Summary
Loperamide is an over-the-counter anti-diarrheal that normally does not cross the blood-brain barrier due to P-glycoprotein efflux. At therapeutic doses (2-16 mg/day), it is safe and effective. High-dose misuse (50-400+ mg) to achieve opioid effects or manage withdrawal is extremely dangerous and has caused numerous deaths from cardiac arrhythmias (QT prolongation, Torsades de Pointes). The FDA issued warnings in 2016 about life-threatening cardiac complications. Combining with P-glycoprotein inhibitors dramatically increases CNS effects and toxicity risk.
Dose Information
| ROA | Light | Common | Strong | Heavy |
|---|---|---|---|---|
| Oral | - | - | - | 16+mg(notrecommended)+ |
| Rectal | - | - | - | 16+mg(notrecommended)+ |
Light
Common
Strong
Heavy
Onset, Duration & After-effects
| ROA | Onset | Comeup | Peak | Offset | After Effects |
|---|---|---|---|---|---|
| Oral | 30-60 min | 1-2 hrs | 2-5 hrs | 12-24 hrs | 24-48 hrs |
| Rectal | 30-60 min | 1-2 hrs | 2-5 hrs | 12-24 hrs | 24-48 hrs |
Tolerance
Build-up
develops within days of regular use; analgesic tolerance faster than respiratory depression tolerance
Reset
7–14 days for partial reset; full reset may take weeks — tolerance loss greatly increases overdose risk
Effects
Positive
- Pain relief
- Physical euphoria
Negative
- Respiratory depression
- Abnormal heartbeat
- Nausea
- Abdominal discomfort
- Sedation
- Itchiness
- Pupil constriction
- Impaired motor control
Positive
- Cognitive euphoria
- Anxiety suppression
- Reduced anxiety
- Euphoria
Negative
- Constipation
- Confusion
- Cognitive impairment
- Dissociation
- Altered time perception
- Time distortion
Positive
- Visual geometry
- Increased music appreciation
- Perception of bodily lightness
Negative
- Spatial disorientation
- Dulled perception
- Visual and auditory hallucinations
- Internal hallucination
- Visual disconnection
- External hallucination
- Optical sliding