Dependence phenotype
- Escalating dose or potency; redosing every 1–3 hours
- Waking overnight or early morning in withdrawal
- Using primarily to avoid sickness
- Rapid return of anxiety, restlessness, chills, pain, or GI symptoms between doses
- Inability to reduce despite attempts; craving and fear of losing access
Symptom domains
Opioid-like: yawning, lacrimation/rhinorrhea, piloerection, chills, sweating, restlessness, myalgias, abdominal cramping, nausea, vomiting, diarrhea, tachycardia, hypertension, insomnia, craving.
Affective/cognitive: anxiety, dysphoria, irritability, poor concentration, fatigue, low mood—often outlasting the most obvious autonomic/GI phase.
Mixed/product-related: tremor, stimulation, severe insomnia, or symptoms from nicotine, stimulants, alcohol, benzodiazepines, gabapentinoids, or undeclared compounds.
Provisional timeline
| Time from last dose | Best-available expectation | Confidence |
|---|---|---|
| 0–8 h | Heavy users may notice interdose withdrawal; others may still feel relatively well. | Practice-based / emerging |
| 8–24 h | Clinically significant withdrawal often becomes clearer. | Emerging |
| 16–36 h | Provisional peak window for many short-acting presentations—not universal. | Provisional |
| Days 2–3 | Often the roughest overall period for autonomic, GI, sleep, anxiety, and craving. | Emerging |
| Days 3–5 | Vomiting/diarrhea, chills, sweating, and pain often begin to ease; sleep/mood/craving may remain. | Practice-based / indirect |
| Day 5–2+ weeks | Acute physical symptoms usually fade; insomnia, low mood, fatigue, and craving can persist. | Practice-based / analogy |
Why COWS can under-read
COWS was not designed around 7-OH products or mixed alkaloids. It can underweight severe insomnia, dysphoria, disproportionate abdominal distress, mixed stimulant/sedative symptoms, and fluctuating state after frequent redosing.
Fentanyl substitution risk
Losing retail access without a treatment plan can drive stockpiling or substitution with counterfeit pills or street opioids. That is a foreseeable failure mode worth preventing—not a measured epidemic curve. See treatment and crisis.