Serotonergic medications like SSRIs have been on the market for treatment of mental health conditions like depression and anxiety for several decades now, and they’ve maintained a steady public backing since their conception.
More recently though, the cultural discussion surrounding these regimens has addressed a wide-reaching dissatisfaction with their often intolerable side effects.
It’s this longing for more deep-rooted and durable antidepressant and integrative mental health treatments that have given our psychedelic renaissance such impassioned communal reinforcement.
To the best of our knowledge, this may be the most comprehensive analysis and review to date on the chemico-biological interactions of these medicines in each of their respective drug classes.
We explore the mechanisms by which antidepressants can reduce or amplify the potency of a psychedelic trip and the safety-first steps you can take to reduce negative interactions.
Whether you’re looking to replace a current medication with psilocybin therapy or seeking to combine traditional talk therapy with psychedelic therapy, this discussion on the psychedelic drug interactions will undoubtedly inform your next steps.
Explore more topics like this one in The Encyclopedia of Psilocybin Mushrooms: From Cultivation to Therapy.
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Antidepressants That Interact With Psychedelic Medicine
Selective serotonin reuptake inhibitors (SSRIs)
Citalopram (Celexa)
Escitalopram (Lexapro)
Fluoxetine (Prozac)
Fluvoxamine (Luvox)
Fluvoxamine CR (Luvox CR)
Paroxetine (Paxil)
Paroxetine CR (Paxil CR)
Sertraline (Zoloft)
Serotonin-norepinephrine reuptake inhibitors (SNRIs)
Desvenlafaxine (Pristiq)
Duloxetine (Cymbalta)
Venlafaxine (Effexor)
Venlafaxine XR (Effexor XR)
Milnacipran (Savella)
Levomilnacipran (Fetzima)
Serotonin partial agonist/reuptake inhibitor (SPARIs)
Vilazodone (Viibryd)
Vortioxetine (Trintellix)
Tricyclic antidepressants (TCAs)
Amitriptyline (Elavil)
Desipramine (Norpramin)
Doxepin (Sinequan)
Imipramine (Tofranil)
Nortriptyline (Pamelor)
Amoxapine
Clomipramine (Anafranil)
Maprotiline (Ludiomil)
Trimipramine (Surmontil)
Protriptyline (Vivactil)
Monoamine oxidase inhibitors (MAOIs)
Phenelzine (Nardil)
Selegiline (Emsam)
Tranylcypromine (Marplan)
Isocarboxazid (Parnate)
Moclobemide
Norepinephrine-dopamine reuptake inhibitors (NDRIs)
Bupropion (Wellbutrin, Aplenzin)
Atypical agents
Mirtazapine (Remeron)
Nefazodone (Serzone)
Trazodone (Desyrel, Oleptro)
Buspirone (Buspar)
Expectation Management for the Psychedelic Trip
Assuming well informed expectations for psilocybin therapy is key for having an experience that’s tailored to your body’s metabolic needs and to your present mental health conditions.
While some studies on the matter have yielded contradicting findings, a substantial number of anecdotal reports draw a significant, negative correlation between prolonged use of serotonergic medications and the degree to which a psychedelic trip can be inwardly experienced.
“I am on 200mg of Sertraline and took 3.5gs of shrooms last night. It basically felt the same as the first time I smoked pot. Got the munchies, but no hallucinations unless I closed my eyes, and even then there was hardly anything.” –Reddit User
“I take Zoloft and can NOT trip on shrooms. I’ve tried a few times. I think the Zoloft blocks the trip” –Reddit User
In other words, people who are prescribed these pharmaceutical drugs and take them routinely, have reported experiencing little to no hallucinogenic effects on a standard dose of tryptamines, like psilocybin mushrooms and LSD.
Though this phenomena seems to expand its presence into a plethora of other psychedelic drugs, like Phenethylamines (MDMA, mescaline), today we’ll be settling our attention on the trip-suppressing effects of antidepressant pharmaceuticals.
Let’s begin by discussing the mechanisms that scientists believe are encouraging this mind-body discord.
Please note that the infancy of the psychedelic medicine industry unfortunately limits the range of controlled research studies and clinical trials that have investigated less-discussed, sometimes case-specific nuances of our highly variant body of psychedelics.
Though that’s caused most of our current research to rely largely on anecdotal reports, it’s important to recognize the high and widespread frequency of these discouraging interactions.
For the purpose of offering a comprehensive analysis, we’ll be piecing together the findings of several observational studies, to paint a more conclusive scientific explanation for this absorption-related dysfunction.
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