its therapeutic benefit. When tolerance occurs, users generally decide to do one of two things: increase the dosage OR discontinue the medication. Increasing the dosage generally delivers a noticeable therapeutic effect, however, it also induces more pronounced side effects. Furthermore, patients will eventually become tolerant to the higher dose. If discontinued after tolerance is established, the withdrawal can be exceptionally debilitating.
- Withdrawal symptoms: Many patients wrongfully assume that the drugs used to manage their opiate detoxification are devoid of withdrawal symptoms. Although gabapentin withdrawal symptoms may be milder than those associated with illicit, potent opioids – they may be more difficult than expected. In fact, certain individuals claim that withdrawing from high-dose gabapentin is more challenging that discontinuing opioids. Regardless of comparative difficulties, gabapentin withdrawal is usually tougher than most expect – and can leave patients struggling with symptoms for months after their final dose.
Gabapentin for Opiate Withdrawal (Review of Research)
To determine whether gabapentin is a therapeutically valuable medication during opiate detoxification, it is necessary to examine results from trials in which its usefulness was evaluated among persons withdrawing from opiates. Included below are summaries of trials that examined the effect of gabapentin administration during opiate detoxification. Understand that while some evidence supports the therapeutic usefulness of gabapentin during opiate withdrawal, larger randomized controlled trials (RCTs) are needed to confirm these preliminary findings.
2015: Trial of Tramadol Plus Gabapentin for Opioid Detoxification.
Ziaaddini, Ziaaddini, Asghari, et al. (2015) conducted a trial comparing the efficacy of a pharmacological combination (gabapentin plus tramadol) to methadone for the management of opiate withdrawal symptoms. A total of 59 individuals who met DSM-IV criteria for opiate dependence participated in the trial and were assigned at random to receive either gabapentin plus tramadol (30 participants) OR standalone methadone (29 participants). To determine the therapeutic usefulness of each intervention, participants were assessed with the Adjective Rating Scale for Withdrawal (ARSW), Clinical Opiate Withdrawal Scale (COWS), and Visual Analogue Scale (VAS) for cravings.
These assessments were conducted on Days 1, 2, 3, 4, 6, and 8 over a 10-day trial duration. Results indicated that ARSW and COWS scores did not significantly differ between those receiving the gabapentin plus tramadol compared to those receiving standalone methadone. The VAS for cravings scores indicated slightly fewer cravings among recipients of the combination (gabapentin plus tramadol) compared to standalone methadone, however, these were not statistically significant.
That said, it was noted that as a whole, the group receiving gabapentin plus tramadol had used significantly more opioids and different types of opioids than the group receiving methadone. One might speculate that if opioid usage and types had been similar in each group, the craving reductions might’ve been statistically significant among recipients of gabapentin plus tramadol – compared to recipients of standalone methadone. Nonetheless, it was concluded that both “gabapentin plus tramadol” and standalone methadone are efficacious interventions for managing opiate detoxification.
Considering that both interventions were of comparable safety and efficacy, perhaps researchers should’ve further analyzed the duration until complete detoxification (i.e. abstinence from all medication) and the severity of withdrawal symptoms associated with each detox method. Furthermore, we must consider that gabapentin and/or tramadol may be effective as standalone interventions during detoxification. In any regard, this study supports the idea that gabapentin is safe and therapeutically valuable during opiate detoxification when administered as an adjunct.
- Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341495/
2013: Randomized, placebo-controlled pilot trial of gabapentin during an outpatient, buprenorphine-assisted detoxification procedure.
Sanders, Mancino, Gentry, et al. (2013) conducted a randomized, double-blind, placebo-controlled pilot study to determine the therapeutic potential of gabapentin during a short-term buprenorphine-assisted opiate detoxification protocol. A total of 24 opioid-dependent outpatients were recruited to participate in the 5-week trial, each of whom sought medical help for opiate detoxification. During Week 1 of detoxification, all 24 patients received sublingual buprenorphine tablets.
In Week 2 of detoxification, the 24 participants were assigned at random to receive either gabapentin (11 participants) OR a placebo (13 participants). Starting in Week 3 and continuing into Week 4, all participants were tapered off of buprenorphine over period of 10 days. Thereafter, during Week 5, participants were tapered off of gabapentin or the placebo.
