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Modafinil: Difference between revisions
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{{SubstanceBox/Modafinil}} | {{SubstanceBox/Modafinil}} | ||
'''Modafinil''' ( | '''Modafinil''' (also known by the brand names '''Provigil''', '''Alertec''', '''Modavigil''', among others) is a [[psychoactive class::eugeroic]] substance of the [[chemical class::benzyhydryl]] class that produces [[wakefulness|wakefulness-promoting]] and [[stimulant]] effects when [[administered]]. It is commonly used to enhance cognition, reduce fatigue, and increase alertness in both medical and non-medical contexts. | ||
Modafinil is approved by the U.S. Food and Drug Administration for the treatment of obstructive sleep apnea, shift work sleep disorder and narcolepsy.<ref>Provigal (Manufacturer's Website) | http://www.provigil.com/</ref> However, studies have shown that modafinil may also be useful off-label for alleviating the symptoms of depression,<ref>Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17729016</ref>, bipolar disorder,<ref> A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17671288</ref> Parkinson's disease,<ref>Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16940766</ref> seasonal depressive disorder,<ref>PubMed - Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/15306145</ref> ADHD,<ref>Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18280848</ref>and various other conditions which have fatigue as a symptom. | Modafinil is approved by the U.S. Food and Drug Administration for the treatment of obstructive sleep apnea, shift work sleep disorder and narcolepsy.<ref>Provigal (Manufacturer's Website) | http://www.provigil.com/</ref> However, studies have shown that modafinil may also be useful off-label for alleviating the symptoms of depression,<ref>Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17729016</ref>, bipolar disorder,<ref> A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/17671288</ref> Parkinson's disease,<ref>Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/16940766</ref> seasonal depressive disorder,<ref>PubMed - Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/15306145</ref> ADHD,<ref>Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents (PubMed.gov / NCBI) | http://www.ncbi.nlm.nih.gov/pubmed/18280848</ref> and various other conditions which have fatigue as a symptom. | ||
Modafinil has also been used as a doping agent by various athletes due to its ability to produce [[Stimulation|physical stimulation]].{{citation needed}} It has recently gained mainstream popularity for its use as a [[nootropic|"smart drug"]] to [[Memory enhancement|improve memory]], counteract the desire or need for sleep, and increase general productivity.{{citation needed}} | Modafinil has also been used as a doping agent by various athletes due to its ability to produce [[Stimulation|physical stimulation]].{{citation needed}} It has recently gained mainstream popularity for its use as a [[nootropic|"smart drug"]] to [[Memory enhancement|improve memory]], counteract the desire or need for sleep, and increase general productivity.{{citation needed}} | ||
==Chemistry== | ==Chemistry== | ||
Modafinil is a synthetic molecule of the | Modafinil is a synthetic molecule of the benzhydryl class. Benzhydryl compounds are comprised of two benzene rings attached to a single carbon molecule. Modafinil is classified as a sulphinyl benzhydryl molecule, as it also contains a sulphinyl group, a sulphur molecule double-bonded to an oxygen molecule, attached to the carbon of the benzhydryl group. From this sulphur group at R<sub>2</sub>, an acetamide group is bound at its free carbon through a carbonyl group to a terminal amine group. Modafinil is structurally analogous to fluorafinil, another benzhydryl stimulant. | ||
While modafinil is a racemic mixture, a similar medication, [[armodafinil]], consists of only the (−)-(R)-enantiomer of modafinil. | While modafinil is a racemic mixture, a similar medication, [[armodafinil]], consists of only the (−)-(R)-enantiomer of modafinil. | ||
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==Subjective effects== | ==Subjective effects== | ||
In comparison to traditional stimulants such as [[amphetamine]], [[methylphenidate]] or [[cocaine]], this compound induces an experience which is far less forceful, recreational | In comparison to traditional stimulants such as [[amphetamine]], [[methylphenidate]] or [[cocaine]], this compound induces an experience which is far less forceful, euphoric, and recreational. It instead emphasizes general [[wakefulness]] and [[motivation enhancement]]. | ||
{{Preamble/SubjectiveEffects}} | {{Preamble/SubjectiveEffects}} | ||
{{effects/base | {{effects/base | ||
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|{{effects/physical| | |{{effects/physical| | ||
