Modafinil: Difference between revisions

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| ''[[Modafinil/Summary|Summary sheet: Modafinil]]''

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'''Modafinil''' ('''Provigil, Alertec, Modavigil''') is a wakefulness promoting agent (eugeroic) with [[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.

==Chemistry==

~~[[File:Benzhydryl.png|150px|thumb|left|Skeletal formula of benzhydryl molecule.]]~~

Modafinil is a synthetic molecule of the [[chemical class::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.

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==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> This is because modafanil has very little history of human usage. Anecdotal evidence from people who have tried modafanil within the community suggest that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed).

It is worth noting however that as this compound is a commonly prescribed prescription medication, it is considerably less likely to have adverse health effects than that of a [[research chemical]].

It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.

===Lethal dosage===

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>

~~It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.~~

===Tolerance and addiction potential===

~~Although it is often used on a daily basis for extended periods~~ of ~~time, the long-term safety and effectiveness of modafinil have~~ not ~~been determined.<ref>Pharmacotherapy for excessive daytime sleepiness | http://www.smrv-journal.com/article/S1087-0792(04)00024-3/abstract</ref> This substance does seem to have~~ a ~~tolerance and has been used by people~~ for ~~many months in a row with no noticeable side effects~~. ~~Despite this, however, it~~ does not seem to be ~~addictive~~.

The chronic use of modafanil 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 certain users.

Tolerance to many of the effects of coluracetam [[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). Coluracetam may presents cross-tolerance with [[Cross-tolerance::all [[benzhydryl]] [[nootropic]]s]], meaning that after the consumption of modafanil certain [[nootropics]]s such as [[armodafanil]] and [[adrafanil]] may have a reduced effect.

===Dangerous interactions===

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*[[Caffeine]]

*[[Amphetamine]]

==External links==

*[http://en.wikipedia.org/wiki/Modafinil Modafanil (Wikipedia)]

*[https://www.erowid.org/smarts/modafinil/ Modafanil (Erowid)]

@@ Line 5: / Line 5: @@
 | ''[[Modafinil/Summary|Summary sheet: Modafinil]]''
 |}
-'''Modafinil''' ('''Provigil, Alertec, Modavigil''') is a wakefulness promoting agent (eugeroic) with [[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.
 ==Chemistry==
-[[File:Benzhydryl.png|150px|thumb|left|Skeletal formula of benzhydryl molecule.]]
 Modafinil is a synthetic molecule of the [[chemical class::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.
@@ Line 43: / Line 42: @@
 ==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> This is because modafanil has very little history of human usage. Anecdotal evidence from people who have tried modafanil within the community suggest that there do not seem to be any negative health effects attributed to simply trying this drug at low to moderate doses by itself and using it sparingly (but nothing can be completely guaranteed).
+It is worth noting however that as this compound is a commonly prescribed prescription medication, it is considerably less likely to have adverse health effects than that of a [[research chemical]].
+It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
 ===Lethal dosage===
-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>
-It is strongly recommended that one use [[responsible drug use|harm reduction practices]] when using this drug.
 ===Tolerance and addiction potential===
-Although it is often used on a daily basis for extended periods of time, the long-term safety and effectiveness of modafinil have not been determined.<ref>Pharmacotherapy for excessive daytime sleepiness | http://www.smrv-journal.com/article/S1087-0792(04)00024-3/abstract</ref> This substance does seem to have a tolerance and has been used by people for many months in a row with no noticeable side effects. Despite this, however, it does not seem to be addictive.
+The chronic use of modafanil 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 certain users.
+Tolerance to many of the effects of coluracetam [[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). Coluracetam may presents cross-tolerance with [[Cross-tolerance::all [[benzhydryl]] [[nootropic]]s]], meaning that after the consumption of modafanil certain [[nootropics]]s such as [[armodafanil]] and [[adrafanil]] may have a reduced effect.
 ===Dangerous interactions===
 {{DangerousInteractions/Intro}}
@@ Line 71: / Line 74: @@
 *[[Caffeine]]
 *[[Amphetamine]]
+==External links==
 *[http://en.wikipedia.org/wiki/Modafinil Modafanil (Wikipedia)]
 *[https://www.erowid.org/smarts/modafinil/ Modafanil (Erowid)]