Throughout the trial, participants were evaluated tri-weekly with opioid withdrawal scales, vital examinations, and urine drug tests. It was reported that, at baseline, characteristics of each group were not subject to significant variation. Results indicated that self-reported and observer-rated opiate withdrawal symptoms were mild during the buprenorphine taper in gabapentin and placebo recipients.
That said, urine drug tests revealed that opioid-positive urine significantly decreased in the gabapentin group between Week 3 and Week 4 compared to the placebo group. This suggests that adjunct administration of gabapentin during a short-term, buprenorphine-assisted opiate detoxification protocol reduces likelihood of relapse. Moreover, although this was a small-scale and short-term trial, the resulting data support the idea that adjunct gabapentin is safe and therapeutically valuable during opiate detoxification.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/23855333
2012: Gabapentin Effect on Pain Associated with Heroin Withdrawal in Iranian Crack: A Randomized Double-blind Clinical Trial.
Behnam, Semnani, Saghafi, et al. (2012) discussed evidence indicating that gabapentin appears safe and tolerable for the treatment of heroin dependence. For this reason, they organized a study to directly test the ability of gabapentin in attenuating symptoms of pain during heroin withdrawal. A total of 60 male inpatients in a psychiatric ward who were dependent upon heroin were assigned at random to receive either: 1800 mg/day gabapentin (30 patients) OR a placebo (30 patients) for a 1-week duration.
To assess the efficacy of gabapentin in attenuating symptoms of withdrawal-related pain, all patients were evaluated with the Subjective Opioid Withdrawal Scale (SOWS) at baseline and at various intervals (Day 1, 2, 3, 4, 6, and 7). Results indicated that average pain scores significantly decreased among recipients of gabapentin and the placebo. That said, the severity of pain during the first 5 days was significantly lower among gabapentin recipients compared to those who received the placebo.
It is worth considering that the therapeutic value of gabapentin during heroin withdrawal may not be limited to attenuation of pain. Perhaps gabapentin effectively addresses other common symptoms of heroin withdrawal such as headaches, anxiety, and mood disturbances. Based on this speculation, some might agree that a longer-term, larger-scale trial is warranted in which the efficacy of standalone gabapentin is evaluated for the attenuation of all opiate withdrawal symptoms. Still, it should be emphasized that this is yet another study in which gabapentin effectively ameliorated unwanted symptoms [of pain] during opiate detoxification.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/24250527
2012: Role of gabapentin in preventing fentanyl- and morphine-withdrawal-induced hyperalgesia in rats.
Wei and Wei (2012) sought to determine whether gabapentin was capable of preventing hyperalgesia (heightened pain sensitivity) in animal models of opiate withdrawal. To induce opioid dependence, researchers administered fentanyl via subcutaneous injection, 4 times at 15-minute intervals, over a 1-hour duration, to Sprague Dawley rats. The fentanyl was administered at a dosage of 60 mcg/kg per injection for a total dose of 240 mcg/kg within the 1-hour timespan.
In addition to the fentanyl, the rats received morphine at dosages of 10 mg/kg (b.i.d.) over a 1-week duration. It was noted that half of the Sprague Dawley rats were assigned to receive gabapentin at dosages of 25/50 mg/kg, whereas the others were assigned to receive saline (as a control). To determine whether gabapentin could prevent withdrawal-induced hyperalgesia, researchers measured the antinociceptive thresholds of rats using behavioral tail-flick and paw-withdrawal tests.
Results from these measures indicated that, among rats receiving the saline control, antinociceptive thresholds significantly decreased after discontinuation of opioids (fentanyl and morphine), suggestive of a pronounced withdrawal-induced hyperalgesia. Comparatively, rats that received gabapentin (25/50 mg/kg) exhibited no change in antinociceptive threshold after opioid discontinuation. Additionally, it was mentioned that gabapentin appeared to prevent onset of morphine tolerance.
Researchers concluded that gabapentin is able to prevent opioid withdrawal-induced hyperalgesia in animal models. While the results of this study cannot be extrapolated to humans, they support the idea that gabapentin could be useful during opiate detoxification, especially among patients with preexisting pain conditions. Furthermore, preliminary data from human trials have reported upon the attenuation of pain symptoms during opiate withdrawal as a result of gabapentin administration.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/22048285
2011: Importance of gabapentin dose in treatment of opioid withdrawal.
