Modafinil: Difference between revisions

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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>{{cite journal | vauthors=((Fava, M.)), ((Thase, M. E.)), ((DeBattista, C.)), ((Doghramji, K.)), ((Arora, S.)), ((Hughes, R. J.)) | journal=Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists | title=Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness | volume=19 | issue=3 | pages=153–159 | date= September 2007 | issn=1040-1237 | doi=10.1080/10401230701464858}}</ref> bipolar disorder,<ref>{{cite journal | vauthors=((Frye, M. A.)), ((Grunze, H.)), ((Suppes, T.)), ((McElroy, S. L.)), ((Keck, P. E.)), ((Walden, J.)), ((Leverich, G. S.)), ((Altshuler, L. L.)), ((Nakelsky, S.)), ((Hwang, S.)), ((Mintz, J.)), ((Post, R. M.)) | journal=The American Journal of Psychiatry | title=A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression | volume=164 | issue=8 | pages=1242–1249 | date= August 2007 | issn=0002-953X | doi=10.1176/appi.ajp.2007.06060981}}</ref> Parkinson's disease,<ref>{{cite journal | vauthors=((Vliet, S. A. M. van)), ((Vanwersch, R. A. P.)), ((Jongsma, M. J.)), ((Gugten, J. van der)), ((Olivier, B.)), ((Philippens, I. H. C. H. M.)) | journal=Behavioural Pharmacology | title=Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects | volume=17 | issue=5–6 | pages=453–462 | date= September 2006 | issn=0955-8810 | doi=10.1097/00008877-200609000-00011}}</ref> seasonal depressive disorder,<ref>{{cite journal | vauthors=((Lundt, L.)) | journal=Journal of Affective Disorders | title=Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study | volume=81 | issue=2 | pages=173–178 | date= August 2004 | issn=0165-0327 | doi=10.1016/S0165-0327(03)00162-9}}</ref> ADHD,<ref>{{cite journal | vauthors=((Biederman, J.)), ((Pliszka, S. R.)) | journal=The Journal of Pediatrics | title=Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents | volume=152 | issue=3 | pages=394–399 | date= March 2008 | issn=1097-6833 | doi=10.1016/j.jpeds.2007.07.052}}</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]].<ref>https://www.cyclingnews.com/news/clinger-given-two-year-suspension-for-doping</ref><ref>https://web.archive.org/web/20120122061356/http://sportsillustrated.cnn.com/2006/baseball/mlb/03/06/news.excerpt/1.html</ref><ref>https://journals.lww.com/acsm-msse/fulltext/2004/06000/effects_of_acute_modafinil_ingestion_on_exercise.23.aspx</ref> 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.<ref>https://pubmed.ncbi.nlm.nih.gov/34632515/<ref>

Modafinil has also been used as a doping agent by various athletes due to its ability to produce [[Stimulation|physical stimulation]].<ref>https://www.cyclingnews.com/news/clinger-given-two-year-suspension-for-doping</ref><ref>https://web.archive.org/web/20120122061356/http://sportsillustrated.cnn.com/2006/baseball/mlb/03/06/news.excerpt/1.html</ref><ref>https://journals.lww.com/acsm-msse/fulltext/2004/06000/effects_of_acute_modafinil_ingestion_on_exercise.23.aspx</ref> 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.<ref>https://pubmed.ncbi.nlm.nih.gov/34632515/<nowiki><ref></nowiki>

==History and culture==

Modafinil was originally developed in France by neurophysiologist professor Michel Jouvet and Lafon Laboratories. Modafinil originated with the late 1970s invention of a series of benzhydryl sulfinyl compounds, including adrafinil, which was first offered as an experimental treatment for narcolepsy in France in 1986. Modafinil is the primary metabolite of adrafinil, lacking the polar -OH group on its terminal amide,<ref>{{cite journal | vauthors=((Ballas, C. A.)), ((Kim, D.)), ((Baldassano, C. F.)), ((Hoeh, N.)) | journal=Expert Review of Neurotherapeutics | title=Modafinil: past, present and future | volume=2 | issue=4 | pages=449–457 | date=1 July 2002 | url=https://doi.org/10.1586/14737175.2.4.449 | issn=1473-7175 | doi=10.1586/14737175.2.4.449}}</ref> and has similar activity to the parent drug but is much more widely used. It has been prescribed in France since 1994 under the name Modiodal, and in the US since 1998 as Provigil.

