Gabapentin: Difference between revisions

Line 7:

==Chemistry==

Gabapentin, or 1-(aminomethyl)cyclohexanacetic 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 ~~analagous~~ 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, or 1-(aminomethyl)cyclohexanacetic 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.

==Pharmacology==

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.<ref>Mechanisms of action of gabapentin (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9686247</ref> As the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the [[sedating]] and [[Anxiety_suppression|anxiolytic]] (or [[Anxiety suppression|calming effects]]) of gabapentin on the nervous system.

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.<ref>Mechanisms of action of gabapentin (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9686247</ref> As the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the [[sedating]] and [[Anxiety_suppression|anxiolytic]] (or [[Anxiety suppression|calming effects]]) of gabapentin on the nervous system.

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.<ref>The mechanisms of action of gabapentin and pregabalin. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/16376147</ref> 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 ~~biovailability~~ than lower doses). The bioavailability of gabapentin is approximately 60%, 47%,

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.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> 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.<ref>Gabapentin ~~data sheet~~ | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>

34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> 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.<ref>Gabapentin datasheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>

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.

==Subjective 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 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.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>

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.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>

Line 26:

|{{effects/physical|

*'''[[Effect::Sedation]]''' - Gabapentin is typically mildly sedating and can produce a lethargic state. At higher doses it may lead to a moderately sedated state.

*'''[[Effect::Sedation]]''' - Gabapentin is typically mildly sedating and can produce a lethargic state. At higher doses, it may lead to a moderately sedated state.

*'''[[Effect::Appetite enhancement]]''' - Appetite enhancement is not particularly prominent, but is sometimes reported. It can have a synergistic effect when combined with [[cannabis]].

*'''[[Effect::Muscle relaxation]]''' - Muscle relaxation is present on gabapentin, although not to the extent of [[benzodiazepines]], [[barbiturates]], or [[GHB]].

Line 54:

{{effects/visual|

====Hallucinatory states====

*'''[[Effect::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.

*'''[[Effect::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.

====Disconnective effects====

*'''[[Effect::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 [[Visual_disconnection#Structures|hallucinatory structures]] in the same way that traditional [[dissociatives]] can.

*'''[[Effect::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 [[Visual_disconnection#Structures|hallucinatory structures]] in the same way that traditional [[dissociatives]] can.

}}

Line 74:

It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.

===Suicide===

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),<ref>http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100190.htm</ref> modifying the packaging insert to reflect this. A 2010 meta analysis confirmed the increased risk of suicide associated with gabapentin use.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20388896</ref>

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),<ref>http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100190.htm</ref> modifying the packaging insert to reflect this. A 2010 meta-analysis confirmed the increased risk of suicide associated with gabapentin use.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20388896</ref>

===Lethal dosage===

Line 81:

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 [[Time to full tolerance::with prolonged ~~continous~~ usage]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::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.

Tolerance will develop to the anxiolytic effects [[Time to full tolerance::with prolonged continuous usage]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::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.

===Dangerous interactions===

@@ Line 7: / Line 7: @@
 ==Chemistry==
-Gabapentin, or 1-(aminomethyl)cyclohexanacetic acid, is an analogue of the neurotransmitter [[GABA]]. It contains a cyclohexane ring bound to a methylamino chain CH<sub>3</sub>NH<sub>2</sub>. At the same location, R<sub>1</sub>, the cyclohexane ring is also substituted with an acetic acid group. Gabapentin is structurally analagous 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 R<sub>3</sub> 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, or 1-(aminomethyl)cyclohexanacetic acid, is an analogue of the neurotransmitter [[GABA]]. It contains a cyclohexane ring bound to a methylamino chain CH<sub>3</sub>NH<sub>2</sub>. At the same location, R<sub>1</sub>, 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 R<sub>3</sub> of the butanoic acid chain in GABA incorporated into an attached cyclohexane ring, converting it into a tertiary carbon while still maintaining the chain.
 ==Pharmacology==
-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.<ref>Mechanisms of action of gabapentin (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9686247</ref> As the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the [[sedating]] and [[Anxiety_suppression|anxiolytic]] (or [[Anxiety suppression|calming effects]]) of gabapentin on the nervous system.
+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.<ref>Mechanisms of action of gabapentin (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/9686247</ref> As the GABA system is the most prolific inhibitory receptor set within the brain, its increase in biosynthesis results in the [[sedating]] and [[Anxiety_suppression|anxiolytic]] (or [[Anxiety suppression|calming effects]]) of gabapentin on the nervous system.
 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.<ref>The mechanisms of action of gabapentin and pregabalin. (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pubmed/16376147</ref> 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 biovailability than lower doses). The bioavailability of gabapentin is approximately 60%, 47%,
+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%,
-%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> 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.<ref>Gabapentin data sheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>
+%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day.<ref>Neurontin Clinical Pharmacology Biopharmaceutics Review | http://www.accessdata.fda.gov/drugsatfda_docs/nda/2002/21-397.pdf_Neurontin_BioPharmr.pdf</ref> 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.<ref>Gabapentin datasheet | http://reference.medscape.com/drug/neurontin-gralise-gabapentin-343011#showall</ref>
 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.
 ==Subjective 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 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.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>
+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.<ref><nowiki>https://www.uofmhealth.org/health-library/d03182a1</nowiki></ref>
 {{Preamble/SubjectiveEffects}}
@@ Line 26: / Line 26: @@
 |{{effects/physical|
-*'''[[Effect::Sedation]]''' - Gabapentin is typically mildly sedating and can produce a lethargic state. At higher doses it may lead to a moderately sedated state.
+*'''[[Effect::Sedation]]''' - Gabapentin is typically mildly sedating and can produce a lethargic state. At higher doses, it may lead to a moderately sedated state.
 *'''[[Effect::Appetite enhancement]]''' - Appetite enhancement is not particularly prominent, but is sometimes reported. It can have a synergistic effect when combined with [[cannabis]].
 *'''[[Effect::Muscle relaxation]]''' - Muscle relaxation is present on gabapentin, although not to the extent of [[benzodiazepines]], [[barbiturates]], or [[GHB]].
@@ Line 54: / Line 54: @@
 {{effects/visual|
 ====Hallucinatory states====
-*'''[[Effect::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.
+*'''[[Effect::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.
 ====Disconnective effects====
-*'''[[Effect::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 [[Visual_disconnection#Structures|hallucinatory structures]] in the same way that traditional [[dissociatives]] can.
+*'''[[Effect::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 [[Visual_disconnection#Structures|hallucinatory structures]] in the same way that traditional [[dissociatives]] can.
 }}
@@ Line 74: / Line 74: @@
 It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
 ===Suicide===
-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),<ref>http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100190.htm</ref> modifying the packaging insert to reflect this. A 2010 meta analysis confirmed the increased risk of suicide associated with gabapentin use.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20388896</ref>
+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),<ref>http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm100190.htm</ref> modifying the packaging insert to reflect this. A 2010 meta-analysis confirmed the increased risk of suicide associated with gabapentin use.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20388896</ref>
 ===Lethal dosage===
@@ Line 81: / Line 81: @@
 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 [[Time to full tolerance::with prolonged continous usage]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::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.
+Tolerance will develop to the anxiolytic effects [[Time to full tolerance::with prolonged continuous usage]]. After cessation, the tolerance returns to baseline in [[Time to zero tolerance::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.
 ===Dangerous interactions===