Combination Safety

Scenario-first guidance for the situations people actually find themselves in. Start here, then dig into the full table if you need it.

Common Scenarios

I'm on an SSRI or antidepressant

Dulled effect, not usually dangerous — but MAOIs are a hard no

SSRIs and SNRIs blunt most classical psychedelics by occupying the same serotonin receptors. The trip is weaker or absent. The real danger is MAOIs, which can cause serotonin syndrome or hypertensive crisis when combined with psychedelics.

What to do: Don't stop your medication for a trip. If you're on an MAOI, do not combine with any psychedelic. Talk to your prescriber if you're curious about tapering — never do it alone.

I drink alcohol

Risky with MDMA and ketamine; muddy and unpredictable with psychedelics

Alcohol plus MDMA strains the liver and cardiovascular system while masking the signs of overheating. With ketamine, the respiratory depression risk rises. With psychedelics, alcohol tends to make experiences chaotic, nauseating, or emotionally sloppy rather than meaningful.

What to do: If you're going to use a psychedelic, skip drinking that day. Your liver, your judgment, and your experience will all be better for it.

I smoke weed daily

Cannabis amplifies psychedelics unpredictably — sometimes gently, sometimes overwhelmingly

Weed on its own is mild, but combined with psilocybin or LSD it can dramatically intensify visuals, paranoia, and confusion. The effect is dose-dependent and hard to predict. What felt fine last time might feel overwhelming this time.

What to do: If you use cannabis during a trip, start with a tiny amount and wait. Better yet, experience the psychedelic on its own first so you know what you're amplifying.

I take ADHD medication

Stimulants + psychedelics or MDMA = elevated cardiovascular risk

Amphetamines and methylphenidate already raise heart rate and blood pressure. Adding a psychedelic or MDMA pushes the same systems harder. The combination can produce anxiety, chest tightness, and in vulnerable people, dangerous cardiac strain.

What to do: Skip your ADHD meds on the day of the experience. If you're prescribed them, talk to your doctor about timing. Do not combine stimulants with MDMA under any circumstances.

Festival weekend / multiple days

The biggest risk isn't one substance — it's the cascade

Sleep deprivation, heat, dehydration, and multiple substances across multiple days compound in ways no chart can capture. MDMA two days in a row is especially neurotoxic because serotonin stores don't replenish overnight. Cross-tolerance between psychedelics builds quickly too.

What to do: Pick one primary substance for the weekend. If you use MDMA, wait at least 3 months before the next roll. Get real sleep between days. Hydrate with electrolytes, not just water.

I'm on lithium

Dangerous with classical psychedelics — documented seizure risk

Lithium combined with LSD or psilocybin has been associated with seizures in multiple case reports. The mechanism isn't fully understood, but the signal is strong enough that this combination is considered contraindicated in clinical and harm-reduction communities.

What to do: Do not combine lithium with any classical psychedelic. If you're curious about psychedelics and take lithium, this is a conversation for your psychiatrist — not a risk to take quietly.

Full reference table The classic combination matrix
Substance PsilocybinLSDMDMADMTMescaline2C-BKetamineCannabisAlcohol
Psilocybin — Caution Caution Safe Safe Caution Caution Caution Caution
LSD Caution — Caution Safe Safe Caution Caution Caution Caution
MDMA Caution Caution — Unsafe Unsafe Unsafe Unsafe Safe Unsafe
DMT Safe Safe Unsafe — Safe Safe Caution Caution Caution
Mescaline Safe Safe Unsafe Safe — Caution Caution Caution Caution
2C-B Caution Caution Unsafe Safe Caution — Caution Caution Unsafe
Ketamine Caution Caution Unsafe Caution Caution Caution — Caution Dangerous
Safe — no significant interaction expected
Caution — interaction possible; monitor closely
Unsafe — significant risk; avoid if possible
Dangerous — potentially life-threatening

Critical Danger Zones

  • MAOIs + any psychedelic: Risk of fatal serotonin syndrome or hypertensive crisis
  • Lithium + LSD or psilocybin: Documented seizure risk
  • Tramadol + MDMA or psychedelics: Serotonin syndrome risk
  • Stimulant stacking: Combining MDMA, cocaine, or amphetamines strains the cardiovascular system unpredictably
  • MAOIs + mescaline or 2C-B: Phenethylamines combined with MAOIs can cause dangerous hypertensive crisis

For the full, detailed chart, visit TripSit's combination chart.