Antidepressant & Psychedelic Drug Interaction Chart
Disclaimer: This chart is for informational purposes only and should not be used to make medical decisions. It is based on available data and some extrapolation. Decisions to start, stop, or taper medication and/or use psychedelic substances should always be made in consultation with your healthcare provider(s). Engaging in illicit activities is not recommended. For personal use only; do not copy or distribute.
Key Abbreviations:
SSRI: Selective Serotonin Reuptake Inhibitor
SPARI: Serotonin Partial Agonist and Reuptake Inhibitor
SNRI: Serotonin Norepinephrine Reuptake Inhibitor
DNRI: Dopamine Norepinephrine Reuptake Inhibitor
MAOI: Monoamine Oxidase Inhibitor
5HT2A: Serotonin 2A Receptor
SERT: Serotonin Reuptake Pump
Unified Drug Interactions Chart
Drug Class
Psychedelic Class
Interaction Notes
Recommendations
SSRIs (e.g., Paroxetine, Sertraline)
Phenethylamines (MDMA, Mescaline)
Drastically reduced effects due to blocked serotonin reuptake pump.
Taper 2 weeks prior (6 weeks for fluoxetine).
Tryptamines (Psilocybin, LSD)
Potential blunted effects due to receptor downregulation; psilocybin may be less affected.
Taper 2 weeks prior (6 weeks for fluoxetine).
MAOI-containing (Ayahuasca, Syrian Rue)
High risk of serotonin syndrome. Strictly contraindicated.
Avoid combination.
Ketamine
Found effective with or without antidepressants.
No taper required.
Ibogaine
Risk of QTc prolongation, arrhythmias. Some SSRIs inhibit liver enzymes, increasing ibogaine concentration.
Taper 2 weeks prior.
SPARI (e.g., Vilazodone, Vortioxetine)
Phenethylamines
Similar to SSRIs, reduced effects of MDMA.
Taper 2 weeks prior.
Tryptamines
Blunted effects possible.
Taper 2 weeks prior.
MAOI-containing
Risk of serotonin syndrome. Contraindicated.
Avoid combination.
SNRIs (e.g., Venlafaxine, Duloxetine)
Phenethylamines
Similar to SSRIs; reduced MDMA effects.
Taper 2 weeks prior.
Tryptamines
Blunted effects likely.
Taper 2 weeks prior.
MAOI-containing
High risk of serotonin syndrome.
Avoid combination.
Ibogaine
Increased risk of cardiotoxicity.
Taper 2 weeks prior.
DNRI (e.g., Bupropion)
Phenethylamines
Increased MDMA effects; higher seizure risk.
Reduce MDMA dose by 25% or taper bupropion.
Tryptamines
Loss of effect not predicted.
Taper based on goals.
MAOI-containing
Serotonin syndrome unlikely.
Taper 2 weeks prior.
Ibogaine
May increase ibogaine concentration; seizure risk.
Taper 2 weeks prior.
Tricyclic Antidepressants (TCA)
Phenethylamines
Reduced MDMA effects.
Taper 2 weeks prior.
Tryptamines
Intensified LSD effects reported.
Taper 2 weeks prior.
MAOI-containing
High serotonin syndrome risk (especially clomipramine).
Avoid combination.
Trazodone
Phenethylamines
Reduced psychedelic effects at low doses.
Taper 5 days prior.
MAOI-containing
Risk of toxicity.
Taper 1 week prior.
Buspirone
Tryptamines
Blunted effects due to competitive inhibition.
Taper 5 days prior.
MAOI-containing
Low serotonin syndrome risk.
Taper 5 days prior.
MAOI-A (e.g., Phenelzine)
All Psychedelics
High risk of serotonin syndrome, hypertensive crisis.
Taper 2 weeks prior.
Intensified experiences or cardiovascular collapse.
Avoid combination.
MAOI-B (e.g., Selegiline)
Phenethylamines
Intensified MDMA effects; serotonin syndrome risk.
Taper 2 weeks prior if ≥9mg/day.
Tryptamines
Likely low risk with psilocybin, LSD.
Taper 2 weeks prior if ≥9mg/day.
Atypical Antipsychotics(e.g., Aripiprazole, Quetiapine)
All Psychedelics
Potential to blunt psychedelic effects or cause unpredictable interactions.
Avoid combination or consult healthcare provider.
Mood Stabilizers (e.g., Lithium, Valproate)
Phenethylamines/Tryptamines
Lithium poses significant risks (e.g., seizures, serotonin syndrome).
Avoid combination.
Benzodiazepines (e.g., Diazepam, Alprazolam)
All Psychedelics
Can reduce or mitigate psychedelic effects. Often used to manage challenging experiences.
Use with caution for acute situations.
Stimulants (e.g., Methylphenidate, Amphetamine salts)
All Psychedelics
May increase risk of overstimulation or cardiovascular events.
Avoid combination or use with caution.
Opioids (e.g., Morphine, Buprenorphine)
All Psychedelics
Interactions less studied; altered psychedelic experience possible.
Avoid combination without medical supervision.
Anticonvulsants (e.g., Phenytoin, Carbamazepine)
All Psychedelics
Potential altered metabolism and efficacy of psychedelics.
Use with caution or avoid.
Over-the-Counter Medications (e.g., Diphenhydramine, DXM)
All Psychedelics
DXM may cause dangerous serotonin-related interactions.
Avoid combination.
Special Notes:
Ketamine: Studied for safe use with antidepressants. The manufacturer recommends combining with oral antidepressants for esketamine therapy.
Ibogaine: CYP2D6 inhibitors (e.g., fluoxetine, bupropion) can double ibogaine concentrations, increasing toxicity risk.