Modafinil: Difference between revisions

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| ''[[Modafinil/Summary|Summary sheet: Modafinil]]''
| ''[[Modafinil/Summary|Summary sheet: Modafinil]]''
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'''Modafinil''' ('''Provigil, Alertec, Modavigil''') is a wakefulness promoting agent (eugeroic) with [[psychoactive class::nootropic]] effects used to enhance cognition, reduce fatigue, and increase alertness. It 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 | 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 | 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 | 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 | 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 | http://www.ncbi.nlm.nih.gov/pubmed/18280848</ref>and various other diseases which cause fatigue as a symptom.  
'''Modafinil''' ('''Provigil, Alertec, Modavigil''') is a wakefulness promoting agent (eugeroic) with [[psychoactive class::nootropic]] effects used to enhance cognition, reduce fatigue, and increase alertness. It 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 | 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 | 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 | 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 | 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 | http://www.ncbi.nlm.nih.gov/pubmed/18280848</ref>and various other diseases which cause fatigue as a symptom.  


The substance has also been used as a doping agent by various athletes due to its effects on [[Stimulation|physical stimulation]]. It has recently gained popularity for its use as a [[nootropic|smart drug]] to [[Memory enhancement|improve memory]] and increase productivity.
The substance has also been used as a doping agent by various athletes due to its effects on [[Stimulation|physical stimulation]]. It has recently gained popularity for its use as a [[nootropic|smart drug]] to [[Memory enhancement|improve memory]] and increase productivity.
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==Pharmacology==
==Pharmacology==
Research suggests that modafinil increases hypothalamic histamine levels in the brains of rats, which may contribute to its locomotor effects. <ref>European Journal of Pharmacology - Involvement of central histaminergic systems in modafinil-induced but not methylphenidate-induced increases in locomotor activity in rats | http://www.sciencedirect.com/science/article/pii/S001429990701031X</ref> Modafinil has recently been shown to act as a [[reuptake inhibitor]] for the [[neurotransmitter]] [[dopamine]], evidently leading to increased extraceullular concentrations of dopamine and dopaminergic neurotransmission. <ref>The Journal of Pharmacology and Experimental Therapeutics - Evidence for the Involvement of Dopamine Transporters in Behavioral Stimulant Effects of Modafinil | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672878</ref> This essentially allows dopamine to accumulate and be reused, causing physically stimulating and motivating effects.
Research suggests that modafinil increases hypothalamic histamine levels in the brains of rats, which may contribute to its locomotor effects.<ref>European Journal of Pharmacology - Involvement of central histaminergic systems in modafinil-induced but not methylphenidate-induced increases in locomotor activity in rats | http://www.sciencedirect.com/science/article/pii/S001429990701031X</ref> Modafinil has recently been shown to act as a [[reuptake inhibitor]] for the [[neurotransmitter]] [[dopamine]], evidently leading to increased extraceullular concentrations of dopamine and dopaminergic neurotransmission.<ref>The Journal of Pharmacology and Experimental Therapeutics - Evidence for the Involvement of Dopamine Transporters in Behavioral Stimulant Effects of Modafinil | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2672878</ref> This essentially allows dopamine to accumulate and be reused, causing physically stimulating and motivating effects.


==Subjective effects==
==Subjective effects==
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It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
===Lethal dosage===
===Lethal dosage===
[[Toxicity::The median lethal dose at which 50% of participants die ([[LD50]]) 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 Modafinilhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725258</ref>
[[Toxicity::The median lethal dose at which 50% of participants die ([[LD50]]) 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 Modafinilhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725258</ref>


===Tolerance and addiction potential===
===Tolerance and addiction potential===
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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.  


*'''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>
*'''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>


==See also==
==See also==