SSRI and psychedelics

Traditionally, people taking antidepressant medications had to stop them (washout period) before using psilocybin or MDMA due to concerns about serotonin syndrome, a dangerous interaction. However, this is unlikely to be a risk of psilocybin though it may be for MDMA.

In fact, a 2022 study showed that combining psilocybin with the SSRI medication escitalopram led to fewer negative side effects for patients compared to those taking a placebo before psilocybin. This promising finding even led to a US patent for using both medications together for depression treatment.

However, some research suggests a slight interaction between psychedelics and SSRIs. Some studies indicate that SSRIs might slightly reduce the intensity of the psychedelic experience, potentially leading to less emotional impact . Interestingly, the long-term antidepressant effects of psilocybin seem to remain even with SSRI use. The main difference is that patients on SSRIs may experience a less intense psychedelic trip, with fewer mystical experiences, emotional breakthroughs, or challenging moments .

SSRIs vs Psychedelics

Much of the scientific data compares the efficacy of psychedelics versus the most popular antidepressant therapy, most of the time this is an SSRI such as citalopram. One of the most recent studies has show a direct comparison of effects of both of the medicines:

Effect	SSRI (Escitalopram)	Psilocybin
Neuroticism	−0.38	−0.63
Introversion	-	−0.38
Disagreeableness	−0.26	−0.47
Impulsivity	−0.35	−0.40
Absorption	-	0.32
Conscientiousness	-	0.30
Openness	0.28	0.23

Psilocybin was associated with a decrease in neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Whereas is escitalopram with neuroticism (B = −0.46) remaining decreased at month 6.

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