Single very low doses of LSD (6.5, 13, and 26 micrograms) produce dose-related subjective effects in healthy young adults. The highest dose (26 μg) increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected. A threshold dose of 13 μg might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.
A very low dose of LSD (13 μg) alters brain connectivity in circuits involved in emotion, even though it produces negligible subjective changes. In healthy young adults, the dose increased amygdala connectivity with the right angular gyrus, right middle frontal gyrus, and cerebellum, while decreasing connectivity with the postcentral and superior temporal gyri. Effects on positive mood were weak and variable, but increases in positive mood correlated with stronger amygdala–middle frontal gyrus connectivity. These preliminary findings suggest that sub-perceptual doses of LSD can modulate limbic brain networks, though further research with repeated dosing is needed to clarify any potential antidepressant effects.