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. However, studies have shown that modafinil may also be useful off-label for alleviating the symptoms of depression,, bipolar disorder, Parkinson's disease, seasonal depressive disorder, ADHD,and various other diseases which cause fatigue as a symptom.

Modafinil
Chemical Nomenclature
Common names	Modafinil, Alertec, Modavigil, Modiodal, Provigil, Modalert
Substitutive name	Modafinil
Systematic name	2-[(Diphenylmethyl)sulfinyl]acetamide
Class Membership
Psychoactive class	Stimulant / Eugeroic
Chemical class	Benzhydryl
Routes of Administration
WARNING: Always start with lower doses due to differences between individual body weight, tolerance, metabolism, and personal sensitivity. See responsible use section. ⇣ Oral Dosage Threshold 25 mg Light 50 - 100 mg Common 100 - 200 mg Strong 200 - 300 mg Heavy 300 mg + Duration Total 5 - 10 hours Onset 20 - 60 minutes Come up 20 - 60 minutes Peak 3.5 - 5 hours Offset 1 - 3 hours After effects 2 - 6 hours DISCLAIMER: PW's dosage information is gathered from users and resources for educational purposes only. It is not a recommendation and should be verified with other sources for accuracy.
Interactions
Hormonal Birth Control
CYP2C19-substrates

Summary sheet: Modafinil

The substance has also been used as a doping agent by various athletes due to its effects on physical stimulation. It has recently gained popularity for its use as a smart drug to improve memory and increase productivity.

Chemistry

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 R₂, 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

(R,S)-modafinil, mechanism of action.

Although the exact mechanisms by which modafinil and its R-enantiomer, armodafinil, decrease sleepiness are not fully understood, evidence suggests that these agents promote wakefulness by acting directly or indirectly on many components of the sleep / wake circuit. Modafinil and armodafinil are hypothesized to inhibit GABA and promote dopamine, norepinephrine, histamine, and hypocretin / orexin.

Modafinil and its R-enantiomer, armodafinil, increase both norepinephrine (NE) and dopamine (DA), possibly via their blockade of both the NE and DA reuptake transporters (NET and DAT, respectively). The actions of NE at alpha-adrenergic receptors and DA at dopamine D2 receptors are thought to contribute to the wake-promoting properties of modafinil. Orexin is a key component of the arousal system; thus, the hypothesized action of modafinil on the orexinergic system may help increase alertness. Additionally, modafinil may indirectly increase histamine, either by reducing GABAergic inhibition of histaminergic neurons or via actions at orexinergic neurons. The increase in histamine may contribute to both the wake-promoting effects of modafinil as well as the potential of modafinil to increase alertness.

In genetically engineered mice lacking the dopamine transporter (DAT), modafinil lacked wake-promoting activity, suggesting that this activity was DAT-dependent. However, the wake-promoting effects of modafinil, unlike those of amphetamine, were not reduced by the dopamine receptor antagonist haloperidol in rats. In addition, alpha-methyl-p-tyrosine, an inhibitor of dopamine synthesis, blocks the action of amphetamine but does not block locomotor activity induced by modafinil.

Subjective effects

Disclaimer: The effects listed below cite the Subjective Effect Index (SEI), an open research literature based on anecdotal user reports and the personal analyses of PsychonautWiki contributors. As a result, they should be viewed with a healthy degree of skepticism.

It is also worth noting that these effects will not necessarily occur in a predictable or reliable manner, although higher doses are more liable to induce the full spectrum of effects. Likewise, adverse effects become increasingly likely with higher doses and may include addiction, severe injury, or death ☠.

In comparison to traditional stimulants such as amphetamine, this compound induces an experience which is far less forceful, recreational and euphoric. It instead focuses on general wakefulness and motivation enhancement.

Physical effects

• 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.
• 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.
• 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.
• Photophobia - Although uncommon, modafinil can cause a temporary visual intolerance to light.
• 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.
• Increased heart rate
• Dizziness
• Nausea
• Body odor alteration - Modafinil can potentially leave a very distinguishable smell of sulphur in one's urine. This is likely because modafinil is classified as a sulphinyl benzhydryl molecule and therefore contains sulphur.

