Modern Clinical Research on LSD

Over the past 25 years, six clinical studies have examined the classic hallucinogen LSD in healthy subjects and patients. In controlled settings, LSD acutely produces bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences, mediated by the 5-HT2A receptor. It increases feelings of closeness, openness, trust, and suggestibility, impairs recognition of sad and fearful faces, reduces left amygdala reactivity to fearful faces, enhances emotional empathy, and increases emotional response to music. LSD also causes sensorimotor gating deficits, weak autonomic stimulation, and elevated cortisol, prolactin, and oxytocin.

Study at a glance

Abstract

All modern clinical studies using the classic hallucinogen lysergic acid diethylamide (LSD) in healthy subjects or patients in the last 25 years are reviewed herein. There were five recent studies in healthy participants and one in patients. In a controlled setting, LSD acutely induced bliss, audiovisual synesthesia, altered meaning of perceptions, derealization, depersonalization, and mystical experiences. These subjective effects of LSD were mediated by the 5-HT2A receptor. LSD increased feelings of closeness to others, openness, trust, and suggestibility. LSD impaired the recognition of sad and fearful faces, reduced left amygdala reactivity to fearful faces, and enhanced emotional empathy. LSD increased the emotional response to music and the meaning of music. LSD acutely produced deficits in sensorimotor gating, similar to observations in schizophrenia. LSD had weak autonomic stimulant effects and elevated plasma cortisol, prolactin, and oxytocin levels. Resting-state functional magnetic resonance studies showed that LSD acutely reduced the integrity of functional brain networks and increased connectivity between networks that normally are more dissociated. LSD increased functional thalamocortical connectivity and functional connectivity of the primary visual cortex with other brain areas. The latter effect was correlated with subjective hallucinations. LSD acutely induced global increases in brain entropy that were associated with greater trait openness 14 days later. In patients with anxiety associated with life-threatening disease, anxiety was reduced for 2 months after two doses of LSD. In medical settings, no complications of LSD administration were observed. These data should contribute to further investigations of the therapeutic potential of LSD in psychiatry.