Salehi, Kheirabadi, Maracy, and Ranjkesh (2011) organized a 3-week open-label trial to assess the efficacy of adjunct gabapentin for the management of opiate withdrawal symptoms during a methadone-assisted detox. A total of 27 patients who met diagnostic criteria for opioid dependence were recruited and assigned to receive gabapentin at a dosage of 1600 mg/day in addition to their methadone. Throughout the 3-week trial, researchers assessed the severity of patients’ withdrawal symptoms with the Subjective Opioid Withdrawal Scale (SOWS).
Results indicated that total SOWS scores significantly decreased after the administration of methadone plus adjunct gabapentin. After SOWS scores were documented, researchers compared them to the SOWS scores from an earlier double-blind, placebo-controlled trial in which adjunct gabapentin was administered at a dosage of 900 mg/day. It appeared as though there was a notable reduction in SOWS scores among those receiving 1600 mg/day of adjunct gabapentin compared to just 900 mg/day.
That said, the difference in SOWS scores between the 1600 mg/day and 900 mg/day dosages was not statistically significant. Still, it appeared as though 1600 mg/day was more effective in managing symptoms of coldness, diarrhea, dysphoria, muscle tension, and yawning during methadone-assisted detoxification. Regardless of the dosage of gabapentin administered, the data indicate that it can reduce certain symptoms of opiate detox.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/21869694
2009: Gabapentin and opioid craving.
A case report presented by Tay (2009) documented therapeutic benefit from the administration of gabapentin to a 55-year-old male patient with a history of intravenous opiate abuse. The patient exhibited chronic knee pain from a deformity plus osteoarthritis associated with a fracture resulting from a motor vehicle accident. The patient’s pain became increasingly severe prior to enrollment in a pain clinic, and was subjectively rated as a “10” out of 10 on a pain scale.
Additionally, the patient experienced depression, muscle spasms, and sleep disturbances – and was set to receive knee replacement surgery. Medical professionals noted that the patient had zero signs of neuropathic pain, but had a history of intravenous drug abuse and was diagnosed with hepatitis C, hypertension, and renal artery stenosis. Furthermore, the patient had a history of administering unauthorized high dosages of a codeine-containing medication and oxycodone.
Before admission to the pain clinic, the patient had been taking 40 mg/day oxycodone and 7.5 mg (b.i.d.) meloxicam. It was noted that the patient was prescribed 100 mg tramadol to be taken 4 times per day, but this was discontinued due to lack of efficacy. Other medications utilized by the patient included 5 mg diazepam and 5 mg nitrazepam to improve sleep.
At the pain clinic, the patient was prescribed 200 mg (b.i.d.) tramadol SR and 400 mg (b.i.d.) gabapentin. Upon release from the pain clinic, the patient’s primary care physician was alerted to discontinue oxycodone prescriptions, and if necessary, prescribe transdermal buprenorphine (10 mcg/h). At a 2-month follow-up appointment with the pain clinic, the patient exhibited a modest reduction in pain severity from a “10/10” to an “8/10”.
The patient’s daily medication regimen consisted of tramadol SR (200 mg, b.i.d.), transdermal buprenorphine (10 mcg/h), and gabapentin (400 mg, b.i.d.). Not only did the patient report improvements in mood and sleep with this combination of medications, but his opioid cravings significantly diminished. Interestingly, the patient specifically attributed the reduced opioid cravings to the initiation of gabapentin (400 mg, b.i.d.).
Tay, the author of this case report, discussed the fact that gabapentin appears to facilitate an analgesic effect for some patients, possibly explaining the pain reduction for the patient described in this case report. Furthermore, based on preexisting evidence indicating that gabapentin can attenuate cravings for alcohol, Tay hypothesizes that the gabapentin may have attenuated the patient’s opioid cravings. The outcome of this case report suggests that gabapentin may be safe and therapeutically useful for the management of opioid dependence in a subset of patients.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/19453959
2008: Effect of add-on gabapentin on opioid withdrawal symptoms in opium-dependent patients.
