Fatal overdose may occur when gabapentinoids are combined with other depressants such as opiates, benzodiazepines, barbiturates, thienodiazepines, alcohol or other GABAergic substances.
It is strongly discouraged to combine these substances, particularly in common to heavy doses.
|Summary sheet: Gabapentin|
|Common names||Gabapentin, Neurontin, Gabarone, Gralise|
|Systematic name||1-(Aminomethyl)cyclohexaneacetic acid|
|Routes of Administration|
Gabapentin (also known as Neurontin) is a depressant substance of the gabapentinoid class. It is a structural analog of the neurotransmitter GABA and acts by inhibiting certain calcium channels in the brain namely α2δ subunit-containing voltage-dependent calcium channels (VGCCs).
Gabapentin was originally developed to treat epilepsy and is currently FDA approved to treat postherpetic neuralgia in adults and as an adjunctive therapy in the treatment of partial onset seizures. It is often prescribed off-label for restless leg syndrome, social anxiety disorder, panic disorder, and generalized anxiety disorder.
However Gabapentin's efficacy in the treatment of anxiety disorders is unclear as the evidence is "somewhat mixed". It is recommended as a first line agent for the treatment of neuropathic pain arising from diabetic neuropathy, post-herpetic neuralgia, and central neuropathic pain.
Subjective effects include mild to moderate anxiety suppression, pain relief, and muscle relaxation. Its analgesic and anxiolytic effects provide gabapentin with some recreational potential in a manner that can be compared to a mild benzodiazepine. However, these recreational effects are reported to diminish quickly with repeated usage and are typically reported by those who do not have a tolerance to this compound.
Gabapentin is considered to have low abuse potential compared to most recreational depressants. However, chronic use can lead to physical dependence. Additionally, there is a risk of fatal overdose when it is combined with other depressants (a somewhat common practice considering its weak effects). It is highly advised to use harm reduction practices if using this substance.
Gabapentin is a 3,3-disubstituted derivative of GABA. Therefore, it is a GABA analogue, as well as a γ-amino acid. Specifically, it is a derivative of GABA with a pentyl disubstitution at 3 position, hence, the name - gabapentin, in such a way as to form a six-membered ring. After formation of the ring, the amine and carboxylic groups are not in the same relative positions as they are in the GABA:. they are more conformationally constrained.
Gabapentin, or 1-(aminomethyl)cyclohexylacetic acid, is an analogue of the neurotransmitter GABA. It contains a cyclohexane ring bound to a methylamino chain CH3NH2. At the same location, R1, the cyclohexane ring is also substituted with an acetic acid group. Gabapentin is structurally analogous to GABA. GABA contains an amino group bound to the terminal carbon of a butanoic acid chain. The structure of gabapentin contains the secondary carbon R3 of the butanoic acid chain in GABA incorporated into an attached cyclohexane ring, converting it into a tertiary carbon while still maintaining the chain.
Gabapentin modulates the action of glutamate decarboxylase (GAD) and branched-chain aminotransferase (BCAT), two enzymes involved in GABA biosynthesis. In human and rat studies, gabapentin was found to increase GABA biosynthesis, and to increase non-synaptic GABA neurotransmission in vitro. As the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the sedating and anxiolytic (or calming effects) of gabapentin on the nervous system.
Another study based on magnetic resonance imaging done at 7 Tesla confirms that Gabapentin appears to increase cerebral GABA concentrations acutely, in vivo, by up to 79% from baseline.
Gabapentin, as a gabapentinoid, has also been shown to bind to the α2δ-1 subunit of Voltage-Gated Calcium Channels to act as a VGCC blocker, which contributes to its inhibitory, analgesic, and anxiolytic effects. It is uncertain exactly how this method of action contributes to gabapentin's psychoactive effects.
The bioavailability of gabapentin is relatively low and is inversely proportional to the dose (i.e. higher doses have lower bioavailability than lower doses). The bioavailability of gabapentin is approximately 60%, 47%, 34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day, given in divided doses of one pill per every 8 hours. Gabapentin is highly lipophilic, making unsaturated fats such as vegetable oil and olive oil significantly boost the total amount of absorption. This means that eating a high fat meal substantially increases gabapentin's bioavailability, due to the fact that unsaturated fats bind to gabapentin to allow for absorption, and that meals slow down and thus increase gabapentin absorption by decreasing gabapentin transporter saturation.
Gabapentin transporter saturation occurs when large enough doses of gabapentin are consumed in a short enough period of time to result in the body being unable to absorb any more gabapentin, causing a significant reduction in bioavailability, which largely accounts for the drop in bioavailability seen with increasing doses.
