A large share of drug deaths involve more than one substance. Some combinations multiply each other's risks instead of adding them. These are the ones to know cold.
Depressant stacking is the number-one killer Opioids, benzodiazepines, alcohol, GHB/GBL, and gabapentinoids all suppress breathing. Combining any of them multiplies that effect and is the most common cause of fatal overdose. Avoid mixing depressants.
The combinations to avoid
Below are the high-danger pairings. When in doubt, check a dedicated interaction chart and this site's per-substance combination data before mixing anything.
| Combination | Why it's dangerous |
|---|---|
| Opioids + benzos / alcohol / GHB | Stacked respiratory depression — breathing can simply stop. |
| Stimulants + MAOIs | Hypertensive crisis — dangerously high blood pressure. |
| MDMA / stimulants + MAOIs | Serotonin syndrome and hyperthermia; can be fatal. |
| Serotonergics together (MDMA + SSRIs / tramadol / MAOIs) | Serotonin syndrome. |
| Lithium / tramadol / bupropion + psychedelics | Raised seizure risk; lithium + psychedelics is linked to seizures. |
| DXM + MAOIs / serotonergics | Serotonin syndrome. |
| Cocaine + alcohol | Forms cocaethylene — extra strain on the heart and liver. |
Use an interaction chart The TripSit drug-combination chart and each substance's combos section here flag "dangerous" and "unsafe" pairings. Check before, not after.
✓ Do
- Check every combination against a chart first.
- If you must combine, space doses out and use less of each.
- Keep naloxone around any opioid, including in mixes.
✕ Don't
- Don't stack depressants — opioids, benzos, alcohol, GHB.
- Don't mix serotonergic drugs (MDMA, SSRIs, MAOIs, tramadol).
- Don't assume "a little" of a second depressant is safe.