Cognitive effects

• Wakefulness
• Focus enhancement
• Thought acceleration
• Memory enhancement
• Motivation enhancement
• Emotion enhancement
• Anxiety
• Time distortion
• Increased music appreciation

Toxicity and harm potential

The long-term safety and effectiveness of modafinil as a drug of regular usage have not been determined. 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 harm reduction practices when using this drug.

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. After overdosing on 5000mg of modafinil in a suicide attempt, a fifteen-year-old female reported a severe headache, nausea, and tachycardia, but did not appear to have any lethal or long-term effects.

Tolerance and addiction potential

The chronic use of modafanil can be considered as 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 modafanil 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 3 - 7 days for the tolerance to be reduced to half and 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 nootropics]], meaning that after the consumption of modafanil certain nootropics such as armodafanil and adrafanil may have a reduced effect.

Dangerous interactions

Warning: Many psychoactive substances that are reasonably safe to use on their own can suddenly become dangerous and even life-threatening when combined with certain other substances. The following list provides some known dangerous interactions (although it is not guaranteed to include all of them).

Always conduct independent research (e.g. Google, DuckDuckGo, PubMed) to ensure that a combination of two or more substances is safe to consume. Some of the listed interactions have been sourced from TripSit.

• "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] & "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - 25x compounds are highly stimulating and physically straining. Combinations with Modafinil should be strictly avoided due to the risk of excessive stimulation and heart strain. This can result in increased blood pressure, vasoconstriction, panic attacks, thought loops, seizures, and heart failure in extreme cases.
• "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combining alcohol with stimulants can be dangerous due to the risk of accidental over-intoxication. Stimulants mask alcohol's depressant effects, which is what most people use to assess their degree of intoxication. Once the stimulant wears off, the depressant effects will be left unopposed, which can result in blackouts and severe respiratory depression. If mixing, the user should strictly limit themselves to only drinking a certain amount of alcohol per hour.
• "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Combinations with DXM should be avoided due to its inhibiting effects on serotonin and norepinephrine reuptake. There is an increased risk of panic attacks and hypertensive crisis, or serotonin syndrome with serotonin releasers (MDMA, methylone, mephedrone, etc.). Monitor blood pressure carefully and avoid strenuous physical activity.
• "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Any neurotoxic effects of MDMA are likely to be increased when other stimulants are present. There is also a risk of excessive blood pressure and heart strain (cardiotoxicity).
• "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Some reports suggest combinations with MXE may dangerously increase blood pressure and increase the risk of mania and psychosis.
• "[[UncertainInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Both classes carry a risk of delusions, mania and psychosis, and these risk may be multiplied when combined.
• "[[UnsafeInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Modafinil may be dangerous to combine with other stimulants like cocaine as they can increase one's heart rate and blood pressure to dangerous levels.
• "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - Tramadol is known to lower the seizure threshold and combinations with stimulants may further increase this risk.
• MDMA - The neurotoxic effects of MDMA may be increased when combined with other stimulants.
• "[[DangerousInteraction" contains a listed "[" character as part of the property label and has therefore been classified as invalid.]] - This combination may increase the amount of neurotransmitters such as dopamine to dangerous or even fatal levels. Examples include syrian rue, banisteriopsis caapi, and some antidepressants.

Legal issues

This legality section is a stub. As such, it may contain incomplete or wrong information. You can help by expanding it.

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.
• Canada: Modafinil is listed as a Schedule F prescription drug in Canada and it can be prescribed for human and veterinary use.
• United Kingdom - Modafinil is a prescription only medication in the U.K.

See also

• Responsible use
• Nootropics
• Stimulants
• Armodafinil
• Caffeine
• Amphetamine

External links

• Modafanil (Wikipedia)
• Modafanil (Erowid)
• Modafinil (Tripsit)
• Modafinil (The Drug Classroom)