Biological Psychiatry
June 3, 2019
Anya K. Bershad, Scott T. Schepers, Michael P. Bremmer et al.
176 citations
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.
Biol Psychiatry Cogn Neurosci Neuroimaging
December 20, 2019
Anya K. Bershad, Katrin H. Preller, Royce Lee et al.
95 citations
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.
Addict Biol
February 1, 2022
Harriet de Wit, Hanna M. Molla, Anya Bershad et al.
82 citations
Repeated low doses of LSD (13 or 26 μg) taken every 3–4 days by healthy adults produced modest subjective effects, such as feeling a drug effect and stimulant-like or LSD-like sensations, but did not improve mood or cognitive performance on psychomotor or most emotional tasks. No lingering effects on mood or task performance were detected at a drug-free follow-up session 3–4 days later. The study concludes that, in a controlled setting with a limited number of administrations, repeated low-dose LSD is safe but yields negligible changes in mood or cognition in healthy volunteers.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
January 1, 2023
James Glazer, Conor H Murray, Robin Nusslock et al.
52 citations
Single low doses of LSD increase reward-related brain activity in healthy adults. In a double-blind, placebo-controlled experiment, 18 participants received 13 μg or 26 μg of LSD or a placebo across three sessions. Brain electrical activity was recorded during a monetary incentive delay task. Compared to placebo, the 13 μg dose enhanced three event-related potential components: Reward-Positivity (RewP), Feedback-P3 (FB-P3), and Late-Positive Potential (LPP), indicating increased hedonic, motivational, and affective processing of reward feedback. The 26 μg dose also increased FB-P3 amplitudes for positive feedback. These effects were not linked to most subjective drug effects. The findings provide the first evidence that low LSD doses boost reward-related brain activity, with potential implications for treating depressive disorders.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
April 1, 2024
Hanna Molla, Royce Lee, Ilaria Tare et al.
37 citations
A single low dose of LSD (26 µg) produces more pronounced positive mood effects and stronger altered states of consciousness in people with mild depressive symptoms than in those without. In a randomized, double-blind, crossover trial, 39 adults received either LSD or placebo. Those scoring 17 or higher on the Beck Depression Inventory reported greater increases in vigor, elation, and positive psychedelic effects, and showed a larger decline in depression scores 48 hours after the dose, compared with placebo. The drug caused only mild physiological and subjective effects overall.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2024
Conor H Murray, Joel Frohlich, Connor J Haggarty et al.
30 citations
Neural complexity, a measure of brain signal diversity, increases after low doses of LSD (13 and 26 µg) even when volunteers do not report an altered state of consciousness. In three separate placebo-controlled experiments with 73 healthy adults, LSD dose-dependently raised neural complexity, while THC and methamphetamine did not. LSD also reduced delta and theta brain wave power, and those reductions correlated with feelings of elation. THC reduced alpha power, which was linked to altered states, and methamphetamine increased alpha power. The findings show that increased neural complexity is neither necessary nor sufficient for an altered state of consciousness, and that different drugs affect brain activity and subjective experience through distinct mechanisms.
Scientific Reports
September 22, 2023
Hanna Molla, Royce Lee, Sonja Lyubomirsky et al.
28 citations
Both MDMA and methamphetamine increase feelings of connectedness during casual conversations with an unfamiliar partner, and both drugs raise oxytocin levels. However, only after MDMA are oxytocin levels linked to feeling closer to the partner. The study involved 18 participants given MDMA or placebo and 19 given methamphetamine or placebo. These results reveal a new aspect of MDMA's pro-social effects and show that methamphetamine produces a similar behavioral effect, though through a different biological pathway.
Psychedelic medicine (New Rochelle, N.Y.)
December 1, 2024
Connor Haggarty, Hanna Molla, James Glazer et al.
2 citations
A low dose of LSD (26 µg) alters the brain's electrical response to neutral and happy faces, but not angry faces. In a double-blind, placebo-controlled experiment with 39 healthy adults, LSD reduced the amplitude of the N170 brain wave to neutral faces and reduced the P300 brain wave to neutral and happy faces, while angry faces were unaffected. These results suggest that low-dose LSD specifically changes how the brain processes non-threatening social cues, which may help explain reports of improved mood.
The European journal of neuroscience
June 1, 2024
Connor J Haggarty, Anya K Bershad, Mahesh K Kumar et al.
1 citation
MDMA, but not methamphetamine, enhances the brain's early visual processing of happy and angry facial expressions, as measured by the N170 event-related potential in an EEG oddball paradigm. This effect was specific to emotional faces compared to neutral ones. Methamphetamine did not affect this neural measure, and neither drug altered other components of the response to emotional faces. The findings suggest a unique neural mechanism for MDMA's effects on socio-emotional processing, which may underlie its therapeutic potential for social anxiety and other psychiatric disorders.
Journal of psychopharmacology (Oxford, England)
January 13, 2026
James Glazer, Hanna Molla, Royce Lee et al.
A low dose of LSD (26 micrograms) altered brain responses to reward feedback in people with mild-to-moderate depression, compared to those without depression. In depressed participants, LSD increased a brain signal called the late positive potential (LPP) when they received loss feedback, suggesting enhanced emotional processing of rewards. This change was linked to immediate positive mood and lower depressed mood two days later. Across all participants, LSD reduced other reward-related brain signals. The findings cautiously support the idea that low-dose LSD may have antidepressant effects.
Biological psychiatry global open science
July 1, 2025
Paul S Myles, Jayashri Kulkarni, Jessica Kasza et al.
In a phase 2b randomized, double-blind trial, 81 adults with major depressive disorder received either nitrous oxide (at 25% or 50% inspired concentration) or an oxygen/air control across four weekly one-hour sessions, with four additional weeks of follow-up. The primary outcome, change in Hamilton Depression Rating Scale scores over the four treatment weeks, was lower with nitrous oxide than control (mean difference -1.9, 95% CI -3.9 to 0.0, p = .051), a result that did not reach conventional statistical significance. However, in the first week, 38% of the nitrous oxide group versus 13% of the control group achieved remission (p = .031). Secondary measures of depression and suicidality also favored nitrous oxide. The findings suggest nitrous oxide likely has beneficial antidepressant effects.
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
June 1, 2022
Conor H Murray, Zhengyi Huang, Royce Lee et al.
Adolescents aged 18-20 are more sensitive than adults aged 30-40 to the performance-impairing effects of THC, the main active component of cannabis. In a double-blind, placebo-controlled study with 12 adolescents and 12 adults who had used THC fewer than 20 times, THC doses of 7.5 and 15 mg impaired reaction time, response accuracy, and time perception more in adolescents. THC also decreased P300 brain-wave amplitude in adolescents but not adults, indicating greater cognitive and brain-function disruption at doses that produced similar subjective intoxication and heart-rate effects in both age groups.