Modern clinical research on LSD
This review (2017) presents the findings from all six modern clinical studies using LSD in the previous 25 years, detailing the effects and suggested mechanism of action in both healthy participants and those with end-of-life anxiety.
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.
Research Summary of 'Modern clinical research on LSD'
Introduction
Liechti reviews modern clinical research on lysergic acid diethylamide (LSD), focusing on controlled clinical studies published in the past 25 years. The article situates recent work against the much larger historical literature from the 1950s–1970s, which has been summarised elsewhere, and notes that modern research is resurging alongside renewed work on other serotonergic hallucinogens such as psilocybin and DMT. The review aims to synthesise findings from all recent controlled clinical LSD studies identified through Medline and clinicaltrials.gov searches, with attention to clinical pharmacology, subjective and objective effects, neuroimaging results, safety, and therapeutic potential. By collating these modern data, the paper seeks to clarify what is known and what remains uncertain about LSD's mechanisms, acute effects, and possible roles in psychiatry.
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Liechti, M. E. (2017). Modern clinical research on LSD. Neuropsychopharmacology, 42(11), 2114-2127. https://doi.org/10.1038/npp.2017.86
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