*'''[[Effect::Stimulation]]''' - In terms of its effects on the user's physical energy levels, modafinil is commonly considered to be stimulating and energetic, but can be considered as much less stimulating when compared to [[amphetamine]]. This stimulation encourages physical movement and activities such as running, playing sports, socializing, and/or exercising. The particular style of stimulation which modafinil presents can result in jaw clenching, teeth grinding, or other involuntary movements comparable to that of traditional stimulants at high doses, but are manifested much less consistently and intensely when compared to [[amphetamine]] or [[cocaine]]. | *'''[[Effect::Stimulation]]''' - In terms of its effects on the user's physical energy levels, modafinil is commonly considered to be stimulating and energetic, but can be considered as much less stimulating when compared to [[amphetamine]]. This stimulation encourages physical movement and activities such as running, playing sports, socializing, and/or exercising. The particular style of stimulation which modafinil presents can result in jaw clenching, teeth grinding, or other involuntary movements comparable to that of traditional stimulants at high doses, but are manifested much less consistently and intensely when compared to [[amphetamine]] or [[cocaine]]. | ||
*'''[[Effect::Increased heart rate]]''' | *'''[[Effect::Increased heart rate]]'''{{citation needed}} | ||
*'''[[Effect::Appetite suppression]]''' - The above components are also accompanied by a suppression of appetite which is usually less intense in strength in comparison to the appetite suppression experienced with [[amphetamine]]. | *'''[[Effect::Appetite suppression]]''' - The above components are also accompanied by a suppression of appetite which is usually less intense in strength in comparison to the appetite suppression experienced with [[amphetamine]]. | ||
*'''[[Effect::Dehydration]]''' - Dehydration and dry mouth commonly occur due to an increase in motivation to engage in physical activities as well as an increased sense of focus which causes one to forget to drink water. | *'''[[Effect::Dehydration]]''' - Dehydration and dry mouth commonly occur due to an increase in motivation to engage in physical activities as well as an increased sense of focus which causes one to forget to drink water. | ||
*'''[[Effect::Headaches]]''' - In terms of physical discomfort, modafinil can cause headaches especially if dehydrated, if you have not eaten food, or if you have been sitting in an awkward position for an extended period of time focused intensely on a task. | *'''[[Effect::Headaches]]''' - In terms of physical discomfort, modafinil can cause headaches especially if dehydrated, if you have not eaten food, or if you have been sitting in an awkward position for an extended period of time focused intensely on a task. | ||
*'''[[Effect::Body odor alteration]]''' - Modafinil can leave a very distinct smell of sulfur in one's urine. This is likely because modafinil, being a member of the sulphinyl benzhydryl chemical class, contains sulfur in its chemical makeup.<ref>Udert, K. M., Larsen, T. A., & Gujer, W. (2006). Fate of major compounds in source-separated urine. Water Science and Technology, 54(11–12), 413–420. https://doi.org/10.2166/wst.2006.921</ref> | *'''[[Effect::Body odor alteration]]''' - Modafinil can leave a very distinct smell of sulfur in one's urine. This is likely because modafinil, being a member of the sulphinyl benzhydryl chemical class, contains sulfur in its chemical makeup.<ref>Udert, K. M., Larsen, T. A., & Gujer, W. (2006). Fate of major compounds in source-separated urine. Water Science and Technology, 54(11–12), 413–420. https://doi.org/10.2166/wst.2006.921</ref> | ||
*'''[[Effect::Pupil dilation]]''' | |||
*'''[[Effect::Photophobia]]''' - Although uncommon, modafinil can cause a temporary visual intolerance to light. | *'''[[Effect::Photophobia]]''' - Although uncommon, modafinil can cause a temporary visual intolerance to light. | ||
*'''[[Effect::Dizziness]]''' | *'''[[Effect::Dizziness]]''' | ||
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}} | }} | ||
==Toxicity and harm potential== | ==Toxicity and harm potential== | ||
The long-term safety and effectiveness of modafinil as a drug of regular usage have not been determined.<ref>Pharmacotherapy for excessive daytime sleepiness | http://www.smrv-journal.com/article/S1087-0792(04)00024-3/abstract</ref> | The long-term safety and effectiveness of modafinil as a drug of regular usage have not been determined.<ref>Pharmacotherapy for excessive daytime sleepiness | http://www.smrv-journal.com/article/S1087-0792(04)00024-3/abstract</ref> | ||
