tuneTypical Dose
Historical clinical use typically ranged from 600 to 1200 mg/day, but this is not a validated modern supplement protocol
Chemical Compound
Adrafinil
2-((diphenylmethyl)sulfinyl)-N-hydroxyacetamide
Evidence TierCWADA PROHIBITED
watchEffect Window
Not well standardized in human trials. Preclinical persistence suggests effects can outlast immediate dosing windows.
lockCompliance
WADA PROHIBITED
Overview
Clinical Summary
Adrafinil is a discontinued wakefulness drug that works mainly by being converted to modafinil. Direct human efficacy evidence for adrafinil itself is sparse.
Historical use and pharmacology make wakefulness and fatigue-reduction effects plausible, but most modern benefit claims are inferred from modafinil rather than established in direct adrafinil trials. The key practical drawback is that adrafinil has slower, less predictable onset because it must be converted in the liver, which adds avoidable uncertainty and more liver-monitoring concern than modafinil itself.
Adrafinil is a prodrug converted to modafinil. Human efficacy remains evidence-limited and should be interpreted with caution until robust modern trials are available.
Outcomes
What This Is Expected To Influence
Primary Outcomes
- Metabolic conversion to modafinil. Limited direct modern human outcome standardization.
Secondary Outcomes
- Preclinical increased locomotor activity and learning-task effects in aged canine models.
Safety
Contraindications and Interactions
Contraindications
- Pregnancy
- Lactation
- Severe hepatic/renal/cardiovascular disease
- Unstable psychiatric illness
Side effects
- Headache
- Nausea
- Anxiety
- Elevated liver enzymes with chronic use
Interactions
- CNS stim overlap
- Hepatically metabolized compounds
Avoid if
- Active malignancy
- Serious heart disease
- Uncontrolled psychiatric instability
Evidence
Study-level References
adrafinil-SRC-001Forensic pharmacology and analytical case context with a human volunteer self-administration component.
Sourceopen_in_newAmeline AS, Gheddar L, Raul JS, Kintz P. "Identification of adrafinil and its main metabolite modafinil in human hair: Self-administration study and interpretation of an authentic case." Forensic Sci Res. 2020;5(4):322–326. doi: 10.1080/20961790.2019.1704482; PMID: 33457050.
Population: One self-administered oral 200 mg exposure plus an authentication case workflow.
Dose protocol: Oral adrafinil exposure with LC-MS/MS-based hair analysis context.
Key findings: Supports pharmacologic identity and metabolic relationship to modafinil rather than quantifying broad efficacy outcomes.
Notes: Not a controlled efficacy trial. Primary output is exposure and metabolic confirmation in a specialized context.
Paper content
Supports pharmacologic identity and metabolic relationship to modafinil rather than quantifying broad efficacy outcomes.
adrafinil-SRC-002Preclinical behavioral study.
Sourceopen_in_newSiwak CT, Gruet P, Woehrlé F, Schneider M, Muggenburg BA, Murphey HL, Callahan H, Milgram NW. "Behavioral activating effects of adrafinil in aged canines." Pharmacol Biochem Behav. 2000;66(2):293-300. doi: 10.1016/S0091-3057(00)00188-X; PMID: 10880681.
Population: Aged dogs, crossover design.
Dose protocol: 10, 20, 30, and 40 mg/kg oral adrafinil over short repeated sessions.
Key findings: Increased locomotor activity relative to control in multiple active-dose contexts. No stereotypic behavioral toxicity reported.
Notes: Species and translational constraints. No direct human efficacy quantification.
Paper content
Increased locomotor activity relative to control in multiple active-dose contexts; no stereotypic behavioral toxicity reported.
adrafinil-SRC-003Preclinical learning-behavior study.
Sourceopen_in_newSiwak CT, Milgram NW, et al. "Oral administration of adrafinil improves discrimination learning in aged beagle dogs." Pharmacol Biochem Behav. 2000;66(2):301-305. doi: 10.1016/S0091-3057(00)00175-1; PMID: 10880682.
Population: Aged beagle dogs, crossover-like task reversal design.
Dose protocol: 20 mg/kg oral adrafinil, behavior task acquisition and reversal testing.
Key findings: Reported improvement in errors-to-criterion and task acquisition metrics.
Notes: Preclinical model and historical dataset. Human cognitive transfer uncertain.
Paper content
Reported improvement in errors-to-criterion and task acquisition metrics.
adrafinil-SRC-004Official anti-doping regulatory reference.
Sourceopen_in_newWorld Anti-Doping Agency Prohibited List, https://www.wada-ama.org/en/content/what-is-prohibited.
Population: Governance framework.
Dose protocol: Not applicable.
Key findings: Indicates compliance-relevant stimulant control context including modafinil-class compounds.
Notes: Policy context changes. Lists may evolve and vary by season.
Paper content
Indicates compliance-relevant stimulant control context including modafinil-class compounds.
adrafinil-SRC-005Official anti-doping regulatory reference.
Sourceopen_in_newUSADA Prohibited List, https://www.usada.org/substances/prohibited-list/.
Population: Governance framework.
Dose protocol: Not applicable.
Key findings: Reinforces the need for sport-season verification before use.
Notes: Regional governance source, not a clinical efficacy source.
Paper content
Reinforces the need for sport-season verification before use.
adrafinil-SRC-006Clinical safety evidence summary.
Sourceopen_in_newK. Zimmerman et al., "Modafinil - LiverTox," NCBI Bookshelf, 2022 (NBK548274).
Population: Modafinil/armodafinil clinical and post-marketing safety summaries.
Dose protocol: Trial and observational settings. No direct adrafinil clinical trial quantification.
Key findings: Modafinil/armodafinil shows low rates of aminotransferase elevation in trials, with low frequency of clinically apparent liver injury. Indirect support for cautious inference only.
Notes: Important inference limit: this source is not a direct adrafinil efficacy/safety corpus.
Paper content
Modafinil/armodafinil shows low rates of aminotransferase elevation in trials, with low frequency of clinically apparent liver injury; indirect support for cautious inference only.