Modafinil

Last updated: May 4, 2025

Modafinil is a wakefulness-promoting medication, available since the 1990s, used primarily to treat sleep disorders like narcolepsy. It works mainly by increasing dopamine levels in the brain through inhibiting the dopamine transporter (DAT), and also influences norepinephrine, histamine, glutamate, GABA, and orexin systems, leading to increased alertness and vigilance. Studies show Modafinil effectively reduces fatigue and enhances wakefulness, with smaller but significant positive effects on attention, executive function, and memory in non-sleep-deprived adults.

Categories & Effectiveness
Dosage & Side Effects
Benefits by Use Case
Mechanism of Action
Frequently Asked Questions
Summary & Expert Opinion
Research Studies

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Categories & Effectiveness

Brain Health

Dopamine Support

7/10

Strong evidence of effectiveness

Cognition

Mental Acuity

7/10

Strong evidence of effectiveness

Concentration & Focus

4/10

Moderate evidence of effectiveness

Memory & Recall

4/10

Moderate evidence of effectiveness

Processing Speed

4/10

Moderate evidence of effectiveness

Energy & Alertness

Alertness & Vigilance

10/10

Strong evidence of effectiveness

Wakefulness Promotion

10/10

Strong evidence of effectiveness

Sleep Quality

Sleep Cycle Regulation

4/10

Moderate evidence of effectiveness

Dosage & Side Effects

Recommended Dosage

Common doses for adults typically range from 100 mg to 400 mg per day, often taken orally in the morning. While doses up to 800 mg have been used in clinical studies, 100 mg and 200 mg are frequently studied for cognitive effects, with no significant difference often found between these two doses in non-sleep-deprived individuals. Use in specific populations, like military personnel facing sleep deprivation, has involved regimens such as 100 mg every 4 hours or daily doses up to 400 mg, though higher doses (e.g., 3 x 200 mg/day) increased side effects.

Potential Side Effects

Common mild side effects can include dizziness and nausea, particularly noted at higher doses. Although generally well-tolerated with adverse events reported in less than 5% of subjects in some trials, high doses or specific conditions might increase risks; for instance, it worsened withdrawal symptoms in tobacco smokers. Modafinil may interact with various neurotransmitter systems and should be used cautiously, considering its complex effects on brain chemistry.

Bioavailability & Half-Life

After oral administration, Modafinil reaches peak plasma concentrations in approximately 2 to 4 hours. Its R-enantiomer (Armodafinil or R-MOD) is known for having a longer duration of action compared to racemic Modafinil. While detailed metabolic pathways involving specific liver enzymes (like CYP enzymes) are part of its processing, the primary focus for users is its relatively long-lasting effect throughout the day, necessitating morning dosage to avoid sleep disturbances.

Interactions & Stacks

Modafinil is sometimes used off-label alongside treatments for conditions like ADHD or as an adjunct to behavioral therapies for substance use disorders, though clinical results vary. Caution is advised when combining Modafinil with other stimulants or substances affecting dopamine, norepinephrine, serotonin, GABA, or glutamate systems due to potential additive effects or unforeseen interactions. While Modafinil has a distinct profile from amphetamines or methylphenidate, it shares the mechanism of dopamine transporter inhibition, suggesting potential overlapping effects.

Benefits by Use Case

Combating Fatigue/Sleepiness

Significantly improves wakefulness and reduces excessive daytime sleepiness, particularly in conditions like narcolepsy or shift work sleep disorder. Effects are potent and long-lasting.

Cognitive Enhancement (Healthy Adults)

Offers small but significant improvements in attention, executive function, and memory in non-sleep-deprived individuals. Benefits may be more pronounced during demanding tasks but are generally limited compared to effects on wakefulness.

ADHD Symptom Management

Shows potential as an alternative to traditional stimulants for improving ADHD symptoms in some adults. Efficacy compared to standard treatments varies, and it's considered a safer option regarding abuse potential.

Supporting Substance Abuse Recovery

Investigated as an adjunct therapy to improve cognitive deficits and potentially aid abstinence in stimulant (cocaine, methamphetamine) dependence. Clinical trial results have been inconsistent, though positive trends exist, especially regarding cognitive function.

Performance Under Sleep Deprivation

Effectively maintains alertness, mood, and cognitive performance (accuracy, reaction time) during periods of prolonged wakefulness, such as in military operations. High doses may cause side effects, and efficacy can depend on the extent of sleep loss.

