This is an unofficial archive of PsychonautWiki as of 2025-08-08T03:33:20Z. Content on this page may be outdated, incomplete, or inaccurate. Please refer to the original page for the most up-to-date information.
'''Zolpidem '''(also known as '''Ambien''', '''Intermezzo''', '''Edluar''', '''Stilnoct''', '''Stilnox''', '''Zolpimist'''<ref name=":0">http://www.drugs.com/zolpidem.html | Zolpidem (Drugs.com)</ref>, and others) is a non-[[benzodiazepine]] [[hypnotic]] of the [[chemical class::imidazopyridine]] chemical class which is primarily used in the treatment of [[insomnia]].<ref name=":0" /><ref>Du, B., Shan, A., Zhong, X., Zhang, Y., Chen, D., & Cai, K. (2014). Zolpidem arouses patients in vegetative state after brain injury: quantitative evaluation and indications. The American Journal of the Medical Sciences, 347(3), 178-182. https://doi.org/10.1097/MAJ.0b013e318287c79c</ref>
'''Zolpidem '''(also known as '''Ambien''', '''Intermezzo''', '''Edluar''', '''Stilnoct''', '''Stilnox''', '''Zolpimist'''<ref name=":0">http://www.drugs.com/zolpidem.html | Zolpidem (Drugs.com)</ref>, and others) is a non-[[benzodiazepine]] [[hypnotic]] of the [[chemical class::imidazopyridine]] chemical class which is primarily used in the treatment of [[insomnia]].<ref name=":0" /><ref>{{cite journal | vauthors=((Du, B.)), ((Shan, A.)), ((Zhong, X.)), ((Zhang, Y.)), ((Chen, D.)), ((Cai, K.)) | journal=The American Journal of the Medical Sciences | title=Zolpidem Arouses Patients in Vegetative State After Brain Injury: Quantitative Evaluation and Indications | volume=347 | issue=3 | pages=178–182 | date= March 2014 | url=https://linkinghub.elsevier.com/retrieve/pii/S0002962915303827 | issn=00029629 | doi=10.1097/MAJ.0b013e318287c79c}}</ref>
When taken at recreational doses, it reportedly produces powerful and notoriously bizarre atypical [[psychoactive class::hallucinogen]]ic, [[dissociative]], [[deliriant]] and even [[psychedelic]] effects.
When taken at recreational doses, it reportedly produces powerful and notoriously bizarre atypical [[psychoactive class::hallucinogen]]ic, [[dissociative]], [[deliriant]] and even [[psychedelic]] effects.
Line 16:
Line 16:
GABA<sub>A</sub>-agonizing imidazopyridines such as zolpidem are often grouped with pyrazolopyrimidines, and cyclopyrrones under the label "nonbenzodiazepines" for their similar effects.
GABA<sub>A</sub>-agonizing imidazopyridines such as zolpidem are often grouped with pyrazolopyrimidines, and cyclopyrrones under the label "nonbenzodiazepines" for their similar effects.
Three syntheses of zolpidem are common. 4-methylacetophenone is used as a common precursor. This is brominated and reacted with 2-amino-5-methylpyridine to give the imidazopyridine. From here the reactions use a variety of reagents to complete the synthesis, either involving thionyl chloride or sodium cyanide. These reagents are challenging to handle and require thorough safety assessments.<ref>ohnson DS, Li JJ (2007). ''The art of drug synthesis''. Hoboken, N.J.: Wiley-Interscience. pp. Chapter 15, Section 2. ISBN <bdi>9780471752158</bdi>.</ref> Though such safety procedures are common in industry, they make clandestine manufacture difficult.
Three syntheses of zolpidem are common. 4-methylacetophenone is used as a common precursor. This is brominated and reacted with 2-amino-5-methylpyridine to give the imidazopyridine. From here the reactions use a variety of reagents to complete the synthesis, either involving thionyl chloride or sodium cyanide. These reagents are challenging to handle and require thorough safety assessments.<ref>{{cite book | veditors=((Johnson, D. S.)), ((Li, J. J.)) | date= 2007 | title=The art of drug synthesis | publisher=Wiley-Interscience | isbn=9780471752158}}</ref> Though such safety procedures are common in industry, they make clandestine manufacture difficult.
A number of major side-products of the sodium cyanide reaction have been characterised and include dimers and mannich products.<ref>Sumalatha Y (2009). "Synthesis and spectral characterization of zolpidem related substances - hypnotic agent". ''Arkivoc''. '''2009''' (7): 143–149. doi:10.3998/ark.5550190.0010.714.</ref>
A number of major side-products of the sodium cyanide reaction have been characterised and include dimers and mannich products.<ref>{{cite journal | vauthors=((Sumalatha, Y.)), ((Reddy, P. P.)), ((Reddy, R.)), ((Satyanarayana, B.)) | journal=Arkivoc | title=Synthesis and spectral characterization of zolpidem related substances - hypnotic agent | volume=2009 | issue=7 | pages=143–149 | date=7 April 2009 | url=https://www.arkat-usa.org/arkivoc-journal/browse-arkivoc/ark.5550190.0010.714 | issn=1551-7012 | doi=10.3998/ark.5550190.0010.714}}</ref>
==Pharmacology==
==Pharmacology==
Zolpidem interacts with the [[GABA]]-BZ [[receptor]] system<ref>Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763231/</ref> and shares some of the pharmacological properties of traditional [[benzodiazepines]].