Gabapentin is a potent activator of voltage-gated potassium channels KCNQ3 and KCNQ5, even at low nanomolar concentrations. However, this activation is unlikely to be the dominant mechanism of gabapentin's therapeutic effects.
The decreasing bioavailability of gabapentin can be lessened by taking lower doses more often instead of higher doses less frequently. As a general rule, using any more than 250-300 mg of gabapentin every 30-45 minutes will result in wasting a significant portion of the total dose of gabapentin, although this number varies depending on the individual. Alkaline environments inhibit the absorption of gabapentin, so lowering the pH of one's stomach using acidic substances (such as soft drinks) will boost bioavailability as well. It is generally not recommended to take antacids 2 hours before or after taking gabapentin, because although not dangerous, it will severely lower the total absorption of gabapentin.
Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.
It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.
- Sedation - Gabapentin is typically mildly sedating and can produce a lethargic state. At higher doses, it may lead to a moderately sedated state.
- Appetite enhancement - Appetite enhancement is not particularly prominent, but is sometimes reported. It can have a synergistic effect when combined with cannabis.
- Muscle relaxation - Muscle relaxation is present on gabapentin, although not to the extent of benzodiazepines, barbiturates, or GHB.
- Physical euphoria - Gabapentin is capable of producing weak to moderate states of physical euphoria in some users. However, it is very inconsistent compared to other depressants (e.g. benzodiazepines, opioids, and GHB) and tolerance builds rapidly. As a result, it is considered to be a poor euphoriant.
- Decreased libido - Many users note a marked decrease in their sex drive when taking gabapentin. This can happen when it is taken both recreationally or as prescribed.
- Perception of bodily lightness - Some users report feeling lighter at very high doses.
- Dizziness - Dizziness is prevalent at higher doses, although many users report that it is not necessarily distressing. However, users should be careful not to slip and fall when walking down slopes or stairs.
- Seizure suppression - Gabapentin is commonly used as an anticonvulsant. It is often combined with other anticonvulsants when used to treat epilepsy and other seizure disorders.
- Pain relief - Gabapentin is used to control pain, particularly fibromyalgic/neuropathic pain (nerve pain) and restless leg syndrome. It is generally considered to be not very effective for the management of acute pain, unlike opiates.
- Muscle twitching
- Motor control loss
- Analysis suppression
- Anxiety suppression
- Dream potentiation
- Thought deceleration
- Cognitive euphoria
- Emotion suppression
- Depersonalization and Derealization - At very high doses, gabapentin can induce a mild dissociative state.
- Amnesia - Gabapentin induces a substantially lower amount of amnesia compared to other GABAergic drugs such as benzodiazepines.
- Suicidal ideation
- Internal hallucination - At higher doses, some users report mild to strong closed eye visuals (CEVs). These can include but are not limited to psychedelic-like geometry and landscapes. It has been noted that smoking cannabis greatly potentiates these effects.
- Visual disconnection - This effect is generally quite mild and appears inconsistently at very high doses. It results in feeling as if one's sense of vision is distant or vague and being viewed through a screen or window. However, it is not capable of higher levels of visual disconnection that produce holes, spaces, and voids or hallucinatory structures in the same way that traditional dissociatives can.
Anecdotal reports which describe the effects of this compound within our experience index include:
- Experience: 2100 mg Gabapentin (Oral) - Nodding Off
- Experience:1.2 g gabapentin, alcohol, and half of 150 mg Effexor XR - Pretty lovely for socializing and giggles
- Experience:7500mg - Analysis of gabapentin
- Experience:A combination of tramadol, clonazepam, gabapentin, and dimenhydrinate
- Experience:Gabapentin (2100mg, Oral) - 2100mg of Gabapentin
Additional experience reports can be found here:
Toxicity and harm potential
This toxicity and harm potential section is a stub.
As a result, it may contain incomplete or even dangerously wrong information! You can help by expanding upon or correcting it.
GABApentin has a low toxicity relative to dose. The most common side effects of gabapentin in adult patients include dizziness, fatigue, drowsiness, weight gain, and peripheral edema (swelling of extremities). Gabapentin may also produce sexual dysfunction in some patients whose symptoms of which may include loss of libido, inability to reach orgasm, and erectile dysfunction. Gabapentin should be used carefully in patients with renal impairment due to possible accumulation and toxicity.
It is strongly recommended that one use harm reduction practices when using this drug.
