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| {{headerpanel|{{Warning/Bupropion}}{{Approval}}}}
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| {{Talk:SubstanceBox/Bupropion}}
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| '''Bupropion''', sold as Wellbutrin (in sustained-release, immediate-release, or extended-release form), Zyban, and known also as amfebutamone, is a [[substituted cathinone|cathinone]]<ref>Iverson, of the ACMD, L. (2010, March 31). Consideration of the Cathinones. Retrieved from https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/119173/acmd-cathinodes-report-2010.pdf</ref> medication used on-label for major depressive disorder and smoking cessation. Bupropion is also used off-label for seasonal affective disorder and ADHD. Bupropion is also taken recreationally for its deliriant-like and stimulant effects. It is a [[norepinephrine]]-[[dopamine]] reuptake inhibitor (NDRI) and nicotinic acetylcholine receptor antagonist. <ref> MedlinePlus. (2017, July 27). Retrieved from https://medlineplus.gov/druginfo/meds/a695033.html</ref><ref name=":0"> I, C. F., E, B. B., W, M. S., A, N. H., J, L. R., & I, D. M. (2014). Bupropion and bupropion analogs as treatments for CNS disorders. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24484978 </ref> It may exert its deliriant-like actions through antagonism of the nicotinic acetylcholine receptors.
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| ==History and culture==
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| {{historyStub}}
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| Bupropion was invented by Nariman Mehta of Burroughs Wellcome (now GlaxoSmithKline) in 1969, and the US patent for it was granted in 1974. It was approved by the U.S. Food and Drug Administration as an antidepressant on 30 December 1985, and marketed under the name Wellbutrin. However, a significant incidence of seizures at the originally recommended dosage (400–600 mg/day) caused the withdrawal of the drug in 1986. Subsequently, the risk of seizures was found to be highly dose-dependent, and bupropion was re-introduced to the market in 1989 with a lower maximum recommended daily dose of 450 mg/day.
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| ==Chemistry==
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| Bupropion, is a molecule of the [[cathinone]] class with substituted a chlorine atom at R<sub>3</sub> of its phenyl ring, and a tert-btylamine at the amino group. Cathinones are a sub-category of [[amphetamines]], sharing the core amphetamine structure of a phenyl ring bound to an amino (NH<sub>2</sub>) group through an ethyl chain and an additional methyl substitution at R<sub>α</sub>. Bupropion and other cathinones are differentiated by their ketone substitution on the beta carbon of the amphetamine skeleton, meaning they are β-keto-amphetamines
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| ==Pharmacology==
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| {{pharmacology}}
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| Bupropion binds to norepinephrine transporter (NET) and dopamine transporter (DAT), therefore inhibiting the reuptake of both monoamines. It also binds to nicotinic acetylcholine receptors as an antagonist. <ref name=":0" /> Bupropion is extensively metabolized to hydroxybupropion, threohydrobupropion, and erythrohydrobupropion. It exerts its deliriant-like actions through antagonism of the nicotinic acetylcholine receptors, inhibiting the action of acetylcholine. The nAChRs it antagonizes are α<sub>3</sub>β<sub>2</sub>, α<sub>3</sub>β<sub>4</sub>, α<sub>4</sub>β<sub>2</sub> nicotinic acetylcholine receptors. It also, very weakly, antagonizes the nicotinic acetylcholine receptor α<sub>7</sub>. <ref> Lemke, Thomas L., Williams, David A. (24 January 2012). [https://books.google.com/books?id=Sd6ot9ul-bUC&pg=PA611#v=onepage&q&f=false| ''Foye's Principles of Medicinal Chemistry.''] Lippincott Williams & Wilkins. pp. 611–613.</ref><ref> I, C. F., E, B. B., W, M. S., A, N. H., J, L. R., & I, D. M. (2014). Bupropion and bupropion analogs as treatments for CNS disorders. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/24484978 </ref> It is likely this antagonism of the nAChRs that causes bupropion to make users hallucinate and have vivid dreams.
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| ==Subjective effects==
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| {{EffectStub}}
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| Bupropion has an effects profile similar to diphenhydramine at high doses; in low doses, it acts as a mild and usually pleasant substance, but in high doses, delirium begins to take over and make for an extremely uncomfortable experience.