Zolpidem interacts with the [[GABA]]-BZ [[receptor]] system<ref>{{cite journal | vauthors=((Kovacic, P.)), ((Somanathan, R.)) | journal=Oxidative Medicine and Cellular Longevity | title=Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation | volume=2 | issue=1 | pages=52–57 | date= 2009 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2763231/ | issn=1942-0900}}</ref> and shares some of the pharmacological properties of traditional [[benzodiazepines]].
In contrast to benzodiazepines, which non-selectively bind to and activate all BZ receptor subtypes among others, zolpidem binds to the BZ1 receptor preferentially with a high affinity ratio of the α1/α5 subunits. It's this selective binding in comparison to traditional benzodiazepines that gives zolpidem very weak [[anxiolytic]], [[muscle relaxant]], and [[anticonvulsant]] properties but very strong [[hypnotic]] or [[sedative]] properties.<ref>Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. | https://www.ncbi.nlm.nih.gov/pubmed/8521677</ref>
In contrast to benzodiazepines, which non-selectively bind to and activate all BZ receptor subtypes among others, zolpidem binds to the BZ1 receptor preferentially with a high affinity ratio of the α1/α5 subunits. It's this selective binding in comparison to traditional benzodiazepines that gives zolpidem very weak [[anxiolytic]], [[muscle relaxant]], and [[anticonvulsant]] properties but very strong [[hypnotic]] or [[sedative]] properties.<ref>{{cite journal | vauthors=((Salvà, P.)), ((Costa, J.)) | journal=Clinical Pharmacokinetics | title=Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications | volume=29 | issue=3 | pages=142–153 | date= September 1995 | issn=0312-5963 | doi=10.2165/00003088-199529030-00002}}</ref>
As the GABA site is the most prolific inhibitory receptor set within the brain, its modulation results in the [[sedating]] (or [[anxiety suppression|calming effects]]) of zolpidem on the nervous system.
As the GABA site is the most prolific inhibitory receptor set within the brain, its modulation results in the [[sedating]] (or [[anxiety suppression|calming)]] effects of zolpidem on the nervous system.
In regards to how the consumption of this compound results in its bizarre hallucinations, the pharmacological mechanics behind this are not understood and do not seem to have been directly studied. It is worth noting, however, that zolpidem may share similar mechanisms as a [[GABA]]<sub>A</sub> receptor [[agonist]] to that of [[muscimol]], which is the active compound within the hallucinogenic [[amanita muscaria]] mushroom.
In regards to how the consumption of this compound results in its bizarre hallucinations, the pharmacological mechanics behind this are not understood and do not seem to have been directly studied. It is worth noting, however, that zolpidem impact on regional activity may overlap with that of other hallucinogenic GABAergic drugs such as [[muscimol]], the active compound within the hallucinogenic [[amanita muscaria]] mushroom.
==Subjective effects==
==Subjective effects==
The subjective effects of zolpidem seem to vary wildly between individuals with certain users experiencing a complete lack of hallucinations whilst others experience them even at lower dosages. Generally, a recreational zolpidem dose has features comparable to [[DXM]], [[DPH]], [[alprazolam]] and [[psilocin]].
The subjective effects of zolpidem seem to vary wildly between individuals with certain users experiencing a complete lack of hallucinations whilst others experience them even at lower dosages. Generally, a recreational zolpidem dose has features comparable to [[DXM]], [[DPH]], [[alprazolam]] and [[psilocin]]. It is also quite similar to the hallucinogen [[amanita muscaria]].
It contains many of the physical and cognitive effects of [[benzodiazepines]] with a moderately [[dissociative#subjective effects|dissociated]] headspace most similar to that of [[DXM]]. This occurs alongside bizarre thought patterns and [[external hallucinations]] similar to those of [[deliriants]] and [[visual distortions]] most similar to those of [[psychedelics]]. Overall, this makes zolpidem an extremely unique and unpredictable [[hallucinogen]] which requires a [[trip sitter]].
It contains many of the physical and cognitive effects of [[benzodiazepines]] with a moderately [[dissociative#subjective effects|dissociated]] headspace most similar to that of [[DXM]]. This occurs alongside bizarre thought patterns and [[external hallucinations]] similar to those of [[deliriants]] and [[visual distortions]] most similar to those of [[psychedelics]]. Overall, this makes zolpidem an extremely unique and unpredictable [[hallucinogen]] which it is strongly recommended to have a [[trip sitter]].
{{Preamble/SubjectiveEffects}}
{{Preamble/SubjectiveEffects}}
Line 43:
Line 43:
* '''[[Effect::Sedation]]''' - The sedation present within this compound is significantly stronger than that of other [[GABAergic]] [[depressant]] when proportionally compared to their other effects. This is why zolpidem is commonly prescribed as a sleep aid to those who struggle with insomnia.
* '''[[Effect::Sedation]]''' - The sedation present within this compound is significantly stronger than that of other [[GABAergic]] [[depressant]] when proportionally compared to their other effects. This is why zolpidem is commonly prescribed as a sleep aid to those who struggle with insomnia.
*'''[[Effect::Physical euphoria]]''' - This manifests itself as a warm, soft glow which emanates from the center of the user's body.
*'''[[Effect::Physical euphoria]]''' - This manifests itself as a warm, soft glow which emanates from the center of the user's body.
