Lysergic acid diethylamide-assisted therapy in patients with anxiety with and without a life-threatening illness A randomized, double-blind, placebo-controlled Phase II study

The authors of this very interesting paper write: "Background This study aimed to investigate the efficacy and safety of lysergic acid diethylamide (LSD)-assisted therapy in patients who suffered from anxiety with or without association to a life threatening illness.  Methods The study is an investigator-initiated two-center trial that used a double-blind, placebo-controlled, two-period, random-order, crossover design with two sessions with either oral LSD (200 μg) or placebo per period. The primary endpoint was anxiety symptoms 16 weeks after the last treatment session, assessed by Spielberger’s State-Trait Anxiety Inventory–Global (STAI-G) score in 42 patients. Further outcome measures included ratings for depression symptoms (BDI [Beck Depression Inventory] and HAM-D-21 [Hamilton Depression Rating Scale]) and ratings for acute subjective drug effects. The outcomes for the first period, (between-subjects analysis) are primarily shown due to carry-over effects.  Results LSD treatment resulted in significant reductions of STAI-G scores up to 16 weeks after treatment (least square mean (± SE) change from baseline difference = -16.2 (5.8), 95% CI=-27.8 to -4.5, d=-1.18, p=0.007). Similar effects were observed for ratings of comorbid depression on the HAM-D-21 (-7.0 (1.9), 95% CI=-10.8 to -3.2, d=-1.1, p=0.0004) and the BDI (-6.1 (2.6), 95% CI=-11.4 to -0.9, d=-0.72, p=0.02). Positive acute subjective drug effects and mystical-type experiences correlated with the long-term reductions in anxiety symptoms. Transient, mild, acute untoward effects of LSD treatment were reported by eight patients (19%). One treatment-related serious adverse event (acute transient anxiety) occurred (2%).  Conclusion LSD produced long-lasting and notable reductions of anxiety and comorbid depression symptoms up to 16 weeks."

There is plenty of interesting detail in this study. For example the authors write: "According to our clinical impression, the 200 μg dose of LSD might be too high for some patients, especially if they are not experienced with the effects of psychedelic drugs. Thus, a first dose of 100 or 150 μg LSD may be more adequate in future studies, with an optional increase to 150-200 μg for further doses. The 200 μg dose of LSD that was used in the present study can be considered equivalent to 40 mg of psilocybin and higher than the psilocybin doses of 15-30 mg that have been used in clinical trials to date. Additionally, the high LSD dose was administered twice. The use of two doses has been strongly recommended, allowing patients to become more familiar with the effects of a psychedelic and potentially have different experiences, particularly in cases in which the first dose produced a challenging experience." and again: "Only one SAE (2%) was considered related to treatment and consisted of acute transient anxiety and delusions during an LSD session. The patient was successfully treated with lorazepam and olanzapine. A single dose of olanzapine was administered because lorazepam alone was not effective enough to fully block all symptoms. The patient was kept overnight and discharged in the morning and experienced no further long-term symptoms. Consequently, the second LSD dose was reduced to 100 μg for this patient."

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