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| {{Preamble/SubjectiveEffects}}
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| {{effects/base
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| |{{effects/physical|
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| *'''[[Effect::Stimulation]]''' - Bupropion's NDRI activity makes it a stimulating substance.
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| *'''[[Effect::Spontaneous physical sensations]]''' - This effect is usually weak. It can be described as a mild and pleasant soft or sharp tingling sensation with warmth radiating from the body, according to other substances with similar pharmacology.
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| *'''[[Effect::Seizure|Seizures]]''' - This effect becomes more likely proportional to dose.
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| *'''[[Effect::Increased heart rate]]'''
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| *'''[[Effect::Increased blood pressure]]'''
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| *'''[[Effect::Pupil dilation]]
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| *'''[[Effect::Appetite suppression]]
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| *'''[[Effect::Nausea]] -Proportional to higher doses, usually occurs after prolonged use.
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| *'''[[Effect::Tactile hallucinations]]''' - This effect is usually only present at high doses.
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| *'''[[Effect::Temperature regulation suppression]]'''
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| }}
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| {{effects/visual|
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| These effects are usually only present when taking high recreational doses, when it begins to act as a deliriant.
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| *'''[[Effect::External hallucinations]]
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| *'''[[Effect::Shadow people]]
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| *'''[[Effect::Drifting]]
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| *'''[[Effect::Pattern recognition enhancement]]
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| *'''[[Effect::Tracers]]
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| *'''[[Effect::Acuity suppression]]
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| }}
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| |{{effects/cognitive|
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| *'''[[Effect::Delirium]]''' - This occurs at high to very high and/or unreasonable doses and is a consequence of bupropion's antagonism of nicotinic acetylcholine receptors (nAChRs). Unlike other deliriants, this effect can be very painful and hard to get away from because of bupropion's ability to keep the user awake, unlike deliriants like [[diphenhydramine]].
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| *'''[[Effect::Paranoia]]'''
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| *'''[[Effect::Disinhibition]]''' - This occurs mainly at recreational doses.
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| *'''[[Effect::Delusions]]''' - This effect is usually only present at very high doses.
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| *'''[[Effect::Anxiety]]''' - Bupropion causes more anxiety than other stimulants.
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| *'''[[Effect::Mania]]''' - Bupropion increases the risk of manic episodes in individuals suffering from bipolar disorder.
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| *'''[[Effect::Motivation enhancement]]''' - This is commonly expressed in the form of being more talkative, fidgety, or having increased interest in tasks. This effect is mild when compared to amphetamines or methylphenidates.
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| *'''[[Effect::Dream potentiation]]''' - Reports list that taking bupropion can lead to wild, vivid, and realistic dreams, usually feeling linear and very immersive, almost like a fun adventure. Time also seems to have passed much more than it actually has from sleep to wake. It is also easier to recall dreams. Consequently, bupropion can also inhibit sleep, but this can be countered with [[melatonin]] safely. This effect is likely exerted by its antagonistic action on nicotinic acetylcholine receptors.
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| *'''[[Effect::Time distortion]]''' - This is in the form of time expansion. A time period such as twenty minutes can feel as if it were up to eight hours. It happens at unreasonably high doses.
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| *'''[[Effect::Increased music appreciation]]'''
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| *'''[[Effect::Immersion enhancement]]'''
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| *'''[[Effect::Cognitive euphoria]]''' - The euphoria produced by bupropion is usually mild but in some people it has been reported to produce intense euphoria on par with that of [[amphetamine]].
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| *'''[[Effect::Ego inflation]]'''
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| *'''[[Effect::Cognitive dysphoria|Dysphoria]]''' - This effect is only present at high doses, usually due to its deliriant actions.
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| *'''[[Effect::Novelty enhancement]]
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| *'''[[Effect::Language suppression]]''' - This effect is only present at high doses, usually due to its deliriant actions.
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| *'''[[Effect::Increased sense of humor]]'''
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| *'''[[Effect::Increased libido]]''' - Bupropion is sometimes prescribed off-label for treatment of [[SSRI|SSRI-induced]] sexual dysfunction.