Modafinil was originally developed in France by neurophysiologist professor Michel Jouvet and Lafon Laboratories. Modafinil originated with the late 1970s invention of a series of benzhydryl sulfinyl compounds, including adrafinil, which was first offered as an experimental treatment for narcolepsy in France in 1986. Modafinil is the primary metabolite of adrafinil, lacking the polar -OH group on its terminal amide,<nowiki><ref></nowiki>{{cite journal | vauthors=((Ballas, C. A.)), ((Kim, D.)), ((Baldassano, C. F.)), ((Hoeh, N.)) | journal=Expert Review of Neurotherapeutics | title=Modafinil: past, present and future | volume=2 | issue=4 | pages=449–457 | date=1 July 2002 | url=https://doi.org/10.1586/14737175.2.4.449 | issn=1473-7175 | doi=10.1586/14737175.2.4.449}}</ref> and has similar activity to the parent drug but is much more widely used. It has been prescribed in France since 1994 under the name Modiodal, and in the US since 1998 as Provigil.

==Chemistry==

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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 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.

Tolerance to many of the stimulant effects of modafinil [[Time to full tolerance::develops with prolonged and repeated use]], however there is clinical evidence that its wakefulness effects persist without significant tolerance.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170336/</ref> This results in users having to administer increasingly large doses to achieve the same stimulant 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===

