Biological Psychiatry
September 15, 2023
Robin J Murphy, Rachael Sumner, William Evans et al.
69 citations
Microdosing LSD (10 μg every three days for six weeks) in healthy adult men produced transient improvements in creativity, connectedness, energy, happiness, irritability, and wellness on dose days compared with nondose days, even after controlling for preintervention expectancy. However, no enduring changes in overall mood or cognition were observed between baseline and six-week assessments. The most notable adverse event was treatment-related anxiety, which led four participants in the LSD group to withdraw. Microdosing appears relatively safe in this population but does not support claims of lasting mood or cognitive benefits.
Pilot and Feasibility Studies
October 5, 2023
Carina Joy Donegan, Dimitri Daldegan-Bueno, Rachael Sumner et al.
23 citations
An estimated 260 million people worldwide have depression, and many self-treat with microdoses of psychedelics like LSD and psilocybin despite limited clinical evidence. A prior phase 1 study in healthy volunteers found LSD microdosing safe, well tolerated, and feasible with good adherence. This open-label pilot trial (LSDDEP1) will test tolerability and feasibility of an 8-week LSD microdosing regimen in 20 patients with major depressive disorder. Participants receive a sublingual LSD formulation (MB-22001) twice weekly at 5–15 µg. Tolerability is measured by withdrawal due to adverse events; feasibility by clinic visit attendance. Antidepressant response will be assessed with MADRS scores over 8 weeks. Results will inform a future randomized controlled trial.
Trials
April 23, 2021
Robin J Murphy, Rachael Sumner, William Evans et al.
23 citations
A proposed study will test whether regular low doses of LSD, known as microdosing, produce the cognitive and emotional benefits reported anecdotally. Eighty healthy men will receive either a placebo or 10 micrograms of LSD every third day for six weeks. The study will measure personality, creativity, mood, cognition, brain plasticity, and brain imaging at baseline and after the protocol, with additional acute measures after the first dose. Daily functioning will be tracked via questionnaires and a wearable device. The goal is to rigorously evaluate microdosing claims using objective measures, with potential future applications for treating depression, addiction, and other conditions.
Palliative & Supportive Care
November 3, 2022
Lisa Reynolds, Brian S. Barnett, Jeremy Weleff et al.
19 citations
Cancer health-care practitioners in New Zealand and the USA perceive psychedelic-assisted therapy as potentially beneficial for cancer patients, especially those with advanced disease no longer receiving curative treatment. They consider research in this area important and express willingness to refer patients to trials, though they emphasize that work should incorporate spiritual and indigenous perspectives of health. US practitioners had greater awareness of psychedelics, while New Zealand practitioners more strongly believed that spiritual and indigenous factors should be considered. The findings suggest that practitioners may be more open to studies beginning in palliative and end-of-life contexts.
Palliative & Supportive Care
August 1, 2023
Xuepeng Jing, Nicholas Hoeh, David B Menkes
18 citations
A scoping review of pipeline clinical trials identified 25 studies of psychedelic treatment for depression, anxiety, and existential distress at end of life, including 13 randomized controlled trials and 12 open-label trials. Investigational drugs included ketamine (11 trials), psilocybin (10), MDMA (2), and LSD (2); three trials involved microdosing, and fifteen incorporated psychotherapy. Only three trials assessed expectancy and blinding effectiveness beyond randomization. The review expects ongoing trials to extend evidence for psychedelic-assisted group therapy and microdosing, but head-to-head comparisons of different psychedelics and more rigorous studies controlling expectancy are still needed.
Translational Psychiatry
April 15, 2024
Nathan Allen, Aron Jeremiah, Robin J Murphy et al.
15 citations
Microdosing LSD (10 µg every third day for six weeks) increased sleep duration in healthy adult male volunteers. On nights after dosing, the LSD group slept an extra 24.3 minutes per night compared to placebo, with no change in sleep on dosing days. Sleep stage proportions and physical activity remained unchanged. The findings indicate that microdosing LSD modifies physiological sleep requirements, and the objective changes are unlikely to be a placebo effect.
Trials
August 24, 2024
Dimitri Daldegan-Bueno, Carina Joy Donegan, Anna Forsyth et al.
14 citations
A phase 2b randomized controlled trial will test whether repeated low doses of LSD (4 to 20 micrograms, taken twice weekly for 8 weeks at home) reduce depressive symptoms in people with major depressive disorder, compared to an active placebo. The trial is triple-blind and includes measures of mood, personality, sleep, brain activity, blood biomarkers, and safety. This is the first controlled trial to test microdosed LSD in patients' natural environment. Results will help determine whether psychedelic microdosing is a viable additional treatment for depression and guide future research.
