Drug interaction checker

High risk — the redose trap. SSRIs block the serotonin transporter (SERT) that MDMA needs, significantly blunting effects. Paradoxically, a 2022 systematic review found SSRIs may actually reduce direct serotonin syndrome risk from MDMA by blocking its mechanism — but the real danger is behavioral: blunted euphoria drives redosing, sharply raising cardiovascular overdose risk. Cardiovascular effects (heart rate, blood pressure, hyperthermia) persist regardless of SERT occupancy. Do not stop SSRIs abruptly to "feel" MDMA — discuss with your prescribing doctor.

Potentially fatal — do not combine. MAOIs block monoamine oxidase, the enzyme responsible for breaking down serotonin. MDMA simultaneously floods the brain with serotonin. The combined serotonin overload can cause fatal serotonin syndrome: agitation, hyperthermia, seizures, cardiac events. Irreversible MAOIs require a 2-week washout period; reversible MAOIs (like moclobemide) require at least 24 hours — but neither is safe to combine with MDMA.

Dangerous — documented seizure risk. Multiple clinical case reports document seizures and cardiac arrhythmia. A 2021 analysis found 47% of 62 lithium+psychedelic online reports involved seizures (PMID 34348413); a 2024 case report documented 3 generalized seizures in 30 minutes in an adolescent on sub-therapeutic lithium (PMID 38986146). The same risk applies to psilocybin. If on lithium, psychedelics are contraindicated.

High risk — respiratory depression. Both ketamine (NMDA antagonist with opioid activity) and alcohol (GABA potentiator) are CNS depressants. Combined, they synergistically suppress the respiratory drive. The k-hole — already a state where you cannot call for help — becomes far more dangerous when alcohol is added. Never let someone who has combined ketamine and alcohol fall asleep unmonitored; place them in the recovery position.

High risk — toxic metabolite formed in the liver. When cocaine and ethanol are present simultaneously, the liver produces cocaethylene via transesterification. Cocaethylene is more cardiotoxic than cocaine and has a longer half-life (~5 hours vs. ~1 hour for cocaine). A 2024 systematic review quantified the risk: cocaethylene carries an 18–25× increased risk of sudden death vs. cocaine alone (PMID 38592322). The more alcohol consumed, the more cocaethylene is produced.

SSRIs blunt effects; anxiety can be amplified. Chronic SSRI use downregulates 5-HT2A receptors — the primary target of psilocybin. Many people on SSRIs report little to no psychedelic effect. Do not escalate the dose to compensate; cardiovascular and physiological effects persist independent of receptor density. If you have anxiety, psilocybin can significantly intensify it; a low dose (<1g dry weight), safe familiar setting, and a trusted sober sitter are essential.

Popular but carries elevated risk. A candy flip combines MDMA and LSD. Because LSD lasts 8–12 hours, the total experience extends to 12–18 hours — a prolonged period of elevated serotonin, cardiovascular strain, and hyperthermia risk. If attempting: take MDMA 3–4 hours into the LSD trip so the peaks align; keep MDMA at 75mg or less; stay cool and hydrated; have a sober person present. Allow at least twice the normal recovery time between sessions.

Yes — benzos are the recommended trip-abort tool. Benzodiazepines (diazepam, lorazepam, alprazolam) reliably reduce psychedelic intensity by potentiating GABA-A receptors. They blunt but don't fully eliminate LSD or psilocybin effects. Diazepam 10–20mg is commonly used in clinical and harm reduction settings. Keep a benzo available as a safety net — don't use them recreationally to "take the edge off" while continuing to dose more substance.

No — one of the most dangerous festival combinations. GHB has an extremely steep dose-response curve: the margin between euphoria and unconsciousness is narrow even alone. Alcohol, benzos, and ketamine are all CNS depressants that synergize with GHB to cause respiratory depression and coma. Clinical toxicology reviews identify alcohol as the primary factor converting GHB intoxication into fatality. GHB + alcohol is responsible for a significant proportion of GHB-related deaths. If someone is unresponsive after taking GHB, place in the recovery position and call emergency services immediately — do not leave them to "sleep it off."

No — tramadol + MDMA or SSRIs risks serotonin syndrome. Tramadol is not a simple painkiller — it inhibits serotonin reuptake (like an SSRI) while also acting as a mild opioid. Combined with MDMA's massive serotonin release or an SSRI's reuptake blockade, the serotonergic load can cause serotonin syndrome. Multiple case reports confirm this with SSRIs (PMID 24153222). Tramadol also lowers seizure threshold — alcohol further reduces it. If you're prescribed tramadol, tell your doctor about all substances you use.

Common but frequently causes anxiety — timing matters. THC amplifies 5-HT2A receptor activity, intensifying all psychedelic effects — including difficult ones. Using cannabis at the peak of a psychedelic experience is riskier than using it during the comedown. If combining: wait until 2–3 hours in (post-peak), use a very small amount of low-THC cannabis, and avoid concentrates entirely. One poorly-timed dab can turn a manageable trip into a psychological crisis.

No — this is an absolute contraindication and has caused deaths. Poppers (alkyl nitrites: amyl nitrite, isobutyl nitrite) and PDE5 inhibitors (sildenafil/Viagra, tadalafil/Cialis, vardenafil/Levitra, avanafil/Stendra) both cause vasodilation through overlapping mechanisms. Poppers release nitric oxide (NO) → activate guanylate cyclase → raise cGMP. PDE5 inhibitors block cGMP breakdown. Combined, cGMP accumulates to extreme levels, producing severe, potentially fatal hypotension (blood pressure crash). Tadalafil (Cialis) has a 36-hour half-life — using poppers within 36 hours of taking Cialis carries risk even if the pill was taken "well before." If you take PDE5 inhibitors regularly, poppers should be completely avoided. See our full Poppers guide →

Alcohol is the most dangerous — it accounts for most GHB-related deaths. GHB and alcohol both act at GABA receptors as CNS depressants. Their combination is synergistic (multiplicative), not additive — even a single drink substantially lowers the dose at which unconsciousness and respiratory failure can occur. There is no antidote for GHB overdose. Other high-risk combinations include benzodiazepines (same mechanism as alcohol), opioids (additive respiratory depression), and ketamine (unpredictable combined CNS depression). Stimulants (MDMA, cocaine) combined with GHB may mask sedation, making it harder to judge intoxication level — a common cause of accidental overdose. See our full GHB / GBL guide →