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Modafinil: Difference between revisions
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'''Modafinil''' (also known by the brand names '''Provigil''', '''Alertec''', '''Modavigil''', among others) is a [[psychoactive class::eugeroic]] substance of the [[chemical class::benzhydryl]] 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''' (also known by the brand names '''Provigil''', '''Alertec''', '''Modavigil''', among others) is a [[psychoactive class::eugeroic]] substance of the [[chemical class::benzhydryl]] 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 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}} | ||
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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. | 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 | While modafinil is a racemic mixture, a similar medication, [[armodafinil]], consists of only the (−)-(R)-enantiomer of modafinil. | ||
{{Modafinil/Pharmacology}} | {{Modafinil/Pharmacology}} | ||
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==Toxicity and harm potential== | ==Toxicity and harm potential== | ||
The long-term safety and effectiveness of | 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> | ||
Anecdotal reports from people who have tried | 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. | 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=== | ||
[[Toxicity::The median lethal dose at which 50% of participants die ([[LD50|LD<sub>50</sub>]]) from | [[Toxicity::The median lethal dose at which 50% of participants die ([[LD50|LD<sub>50</sub>]]) from modafinil for human beings has never been reached]]. No life-threatening effects have taken place in clinical trials involving the administration of 1000mg to 1600mg of modafinil per day for 7 to 21 consecutive days. Intentional acute overdoses of 4500mg and 4000mg in two adult subjects and an accidental ingestion of 800mg by a three-year-old child did not result in any life-threatening effects or death.<ref>The National Library of Medicine - PROVIGIL | http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=fd75a8a7-a8ab-4141-9af9-989a220b9c19</ref> After overdosing on 5000mg of modafinil in a suicide attempt, a fifteen-year-old female reported a severe [[Headaches|headache]], [[Nausea|nausea]], and [[Abnormal heartbeat|tachycardia]], but did not appear to have any lethal or long-term effects.<ref>Journal of Clinical Sleep Medicine - Unsuccessful Suicide Attempt of a 15 Year Old Adolescent with Ingestion of 5000 mg Modafinil http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725258</ref> | ||
===Tolerance and addiction potential=== | ===Tolerance and addiction potential=== | ||
The chronic use of | The chronic use of modafinil can be considered as [[Addiction potential::not addictive with a low potential for abuse]]. It does not seem to be capable of causing psychological dependence among most users.{{citation needed}} | ||
Tolerance to many of the effects of | Tolerance to many of the effects of modafinil [[Time to full tolerance::develops with prolonged and repeated use]]. This results in users having to administer increasingly large doses to achieve the same effects. After that, it takes about [[Time to half tolerance::3 - 7 days]] for the tolerance to be reduced to half and [[Time to zero tolerance::1 - 2 weeks]] to be back at baseline (in the absence of further consumption). Modafinil may present a cross-tolerance with [[Cross-tolerance::all [[benzhydryl]] [[nootropic|nootropics]]]], meaning that after the consumption of modafinil, all related eugeroic compounds such as [[armodafinil]] and [[adrafinil]] will display a reduced effect. | ||
===Dangerous interactions=== | ===Dangerous interactions=== | ||
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{{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> | *'''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> | *'''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 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, | *'''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== | ||