GHB: Difference between revisions

Line 22:

Activation of both the GHB receptor and [[GABA]]B is responsible for the addictive profile of GHB. GHB's effect on [[dopamine]] release is biphasic.<ref>Drosophila [[GABA]]B receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> This means that while low concentrations stimulate [[dopamine]] release via the GHB receptor,<ref>A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and [[anticonvulsant]] properties (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2173754</ref> higher concentrations inhibit [[dopamine]] release via [[GABA]]B receptors.<ref>Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/001429999500369V</ref> After an initial phase of inhibition, [[dopamine]] release is then increased via the GHB receptor.

GHB induces the accumulation of either a derivative of [[tryptophan]] or [[tryptophan]] itself, possibly by increasing [[tryptophan]] transport across the blood–brain barrier. GHB-induced stimulation may be due to this increase in [[tryptophan]] transport to the brain and in its uptake by serotonergic cells. As the [[Serotonin|serotonergic]] system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.

GHB induces the accumulation of either a derivative of tryptophan or [[tryptophan]] itself, possibly by increasing tryptophan transport across the blood–brain barrier. GHB-induced stimulation may be due to this increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the [[Serotonin|serotonergic]] system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.

These findings may explain the paradoxical mix of sedative and stimulatory properties of GHB as well as the so-called "rebound" effect reported by individuals using GHB as a sleeping agent wherein they awake suddenly after several hours of GHB-induced deep sleep. Over time, the concentration of GHB in the system decreases below the threshold for significant [[GABA]]B receptor activation and activates predominantly the GHB receptor, leading to wakefulness.

Line 39:

*'''[[Effect::Motor control loss]]'''

*'''[[Effect::Nausea]]'''

*'''[[Effect::Increased salivation]]''' - Increased salivation is very common.

*'''[[Effect::Stomach cramps]]'''

*'''[[Effect::Muscle cramps]]'''

*'''[[Effect::Optical sliding]]'''

*'''[[Effect::Increased salivation]]'''

*'''[[Effect::Pupil dilation]]'''

*'''[[Effect::Vasodilation]]'''

*'''[[Effect::Headaches]]'''

*'''[[Effect::Seizure]]''' - Very high dosages of GHB have consistently produced convulsions.

}}

{{effects/visual|

*'''[[Effect::Visual acuity suppression]]'''

*'''[[Effect::After images]]'''

*'''[[Effect::Perspective distortions]]'''

*'''[[Effect::Depth perception distortions]]'''

*'''[[Effect::Scenery slicing]]'''

}}

|{{effects/cognitive|

*'''[[Effect::Sleepiness]]''' & '''[[Effect::Wakefulness]]''' - At very low dosages, GHB can make one tired, while common doses are primarly wakefullness-promoting. High doses can lead to feelings of being extremely sleepy.

*'''[[Effect::Analysis suppression]]'''

*'''[[Effect::Disinhibition]]'''

*'''[[Effect::Anxiety suppression]]'''

*'''[[Effect::Cognitive euphoria]]''' - GHB produces intense states of euphoria comparable to that of [[cocaine]], [[MDMA]], and [[opiates]]. For this reason, it is sometimes called "liquid ecstasy". It is commonly described as a more euphoric and disinhibiting version of alcohol. While this may be accurate, it is also far easier to overdose on.

*'''[[Effect::Disinhibition]]''' - Social and behavioral disinhibition on GHB is extremely powerful and perhaps its most prominent feature. Users are more liable to exhibit impaired decision-making and engage in risky activities such as unprotected sex or unsafe substance combinations. Users are advised to only take GHB in safe environments with people they trust not to take advantage of their vulnerable state.

*'''[[Effect::Compulsive redosing]]''' - This is somewhat prevalent due to its short duration.

*'''[[Effect::Creativity enhancement]]''' - Creativity enhancement is most apparent at low to common doses.

