What Does Psychedelic Therapy Actually Feel Like?

Lysergic acid diethylamide (LSD) and psilocybin are now used on a limited basis in the treatment of anxiety and major depressive disorders. Prior to being administered, patients, most of whom report no prior experience with these psychedelics, are cautious and want to know what to expect.

LSD and psilocybin have separate and overlapping mechanisms of action that depend on the dose administered. LSD and psilocybin, via its active metabolite psilocin, are thought to act primarily on at least six different serotonin receptors. Both compounds’ affinity for most of the dopamine, norepinephrine, and histamine receptors are simply too low to influence the functions of these receptors at levels typically achieved in the brain.

A recent study, by Friederike, et al., was performed to determine how therapeutic doses of these two psychedelic drugs “feel” in healthy human volunteers.

The doses of LSD (100 and 200 µg) and psilocybin (15 and 30 mg) used covered the range of therapeutically effective doses. This is the first study to use a double-blind, randomized, placebo-controlled, crossover design and the first to describe acute effects of fixed doses of psilocybin in healthy, i.e., non-depressed, subjects. Drug test days were separated by at least 10 days to allow wash-out of the metabolites and recovery time. The major outcome measure was a self-rating scale for subjective effects. In addition, the authors monitored changes in heart rate and blood pressure, effect durations, plasma levels of the hormones prolactin, cortisol, and oxytocin, and the rate at which the drugs were metabolized. Both drugs are known to alter the levels of these hormones.

The doses of 100 and 200 µg LSD and 30 mg psilocybin produced similar subjective effects. The low dose of psilocybin dose produced noticeably weaker subjective effects. The 200 µg dose of LSD induced higher ratings of ego-dissolution. Ego-dissolution is a distortion of the subjective experience of one’s “self,” or “ego,” that is central to the psychedelic experience. The subjects also displayed impairments in behavior control and cognition, as well as anxiety. The 200 µg dose of LSD significantly increased ratings of ineffability as compared to 30 mg psilocybin.

The duration of effects was much longer for LSD than for psilocybin. Both LSD and psilocybin increased heart rate and blood pressure and produced similar changes in the levels of the target hormones. Psilocybin increased body temperature more than LSD.

The authors concluded that both doses of LSD and the high dose of psilocybin produced qualitatively and quantitatively very similar subjective effects, indicating that alterations of mind that are induced by LSD and psilocybin do not differ beyond the effect duration. Any differences between LSD and psilocybin are dose-dependent rather than substance-dependent. Overall, however, these autonomic effects were moderate and transient and thus not a safety concern.

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