@@ Line 6: / Line 6: @@
 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>{{cite journal | vauthors=((Fava, M.)), ((Thase, M. E.)), ((DeBattista, C.)), ((Doghramji, K.)), ((Arora, S.)), ((Hughes, R. J.)) | journal=Annals of Clinical Psychiatry: Official Journal of the American Academy of Clinical Psychiatrists | title=Modafinil augmentation of selective serotonin reuptake inhibitor therapy in MDD partial responders with persistent fatigue and sleepiness | volume=19 | issue=3 | pages=153–159 | date= September 2007 | issn=1040-1237 | doi=10.1080/10401230701464858}}</ref> bipolar disorder,<ref>{{cite journal | vauthors=((Frye, M. A.)), ((Grunze, H.)), ((Suppes, T.)), ((McElroy, S. L.)), ((Keck, P. E.)), ((Walden, J.)), ((Leverich, G. S.)), ((Altshuler, L. L.)), ((Nakelsky, S.)), ((Hwang, S.)), ((Mintz, J.)), ((Post, R. M.)) | journal=The American Journal of Psychiatry | title=A placebo-controlled evaluation of adjunctive modafinil in the treatment of bipolar depression | volume=164 | issue=8 | pages=1242–1249 | date= August 2007 | issn=0002-953X | doi=10.1176/appi.ajp.2007.06060981}}</ref> Parkinson's disease,<ref>{{cite journal | vauthors=((Vliet, S. A. M. van)), ((Vanwersch, R. A. P.)), ((Jongsma, M. J.)), ((Gugten, J. van der)), ((Olivier, B.)), ((Philippens, I. H. C. H. M.)) | journal=Behavioural Pharmacology | title=Neuroprotective effects of modafinil in a marmoset Parkinson model: behavioral and neurochemical aspects | volume=17 | issue=5–6 | pages=453–462 | date= September 2006 | issn=0955-8810 | doi=10.1097/00008877-200609000-00011}}</ref> seasonal depressive disorder,<ref>{{cite journal | vauthors=((Lundt, L.)) | journal=Journal of Affective Disorders | title=Modafinil treatment in patients with seasonal affective disorder/winter depression: an open-label pilot study | volume=81 | issue=2 | pages=173–178 | date= August 2004 | issn=0165-0327 | doi=10.1016/S0165-0327(03)00162-9}}</ref> ADHD,<ref>{{cite journal | vauthors=((Biederman, J.)), ((Pliszka, S. R.)) | journal=The Journal of Pediatrics | title=Modafinil improves symptoms of attention-deficit/hyperactivity disorder across subtypes in children and adolescents | volume=152 | issue=3 | pages=394–399 | date= March 2008 | issn=1097-6833 | doi=10.1016/j.jpeds.2007.07.052}}</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]].<ref>https://www.cyclingnews.com/news/clinger-given-two-year-suspension-for-doping</ref><ref>https://web.archive.org/web/20120122061356/http://sportsillustrated.cnn.com/2006/baseball/mlb/03/06/news.excerpt/1.html</ref><ref>https://journals.lww.com/acsm-msse/fulltext/2004/06000/effects_of_acute_modafinil_ingestion_on_exercise.23.aspx</ref> 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.<ref>https://pubmed.ncbi.nlm.nih.gov/34632515/<ref>
+Modafinil has also been used as a doping agent by various athletes due to its ability to produce [[Stimulation|physical stimulation]].<ref>https://www.cyclingnews.com/news/clinger-given-two-year-suspension-for-doping</ref><ref>https://web.archive.org/web/20120122061356/http://sportsillustrated.cnn.com/2006/baseball/mlb/03/06/news.excerpt/1.html</ref><ref>https://journals.lww.com/acsm-msse/fulltext/2004/06000/effects_of_acute_modafinil_ingestion_on_exercise.23.aspx</ref> 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.<ref>https://pubmed.ncbi.nlm.nih.gov/34632515/<nowiki><ref></nowiki>
 ==History and culture==
-Modafinil was originally developed in France by neurophysiologist professor Michel Jouvet and Lafon Laboratories. Modafinil originated with the late 1970s invention of a series of benzhydryl sulfinyl compounds, including adrafinil, which was first offered as an experimental treatment for narcolepsy in France in 1986. Modafinil is the primary metabolite of adrafinil, lacking the polar -OH group on its terminal amide,<ref>{{cite journal | vauthors=((Ballas, C. A.)), ((Kim, D.)), ((Baldassano, C. F.)), ((Hoeh, N.)) | journal=Expert Review of Neurotherapeutics | title=Modafinil: past, present and future | volume=2 | issue=4 | pages=449–457 | date=1 July 2002 | url=https://doi.org/10.1586/14737175.2.4.449 | issn=1473-7175 | doi=10.1586/14737175.2.4.449}}</ref> and has similar activity to the parent drug but is much more widely used. It has been prescribed in France since 1994 under the name Modiodal, and in the US since 1998 as Provigil.
+Modafinil was originally developed in France by neurophysiologist professor Michel Jouvet and Lafon Laboratories. Modafinil originated with the late 1970s invention of a series of benzhydryl sulfinyl compounds, including adrafinil, which was first offered as an experimental treatment for narcolepsy in France in 1986. Modafinil is the primary metabolite of adrafinil, lacking the polar -OH group on its terminal amide,<nowiki><ref></nowiki>{{cite journal | vauthors=((Ballas, C. A.)), ((Kim, D.)), ((Baldassano, C. F.)), ((Hoeh, N.)) | journal=Expert Review of Neurotherapeutics | title=Modafinil: past, present and future | volume=2 | issue=4 | pages=449–457 | date=1 July 2002 | url=https://doi.org/10.1586/14737175.2.4.449 | issn=1473-7175 | doi=10.1586/14737175.2.4.449}}</ref> and has similar activity to the parent drug but is much more widely used. It has been prescribed in France since 1994 under the name Modiodal, and in the US since 1998 as Provigil.
 ==Chemistry==
@@ Line 75: / Line 75: @@
 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 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.
+Tolerance to many of the stimulant effects of modafinil [[Time to full tolerance::develops with prolonged and repeated use]], however there is clinical evidence that its wakefulness effects persist without significant tolerance.<ref>https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170336/</ref> This results in users having to administer increasingly large doses to achieve the same stimulant 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===