A randomized, double-blind, placebo-controlled, trial was conducted by Kheirabadi, Ranjkesh, Maracy, and Salehi (2008) to determine whether adjunct gabapentin could ameliorate symptoms of opiate withdrawal during a methadone-assisted detox. A total of 40 outpatients who met DSM-IV criteria for opiate dependence were recruited to participate in the trial. The participants were assigned at random to receive either 900 mg/day gabapentin OR a placebo as an adjunct to their methadone during a 3-week detoxification protocol.
At 6 intervals throughout the detoxification protocol, the Subjective Opiate Withdrawal Scale (SOWS) was administered to measure symptomatic severity. Results indicated that, although adjunct gabapentin was more efficacious than the adjunct placebo in attenuating a subset of withdrawal symptoms, average SOWS scores did not differ between the gabapentin and placebo recipients. Researchers concluded that 900 mg/day of adjunct gabapentin was no more effective than an adjunct placebo in attenuating opioid withdrawal symptoms.
It is reasonable to suspect that the adjunct gabapentin dosage of 900 mg/day may have been too small to facilitate substantial benefit. For this reason, perhaps another study would prove useful in which a larger dosage of gabapentin was administered. That said, the results of this study do not support the therapeutic usefulness of gabapentin during opiate withdrawal.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/18783503
2004: Add-on gabapentin in the treatment of opiate withdrawal.
Martínez-Raga, Sabater, Perez-Galvez, et al. (2004) reflected upon the fact that gabapentin is sometimes effective for the management of pain disorders, neuropsychiatric disorders, and alcohol withdrawal symptoms. Considering the therapeutic properties of gabapentin, researchers sought to evaluate its adjunctive usefulness when administered as part of a heroin detoxification protocol. A total of 7 patients who met diagnostic criteria for heroin dependence received gabapentin (600 mg, t.i.d.) as an “add-on” to their existing medication regimen during an outpatient heroin detoxification protocol.
All 7 patients managed to complete heroin detoxification and received naltrexone on Day 5 of their withdrawal. No adverse effects were observed in any of the participants, indicating that gabapentin was well-tolerated. Researchers reported that adjunct gabapentin appears safe and effective for managing unwanted symptoms of heroin detoxification.
Nevertheless, it is important to discuss some limitations associated with this report including the small sample size (of just 7 patients), plus the lack of randomization and controlling. A randomized controlled trial (RCT) is needed to substantiate the safety and usefulness of adjunct gabapentin (600 mg, t.i.d.) during opiate detoxification. Despite the need for further research, this preliminary evidence supports the idea that adjunct gabapentin is of therapeutic value during heroin detox.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/15093968
2004: Use of gabapentin for attenuation of symptoms following rapid opiate detoxification (ROD)–correlation with neurophysiological parameters–.
Rapid opiate detoxification (ROD) is a technique in which an opioid-dependent individual is abruptly discontinued from opioids while under anesthesia. In most cases, rapid opiate detoxification yields severe unwanted symptoms such as pain [throughout the body] and [bouts of extreme] restlessness. Knowing that pain and restlessness in rapid opiate detoxification can be difficult to manage, Freye, Levy, and Partecke (2004) organized a study to evaluate whether gabapentin might attenuate these symptoms to make the process more manageable for patients.
For the study, they recruited 21 opioid-dependent patients undergoing rapid opiate detoxification. The rapid detoxification process involved the administration of naltrexone (50 mg, b.i.d.) while under propofol anesthesia with artificial ventilation (IPPV). It was further mentioned that spikes in sympathetic activation were treated with clonidine, whereas frequent bowel movements were treated with intravenous somatostatin.
While in the intensive-care unit (ICU), gabapentin was administered at a dosage of 1200 mg after the rapid opiate detoxification process. At various intervals including: prior to the rapid opiate detox, briefly after detoxification, and post-gabapentin – researchers tracked the severity of patients’ pain, restlessness, and restless leg syndrome (RLS). Restlessness was measured with a subjective rating scale from 0 to 4, whereas pain was measured based on N100-peak of somatosensory evoked potentials (SEPs) and tolerance to an electrical nociceptive stimulus.
