Psychedelic Therapy: A Primer for Primary Care Clinicians – Part II. Lysergic acid diethylamide (LSD)

Background: Lysergic acid diethylamide (LSD) is a hallucinogenic agent. In the mid-20th century, it was used to augment psychoanalysis and to treat alcohol use disorder. However, LSD was banned in 1970 in part due to concerns that it could bring about or exacerbate mental illness. Its therapeutic potential remains incompletely understood.Areas of Uncertainty: While uncontrolled recreational use of LSD can, in rare instances, lead to long-term psychosis, adverse events in clinical trials of LSD, such as anxiety, headache, and nausea, have almost always been mild and transient. Serious adverse events, such as intense panic, suicidal ideation, and psychosis, were reported in either none or very few of the participants. However, patient selection criteria, optimal dosing strategy, and appropriate clinical follow-up guidelines remain to be established.Therapeutic Advances: Preliminary data suggests that LSD may be effective for the management of alcohol use disorder (AUD), anxiety, and depression. In trials of LSD for treating anxiety and depression associated with life-threatening illnesses, 77% of participants demonstrate durable relief at one year post-treatment. According to a meta-analysis of RCTs on LSD from the mid-20th century, single-dose regimens of LSD significantly improve AUD (p<0.0003) with an odds ratio (OR) of 1.96.

Conclusions: LSD represents a promising but incompletely understood therapeutic. Limited data suggest that it can aid in managing substance use disorders, as well as depression and anxiety. Large-scale prospective studies are needed to explore potential clinical applications.