It is worth noting | Anecdotal reports from people who have tried modafinil suggest that there do not seem to be any negative health effects attributed to simply trying this substance at low to moderate doses by itself or using it sparingly (but nothing can be completely guaranteed). | ||
It is worth noting that as this compound is a commonly prescribed pharmaceutical, it is considerably less likely to have unpredictable adverse health effects than the typical [[research chemical]]. Nevertheless, it is strongly recommended that one use [[responsible drug use|harm reduction practices]] if using this substance. | |||
===Lethal dosage=== | ===Lethal dosage=== | ||
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*'''[[DangerousInteraction::Hormonal Birth Control]]''' - Modafinil reduces the effectiveness of hormonal birth control for up to a month after use by increasing the activity of the enzyme CYP3A4/5.<ref>{{cite journal | last=Robertson | first=P | title=Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers | journal=Clinical Pharmacology & Therapeutics | publisher=Springer Nature | volume=71 | issue=1 | year=2002 | issn=0009-9236 | doi=10.1067/mcp.2002.121217 | pages=46–56}}</ref> Notably, the same enzyme is inhibited by grapefruit juice.<ref>{{cite journal | last=Bailey | first=D. G. | last2=Dresser | first2=G. | last3=Arnold | first3=J. M. O. | title=Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? | journal=Canadian Medical Association Journal | publisher=Joule Inc. | volume=185 | issue=4 | date=2012-11-26 | issn=0820-3946 | doi=10.1503/cmaj.120951 | pages=309–316}}</ref> | *'''[[DangerousInteraction::Hormonal Birth Control]]''' - Modafinil reduces the effectiveness of hormonal birth control for up to a month after use by increasing the activity of the enzyme CYP3A4/5.<ref>{{cite journal | last=Robertson | first=P | title=Effect of modafinil on the pharmacokinetics of ethinyl estradiol and triazolam in healthy volunteers | journal=Clinical Pharmacology & Therapeutics | publisher=Springer Nature | volume=71 | issue=1 | year=2002 | issn=0009-9236 | doi=10.1067/mcp.2002.121217 | pages=46–56}}</ref> Notably, the same enzyme is inhibited by grapefruit juice.<ref>{{cite journal | last=Bailey | first=D. G. | last2=Dresser | first2=G. | last3=Arnold | first3=J. M. O. | title=Grapefruit-medication interactions: Forbidden fruit or avoidable consequences? | journal=Canadian Medical Association Journal | publisher=Joule Inc. | volume=185 | issue=4 | date=2012-11-26 | issn=0820-3946 | doi=10.1503/cmaj.120951 | pages=309–316}}</ref> | ||
== | ==Legal status== | ||
{{legalStub}} | {{legalStub}} | ||
Modafinil is legally approved for medical purposes worldwide. However, it is illegal to sell and possess in most countries without a prescription. | Modafinil is legally approved for medical purposes worldwide. However, it is illegal to sell and possess in most countries without a prescription. | ||
*'''Canada:''' Modafinil is listed as a Schedule F prescription drug in Canada and it can be prescribed for human and veterinary use.<ref>National Association of Pharmacy Regulatory Authorities - Regulations Amending the Food and Drug Regulations (1184 — Modafinil) | http://napra.ca/Content_Files/Files/FDR-Project1184-Modafinil-Oct122006.pdf</ref> | |||
*'''Russian Federation:''' Modafinil is classed as a Schedule II substance. <ref>{{cite web |url = http://www.consultant.ru/cons/cgi/online.cgi?req=doc;base=LAW;n=142882;fld=134;dst=4294967295;rnd=0.8965571122244;from=141820-563|title = Narcotics}}</ref> | |||
*'''United Kingdom:''' Modafinil is a licensed prescription-only medicine (POM) in the United Kingdom.<ref>{{cite web |url = http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con273748.pdf|title = MHRA license for Modafinil in UK|date = April 3, 2013|author = MHRA|publisher = MHRA}}</ref> It is not a criminal offence to possess this medicine without a valid prescription. This medicine can legally be obtained with a valid prescription or through legal import of the medicine for personal use as outlined in Section 13 of the Medicines Act 1968.<ref>{{cite web |url = http://www.legislation.gov.uk/ukpga/1968/67/section/13|title = Medicines Act 1968 Section 13}}</ref> | |||
*'''United States:''' In the United States, modafinil is a Schedule IV controlled substance. It is illegal to buy, sell, or possess the drug without a prescription or DEA license.<ref>Placement of Modafinil Into Schedule IV - U.S. Department of Justice | http://www.deadiversion.usdoj.gov/fed_regs/rules/1999/fr0127.htm</ref> | *'''United States:''' In the United States, modafinil is a Schedule IV controlled substance. It is illegal to buy, sell, or possess the drug without a prescription or DEA license.<ref>Placement of Modafinil Into Schedule IV - U.S. Department of Justice | http://www.deadiversion.usdoj.gov/fed_regs/rules/1999/fr0127.htm</ref> | ||
==See also== | ==See also== | ||