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| *'''[[Effect::Addiction suppression|Craving suppression]]''' - Bupropion reduces the enjoyment and therefore the need for [[nicotine]]. Alone or with varenicline, bupropion SR and ER can be used for treatment of tobacco addiction and dependence. <ref>Ebbert, J. O., MD, MSc, Hatsukami, D. K., Ph.D., Croghan, I. T., Ph.D., Schroeder, D. R., MS, Allen, S. S., MD, Hays, T. J., MD, & Hurt, R. D., MD. (2014, January 8). Combination Varenicline and Bupropion SR for Tobacco Dependence Treatment in Cigarette Smokers: A Randomized Trial. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3959999/</ref>
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| }}
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| {{effects/auditory|
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| *'''[[Effect::Auditory hallucinations]]''' - This effect is only present at high doses, usually due to its deliriant actions.
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| *'''[[Effect::Auditory enhancement]]''' - Sounds may be easier or more painful to hear. Usually, this isn't part of delirium necessarily, but it can be.
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| }}
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| }}
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| ===Experience reports===
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| There are currently no anecdotal reports which describe the effects of this compound within our experience index. Additional experience reports can be found here:
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| *[https://www.erowid.org/experiences/subs/exp_Pharms_Bupropion.shtml| Erowid Experience Vaults: Bupropion]
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| ==Toxicity and harm potential==
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| {{toxicity}}
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| It is strongly recommended that one use [[responsible use|harm reduction practices]] when using bupropion; bupropion can cause seizures and therefore should not be combined with other substances that lower the seizure threshold such as [[tramadol]] or be used during GABAergic withdrawal.
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| ===Lethal dosage===
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| Bupropion, despite having a relatively average LD<sub>50</sub> for rats and mice,<ref>Cayman Chemicals. (2012, July 19). Retrieved from https://www.caymanchem.com/msdss/10488m.pdf</ref> is still very dangerous in overdose due to the risk of monoamine flood, seizures, and heart attacks or strokes.
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| ===Tolerance and addiction potential===
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| Bupropion has potential for addiction because of its activity as an NDRI.
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| ===Dangerous interactions===
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| {{DangerousInteractions}}
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| {{DangerousInteractions/Intro}}
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| *'''[[UnsafeInteraction::Stimulants]]''' (''[[Amphetamine]], [[lisdexamfetamine]], [[methylphenidate]], [[cocaine]]'') - This combination can increase the chance of a heart attack, stroke, or [[adrenaline|adrenergic]] flood. These agents often individually '''lowers the seizure threshold''' and may have additive effects when combined with Bupropion.
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| *'''[[DangerousInteraction::Tramadol]], [[DangerousInteraction::Tapentadol]], or any other drug or substance that lowers the seizure threshold such as [[DangerousInteraction::dextropropoxyphene]] or [[DangerousInteraction::lithium]].''' - This combination can increase the risk of seizures, death from seizures, or status epilepticus (seizure lasting longer than five minutes).
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| *'''[[Sedative|Sedatives]]''' (''[[Alprazolam]], [[clonazolam]], [[diazepam]], [[opioids]], [[phenobarbital]], [[secobarbital]], [[quetiapine]]'') - Bupropion's effects are masked by sedatives such as benzodiazepines, barbiturates, alcohol, and antipsychotics. If the effects of sedatives wear off before bupropion's, bupropion's effects may seem or become more pronounced.
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| *'''[[Alcohol]]''' - This combination increases the risk of atypical and unpleasant or dangerous side effects such as seizures, paranoia, or depression.
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| *'''[[DangerousInteraction::DXM]]''' - Bupropion is a potent inhibitor of CYP2D6, the enzyme primarily responsible for breaking down DXM. This can lead to prolonged effects and excessive accumulation of DXM in the bloodstream.<ref>Journal of Clinical Psychopharmacology (June 2005). Inhibition of CYP2D6 activity by bupropion; Retrieved from https://pubmed.ncbi.nlm.nih.gov/15876900/</ref> and both substances raise heart rate, in extreme cases, panic attacks caused by these substances have led to more serious heart issues.
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| *'''[[UnsafeInteraction::Cannabis]]''' - Bupropion causes [[anxiety]], [[thought loops]] and [[paranoia]] more often than other stimulants.
