New research published in Neuropsychopharmacology provides insight into the acute dose dependent effects of LSD. The findings will help in the planning of clinical trials examining the use of the psychedelic drug in patients with psychiatric conditions.
Previous research has provided initial evidence that LSD might be a viable treatment for certain mental disorders when combined with psychotherapy. But these studies have compared a placebo against a single dose of LSD. The authors of the new research set out to scientifically test the effects of LSD across a range of different doses.
“We wanted to generate clinical data on LSD for its later use as medication in patients,” said research Matthias E. Liechti of University Hospital Basel. “The new study provides information on the acute effects of different doses of LSD. This will help to select the right dose for future trials in patient to treat anxiety and depression.”
During six experimental sessions, which occurred under double-blind conditions in a controlled laboratory setting, eight men and eight women received a placebo, four different doses of LSD, and a high dose of LSD combined with ketanserin, a serotonin 2A antagonist that blocks the effects of LSD.
The researchers found that all four doses of LSD — 25 µg, 50 µg, 100 µg, and 200 µg — increased experiences of “oceanic boundlessness” and “visionary restructuralization” compared to placebo. But only the 50, 100, and 200 µg doses of LSD were associated with “ego dissolution,” the experience of losing one’s sense of self.
There was also evidence of a ceiling effect. The positive subjective effects of LSD increased from the lowest dose to 100 µg, but there was no difference in positive drug effects between the 100 and 200 µg doses. Similarly, ratings of oceanic boundlessness and visionary restructuralization also increased from the lowest dose to 100 µg before leveling off.
But the 200 µg dose of LSD produced significantly greater ego dissolution and was the only dose that significantly increased ratings of anxiety compared with placebo.
“Based on the available data, the following dosing terminology may be useful for future LSD research: ‘microdose’ (1–20 µg), ‘minidose’ (21–30 µg), and ‘psychedelic dose’ (>30 µg). Within the psychedelic LSD dose range, good effects likely predominate at doses of 30–100 µg (good-effect dose), whereas ego dissolution and anxiety increase at doses above 100 µg (ego-dissolution dose),” the researchers said.
Some physiological effects were also observed. LSD increased blood pressure at doses of 50 µg and higher, and increased heart rate at 100 and 200 µg
As expected, administration of ketanserin caused significant reductions in the effects of LSD. “Retrospective reports showed that ketanserin and LSD together were identified correctly by the participants or mistaken as a low dose of LSD but never mistaken for a high dose of LSD,” the researchers explained.
Although the findings help to zero in on the ideal dose to use in psychiatric settings, scientists are likely to further fine tune dosages in additional research.
“Only a limited amount of doses were tested,” Liechti said. “Thus an ideal dose may be between two selected doses. Additionally, the ultimate right doses need to be tested and selected in patients and there are patient characteristics that may result in dose adjustments.”
The study, “Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects“, was authored by Friederike Holze, Patrick Vizeli, Laura Ley, Felix Müller, Patrick Dolder, Melanie Stocker, Urs Duthaler, Nimmy Varghese, Anne Eckert, Stefan Borgwardt, and Matthias E. Liechti.