*'''[[Effect::Disinhibition]]''' - Social and behavioral disinhibition on GHB is extremely powerful and perhaps its most prominent feature. Users are more liable to exhibit impaired decision-making and engage in risky activities such as unprotected sex or unsafe substance combinations. Users are advised to only take GHB in safe environments with people they trust not to take advantage of their vulnerable state.

*'''[[Effect::Dream potentiation]]''' - GHB can have a very pronounced effect on dream recall and vividness. Conversely, discontinuation can result in bad dreams or nightmares. Additionally, intoxication on GBL can lead to one seeing their own dream being manifested, similar to a [[WILD|wake-induced lucid dream]] (WILD) and simultaneous states of wakefulness and dreaming.

*'''[[Effect::Empathy, affection, and sociability enhancement]]''' - GHB presents strong [[entactogenic]] effects which, although weaker than that of [[MDMA]], are still prominent and well defined.

*'''[[Effect::Immersion enhancement]]'''

*'''[[Effect::Increased libido]]'''

*'''[[Effect::Increased libido]]''' - GBL reportedly produces less increases of libido than [[GHB]] does.

*'''[[Effect::Increased music appreciation]]'''

*'''[[Effect::Introspection]]'''

*'''[[Effect::Rejuvenation]]'''

*'''[[Effect::Suggestibility enhancement]]'''

*'''[[Effect::Memory suppression]]'''

**'''[[Effect::Amnesia]]'''

*'''[[Effect::~~Thought deceleration~~]]'''

*'''[[Effect::Motivation enhancement]]''' & '''[[Effect::Motivation suppression]]''' - As with other coinciding effects, common doses can lead to greater motivation whilst high doses generally result in lethargy.

*'''[[Effect::Spatial disorientation]]'''

*'''[[Effect::Spatial disorientation]]''' - Disorientation is very common in dark areas.

*'''[[Effect::Suggestibility enhancement]]'''

*'''[[Effect::Thought acceleration]]''' or '''[[Effect::Thought deceleration]]''' - Low to common doses are primarly stimulating and one finds themselves constantly generating thoughts.

}}

{{effects/auditory|

*'''[[Effect::Tinnitus]]'''

*'''[[Effect::Auditory distortion]]'''

}}

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==Toxicity and harm potential==

[[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of GHB<ref>Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]]

GHB is [[toxicity::considered to be a safe and non-toxic substance when used responsibly]] ~~or medically~~. The [[LD50|LD50]] is above the active dosage, and there is no danger of acute toxicity. However, it can be dangerous when used as a recreational drug or abused. There have been many negative reports from recreational users who have overdosed, combined GHB with alcohol or other drugs, or accidentally dosed themselves unexpectedly.<ref>https://www.erowid.org/experiences/exp.php?ID=1926 | Erowid. "GHB Overdoses & Poisonings: An Experience with GHB (ID 1926)". Erowid.org. Jun 19, 2000. erowid.org/exp/1926 </ref>

GHB is [[toxicity::considered to be a safe and non-toxic substance when used responsibly or medically]]. The [[LD50|LD50]] is above the active dosage, and there is no danger of acute toxicity. However, it can become dangerous when used as a recreational drug or abused. There have been many negative reports from recreational users who have overdosed, combined GHB with alcohol or other drugs, or accidentally dosed themselves unexpectedly.<ref>https://www.erowid.org/experiences/exp.php?ID=1926 | Erowid. "GHB Overdoses & Poisonings: An Experience with GHB (ID 1926)". Erowid.org. Jun 19, 2000. erowid.org/exp/1926 </ref>

One publication investigated 226 deaths attributed to GHB.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20825811 | Zvosec DL, Smith SW, Porrata T, Strobl AQ, Dyer JE (2011). "Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and trauma". The American Journal of Emergency Medicine 29 (3): 319–32.</ref> Seventy-one deaths (34%) were caused by GHB alone while the other deaths were from [[respiratory depression]] caused by interaction with alcohol or other drugs.

