LSD reduces anxiety symptoms in Phase 2 trial

The effort to identify alternative treatments for anxiety has led to research into the potential of lysergic acid diethylamide (LSD) in reducing anxiety symptoms. Based on results of a placebo‐controlled pilot study showing that two high doses of LSD in patients with a life‐threatening illness resulted in reductions in anxiety for up to 2 months, investigators conducted a Phase 2 study to evaluate the effects of LSD on anxiety in patients both with and without a life‐threatening illness. The study recruited adults aged 25 and older with an anxiety disorder or significant anxiety associated with a life‐threatening illness. Among those excluded were individuals with a history of a psychotic or bipolar disorder and those with a current substance use disorder. Participants in the crossover study were randomized to two sessions of LSD 200 µg or placebo over two 24‐week treatment periods, with the treatment sessions separated by 6 weeks and with each treatment period including five study visits involving use of talk therapy. The primary outcome was change in Spielberger's State‐Trait Anxiety Inventory‐Global (STAI‐G) score from baseline to 16 weeks after the last treatment session. Forty‐two individuals were randomized to treatment; 20 of the 42 had a life‐threatening illness. LSD resulted in significant reductions in STAI‐G scores compared with placebo. Maximum effects were observed 2 weeks after the second LSD session and were sustained up to 16 weeks. Sixty‐five percent of the LSD group and 9% of the placebo group showed clinical response at an outcome visit, with response defined as at least a 30% reduction in STAI‐G score. LSD also resulted in rapid and sustained improvement in depressive symptoms. Only one serious adverse event in the LSD group was attributed to treatment, involving a participant who experienced anxiety and delusions during a session. The researchers concluded that the results suggest long‐term benefits of LSD‐assisted therapy for anxiety, adding that larger trials should be conducted to confirm these findings. [Holze F, et al. Biol Psychiatry 2022; published online Sep 5; doi: 10.1016/j.biopsych.2022.08.025]