Results indicated that the N100-peak of SEPs increased from ~8.4 mV pre-detox to ~12.3 mV immediately after detoxification, however, the N100-peak of SEPs decreased to ~3.5 mV post-gabapentin. Additionally, nociceptive tolerance increased from ~4.4 mA immediately after detoxification to ~12.5 mA post-gabapentin. Patient-rated restlessness scores also plummeted from ~3.2 immediately after detoxification to ~1.2 post-gabapentin.
The findings of this study support the idea that gabapentin is of therapeutic value during opiate detoxification. Specifically, gabapentin is able to increase pain threshold and decrease restlessness, thereby making it easier for patients to cope with back pain, limb thrashing, and restless leg syndrome (RLS). That said, since this trial was small-scale, non-randomized, and uncontrolled – some may question the quality of these findings.
- Source: https://www.ncbi.nlm.nih.gov/pubmed/15130554
Limitations associated with the research of Gabapentin for opiate withdrawal
There are many limitations associated with trials investigating the therapeutic value of gabapentin among patients undergoing opiate detoxification. Perhaps the most significant limitation is that gabapentin has not been tested in large-scale, randomized controlled trials. Other limitations associated with the research include: adjunct-only testing, mixed data, and small sample sizes. Until some of these limitations are addressed, it’ll be difficult to know whether gabapentin provides sufficient benefit to patients during opiate detoxification.
- Adjunct-only: Every trial in which gabapentin has been evaluated for the management of opiate detoxification involved its administration as an adjunct. In some cases, testing gabapentin as an adjunct makes it difficult to determine the degree of benefit that gabapentin provides relative to the substance(s) with which it is administered. Additionally, with adjunct-only testing, it remains unclear as to whether gabapentin could prove efficacious as a monotherapy. Future adjunct-only testing of gabapentin during opiate detoxification should implement placebo controls. That said, even with adjunct placebo controls, a primary detox medication (e.g. buprenorphine) may exert such a potent therapeutic effect that there may be insufficient benefit to be derived from any adjunct. Moreover, gabapentin warrants investigation as a monotherapeutic intervention.
- Few trials: As of 2016 there are approximately 7 trials in which gabapentin has been evaluated for the management of opiate detoxification symptoms. What’s more problematic than the limited number of trials is that many implement small sample sizes, utilize poor designs, and/or are of extremely short duration. With this limited number of trials, it’s difficult to know whether gabapentin is useful during opiate detoxification. A greater number of well-designed trials with larger sample sizes are needed to determine gabapentin’s therapeutic value.
- Incentive: Since gabapentin is a generic medication and relatively inexpensive, there’s little financial incentive for pharmaceutical companies to showcase its usefulness during opiate detoxification. Researchers may not wish to allocate finances to investigate a generic medication during opiate detox for numerous reasons, including: there may be newer/novel compounds to evaluate; there may be other medications that have a better chance of working; and/or they may be satisfied with the currently-available treatments for opiate detoxification. Until there’s stronger incentive to test gabapentin during detox (e.g. other treatments aren’t very effective), it will likely remain under-evaluated.
- Mixed data: The data are mixed regarding gabapentin’s adjunct efficacy for attenuation of opiate withdrawal symptoms. Some studies noted that gabapentin provides significant additive benefit to conventional detox medications, yet others suggest that it is no more effective than a placebo. Due to this mixed data, it is unclear as to whether gabapentin is legitimately effective in opiate detox or withdrawal-related scenarios.
- Sample sizes: Thus far, the largest trial in which gabapentin was tested as an adjunct for the management of opiate withdrawal included 60 participants. Although 60 is a moderate sample, it may not be large enough to yield accurate data in a randomized controlled trial. Other trials have implemented sample sizes ranging from 21 to 59 participants. Samples with hundreds of participants would provide more accurate results if paired with an effective randomized controlled design.
Verdict: Gabapentin may be therapeutically valuable for a subset of patients during opiate detox
Most research investigating the efficacy of gabapentin for the management of opiate withdrawal symptoms indicates that it can provide some degree of therapeutic benefit. For example, a 59-participant trial conducted by Ziaaddini, Ziaaddini, Asghari, et al. (2015) discovered that gabapentin plus tramadol worked as well as methadone, a well-established detox intervention, for the attenuation of opiate withdrawal symptoms. Additionally, a randomized controlled 24-participant trial by Sanders, Mancino, Gentry, et al. (2013) mentioned that gabapentin was able to prevent relapse during opiate detoxification [over a 4-week duration].