*'''[[Effect::Appetite enhancement]]''' - Many users of zolpidem report binge eating bizarre mixtures of various foods while they are "asleep" with little or no memory of the activity upon waking up.<ref>Ambien Linked to 'Sleep Eating' | http://www.webmd.com/sleep-disorders/news/20060315/ambien-linked-to-sleep-eating</ref> This likely occurs as a result of zolpidem's cognitive effects such as [[disinhibition]] and [[amnesia]].
*'''[[Effect::Appetite enhancement]]''' - Many users of zolpidem report binge eating bizarre mixtures of various foods while they are "asleep" with little or no memory of the activity upon waking up.<ref>{{Citation | vauthors=((DeNoon, D. J.)) | title=Ambien Linked to “Sleep Eating” | url=https://www.webmd.com/sleep-disorders/news/20060315/ambien-linked-to-sleep-eating}}</ref> This likely occurs as a result of zolpidem's cognitive effects such as [[disinhibition]] and [[amnesia]].
*'''[[Effect::Changes in felt gravity]]''' - This is not as strong or apparent as it is with [[dissociatives]] or [[salvia]].
*'''[[Effect::Changes in felt gravity]]''' - This is not as strong or apparent as it is with [[dissociatives]] or [[salvia]].
*'''[[Effect::Drifting]]''' - At heavier dosages, this compound may induce the experience of scenery, walls, objects and people appearing to melt and distort in a manner which is comparable to traditional [[psychedelic]]s such as [[psilocin]] or [[LSD]].
*'''[[Effect::Drifting]]''' - At heavier dosages, this compound may induce the experience of scenery, walls, objects and people appearing to melt and distort in a manner which is comparable to traditional [[psychedelic]]s such as [[psilocin]] or [[LSD]].
*'''[[Effect::Geometry]]''' - The geometry produced by zolpidem shares similarities with [[DXM]] and genereally shifts between jitteriness and static.
*'''[[Effect::Geometry]]''' - The geometry produced by zolpidem shares similarities with [[DXM]] and generally shifts between jitteriness and static.
*'''[[Effect::Internal hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - The internal hallucinations present on this compound can be described as vivid dream-like states similar in style to that of [[deliriants]]. This effect typically occurs briefly and spontaneously at moderate dosages but becomes progressively extended in its occurrence and duration proportional to dosage consumed before eventually becoming all-encompassing. It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, interactive in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style.
*'''[[Effect::Internal hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - The internal hallucinations present on this compound can be described as vivid dream-like states similar in style to that of [[deliriants]]. This effect typically occurs briefly and spontaneously at moderate dosages but becomes progressively extended in its occurrence and duration proportional to dosage consumed before eventually becoming all-encompassing. It can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, interactive in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style.
*'''[[Effect::External hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - In comparison to other classes of [[hallucinogen]], this effect exclusively occurs at heavy dosages and is comparable to [[deliriant]]s such as [[DPH]] and [[datura]]. This effect can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, autonomous in controllability and solid in style. The most common themes for these hallucinations include those of both everyday occurrences such as talking to people who are not there and impossible occurrences such as inanimate objects coming to life or [[shadow people]].
*'''[[Effect::External hallucination]]''' (''[[effect::autonomous entities]]''; ''[[effect::settings, sceneries, and landscapes]]''; ''[[effect::perspective hallucinations]]'' and ''[[effect::scenarios and plots]]'') - In comparison to other classes of [[hallucinogen]], this effect exclusively occurs at heavy dosages and is comparable to [[deliriant]]s such as [[DPH]] and [[datura]]. This effect can be comprehensively described through its [[Visual_effects:_Internal_hallucinations#Variations|variations]] as delirious in believability, autonomous in controllability and solid in style. The most common themes for these hallucinations include those of both everyday occurrences such as talking to people who are not there and impossible occurrences such as inanimate objects coming to life or [[shadow people]].
Line 93:
Line 93:
*'''[[Effect::Cognitive euphoria]]'''
*'''[[Effect::Cognitive euphoria]]'''
*'''[[Effect::Psychosis]]'''
*'''[[Effect::Psychosis]]'''
*'''[[Effect::Delusion]]'''<ref>Ambien, delusions, and violence: Is there a link? | https://www.psychologytoday.com/blog/the-measure-madness/201005/ambien-delusions-and-violence-is-there-link</ref><ref>Ambien Side Effects Center (rxlist) | http://www.rxlist.com/ambien-side-effects-drug-center.htm</ref> - At heavier dosages, this effect may become present in a manner which is comparable to traditional deliriants. It is often accompanied by [[external hallucinations]] which tend to reinforce one's belief of the delusion.
*'''[[Effect::Delusion]]'''<ref>{{Citation | title=Ambien, delusions, and violence: Is there a link?, Psychology Today | url=https://www.psychologytoday.com/us/blog/the-measure-madness/201005/ambien-delusions-and-violence-is-there-link}}</ref><ref>{{Citation | title=Side Effects of Ambien (Zolpidem Tartrate), Warnings, Uses | url=https://www.rxlist.com/ambien-side-effects-drug-center.htm}}</ref> - At heavier dosages, this effect may become present in a manner which is comparable to traditional deliriants. It is often accompanied by [[external hallucinations]] which tend to reinforce one's belief of the delusion.