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| *'''[[UncertainInteraction::Caffeine]]''' - This combination of stimulants is generally considered unnecessary and may increase strain on the heart, as well as potentially causing anxiety and physical discomfort.
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| *'''[[UncertainInteraction::Ketamine]]''' - Combining amphetamine and ketamine may result in psychoses that resemble schizophrenia, but not worse than the psychoses produced by either substance alone, but this is debatable. This is due to amphetamines ability to attenuated the disruption of working memory caused by ketamine. Amphetamine alone may result in grandiosity, paranoia, or somatic delusions with little to no effect on negative symptoms. Ketamine, however, will result in thought disorders, disruption of executive functioning, and delusions due to a modification of conception. These mechanisms are due to an increase of dopaminergic activity in the mesolimbic pathway caused by amphetamine due to its pharmacology effecting dopamine, and due to a disruption of dopaminergic functioning in the mesocortical pathways via NMDA antagonism effects of ketamine. Combining the two, you may expect mainly thought disorder along with positive symptoms.<ref name="Krystal2005">{{cite journal | vauthors=((Krystal, J. H.)), ((Perry, E. B.)), ((Gueorguieva, R.)), ((Belger, A.)), ((Madonick, S. H.)), ((Abi-Dargham, A.)), ((Cooper, T. B.)), ((MacDougall, L.)), ((Abi-Saab, W.)), ((D’Souza, D. C.)) | journal=Archives of General Psychiatry | title=Comparative and Interactive Human Psychopharmacologic Effects of Ketamine and Amphetamine: Implications for Glutamatergic and Dopaminergic Model Psychoses and Cognitive Function | volume=62 | issue=9 | pages=985 | date=1 September 2005 | url=http://archpsyc.jamanetwork.com/article.aspx?doi=10.1001/archpsyc.62.9.985 | issn=0003-990X | doi=10.1001/archpsyc.62.9.985}}</ref>
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| *'''[[UnsafeInteraction::PCP]]''' - Increases risk of tachycardia, hypertension, and manic states.
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| *'''[[UncertainInteraction::Methoxetamine]]''' - Increases risk of tachycardia, hypertension, and manic states.
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| *'''[[UncertainInteraction::Psychedelics]]''' (e.g. '''''[[LSD]], [[mescaline]], [[psilocybin]]''''') - Bupropion significantly increases risk of [[anxiety]], [[paranoia]], and [[thought loops]].
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| **'''[[UnsafeInteraction::25x-NBOMe]]''' - Amphetamines and NBOMes both provide considerable stimulation that when combined they can result in tachycardia, hypertension, vasoconstriction and, in extreme cases, heart failure. The anxiogenic and focusing effects of stimulants are also not good in combination with psychedelics as they can lead to unpleasant thought loops. NBOMes are known to cause seizures and stimulants can increase this risk.
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| **'''[[UnsafeInteraction::2C-T-x]]''' - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.
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| **'''[[UnsafeInteraction::5-MeO-xxT]]''' - Suspected of mild MAOI properties. May increase the risk of hypertensive crisis.
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| **'''[[UnsafeInteraction::DOx]]'''
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| *'''[[DangerousInteraction::aMT]]''' - aMT has MAOI properties which may interact unfavorably with amphetamines.
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| *'''[[DangerousInteraction::MAOIs]]''' - MAO-B inhibitors can increase the potency and duration of phenethylamines unpredictably. MAO-A inhibitors with amphetamine can lead to hypertensive crises.
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| ==Legal status==
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| {{LegalStub}}
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| Internationally, bupropion is usually not controlled, but it is prescription-only.
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| ==See also==
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| *[[Responsible use]]
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| *[[Substituted cathinone]]
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| ==External links==
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| *[https://en.wikipedia.org/wiki/Bupropion Bupropion (Wikipedia)]
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| *[https://erowid.org/pharms/bupropion/bupropion.shtml Bupropion (Erowid Vault)]
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| *[https://isomerdesign.com/PiHKAL/explore.php?id=2343 Bupropion (Isomer Design)]
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| ==Literature==
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| ==References==
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| <references />
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| [[Category:Psychoactive substance]]
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| [[Category:Proofread]]
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| [[Category:Approval]]
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| ==Discussion==
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