Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity

Abstract

The practice of "microdosing", or the use of repeated, very low doses of LSD to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment. Methods. The present study was designed to examine the effects of a single low dose of LSD (13 micrograms) vs placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, aged 18-35, participated in two fMRI scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state BOLD and ASL scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed. Results. LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala -middle frontal gyrus connectivity strength. Conclusions. These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug's purported antidepressant effect. NCT03790358

Pharmacokinetics and Pharmacodynamics of Lysergic Acid Diethylamide Microdoses in Healthy Participants

“…17 Interestingly, although having negligible subjective effects, 13 µg LSD tartrate (equivalent to 10 µg LSD base) has been shown to alter brain connectivity in the limbic system. 18 These data indicate that healthy subjects begin to subjectively perceive effects of LSD at a threshold dose of 10 µg LSD base. Thus, doses < 10 µg LSD base could be considered subperceptual and would qualify as "microdoses."…”

The therapeutic potential of microdosing psychedelics in depression

“…The increase in connectivity was related to the changes in positive mood, measured by the Positive and Negative Affect Schedule (PANAS). 49 Study in patients with anxiety. Gasser and colleagues investigated the safety and efficacy of LSD-psychotherapy in patients with anxiety related to life-threatening diseases.…”

“…While this (microdosing) psychedelics research field is still in its infancy, preliminary findings indicate that low doses of both LSD and psilocybin affect assessed biological processes. 30,38 A first study showed changed connectivity in brain areas involved in affective behaviour, after a single dose of LSD (13 mcg tartrate, p.o.). Interestingly these changes were also related to positive mood effects, 38 which suggests this might be a potential mechanism underlying alleged therapeutic effects in depression.…”

“…30,38 A first study showed changed connectivity in brain areas involved in affective behaviour, after a single dose of LSD (13 mcg tartrate, p.o.). Interestingly these changes were also related to positive mood effects, 38 which suggests this might be a potential mechanism underlying alleged therapeutic effects in depression. Of note, studies need to confirm (the persistence of) these effects in patient populations since this study was conducted in healthy volunteers, and the effect at brain and behavioural level was assessed at the acute state, not when the drug left the bloodstream.…”

“…16 Apparently, the older research used LSD tartrate, whereas modern research, with full psychedelic doses, uses LSD base. 4 The recent microdosing studies in this review all used LSD tartrate, 27,33,37,38 except for one. 39 With regard to the dosing schedule, only one recent study aimed to test the effects of repeated LSD doses on psychological and cognitive functions.…”