*'''[[Effect::Delusions|Delusions of sobriety]]''' - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages. Experience reports indicate that zolpidem may provoke these delusions in equal or greater strength than benzodiazepines.
*'''[[Effect::Delusions|Delusions of sobriety]]''' - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages. Experience reports indicate that zolpidem may provoke these delusions in equal or greater strength than benzodiazepines.
*'''[[Effect::Disinhibition]]'''
*'''[[Effect::Disinhibition]]'''
Line 131:
Line 131:
==Toxicity and harm potential==
==Toxicity and harm potential==
{{Further|Responsible use#Hallucinogens}}
{{Further|Responsible use#Hallucinogens}}
Zolpidem has a [[Toxicity::low toxicity]] relative to dose.<ref>zolpidem | C19H21N3O - PubChem | https://pubchem.ncbi.nlm.nih.gov/compound/zolpidem#section=Biological-Half-Life</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]].
Zolpidem has a [[Toxicity::low toxicity]] relative to dose.<ref>{{Citation | vauthors=PubChem | title=Zolpidem | url=https://pubchem.ncbi.nlm.nih.gov/compound/5732}}</ref> However, it is [[Toxicity::potentially [[respiratory depression|lethal]] when mixed with [[depressants]] like [[alcohol]] or [[opioids]]]].
Zolpidem has been reported to cause [[psychosis]], [[delusions]] and delirium at a significantly higher rate than other [[hallucinogens]] like [[LSD]], [[ketamine]], or [[DMT]]. There are a large number of experience reports online which describe states of delirium, amnesia, bizarre behavior,<ref>/r/ambien (reddit) | https://www.reddit.com/r/ambien/top/</ref> sleep walking,<ref>Zolpidem-Induced Sleepwalking, Sleep Related Eating Disorder, and Sleep-Driving: Fluorine-18-Flourodeoxyglucose Positron Emission Tomography Analysis, and a Literature Review of Other Unexpected Clinical Effects of Zolpidem (NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762721/</ref> driving while impaired<ref>Zolpidem-Induced Sleepwalking, Sleep Related Eating Disorder, and Sleep-Driving: Fluorine-18-Flourodeoxyglucose Positron Emission Tomography Analysis, and a Literature Review of Other Unexpected Clinical Effects of Zolpidem (NCBI) | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762721/</ref><ref>http://www.nhcriminaldefense.com/auto_accident_injury.html</ref> and other serious consequences after abusing the drug. In many cases this has resulted in hospitalization, arrests,<ref>Passengers recount horror as Air Force vet threatens to bring down transatlantic Delta flight (ny daily news) | http://www.nydailynews.com/news/national/passengers-recount-horror-air-force-vet-threatens-bring-transatlantic-delta-flight-article-1.169677</ref> car crashes,<ref>Kerry Kennedy Says Ambien 'Overtook' Her, Causing Car Crash (ABC NEWS) | http://abcnews.go.com/US/kerry-kennedy-ambien-overtook-causing-car-crash/story?id=22679672</ref> lengthy court cases and even death.<ref>http://www.huffingtonpost.com/2014/01/15/ambien-side-effect-sleepwalking-sleep-aid_n_4589743.html</ref>
Zolpidem has been reported to cause [[psychosis]], [[delusions]] and delirium at a significantly higher rate than other [[hallucinogens]] like [[LSD]], [[ketamine]], or [[DMT]]. There are a large number of experience reports online which describe states of delirium, amnesia, bizarre behavior,<ref>/r/ambien (reddit) | https://www.reddit.com/r/ambien/top/</ref> sleep walking,<ref name="Hoque2009">{{cite journal | vauthors=((Hoque, R.)), ((Chesson, A. L.)) | journal=Journal of Clinical Sleep Medicine : JCSM : Official Publication of the American Academy of Sleep Medicine | title=Zolpidem-Induced Sleepwalking, Sleep Related Eating Disorder, and Sleep-Driving: Fluorine-18-Flourodeoxyglucose Positron Emission Tomography Analysis, and a Literature Review of Other Unexpected Clinical Effects of Zolpidem | volume=5 | issue=5 | pages=471–476 | date=15 October 2009 | url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762721/ | issn=1550-9389}}</ref> driving while impaired<ref name="Hoque2009" /><ref>http://www.nhcriminaldefense.com/auto_accident_injury.html</ref> and other serious consequences after abusing the drug. In many cases this has resulted in hospitalization, arrests,<ref>{{Citation | title=Passengers recount horror as Air Force vet threatens to bring down transatlantic Delta flight | url=https://www.nydailynews.com/news/national/passengers-recount-horror-air-force-vet-threatens-bring-transatlantic-delta-flight-article-1.169677}}</ref> car crashes,<ref>{{Citation | vauthors=((News, A. B. C.)) | title=Kerry Kennedy Says Ambien “Overtook” Her, Causing Car Crash | url=https://abcnews.go.com/US/kerry-kennedy-ambien-overtook-causing-car-crash/story?id=22679672}}</ref> lengthy court cases and even death.<ref>{{Citation | year=2014 | title=The Disturbing Side Effect Of The No. 1 Prescription Sleep Aid | url=https://www.huffpost.com/entry/ambien-side-effect-sleepwalking-sleep-aid_n_4589743}}</ref>
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] and have a [[trip sitter]] when using this drug.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] and have a [[trip sitter]] when using this drug.