In 2009, the U.S. Food and Drug Administration issued a warning of an increased risk of depression and suicidal thoughts and behaviors in patients taking gabapentin (along with other anticonvulsant drugs), modifying the packaging insert to reflect this. A 2010 meta-analysis confirmed the increased risk of suicide associated with gabapentin use.
In 2010, a study conducted by Patorno E, Bohn RL, Wahl PM, et al, found that the use of gabapentin compared to the use of topiramate may be associated with an increase in suicidal acts and or violent deaths.
It should be noted that in both studies along with others that the patients evaluated had a higher suicide risk and the studies were both limited and imprecise.
People who accidentally or intentionally overdose may experience drowsiness, sedation, blurred vision, slurred speech, somnolence and possibly death (if a very high amount was taken and particularly if combined with alcohol). Serum gabapentin concentrations may be measured to confirm diagnosis.
Dependence and abuse potential
Gabapentin is not considered psychologically addictive. However, it is possible to develop a physical dependence on the drug. In fact, people can experience withdrawal symptoms for up to 45 days after they stop taking gabapentin. Although gabapentin does give some people a euphoric “high” which can cause abuse, gabapentin abusers do not present with the kind of compulsive, drug-seeking behavior or strong cravings associated with other more common depressants such as opioids, alcohol or benzodiazepines.
Tolerance will develop to the anxiolytic effects with prolonged continuous usage. After cessation, the tolerance returns to baseline in 7-14 days. Withdrawal symptoms or rebound symptoms may occur after ceasing usage abruptly following a few weeks or longer of steady dosing and may necessitate a gradual dose reduction.
- Opioids - Combining opioids with gabapentin can cause death from respiratory failure.
- Depressants (GABAergic) - Gabapentin significantly potentiates the effects of alcohol, benzodiazepines and other GABAergics which may lead to blackouts, and dangerous behaviour.
This legality section is a stub.
As such, it may contain incomplete or wrong information. You can help by expanding it.
Gabapentin is a prescription-only medicine and can only be prescribed following a consultation with a doctor.
- Germany: Gabapentin is a prescription medicine, according to Anlage 1 AMVV.
- Switzerland: Gabapentin is listed as a "Abgabekategorie B" pharmaceutical, which requires a prescription.
- United States: Gabapentin is not a scheduled substance but may only be sold with prescription.
- Exceptions: Gabapentin is a Schedule 5 controlled substance in: Alabama, Kentucky, Michigan, North Dakota, Tennessee, Virginia, and West Virginia. With prescription drug monitoring in: Connecticut, District of Columbia, Indiana, Kansas, Massachusetts, Minnesota, Nebraska, New Jersey, Ohio, Oregon, Utah, and Wyoming.
- ↑ Risks of Combining Depressants - TripSit
- ↑ 2.0 2.1 Neurontin, Gralise (gabapentin) dosing, indications, interactions, adverse effects, and more
- ↑ Calandre, Elena P.; Rico-Villademoros, Fernando; Slim, Mahmoud (2016). "Alpha2delta ligands, gabapentin, pregabalin and mirogabalin: a review of their clinical pharmacology and therapeutic use". Expert Review of Neurotherapeutics. 16 (11): 1263–1277. doi:10.1080/14737175.2016.1202764. ISSN 1473-7175.
- ↑ Schatzberg, A. F., Cole, J. O., DeBattista, C. (2010). Manual of Clinical Psychopharmacology. American Psychiatric Pub. ISBN 9781585623778.
- ↑ Sobel, S. V. (5 November 2012). Successful Psychopharmacology: Evidence-Based Treatment Solutions for Achieving Remission. W. W. Norton & Company. ISBN 9780393708578.
- ↑ Richards, D., Aronson, J., Coleman, J., Reynolds, D. J. (10 November 2011). Oxford Handbook of Practical Drug Therapy. OUP Oxford. ISBN 9780199562855.
- ↑ Mula, M., Pini, S., Cassano, G. B. (June 2007). "The role of anticonvulsant drugs in anxiety disorders: a critical review of the evidence". Journal of Clinical Psychopharmacology. 27 (3): 263–272. doi:10.1097/jcp.0b013e318059361a. ISSN 0271-0749.
- ↑ Hamer, A. M., Haxby, D. G., McFarland, B. H., Ketchum, K. (July 2002). "Gabapentin Use in a Managed Medicaid Population". Journal of Managed Care Pharmacy. 8 (4): 266–271. doi:10.18553/jmcp.2002.8.4.266. ISSN 1083-4087.