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===Tolerance and addiction potential===

GHB is [[Addiction potential::moderately physically and psychologically addictive]]. The frequent use of GHB can cause withdrawal symptoms similar to those caused by other [[depressants]] such as [[alcohol]] and [[benzodiazepines]] if abruptly discontinued.<ref>Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759403/</ref><ref>Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713368/</ref> These symptoms seem to depend on the dosage and the length of time the drug was used for. Light to moderate users often experience anxiety, insomnia, sleep-related problems, and tremors whereas heavy use can cause severe withdrawal symptoms like delirium, psychosis, and hallucinations.<ref>https://www.ncbi.nlm.nih.gov/pubmed/11174231 | Gamma-hydroxybutyrate withdrawal syndrome.</ref><ref name="GHB" />

GHB is [[Addiction potential::moderately to highly physically and moderately psychologically addictive]]. The frequent use of GHB can cause withdrawal symptoms similar to those caused by other [[depressants]] such as [[alcohol]] and [[benzodiazepines]] if abruptly discontinued.<ref>Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759403/</ref><ref>Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713368/</ref> These symptoms seem to depend on the dosage and the length of time the drug was used for. Light to moderate users often experience anxiety, insomnia, sleep-related problems, and tremors whereas heavy use can cause severe withdrawal symptoms like delirium, psychosis, and hallucinations.<ref>https://www.ncbi.nlm.nih.gov/pubmed/11174231 | Gamma-hydroxybutyrate withdrawal syndrome.</ref><ref name="GHB" />

GHB, when used medicinally (two medicinal doses per day, four hours apart), creates little to no dependance while the more frequent one uses GHB, it causes exponentially more dependance and withdrawal symptoms.<ref>https://drugs-forum.com/threads/important-ghb-gbl-addiction-withdrawal.43390/page-4</ref>

Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed.<ref>Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence | http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.1997.tb03640.x/abstract</ref>

Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within several ~~weeks~~ of continuous use]]. 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. GHB presents cross-tolerance with [[1,4-Butanediol]] and [[GBL]], since these act as [[Prodrug|prodrugs]] for GHB. Cross-tolerance with [[alcohol]] and [[baclofen]] has been shown in rats.<ref>https://www.sciencedirect.com/science/article/pii/0014299994006873</ref><ref>https://www.sciencedirect.com/science/article/pii/S0014299906009964</ref>

Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within several days of continuous use]]. 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 to minimize neurotoxicity from withdrawal. It is proposed that GHB and especially GBL can lead to dependence at a significantly faster rate than longer-acting depressants.

GHB presents cross-tolerance with [[1,4-Butanediol]] and [[GBL]], since these act as [[Prodrug|prodrugs]] for GHB. Cross-tolerance with [[alcohol]] and [[baclofen]] has been shown in rats,<ref>https://www.sciencedirect.com/science/article/pii/0014299994006873</ref><ref>https://www.sciencedirect.com/science/article/pii/S0014299906009964</ref> and is likely with other GABAB-agonists.