===Tolerance and addiction potential===
===Tolerance and addiction potential===
Zolpidem is [[Addiction potential::moderately addictive]]. A review of 36 human case reports found that reported dependence to zolpidem was lower than that of benzodiazepines.<ref>Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data - http://onlinelibrary.wiley.com/doi/10.1046/j.1360-0443.2003.00491.x/abstract?userIsAuthenticated=false&deniedAccessCustomisedMessage=</ref>
Zolpidem is [[Addiction potential::moderately addictive]]. A review of 36 human case reports found that reported dependence to zolpidem was lower than that of benzodiazepines.<ref>{{cite journal | vauthors=((Hajak, G.)), ((Müller, W. E.)), ((Wittchen, H. U.)), ((Pittrow, D.)), ((Kirch, W.)) | journal=Addiction | title=Abuse and dependence potential for the non-benzodiazepine hypnotics zolpidem and zopiclone: a review of case reports and epidemiological data: Abuse and dependence of zolpidem and zopiclone | volume=98 | issue=10 | pages=1371–1378 | date= October 2003 | url=http://doi.wiley.com/10.1046/j.1360-0443.2003.00491.x | issn=09652140 | doi=10.1046/j.1360-0443.2003.00491.x}}</ref>
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.<ref>Zolpidem at Supratherapeutic Doses can Cause Drug
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.<ref name="Sethi2005">{{cite journal | vauthors=((Sethi, P. K.)), ((Khandelwal, D. C.)) | journal=The Journal of the Association of Physicians of India | title=Zolpidem at supratherapeutic doses can cause drug abuse, dependence and withdrawal seizure | volume=53 | pages=139–140 | date= February 2005 | issn=0004-5772}}</ref> For more information on tapering from zolpidem in a controlled manner, please see [http://www.benzo.org.uk/manual/bzcha02.htm this guide] while keeping in mind it is intended for benzodiazepines.
Abuse, Dependence and Withdrawal Seizure - http://www.japi.org/february2005/CR-139.pdf</ref> For more information on tapering from zolpidem in a controlled manner, please see [http://www.benzo.org.uk/manual/bzcha02.htm this guide] while keeping in mind it is intended for benzodiazepines.
Although dependence builds up more slowly than in benzodiazepines, discontinuation from regular recreational doses of zolpidem appear to be as difficult as [[Benzodiazepine#Discontinuation|benzodiazepine discontinuation]];<ref>Zolpidem at Supratherapeutic Doses can Cause Drug
Although dependence builds up more slowly than in benzodiazepines, discontinuation from regular recreational doses of zolpidem appear to be as difficult as [[Benzodiazepine#Discontinuation|benzodiazepine discontinuation]];<ref name="Sethi2005" /> it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[hypertension]], [[seizures]], and death.<ref>{{cite journal | vauthors=((Lann, M. A.)), ((Molina, D. K.)) | journal=The American Journal of Forensic Medicine and Pathology | title=A fatal case of benzodiazepine withdrawal | volume=30 | issue=2 | pages=177–179 | date= June 2009 | issn=1533-404X | doi=10.1097/PAF.0b013e3181875aa0}}</ref> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
Abuse, Dependence and Withdrawal Seizure - http://www.japi.org/february2005/CR-139.pdf</ref> it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of [[hypertension]], [[seizures]], and death.<ref>A fatal case of benzodiazepine withdrawal. (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/19465812</ref> Drugs which lower the seizure threshold such as [[tramadol]] should be avoided during withdrawal.
===Dangerous interactions===
===Dangerous interactions===
Line 151:
Line 149:
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]], [[benzodiazepines]]'')- This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
*'''[[Depressants]]''' (''[[1,4-Butanediol]], [[2-methyl-2-butanol]], [[alcohol]], [[barbiturates]], [[GHB]]/[[GBL]], [[methaqualone]], [[opioids]], [[benzodiazepines]]'')- This combination can result in dangerous or even fatal levels of [[respiratory depression]]. These substances potentiate the [[muscle relaxation]], [[sedation]] and [[amnesia]] caused by one another and can lead to unexpected loss of consciousness at high doses. There is also an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
*'''[[Dissociatives]]''' - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
*'''[[Dissociatives]]''' - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the [[recovery position]] or have a friend move them into it.
*'''[[Stimulants]]''' - It is dangerous to combine zolpidem with [[stimulant]]s due to the risk of excessive intoxication. Stimulants decrease the [[sedation|sedative]] effect of zolpidem, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of zolpidem will be significantly increased, leading to intensified [[disinhibition]] as well as [[Zolpidem#Subjective effects|other effects]]. If combined, one should strictly limit themselves to only dosing a certain amount of zolpidem per hour. This combination can also potentially result in severe dehydration if hydration is not monitored.
*'''[[Stimulants]]''' - It is dangerous to combine zolpidem with [[stimulant]]s due to the risk of excessive intoxication. Stimulants decrease the [[sedation|sedative]] effect of zolpidem, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of zolpidem will be significantly increased, leading to intensified [[disinhibition]] as well as [[Zolpidem#Subjective effects|other effects]]. If combined, one should strictly limit themselves to only dosing a certain amount of zolpidem every few hours at minimum. This combination can also potentially result in severe dehydration if hydration is not monitored.