- ↑ Steinman, M. A., Bero, L. A., Chren, M.-M., Landefeld, C. S. (15 August 2006). "Narrative Review: The Promotion of Gabapentin: An Analysis of Internal Industry Documents". Annals of Internal Medicine. 145 (4): 284–293. doi:10.7326/0003-4819-145-4-200608150-00008. ISSN 0003-4819.
- ↑ Wijemanne, S., Jankovic, J. (1 June 2015). "Restless legs syndrome: clinical presentation diagnosis and treatment". Sleep Medicine. 16 (6): 678–690. doi:10.1016/j.sleep.2015.03.002. ISSN 1389-9457.
- ↑ Attal, N., Cruccu, G., Baron, R., Haanpää, M., Hansson, P., Jensen, T. S., Nurmikko, T. (September 2010). "EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision". European Journal of Neurology. 17 (9): 1113–e88. doi:10.1111/j.1468-1331.2010.02999.x. ISSN 1468-1331.
- ↑ Wyllie, E. (2012). Wyllie’s treatment of epilepsy: principles and practice. ISBN 9781451153484.
- ↑ Sneader, W. (2005). Drug Discovery A History. ISBN 9780470015520.
- ↑ Levandovskiy, I. A., Sharapa, D. I., Shamota, T. V., Rodionov, V. N., Shubina, T. E. (February 2011). "Conformationally restricted GABA analogs: from rigid carbocycles to cage hydrocarbons". Future Medicinal Chemistry. 3 (2): 223–241. doi:10.4155/fmc.10.287. ISSN 1756-8919.
- ↑ Taylor, C. P. (1997). "Mechanisms of action of gabapentin". Revue Neurologique. 153 Suppl 1: S39–45. ISSN 0035-3787.
- ↑ Cai, K., Nanga, R. P., Lamprou, L., Schinstine, C., Elliott, M., Hariharan, H., Reddy, R., Epperson, C. N. (December 2012). "The Impact of Gabapentin Administration on Brain GABA and Glutamate Concentrations: A 7T 1H-MRS Study". Neuropsychopharmacology. 37 (13): 2764–2771. doi:10.1038/npp.2012.142. ISSN 0893-133X.
- ↑ Sills, G. J. (February 2006). "The mechanisms of action of gabapentin and pregabalin". Current Opinion in Pharmacology. 6 (1): 108–113. doi:10.1016/j.coph.2005.11.003. ISSN 1471-4892.
- ↑ Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf
- ↑ Manville, R. W., Abbott, G. W. (1 October 2018). "Gabapentin Is a Potent Activator of KCNQ3 and KCNQ5 Potassium Channels". Molecular Pharmacology. 94 (4): 1155–1163. doi:10.1124/mol.118.112953. ISSN 0026-895X.
- ↑ gabapentin, Michigan Medicine
- ↑ 21.0 21.1 21.2 Patorno, E., Bohn, R. L., Wahl, P. M., Avorn, J., Patrick, A. R., Liu, J., Schneeweiss, S. (14 April 2010). "Anticonvulsant medications and the risk of suicide, attempted suicide, or violent death". JAMA. 303 (14): 1401–1409. doi:10.1001/jama.2010.410. ISSN 1538-3598.
- ↑ http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020235s041,020882s028,021129s027lbl.pdf
- ↑ Aronson, J. K. (4 March 2014). Side Effects of Drugs Annual: A worldwide yearly survey of new data in adverse drug reactions. Newnes. ISBN 9780444626363.
- ↑ http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/020235s057,020882s041,021129s039lbl.pdf
- ↑ http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100190.htm
- ↑ Patorno, E., Bohn, R. L., Wahl, P. M., Avorn, J., Patrick, A. R., Liu, J., Schneeweiss, S. (14 April 2010). "Anticonvulsant Medications and the Risk of Suicide, Attempted Suicide, or Violent Death". JAMA. 303 (14): 1401–1409. doi:10.1001/jama.2010.410. ISSN 0098-7484.
- ↑ R.C. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 677–8. ISBN 978-0-9626523-7-0.
- ↑ AMVV - Verordnung über die Verschreibungspflicht von Arzneimitteln
- ↑ Peckham, A. M., Ananickal, M. J., Sclar, D. A. (17 August 2018). "Gabapentin use, abuse, and the US opioid epidemic: the case for reclassification as a controlled substance and the need for pharmacovigilance". Risk Management and Healthcare Policy. 11: 109–116. doi:10.2147/RMHP.S168504.
- ↑ Collins, S. (October 2021). "More states make gabapentin a Schedule V Controlled Substance". Pharmacy Today. 27 (10): 33. doi:10.1016/j.ptdy.2021.09.016. ISSN 1042-0991.