Mechanism of Action

Modafinil's primary mechanism involves inhibiting the dopamine transporter (DAT), which increases extracellular dopamine levels, particularly in brain regions like the nucleus accumbens and prefrontal cortex. Unlike typical psychostimulants, it has lower affinity for DAT but achieves comparable occupancy at clinical doses. Modafinil also indirectly affects other neurotransmitter systems: it may increase norepinephrine (possibly via DAT blockade effects on NET or electronic coupling in the locus coeruleus), glutamate (via reduced GABAergic tone or increased synthesis), and histamine and orexin/hypocretin (potentially via indirect pathways involving GABA or glutamate). It consistently lowers GABA levels in several brain regions, possibly through indirect catecholamine-dependent mechanisms. Modafinil shows minimal direct interaction with serotonin or acetylcholine systems but may influence them indirectly, and it increases electrical coupling (gap junctions) between certain neuronal populations, potentially enhancing neuronal synchrony and contributing to wakefulness and cognitive effects.

Frequently Asked Questions

Is Modafinil addictive?

When should I take Modafinil?

How does Modafinil compare to Adderall or Ritalin?

Can Modafinil improve cognition in healthy people?

Is Modafinil legal to buy?

Does Modafinil affect sleep quality?

Are there long-term effects of using Modafinil?

Can Modafinil help with depression or anxiety?

Summary & Expert Opinion

Modafinil is a well-established wakefulness-promoting agent with demonstrated efficacy in treating sleep disorders and combating fatigue, particularly under conditions of sleep deprivation. Its strengths lie in its potent alerting effects combined with a relatively low abuse potential compared to traditional stimulants, and it shows modest benefits for cognitive functions like attention and executive control in non-sleep-deprived individuals. Individuals needing to manage excessive sleepiness due to diagnosed conditions or maintain performance during unavoidable sleep loss (e.g., shift work, military operations) are the primary candidates for its use under medical guidance. Due to its prescription status, complex interactions with neurotransmitter systems, and potential side effects (especially at higher doses), individuals without a diagnosed sleep disorder, those sensitive to stimulants, or people taking interacting medications should avoid self-prescribing Modafinil.

Research Studies

Showing 5 of 8 studies

Student Cognitive Enhancement with Non-Prescribed Modafinil. Is it Cheating? (2024)

cheating cognitive enhancement ethics +2 more

Authors:

Alexia Kesta, Philip M. Newton

Findings:

Most UK university students surveyed did not view non-prescribed modafinil use for cognitive enhancement as cheating, often comparing it to caffeine or believing it doesn't grant new knowledge. A minority held strong opposing views based on fairness and access. These perspectives remained largely stable even when presented with ethical moderators.

Participants:

UK University students

Study Quality Assessment:

Preprint, not peer-reviewed. Used a scenario-based approach. No competing interests declared. No specific funding received. Ethical guidelines followed, IRB approval obtained (Swansea University Medical School Research Ethics Committee), participant consent obtained. Reporting guidelines followed. Data available as supplementary material.

All Effects:

cheating cognitive enhancement ethics modafinil student views

Modafinil (2023)

Authors:

Karl Greenblatt, Ninos Adams

Participants:

patients with fatigue or excessive daytime sleepiness (EDS) secondary to traumatic brain injury (TBI)

Study Quality Assessment:

Literature search of Medline and PubMed using EBSCOhost database. Included primary literature, observational studies, meta-analyses, case reports.

Systematic review shows 'smart drug' modafinil does enhance cognition (2015)

attention cognitive enhancement executive functioning +2 more

Findings:

The overall positive effect of single-dose modafinil over placebo across cognitive domains (attention, executive functioning, memory, processing speed) was small but significant (g = 0.10). No significant differences were found between cognitive domains, modafinil doses (100 mg vs 200 mg), or populations studied (psychiatric vs nonpsychiatric). The evidence indicates limited potential for modafinil as a cognitive enhancer in non-sleep-deprived populations.

Participants:

Non-sleep-deprived adults (including psychiatric vs nonpsychiatric populations).

Dosage:

Single-dose effects studied; doses compared were 100 mg vs 200 mg.

Study Quality Assessment:

Systematic Review and Meta-Analysis of 19 placebo-controlled trials; calculated 67 cognitive domain-specific effect sizes.

All Effects:

attention cognitive enhancement executive functioning memory processing speed

The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders (2013)

attention cognitive enhancement dopamine transporter inhibition +2 more

Authors:

Maddalena Mereu

Findings:

Modafinil (MOD) enhances cognitive functions like attention, learning, and memory, likely via dopamine transporter (DAT) inhibition and effects on other neurotransmitter systems (e.g., glutamate, GABA, histamine, orexin) and brain areas distinct from typical psychostimulants. Despite inconsistent results in clinical trials for substance use disorders, it shows potential for improving cognitive deficits in these populations and as an ADHD treatment, with relatively low abuse liability. Non-dopaminergic mechanisms may contribute significantly to its wake-promoting and cognitive effects.

Participants:

The review covers studies involving human participants (healthy volunteers, patients with mental disorders including schizophrenia, substance abusers [cocaine, methamphetamine, tobacco smokers], individuals with ADHD, military personnel/pilots) and animal models (rats, mice, monkeys, marmosets, guinea-pigs). Specific human clinical studies mentioned include sample sizes ranging from N=6 to N=210.