==Legal status==
==Legal status==
Line 158:
Line 156:
*'''Australia:''' Zolpidem is only available by prescription.{{citation needed}}
*'''Australia:''' Zolpidem is only available by prescription.{{citation needed}}
*'''Canada:''' Zolpidem is only available by prescription.{{citation needed}}
*'''Canada:''' Zolpidem is only available by prescription.{{citation needed}}
*'''Germany:''' Zolpidem is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form. There is an exception for oral preperations, containing up to 8,5mg zolpidem per unit, which can be prescribed on a regular prescription form.<ref>http://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html</ref>
*'''China:''' Zolpidem is a controlled Class II psychotropic substances.<ref>《麻醉药品和精神药品品种目录（2023版）》-国有资产管理处 (tjnu.edu.cn)</ref> Prescriptions for psychotropic substances in Class II are generally limited to a 7-day supply.<ref>卫生部关于印发《麻醉药品、精神药品处方管理规定》的通知 麻醉药品、精神药品处方管理规定__2006年第28号国务院公报_中国政府网 (www.gov.cn)</ref>
*'''Germany:''' Zolpidem is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form. There is an exception for oral preperations, containing up to 8,5mg zolpidem per unit, which can be prescribed on a regular prescription form.<ref>{{Citation | title=Anlage III BtMG - Einzelnorm | url=http://www.gesetze-im-internet.de/btmg_1981/anlage_iii.html}}</ref>
*'''Netherlands:''' Zolpidem is only available by prescription.{{citation needed}}
*'''Netherlands:''' Zolpidem is only available by prescription.{{citation needed}}
*'''Russia:''' In Russia, since 2013, zolpidem is a Schedule III controlled substance.<ref>Постановление Правительства РФ от 04.02.2013 N 78 | https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=141744&dst=100002&date=02.12.2019</ref>
*'''Russia:''' In Russia, since 2013, zolpidem is a Schedule III controlled substance.<ref>{{Citation | title=Постановление Правительства РФ от 04.02.2013 N 78 “О внесении изменений в некоторые акты Правительства Российской Федерации” - КонсультантПлюс | url=https://www.consultant.ru/cons/cgi/online.cgi?req=doc&base=LAW&n=141744&dst=100002&date=02.12.2019}}</ref>
*'''Switzerland''': Zolpidem is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''Switzerland''': Zolpidem is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.<ref>{{cite web|url=https://www.admin.ch/opc/de/classified-compilation/20101220/index.html|title=Verordnung des EDI über die Verzeichnisse der Betäubungsmittel, psychotropen Stoffe, Vorläuferstoffe und Hilfschemikalien|publisher=Bundeskanzlei [Federal Chancellery of Switzerland]|access-date=January 1, 2020|language=de}}</ref>
*'''United Kingdom:''' Zolpidem has been a class C drug in the UK since 2003.<ref>The Misuse of Drugs Act 1971 (Modification) Order 2003 (Legislation.gov.uk) | http://www.legislation.gov.uk/uksi/2003/1243/contents/made</ref> It is illegal to possess (without a legitimate prescription), supply, produce or import.{{citation needed}}
*'''The Netherlands''': Zolpidem is a List 2 substance of the Opium Law.<ref>{{Citation|title=Opiumwet, Lijst II (Dutch) | year=2023|url=https://wetten.overheid.nl/BWBR0001941/2023-09-12#BijlageII}}</ref>
*'''United Kingdom:''' Zolpidem has been a class C drug in the UK since 2003.<ref>{{Citation | title=The Misuse of Drugs Act 1971 (Modification) Order 2003 | url=https://www.legislation.gov.uk/uksi/2003/1243/contents/made}}</ref> It is illegal to possess (without a legitimate prescription), supply, produce or import.{{citation needed}}
*'''United States:''' Zolpidem is listed as a Schedule IV drug due to evidence that the drug has addictive properties similar to [[benzodiazepines]].{{citation needed}}
*'''United States:''' Zolpidem is listed as a Schedule IV drug due to evidence that the drug has addictive properties similar to [[benzodiazepines]].{{citation needed}}
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section.
DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Zolpidem (also known as Ambien, Intermezzo, Edluar, Stilnoct, Stilnox, Zolpimist[2], and others) is a non-benzodiazepinehypnotic of the imidazopyridine chemical class which is primarily used in the treatment of insomnia.[2][3]
Zolpidem is a member of a family colloquially known as a "Z-drug." Other Z-drugs include zaleplon (Sonata) and zopiclone (Imovane). These drugs were initially thought to be less addictive and/or habit-forming than benzodiazepines. However, this evaluation has shifted in the last few years as cases of addiction and habituation have accumulated.[citation needed]
Zolpidem should not be taken on a full stomach and it is recommended on a short-term basis only. Daily or continuous use of the drug is not usually advised.
Zolpidem is a hypnotic nonbenzodiazepine drug of the imidazopyridine class. This class of drugs is named for having an imidazole constituent, a five-membered ring with two non-adjacent nitrogen constituents fused to a pyridine ring, a six-membered nitrogenous ring which shares a nitrogen with the imidazole group.
GABAA-agonizing imidazopyridines such as zolpidem are often grouped with pyrazolopyrimidines, and cyclopyrrones under the label "nonbenzodiazepines" for their similar effects.