===Dangerous interactions===

@@ Line 22: / Line 22: @@
 Activation of both the GHB receptor and [[GABA]]<sub>B</sub> is responsible for the addictive profile of GHB. GHB's effect on [[dopamine]] release is biphasic.<ref>Drosophila [[GABA]]<sub>B</sub> receptors are involved in behavioral effects of γ-hydroxybutyric acid (GHB) (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0014299905007442</ref> This means that while low concentrations stimulate [[dopamine]] release via the GHB receptor,<ref>A specific gamma-hydroxybutyrate receptor ligand possesses both antagonistic and [[anticonvulsant]] properties (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/2173754</ref> higher concentrations inhibit [[dopamine]] release via [[GABA]]<sub>B</sub> receptors.<ref>Tonic GABA-ergic modulation of striatal dopamine release studied by in vivo microdialysis in the freely moving rat (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/001429999500369V</ref> After an initial phase of inhibition, [[dopamine]] release is then increased via the GHB receptor.
-GHB induces the accumulation of either a derivative of [[tryptophan]] or [[tryptophan]] itself, possibly by increasing [[tryptophan]] transport across the blood–brain barrier. GHB-induced stimulation may be due to this increase in [[tryptophan]] transport to the brain and in its uptake by serotonergic cells. As the [[Serotonin|serotonergic]] system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.
+GHB induces the accumulation of either a derivative of tryptophan or [[tryptophan]] itself, possibly by increasing tryptophan transport across the blood–brain barrier. GHB-induced stimulation may be due to this increase in tryptophan transport to the brain and in its uptake by serotonergic cells. As the [[Serotonin|serotonergic]] system may be involved in the regulation of sleep, mood, and anxiety, the stimulation of this system by high doses of GHB may be involved in certain neuropharmacological events induced by GHB administration.
 These findings may explain the paradoxical mix of sedative and stimulatory properties of GHB as well as the so-called "rebound" effect reported by individuals using GHB as a sleeping agent wherein they awake suddenly after several hours of GHB-induced deep sleep. Over time, the concentration of GHB in the system decreases below the threshold for significant [[GABA]]<sub>B</sub> receptor activation and activates predominantly the GHB receptor, leading to wakefulness.
@@ Line 39: / Line 39: @@
 *'''[[Effect::Motor control loss]]'''
 *'''[[Effect::Nausea]]'''
+*'''[[Effect::Increased salivation]]''' - Increased salivation is very common.
+*'''[[Effect::Stomach cramps]]'''
 *'''[[Effect::Muscle cramps]]'''
 *'''[[Effect::Optical sliding]]'''
-*'''[[Effect::Increased salivation]]'''
 *'''[[Effect::Pupil dilation]]'''
+*'''[[Effect::Vasodilation]]'''
+*'''[[Effect::Headaches]]'''
+*'''[[Effect::Seizure]]''' - Very high dosages of GHB have consistently produced convulsions.
+}}
+{{effects/visual|
+*'''[[Effect::Visual acuity suppression]]'''
+*'''[[Effect::After images]]'''
+*'''[[Effect::Perspective distortions]]'''
+*'''[[Effect::Depth perception distortions]]'''
+*'''[[Effect::Scenery slicing]]'''
 }}
 |{{effects/cognitive|
+*'''[[Effect::Sleepiness]]''' & '''[[Effect::Wakefulness]]''' - At very low dosages, GHB can make one tired, while common doses are primarly wakefullness-promoting. High doses can lead to feelings of being extremely sleepy.
 *'''[[Effect::Analysis suppression]]'''
+*'''[[Effect::Disinhibition]]'''
 *'''[[Effect::Anxiety suppression]]'''
 *'''[[Effect::Cognitive euphoria]]''' - GHB produces intense states of euphoria comparable to that of [[cocaine]], [[MDMA]], and [[opiates]]. For this reason, it is sometimes called "liquid ecstasy". It is commonly described as a more euphoric and disinhibiting version of alcohol. While this may be accurate, it is also far easier to overdose on.
-*'''[[Effect::Disinhibition]]''' - Social and behavioral disinhibition on GHB is extremely powerful and perhaps its most prominent feature. Users are more liable to exhibit impaired decision-making and engage in risky activities such as unprotected sex or unsafe substance combinations. Users are advised to only take GHB in safe environments with people they trust not to take advantage of their vulnerable state.
