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.

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|200px|thumb|left|Skeletal formula of benzhydryl molecule.]]

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.

==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 an uptake 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==

The effects listed below are based upon the [[subjective effects index]] and personal experiences of [[PsychonautWiki]] [[Special:TopUsers|contributors]]. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.

===Physical effects===

The physical effects of modafinil can be broken down into several components. These are described below and generally include:

*'''[[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::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::Photophobia]]''' - Although uncommon, modafinil can cause a temporary visual intolerance to light.

*'''[[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::Diarrhea]]''' - Modafinil has the tendency to increase the frequency of bowel movements in certain individuals.

*'''[[Effect::Increased heart rate]]'''

*'''[[Effect::Dizziness]]'''

*'''[[Effect::Nausea]]'''

*'''[[Effect::Body odor alteration]]''' - Modafinil can potentially leave a very distinguishable smell of sulphur in one's urine.<ref>Urine smell of sulphur? (Wiki talk page) |https://en.wikipedia.org/wiki/Talk:Modafinil/Archive_1#Urine_smell_of_sulphur.3F</ref> This is likely because modafinil is classified as a sulphinyl benzhydryl molecule and therefore contains sulphur.

===Cognitive effects===

The cognitive effects of modafinil can be broken down into several components. These are described below and generally include:

*'''[[Effect::Wakefulness]]'''

*'''[[Effect::Focus enhancement]]'''

*'''[[Effect::Thought acceleration]]

*'''[[Effect::Memory enhancement]]'''

*'''[[Effect::Motivation enhancement]]'''

*'''[[Effect::Current mind state enhancement]]'''

*'''[[Effect::Anxiety]]'''

==Toxicity and harm potential==

===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>

===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.

===Dangerous interactions===

*'''[[MDMA]]''' - The neurotoxic effects of [[MDMA]] may be increased when combined with other stimulants.

==Legal issues==

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>

*'''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==

*[[Nootropics]]

*[[Stimulants]]

*[[Armodafinil]]

*[[Caffeine]]

*[[Amphetamine]]

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

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

==References==

[[Category:Psychoactive substance]]

[[Category:Benzhydryl]]

[[Category:Nootropic]]

[[Category:Stimulant]]

[[Category:Substance]]

@@ Line 1: / Line 1: @@
+{{SubstanceBox/Modafinil}}
+{|
+|-
+|-
+| ''[[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.
+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|200px|thumb|left|Skeletal formula of benzhydryl molecule.]]
+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.
+==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 an uptake 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==
+The effects listed below are based upon the [[subjective effects index]] and personal experiences of [[PsychonautWiki]] [[Special:TopUsers|contributors]]. The listed effects will rarely (if ever) occur all at once, but heavier dosages will increase the chances and are more likely to induce a full range of effects.
+===Physical effects===
+The physical effects of modafinil can be broken down into several components. These are described below and generally include:
+*'''[[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::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::Photophobia]]''' - Although uncommon, modafinil can cause a temporary visual intolerance to light.
+*'''[[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::Diarrhea]]''' - Modafinil has the tendency to increase the frequency of bowel movements in certain individuals.
+*'''[[Effect::Increased heart rate]]'''
+*'''[[Effect::Dizziness]]'''
+*'''[[Effect::Nausea]]'''
+*'''[[Effect::Body odor alteration]]''' - Modafinil can potentially leave a very distinguishable smell of sulphur in one's urine.<ref>Urine smell of sulphur? (Wiki talk page) |https://en.wikipedia.org/wiki/Talk:Modafinil/Archive_1#Urine_smell_of_sulphur.3F</ref> This is likely because modafinil is classified as a sulphinyl benzhydryl molecule and therefore contains sulphur.
+===Cognitive effects===
+The cognitive effects of modafinil can be broken down into several components. These are described below and generally include:
+*'''[[Effect::Wakefulness]]'''
+*'''[[Effect::Focus enhancement]]'''
+*'''[[Effect::Thought acceleration]]
+*'''[[Effect::Memory enhancement]]'''
+*'''[[Effect::Motivation enhancement]]'''
+*'''[[Effect::Current mind state enhancement]]'''
+*'''[[Effect::Anxiety]]'''
+==Toxicity and harm potential==
+===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>
+===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.
+===Dangerous interactions===
+{{DangerousInteractions/Intro}}
+{{DangerousInteractions/Stimulants|self=modafinil}}
+*'''[[MDMA]]''' - The neurotoxic effects of [[MDMA]] may be increased when combined with other stimulants.
+{{DangerousInteractions/MAOI|nt=dopamine}}
+==Legal issues==
+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>
+*'''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==
+*[[Nootropics]]
+*[[Stimulants]]
+*[[Armodafinil]]
+*[[Caffeine]]
+*[[Amphetamine]]
+*[http://en.wikipedia.org/wiki/Modafinil Modafanil (Wikipedia)]
+*[https://www.erowid.org/smarts/modafinil/ Modafanil (Erowid)]
+==References==
+<references />
+[[Category:Psychoactive substance]]
+[[Category:Benzhydryl]]
+[[Category:Nootropic]]
+[[Category:Stimulant]]
+[[Category:Substance]]
+{{#set:Featured=true}}