Quick Comparison
| Adrafinil | Rhodiola Rosea | |
|---|---|---|
| Half-Life | 1 hour (adrafinil itself), but modafinil metabolite: 12-15 hours | 6-8 hours (salidroside) |
| Typical Dosage | Standard: 300-600 mg once in the morning. 600 mg adrafinil roughly equals 200 mg modafinil. Do not use daily for extended periods due to liver metabolism. Cycle 2-3 times per week maximum. | Standard: 200-400 mg daily of extract standardized to 3% rosavins and 1% salidroside. SHR-5 is the most studied extract. Take in the morning — can be mildly stimulating. |
| Administration | Oral (capsules, powder). Takes 45-60 minutes for effects (liver conversion time). | Oral (capsules, tablets, tincture). Standardized extracts preferred. |
| Research Papers | 10 papers | 10 papers |
| Categories |
Mechanism of Action
Adrafinil
Adrafinil is a prodrug—it is pharmacologically inactive until metabolized by hepatic cytochrome P450 enzymes (primarily CYP3A4) and possibly esterases into modafinil (the active metabolite) and modafinilic acid (inactive byproduct). The conversion involves oxidation of the sulfinyl group. Once converted, adrafinil acts identically to modafinil: inhibition of the dopamine transporter (DAT), activation of orexin/hypocretin neurons in the lateral hypothalamus, increased histamine release from tuberomammillary nuclei, and elevation of norepinephrine and serotonin in cortical regions. The hepatic first-pass conversion step explains the delayed onset (45-60 minutes vs 20-30 for modafinil) and the concern about liver enzyme elevation and oxidative stress with chronic daily use.
Rhodiola Rosea
Rhodiola modulates the hypothalamic-pituitary-adrenal (HPA) axis and reduces cortisol release under stress, possibly through modulation of glucocorticoid receptor sensitivity. Salidroside and rosavins inhibit catechol-O-methyltransferase (COMT) and monoamine oxidase A and B (MAO-A, MAO-B), slowing the breakdown of dopamine, serotonin, and norepinephrine in the brain — increasing catecholamine availability in the prefrontal cortex and limbic system during stress. Rhodiola activates AMP-activated protein kinase (AMPK), a cellular energy sensor that enhances glucose uptake and mitochondrial biogenesis. It has antioxidant effects via activation of Nrf2 and HO-1, protecting neurons from stress-induced oxidative damage. Salidroside may also modulate opioid peptide (beta-endorphin) release and enhance nitric oxide production.
Risks & Safety
Adrafinil
Common
Headache, nausea, anxiety, insomnia, stomach discomfort.
Serious
Liver enzyme elevation with chronic daily use — periodic liver function tests recommended. Same SJS risk as modafinil (extremely rare).
Rare
Skin irritation, orofacial dyskinesia.
Rhodiola Rosea
Common
Mild dizziness, dry mouth, jitteriness.
Serious
May have MAOI-like properties at high doses — avoid combining with MAOI medications.
Rare
Insomnia, vivid dreams, agitation.
Full Profiles
Adrafinil →
A prodrug that is metabolized in the liver to modafinil. Adrafinil provides the same wakefulness and cognitive effects as modafinil but is available without a prescription in most countries. The tradeoff is that it takes longer to kick in (45-60 minutes vs 20-30 for modafinil) and puts additional load on the liver due to first-pass metabolism.
Rhodiola Rosea →
An arctic adaptogen used traditionally in Scandinavia and Russia for physical endurance and mental resilience. Rhodiola's key compounds, salidroside and rosavin, reduce mental fatigue and improve performance under stress. It is one of the few adaptogens with robust evidence for acute cognitive effects — improvements can be noticed within hours of a single dose.