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A method of enhancing positive effects of a psychedelic, by pretreating an individual with an antidepressant, administering a psychedelic to the individual, and inducing a more positive psychological state in the individual with the antidepressant-psychedelic combination compared with the psychedelic alone. A method of enhancing positive effects of a psychedelic, by inhibiting serotonin transport in an individual, increasing levels of endogenous monoamines in the individual, and stimulating 5-HT 2A receptors in the individual. A composition including an antidepressant and a psychedelic in the same dosage form.