Three syntheses of zolpidem are common. 4-methylacetophenone is used as a common precursor. This is brominated and reacted with 2-amino-5-methylpyridine to give the imidazopyridine. From here the reactions use a variety of reagents to complete the synthesis, either involving thionyl chloride or sodium cyanide. These reagents are challenging to handle and require thorough safety assessments.[4] Though such safety procedures are common in industry, they make clandestine manufacture difficult.
A number of major side-products of the sodium cyanide reaction have been characterised and include dimers and mannich products.[5]
Pharmacology
Zolpidem interacts with the GABA-BZ receptor system[6] and shares some of the pharmacological properties of traditional benzodiazepines.
In contrast to benzodiazepines, which non-selectively bind to and activate all BZ receptor subtypes among others, zolpidem binds to the BZ1 receptor preferentially with a high affinity ratio of the α1/α5 subunits. It's this selective binding in comparison to traditional benzodiazepines that gives zolpidem very weak anxiolytic, muscle relaxant, and anticonvulsant properties but very strong hypnotic or sedative properties.[7]
As the GABA site is the most prolific inhibitory receptor set within the brain, its modulation results in the sedating (or calming) effects of zolpidem on the nervous system.
In regards to how the consumption of this compound results in its bizarre hallucinations, the pharmacological mechanics behind this are not understood and do not seem to have been directly studied. It is worth noting, however, that zolpidem impact on regional activity may overlap with that of other hallucinogenic GABAergic drugs such as muscimol, the active compound within the hallucinogenic amanita muscaria mushroom.
Subjective effects
The subjective effects of zolpidem seem to vary wildly between individuals with certain users experiencing a complete lack of hallucinations whilst others experience them even at lower dosages. Generally, a recreational zolpidem dose has features comparable to DXM, DPH, alprazolam and psilocin. It is also quite similar to the hallucinogen amanita muscaria.
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 PsychonautWikicontributors. 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 ☠.
Physical effects
The physical effects of zolpidem are almost identical to that of benzodiazepines such as alprazolam, although with less intensive muscle relaxation. They can be broken down into several components.
These are described below and generally include:
Sedation - The sedation present within this compound is significantly stronger than that of other GABAergicdepressant when proportionally compared to their other effects. This is why zolpidem is commonly prescribed as a sleep aid to those who struggle with insomnia.
Physical euphoria - This manifests itself as a warm, soft glow which emanates from the center of the user's body.
Appetite enhancement - Many users of zolpidem report binge eating bizarre mixtures of various foods while they are "asleep" with little or no memory of the activity upon waking up.[8] This likely occurs as a result of zolpidem's cognitive effects such as disinhibition and amnesia.
Nausea - At moderate to heavy dosages, a slight discomfort may be felt in the stomach. This will go away once the user has vomited.
Muscle relaxation - Although muscle relaxation is definitely present, it usually only manifests itself at heavier dosages and is significantly weaker than that of benzodiazepines.
Visual disconnection - This effect is only present at moderate to heavy recreational dosages and is comparable to that of a dissociatives such as DXM and ketamine. It commonly 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 end visual disconnection such as holes, spaces and voids or hallucinatory structures in the same way that traditional dissociatives are. This is likely due to the way in which zolpidem's sedative effects render the user unconscious at dosages far lower than one could consume to reach such a state.
Consciousness disconnection - This effect is only present at moderate to heavy recreational dosages and is comparable to that of dissociatives such as DXM and ketamine. However, it is not capable of higher end cognitive disconnection in the same way that dissociatives are. This is likely due to the way in which zolpidem's sedative effects render the user unconscious at dosages far lower than one could consume to reach such a state.
Visual effects
The visual effects of zolpidem are comparable to that of certain aspects deliriants, dissociatives and psychedelics. At lower dosages, these effects manifest as simple visual suppressions but at higher doses, they may escalate into full-blown complex hallucinatory states of a bizarre and unique nature.
Double vision - Double vision produced by zolpidem may apply to the whole field of view or alternatively on single or multiple objects only, sometimes alongside transformations.
Drifting - At heavier dosages, this compound may induce the experience of scenery, walls, objects and people appearing to melt and distort in a manner which is comparable to traditional psychedelics such as psilocin or LSD.
Geometry - The geometry produced by zolpidem shares similarities with DXM and generally shifts between jitteriness and static.
Internal hallucination (autonomous entities; settings, sceneries, and landscapes; perspective hallucinations and scenarios and plots) - The internal hallucinations present on this compound can be described as vivid dream-like states similar in style to that of deliriants. This effect typically occurs briefly and spontaneously at moderate dosages but becomes progressively extended in its occurrence and duration proportional to dosage consumed before eventually becoming all-encompassing. It can be comprehensively described through its variations as delirious in believability, interactive in style, equal in new experiences and memory replays in content, autonomous in controllability and solid in style.
The cognitive effects of zolpidem are comparable to that of benzodiazepines although with less intensive anxiety suppression. At heavier more recreational dosages, additional effects which are usually associated with deliriants may become present. These include thought disorganization and delusions. The specific effects can be broken down into several components.
These are described below and generally include:
Amnesia - The amnesia following zolpidem varies greatly between people with some people not experiencing this effect as much while others experience complete blackouts for extended periods of time even at low or therapeutic dosages. There have been many cases of bizarre behavior where people can't recall the entire event.
Anxiety suppression - Although anxiety suppression is definitely present, it usually only manifests itself at heavier dosages and is significantly weaker than that of benzodiazepines.