+*'''[[Effect::Compulsive redosing]]''' - This is somewhat prevalent due to its short duration.
+*'''[[Effect::Creativity enhancement]]''' - Creativity enhancement is most apparent at low to common doses.
+*'''[[Effect::Disinhibition]]''' - Social and behavioral disinhibition on GHB is extremely powerful and perhaps its most prominent feature. Users are more liable to exhibit impaired decision-making and engage in risky activities such as unprotected sex or unsafe substance combinations. Users are advised to only take GHB in safe environments with people they trust not to take advantage of their vulnerable state.
+*'''[[Effect::Dream potentiation]]''' - GHB can have a very pronounced effect on dream recall and vividness. Conversely, discontinuation can result in bad dreams or nightmares. Additionally, intoxication on GBL can lead to one seeing their own dream being manifested, similar to a [[WILD|wake-induced lucid dream]] (WILD) and simultaneous states of wakefulness and dreaming.
 *'''[[Effect::Empathy, affection, and sociability enhancement]]''' - GHB presents strong [[entactogenic]] effects which, although weaker than that of [[MDMA]], are still prominent and well defined.
 *'''[[Effect::Immersion enhancement]]'''
-*'''[[Effect::Increased libido]]'''
+*'''[[Effect::Increased libido]]''' - GBL reportedly produces less increases of libido than [[GHB]] does.
 *'''[[Effect::Increased music appreciation]]'''
+*'''[[Effect::Introspection]]'''
+*'''[[Effect::Rejuvenation]]'''
+*'''[[Effect::Suggestibility enhancement]]'''
 *'''[[Effect::Memory suppression]]'''
 **'''[[Effect::Amnesia]]'''
-*'''[[Effect::Thought deceleration]]'''
+*'''[[Effect::Motivation enhancement]]''' & '''[[Effect::Motivation suppression]]''' - As with other coinciding effects, common doses can lead to greater motivation whilst high doses generally result in lethargy.
-*'''[[Effect::Spatial disorientation]]'''
+*'''[[Effect::Spatial disorientation]]''' - Disorientation is very common in dark areas.
 *'''[[Effect::Suggestibility enhancement]]'''
+*'''[[Effect::Thought acceleration]]''' or '''[[Effect::Thought deceleration]]''' - Low to common doses are primarly stimulating and one finds themselves constantly generating thoughts.
+}}
+{{effects/auditory|
+*'''[[Effect::Tinnitus]]'''
+*'''[[Effect::Auditory distortion]]'''
 }}
 }}
@@ Line 70: / Line 96: @@
 ==Toxicity and harm potential==
 [[File:harmchart.png|thumb|right|300px|Radar plot showing relative physical harm, social harm, and dependence of GHB<ref>Development of a rational scale to assess the harm of drugs of potential misuse (ScienceDirect) | http://www.sciencedirect.com/science/article/pii/S0140673607604644</ref>]]
-GHB is [[toxicity::considered to be a safe and non-toxic substance when used responsibly]] or medically. The [[LD50|LD<sub>50</sub>]] is above the active dosage, and there is no danger of acute toxicity. However, it can be dangerous when used as a recreational drug or abused. There have been many negative reports from recreational users who have overdosed, combined GHB with alcohol or other drugs, or accidentally dosed themselves unexpectedly.<ref>https://www.erowid.org/experiences/exp.php?ID=1926 | Erowid. "GHB Overdoses & Poisonings: An Experience with GHB (ID 1926)". Erowid.org. Jun 19, 2000. erowid.org/exp/1926 </ref>
+GHB is [[toxicity::considered to be a safe and non-toxic substance when used responsibly or medically]]. The [[LD50|LD<sub>50</sub>]] is above the active dosage, and there is no danger of acute toxicity. However, it can become dangerous when used as a recreational drug or abused. There have been many negative reports from recreational users who have overdosed, combined GHB with alcohol or other drugs, or accidentally dosed themselves unexpectedly.<ref>https://www.erowid.org/experiences/exp.php?ID=1926 | Erowid. "GHB Overdoses & Poisonings: An Experience with GHB (ID 1926)". Erowid.org. Jun 19, 2000. erowid.org/exp/1926 </ref>
 One publication investigated 226 deaths attributed to GHB.<ref>https://www.ncbi.nlm.nih.gov/pubmed/20825811 | Zvosec DL, Smith SW, Porrata T, Strobl AQ, Dyer JE (2011). "Case series of 226 gamma-hydroxybutyrate-associated deaths: lethal toxicity and trauma". The American Journal of Emergency Medicine 29 (3): 319–32.</ref> Seventy-one deaths (34%) were caused by GHB alone while the other deaths were from [[respiratory depression]] caused by interaction with alcohol or other drugs.