An uncontrolled trial by Martínez-Raga, Sabater, Perez-Galvez, et al. (2004) reported that adjunct gabapentin was effective and well-tolerated among 7 patients rapidly detoxifying from heroin. It was particularly helpful for reducing restlessness and restless leg syndrome (RLS), and increased nociceptive threshold whereby it became easier to tolerate pain. Furthermore, a case report presented by Tay (2009) documented that gabapentin (400 mg, b.i.d.) reduced cravings for opiates in a patient with a history of intravenous opiate abuse.
Contrary to evidence supporting the efficacy of gabapentin during opiate detox, a 60-participant randomized controlled trial by Behnam, Semnani, Saghafi, et al. (2012) discovered that gabapentin (1800 mg/day) was no more effective than a placebo for the treatment of heroin dependence. That said, in this trial both gabapentin and the placebo significantly reduced SOWS (Subjective Opiate Withdrawal Symptom) scores, indicating an abnormally strong placebo effect. In other words, the marked reduction in SOWS score from the placebo does not negate the therapeutic effect facilitated by gabapentin.
In this same trial, gabapentin was significantly more effective than the placebo for attenuating pain within the first 5 days of detox. A 40-participant randomized controlled trial by Kheirabadi, Ranjkesh, Maracy, and Salehi (2008) also warrants mentioning due to the finding that adjunct gabapentin (900 mg/day) was no more effective in reducing SOWS scores than a placebo during methadone-assisted detoxification. Still, even in this trial, gabapentin was more effective than the placebo in alleviating specific symptoms (rather than total SOWS scores), suggestive of some benefit.
Everything considered, it’s likely that a subset of individuals will derive noticeable therapeutic benefit from the administration of gabapentin during opiate withdrawal. It should be assumed that the degree of therapeutic benefit attained from gabapentin during opiate withdrawal will be subject to significant variation based on individual factors such as: severity of withdrawal symptoms, specific symptoms experienced, medical diagnoses, neurochemistry, genes, and co-administered substances (plus their respective dosages). Research suggests that gabapentin may be most useful for attenuating opiate withdrawal symptoms such as restlessness, back pain, and anxiety.
Gabapentin may also attenuate a host of other detox symptoms such as: allodynia, coldness, insomnia, hypertension, migraine/headache, sleep disturbances, and yawning. Nonetheless, there is insufficient evidence to recommend usage of gabapentin as a first-line intervention and/or monotherapy for the management of opiate withdrawal symptoms. For this reason, gabapentin should only be considered for usage during opiate withdrawal when patients have exhausted all conventional medications and respective combinations with inadequate relief.
Have you tried Gabapentin for opiate withdrawal?
If you’ve taken gabapentin to help manage opiate withdrawal symptoms, feel free to share your experience in the comments section below. To help others get a better understanding of your situation, provide details in your comment such as: the dosage of gabapentin you used, the frequency of its administration (e.g. 3 times per day), and the cumulative duration over which it was administered (e.g. 2 months). Did you take gabapentin as a standalone monotherapeutic agent to manage opiate detoxification or was it prescribed as an adjunct to other medications?
In the event that gabapentin was prescribed as an adjunct to other medications, how can you be sure that the gabapentin provided any benefit? Have you considered that the benefit you perceive as being derived from gabapentin may be more attributable to another medication (e.g. buprenorphine)? Subjectively, if you had to rate the effectiveness of gabapentin for the management of opiate withdrawal symptoms on a scale from 1 to 10 (with “1” being “ineffective” and “10” being “extremely effective”), what number would you assign it?
Assuming you consider gabapentin to be of therapeutic value during opiate withdrawal, mention the specific detox-related symptoms that it most effectively managed for you (e.g. anxiety, cravings, muscle pain, restlessness). Did you experience any unwanted side effects and/or severe withdrawal symptoms upon discontinuation of gabapentin? In conclusion, while gabapentin may effectively manage symptoms of opiate withdrawal in a subset of users, it cannot be considered a therapeutically-relevant intervention in detoxification until higher-quality research substantiates its efficacy.