Pilot and Feasibility Studies
February 12, 2024
Alesha Wells, A P Suresh Muthukumaraswamy, Eva Morunga et al.
10 citations
A proposed trial will test whether adding a low, non-hallucinogenic dose of LSD to meaning-centred psychotherapy (MCP) is feasible for advanced cancer patients with anxiety or depression. Forty participants (20 Māori, 20 non-Māori) will receive seven MCP sessions plus either an LSD microdose (4-20 µg) or a placebo, under double-blind conditions. Outcomes include feasibility, acceptability, safety, and psychological measures at baseline, during treatment, and at one- and six-month follow-ups. The study aims to determine whether a full-scale trial is possible and to provide initial evidence on whether microdosing may enhance psychological care in this population.
Neuropharmacology
December 1, 2025
Carina Joy Donegan, Dimitri Daldegan-Bueno, Tehseen Noorani et al.
4 citations
Before starting a low-dose LSD regimen, people with major depression held varied expectations shaped largely by media and personal experience. Over half had tried other treatments that failed. Many expected subtle effects or had no specific expectations, while some anticipated changes in consciousness or neural rewiring. Hope served both as a motivator and a buffer against disappointment. The findings underscore how media influences expectations and suggest that current expectancy measures miss important factors specific to psychedelic therapy.
Neuropharmacology
November 5, 2025
Dimitri Daldegan-Bueno, C Donegan, Rachael Sumner et al.
4 citations
In an open-label phase 2A trial, 19 participants with major depressive disorder, most of whom were taking antidepressants, took microdoses of LSD twice weekly for eight weeks. No serious adverse events occurred, and one participant withdrew due to anxiety. Depression scores on the Montgomery-Åsberg Depression Rating Scale dropped by 59.5% at the end of the intervention, with improvements sustained for up to six months. Anxiety, rumination, stress, and quality of life also improved. The results provide preliminary evidence that microdosed LSD is safe and feasible for treating moderate depression, but randomized controlled trials are needed.
Journal of Psychoactive Drugs
July 2, 2025
Grace Stockwell, Nicholas Hoeh, Francesca Fogarty et al.
2 citations
In-depth interviews with 12 people receiving ketamine-assisted therapy for treatment-resistant depression reveal that preparation of mind-set—including openness, clear intentions, mindfulness, and understanding how the therapy works—supports therapeutic benefit. Comfort in the setting, fostered by learning about the therapist's personal experiences, a strong therapeutic alliance, and feeling safe, helps patients 'let go.' External cues like music can guide a spiritual journey. Caution is warranted when trauma surfaces and letting go leaves patients feeling vulnerable. These contextual processes inform future clinical trials and improve the efficacy of ketamine-assisted therapy.
Progress in Neuro-psychopharmacology and Biological Psychiatry
February 18, 2026
Dimitri Henriques Daldegan-Bueno, C Donegan, Rachael Sumner et al.
1 citation
Taking very low doses of LSD (8 micrograms) repeatedly over a short period may temporarily improve mood in people with depression, though the effect needs confirmation in controlled experiments. The drug's behavior in the body was measured in this group, and no evidence of tolerance or increased sensitivity appeared, even when the dose was gradually increased.
Ther Adv Psychopharmacol
December 4, 2025
Carina Joy Donegan, Dimitri Daldegan-Bueno, Rachael Sumner et al.
People with depression who microdosed LSD described their experiences in interviews from an open-label trial. The analysis identified themes such as improved mood, increased energy, and greater emotional openness, though some participants also reported anxiety or discomfort. The findings suggest that microdosing may offer benefits for some individuals, but the open-label design means results should be interpreted cautiously.
The International Journal of Neuropsychopharmacology
August 1, 2025
C Donegan, D Daldagen-Bueno, Robin J Murphy et al.
In an open label trial, 17 people with major depressive disorder took 15 doses of LSD at home and one in a clinic over 8 weeks. Afterward, participants reported increased connectedness to self, others, and nature; greater motivation for activities; improved mood; and better coping with negative situations. Some experienced side effects or no change in symptoms. The findings suggest that microdosing LSD may create a positive feedback loop where improved mood, behavioral activation, and connectedness reinforce each other, and that adding a titration protocol and encouraging psychologically beneficial activities could enhance benefits and reduce side effects.