Delusion[9][10] - At heavier dosages, this effect may become present in a manner which is comparable to traditional deliriants. It is often accompanied by external hallucinations which tend to reinforce one's belief of the delusion.
Delusions of sobriety - This is the false belief that one is perfectly sober despite obvious evidence to the contrary such as severe cognitive impairment and an inability to fully communicate with others. It most commonly occurs at heavy dosages. Experience reports indicate that zolpidem may provoke these delusions in equal or greater strength than benzodiazepines.
Language suppression - At heavier dosages of zolpidem, one may find that they have a distinct difficulty vocalizing their thoughts in a coherent manner.
Short-term memory suppression - At heavier dosages, many users find that they cannot recall things from 10 or 30 seconds ago due to suppression of their short-term memory. This can potentially lead to confusion, repetitive behaviour and thought loops.
Thought disorganization - This effect is present at heavier dosages and tends to synergise with disinihibition and delusions in a manner which results in bizarre decision-making processes or thought processes which are often out of character and make little to no sense once the user has sobered up from the experience.
Auditory hallucination - At heavier dosages, one may experience the perception of imagined sounds such as voices or music, sometimes incorporated into ambient sounds or music. These are often accompanied by external hallucinations and delusions.
Zolpidem has a low toxicity relative to dose.[11] However, it is [[Toxicity::potentially lethal when mixed with depressants like alcohol or opioids]].
Zolpidem has been reported to cause psychosis, delusions and delirium at a significantly higher rate than other hallucinogens like LSD, ketamine, or DMT. There are a large number of experience reports online which describe states of delirium, amnesia, bizarre behavior,[12] sleep walking,[13] driving while impaired[13][14] and other serious consequences after abusing the drug. In many cases this has resulted in hospitalization, arrests,[15] car crashes,[16] lengthy court cases and even death.[17]
Zolpidem is moderately addictive. A review of 36 human case reports found that reported dependence to zolpidem was lower than that of benzodiazepines.[18]
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.[19] For more information on tapering from zolpidem in a controlled manner, please see this guide while keeping in mind it is intended for benzodiazepines.
Although dependence builds up more slowly than in benzodiazepines, discontinuation from regular recreational doses of zolpidem appear to be as difficult as benzodiazepine discontinuation;[19] it is potentially life-threatening for individuals using regularly to discontinue use without tapering their dose over a period of weeks. There is an increased risk of hypertension, seizures, and death.[20] Drugs which lower the seizure threshold such as tramadol should be avoided during withdrawal.
Dangerous interactions
Although many drugs are safe on their own, they can become dangerous and even life-threatening when combined with other substances. The list below contains some common potentially dangerous combinations, but may not include all of them. Certain combinations may be safe in low doses of each but still increase the potential risk of death. Independent research should always be done to ensure that a combination of two or more substances is safe before consumption.
Dissociatives - This combination can result in an increased risk of vomiting during unconsciousness and death from the resulting suffocation. If this occurs, users should attempt to fall asleep in the recovery position or have a friend move them into it.
Stimulants - It is dangerous to combine zolpidem with stimulants due to the risk of excessive intoxication. Stimulants decrease the sedative effect of zolpidem, which is the main factor most people consider when determining their level of intoxication. Once the stimulant wears off, the effects of zolpidem will be significantly increased, leading to intensified disinhibition as well as other effects. If combined, one should strictly limit themselves to only dosing a certain amount of zolpidem every few hours at minimum. This combination can also potentially result in severe dehydration if hydration is not monitored.
Legal status
Internationally, zolpidem is a Schedule IV substance under the Convention on Psychotropic Substances.[21]
Australia: Zolpidem is only available by prescription.[citation needed]
Canada: Zolpidem is only available by prescription.[citation needed]
China: Zolpidem is a controlled Class II psychotropic substances.[22] Prescriptions for psychotropic substances in Class II are generally limited to a 7-day supply.[23]
Germany: Zolpidem is a controlled substance under Anlage III of the BtMG. It can only be prescribed on a narcotic prescription form. There is an exception for oral preperations, containing up to 8,5mg zolpidem per unit, which can be prescribed on a regular prescription form.[24]
Netherlands: Zolpidem is only available by prescription.[citation needed]
Russia: In Russia, since 2013, zolpidem is a Schedule III controlled substance.[25]
Switzerland: Zolpidem is a controlled substance specifically named under Verzeichnis B. Medicinal use is permitted.[26]
The Netherlands: Zolpidem is a List 2 substance of the Opium Law.[27]
United Kingdom: Zolpidem has been a class C drug in the UK since 2003.[28] It is illegal to possess (without a legitimate prescription), supply, produce or import.[citation needed]
United States: Zolpidem is listed as a Schedule IV drug due to evidence that the drug has addictive properties similar to benzodiazepines.[citation needed]
↑ 19.019.1Sethi, P. K., Khandelwal, D. C. (February 2005). "Zolpidem at supratherapeutic doses can cause drug abuse, dependence and withdrawal seizure". The Journal of the Association of Physicians of India. 53: 139–140. ISSN0004-5772.
↑Lann, M. A., Molina, D. K. (June 2009). "A fatal case of benzodiazepine withdrawal". The American Journal of Forensic Medicine and Pathology. 30 (2): 177–179. doi:10.1097/PAF.0b013e3181875aa0. ISSN1533-404X.