@@ Line 90: / Line 117: @@
 ===Tolerance and addiction potential===
 [[File:GHBwithdrawal2.png|350px|thumbnail|right|This table compares the withdrawal symptoms of GHB, [[benzodiazepines]], and [[alcohol]].<ref name="GHB">GHB Withdrawal Syndrome | Texas Commission on Alcohol and Drug Abuse | https://www.erowid.org/chemicals/ghb/ghb_addiction2.pdf</ref>]]
-GHB is [[Addiction potential::moderately physically and psychologically addictive]]. The frequent use of GHB can cause withdrawal symptoms similar to those caused by other [[depressants]] such as [[alcohol]] and [[benzodiazepines]] if abruptly discontinued.<ref>Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759403/</ref><ref>Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713368/</ref> These symptoms seem to depend on the dosage and the length of time the drug was used for. Light to moderate users often experience anxiety, insomnia, sleep-related problems, and tremors whereas heavy use can cause severe withdrawal symptoms like delirium, psychosis, and hallucinations.<ref>https://www.ncbi.nlm.nih.gov/pubmed/11174231 | Gamma-hydroxybutyrate withdrawal syndrome.</ref><ref name="GHB" />
+GHB is [[Addiction potential::moderately to highly physically and moderately psychologically addictive]]. The frequent use of GHB can cause withdrawal symptoms similar to those caused by other [[depressants]] such as [[alcohol]] and [[benzodiazepines]] if abruptly discontinued.<ref>Systematic Assessment of Gamma Hydroxybutyrate (GHB) Effects During and After Acute Intoxication (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759403/</ref><ref>Illicit gamma-hydroxybutyrate (GHB) and pharmaceutical sodium oxybate (Xyrem®): differences in characteristics and misuse (PubMed.gov / NCBI) | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2713368/</ref> These symptoms seem to depend on the dosage and the length of time the drug was used for.  Light to moderate users often experience anxiety, insomnia, sleep-related problems, and tremors whereas heavy use can cause severe withdrawal symptoms like delirium, psychosis, and hallucinations.<ref>https://www.ncbi.nlm.nih.gov/pubmed/11174231 | Gamma-hydroxybutyrate withdrawal syndrome.</ref><ref name="GHB" />
+GHB, when used medicinally (two medicinal doses per day, four hours apart), creates little to no dependance while the more frequent one uses GHB, it causes exponentially more dependance and withdrawal symptoms.<ref>https://drugs-forum.com/threads/important-ghb-gbl-addiction-withdrawal.43390/page-4</ref>
 Although there have been reported fatalities due to GHB withdrawal, reports are inconclusive and further research is needed.<ref>Gamma-hydroxybutyrate: an emerging drug of abuse that causes physical dependence | http://onlinelibrary.wiley.com/doi/10.1111/j.1360-0443.1997.tb03640.x/abstract</ref>
-Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within several weeks of continuous use]]. 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. GHB presents cross-tolerance with [[1,4-Butanediol]] and [[GBL]], since these act as [[Prodrug|prodrugs]] for GHB. Cross-tolerance with [[alcohol]] and [[baclofen]] has been shown in rats.<ref>https://www.sciencedirect.com/science/article/pii/0014299994006873</ref><ref>https://www.sciencedirect.com/science/article/pii/S0014299906009964</ref>
+Tolerance will develop to the sedative-hypnotic effects [[Time to full tolerance::within several days of continuous use]]. 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 to minimize neurotoxicity from withdrawal. It is proposed that GHB and especially GBL can lead to dependence at a significantly faster rate than longer-acting depressants.
+GHB presents cross-tolerance with [[1,4-Butanediol]] and [[GBL]], since these act as [[Prodrug|prodrugs]] for GHB. Cross-tolerance with [[alcohol]] and [[baclofen]] has been shown in rats,<ref>https://www.sciencedirect.com/science/article/pii/0014299994006873</ref><ref>https://www.sciencedirect.com/science/article/pii/S0014299906009964</ref> and is likely with other GABA<sub>B</sub>-agonists.
 ===Dangerous interactions===