Dosage:

Human studies reviewed used various oral dosages, including single doses (e.g., 200-800mg), daily doses (e.g., 100mg, 200mg, 400mg, 800mg) for periods ranging from days to 12 weeks. Specific regimens mentioned include 100mg/day, 200mg/day, 400mg/day, 200-600mg, 200-800mg ranges, and high-dose military use (e.g., 3x100mg or 3x200mg per day). Animal studies used doses like 75 mg/kg and 300 mg/kg. The R-enantiomer (R-MOD/Armodafinil) is also mentioned.

Study Quality Assessment:

The review discusses studies using various methodologies including preclinical (in vitro, in vivo animal studies using techniques like microdialysis, c-Fos, PET, single unit recordings, behavioral tasks) and clinical studies (human PET, functional neuroimaging, clinical trials). Several clinical trials are described as double-blind, placebo-controlled, or open-label. Methods mentioned include subjective effects ratings, urine analysis for metabolites, cognitive/neuropsychological testing (e.g., working memory, attention tasks), assessment of safety/tolerability, and use of specific questionnaires. Some trials included cognitive behavioral therapy. Challenges like medication compliance in trials are noted.

All Effects:

attention cognitive enhancement dopamine transporter inhibition substance use disorder treatment wakefulness

Archival Report Modafinil Improves Episodic Memory and Working ...

Modafinil

Participants:

patients with fatigue or excessive daytime sleepiness (EDS) secondary to traumatic brain injury (TBI)

Study Quality Assessment:

Literature search of Medline and PubMed was performed using the EBSCOhost database. Included primary literature, observational studies, meta-analyses, case reports.

Modafinil, an atypical CNS stimulant?

CNS stimulant cognitive functions sleep disorders +1 more

Findings:

Modafinil exhibits an 'atypical' CNS stimulant profile based on its pharmacokinetics/pharmacodynamics and shows beneficial effects in treating sleep disorders, enhancing cognitive functions, and managing substance use disorders.

All Effects:

CNS stimulant cognitive functions sleep disorders substance use disorders

What keeps us awake: the neuropharmacology of stimulants and wakefulness-promoting medications

neuropharmacology neurotransmitter systems sleep regulation +2 more

Findings:

Sleep-wake transitions are regulated by oscillating neurobiologic mechanisms involving multiple neurotransmitter systems (e.g., noradrenergic, dopaminergic, adenosinergic, hypocretin/orexin). Stimulants like amphetamines (dopamine), modafinil (noradrenergic/dopaminergic/hypocretin), caffeine (adenosinergic), and nicotine (acetylcholine/dopamine) promote wakefulness by modulating these systems. Understanding hypocretin/orexin and dopamine pathways is key for developing future wakefulness-promoting drugs.

Study Quality Assessment:

Article type: Review. Based on 'Numerous studies'. Funding mentioned: 'Research Support, Non-U.S. Gov't', 'Research Support, U.S. Gov't, P.H.S.', 'Grants and funding DA04398/DA/NIDA NIH HHS/United States'.

All Effects:

neuropharmacology neurotransmitter systems sleep regulation stimulants wakefulness

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Categories & Effectiveness

Brain Health

Dopamine Support

Cognition

Mental Acuity

Concentration & Focus

Memory & Recall

Processing Speed

Energy & Alertness

Alertness & Vigilance

Wakefulness Promotion

Sleep Quality

Sleep Cycle Regulation

Dosage & Side Effects

Recommended Dosage

Potential Side Effects

Bioavailability & Half-Life

Interactions & Stacks

Benefits by Use Case

Combating Fatigue/Sleepiness

Cognitive Enhancement (Healthy Adults)

ADHD Symptom Management

Supporting Substance Abuse Recovery

Performance Under Sleep Deprivation

Mechanism of Action

Frequently Asked Questions

Summary & Expert Opinion

Research Studies

Student Cognitive Enhancement with Non-Prescribed Modafinil. Is it Cheating? (2024)

Authors:

Findings:

Participants:

Study Quality Assessment:

All Effects:

Modafinil (2023)

Authors:

Participants:

Study Quality Assessment:

Systematic review shows 'smart drug' modafinil does enhance cognition (2015)

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

The neurobiology of modafinil as an enhancer of cognitive performance and a potential treatment for substance use disorders (2013)

Authors:

Findings:

Participants:

Dosage:

Study Quality Assessment:

All Effects:

Archival Report Modafinil Improves Episodic Memory and Working ...

Study Quality Assessment:

Modafinil

Participants:

Study Quality Assessment:

Modafinil, an atypical CNS stimulant?

Findings:

All Effects:

What keeps us awake: the neuropharmacology of stimulants and wakefulness-promoting medications

Findings:

Study Quality Assessment:

All Effects:

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