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LSD

A substance page: what the research shows, where it is thin, and what Metanoia asks

Research page · fullLast reviewed 5 October 2026

Read this first. This page is education, not instructions to use. Metanoia does not supply any substance. In the United States, most of the substances discussed here are Schedule I under federal law (21 CFR 1308.11), their legal status differs between countries and between US states, and none of this is legal advice. Nothing here is medical advice, and nothing here describes or recommends a dose. "Healthy adults" means people with no diagnosed psychiatric or major medical condition, the population Metanoia studies. Most of the controlled research on LSD was done in small groups of screened volunteers in hospital or laboratory rooms with staff present, and a growing part was done in patients with anxiety or depression, so the text names the group each study used, because that changes what the result can mean for everyone else.

What it is

LSD is short for lysergic acid diethylamide, a molecule that does not occur in nature in this form. The European Union's drug agency calls it semi-synthetic, made from lysergic acid, which can be obtained from ergot alkaloids found in a fungus that parasitizes rye [1] [2]. Albert Hofmann first synthesized LSD in 1938 at Sandoz Laboratories in Basel [1] [2], and its mental effects came to light in 1943, when he accidentally took a small amount [2] [3]. The EUDA profile describes the accident but gives no year for it [1]. Psychiatric research with LSD flourished through the 1950s and 1960s and largely ended around 1970, as legal controls tightened in the United States [2] [3] [4].

Like psilocybin, mescaline and DMT, LSD is called a classic psychedelic, meaning it acts as a full or partial agonist at the serotonin 5-HT2A receptor, an action considered necessary for the characteristic effects, though perhaps not sufficient to explain every difference between drugs [4]. In people, the receptor blocker ketanserin reduced the response to LSD to roughly the level seen with the lowest amount tested, leaving only a small, late feeling of a good effect [5]. A later trial found that giving the blocker an hour after LSD shortened the subjective effects from 8.5 hours to 3.5, but it had no placebo session for LSD, and a score for mystical-type experience did not fall significantly [6].

Metanoia is a California 501(c)(3) public charity advancing the science of natural psychedelics for personal growth and human flourishing in healthy adults. Not treating illness. Expanding potential. LSD is semi-synthetic and not a natural psychedelic, so it is not the center of that work. It has a page here because it is among the better-studied members of the family in healthy volunteers, a useful anchor for comparison, and its clinical development is shaping public expectations of every other psychedelic.

What is known

The short version. Controlled studies in healthy adults show that LSD produces strong, long-lasting changes in perception, mood and sense of self that grow with the amount taken, with moderate rises in heart rate and blood pressure, and at matched strength the experience is close to that of psilocybin. Evidence for lasting benefit in healthy people is thin, trials of very small repeated amounts mostly found little beyond the immediate drug effect, and a blood marker once proposed as a window on plasticity did not hold up in the larger controlled work. The headline Phase 3 results come from company announcements in patients with diagnosed disorders, no peer-reviewed publication of them was found, and they cannot answer questions about healthy adults.

The Basel studies

Most modern controlled data come from one group at the University Hospital Basel [7], with healthy, mostly young volunteers, placebo control, a crossover design and an investigator present in a hospital room.

The first study gave 16 healthy volunteers (8 women) a high amount of LSD and a placebo. The effects lasted about 12 hours, with visual hallucinations, blending of the senses and positively experienced feelings of unreality and detachment from the self, and well-being, happiness, closeness to others, openness and trust rose. Seven of the 16 had used a hallucinogen before, the main outcome was a startle-reflex measure and not well-being, two volunteers had brief anxiety, including fear of losing control, that passed within two to three hours, and the effects were obvious enough that blinding was lost [8]. In a pooled analysis of two linked studies in 40 volunteers, who received different amounts, LSD impaired recognition of fearful faces, emotional empathy rose only at the higher amount and mostly for positive material, cognitive empathy fell, and prosocial orientation rose only in the combined sample [9]. A report from the 16-volunteer dose-response study described next found the same emotional empathy rise at the highest amount and no cognitive empathy change, and the blocker weakened it only slightly and not significantly, but it is the same 16 volunteers and not an independent replication [10].

A dose-response study in 16 healthy volunteers tested four amounts and a blocker condition. Effects began at the lowest amount, positive effects reached a ceiling at the third, and the highest amount produced more ego dissolution, a loss of the usual sense of being a separate self, and significant anxiety. Six of the 16 had used LSD before, and the many comparisons were not statistically corrected [5]. In a direct comparison in 28 healthy volunteers, LSD and psilocybin produced very similar subjective effects. LSD lasted longer, as its pharmacokinetics explain, psilocybin raised blood pressure and temperature more and LSD heart rate more, the one significant difference between the higher amounts was a single rating, the sense that the experience cannot be put into words, and the measured LSD content was 11 to 14 percent below the planned amount [11]. A third study put mescaline, LSD and psilocybin in one crossover with 32 healthy volunteers and again found comparable effects at matched strength. Most had used a psychedelic before, the mescaline amount was raised partway through, so the two mescaline amounts were not randomly assigned, and LSD was identified in 58 percent of sessions on the day and 69 percent at the end [12].

In a pooled analysis of 213 healthy volunteers the amount taken was the strongest predictor of the experience. The abstract reports that sex and body weight were not significant, but female sex was linked to smaller rises in some positive effects in the main analysis and not in a sensitivity analysis, and lower body weight to stronger bad-effect ratings, so these are unstable predictors [13]. In 81 volunteers of European ancestry, 7 poor metabolizers of the liver enzyme CYP2D6 had a longer LSD half-life (about 7.5 hours against 4.1) and, by the paper's model, about 75 percent more total exposure, but the peak effect did not differ, other scores and the duration differed in some analyses and not in others, and the comparisons were not fully corrected. Seven people is a small group, and no independent study has repeated the finding [14].

Lasting effects after a single session

In a follow-up of 16 volunteers from the first Basel study, participants rated positive changes in attitudes, mood and well-being at one and twelve months and attributed them to the LSD session, and ten of 14 placed it among the ten most meaningful experiences of their lives. Openness, which the authors had expected to rise, did not, and trait anxiety did not change. Fourteen of the 16 completed all the measures, ten held a postgraduate degree, and results were not corrected for multiple comparisons. With no control group, it shows what people believed about the cause, not the cause [15].

A 2026 crossover from the University of Fribourg tested after-effects under control. Forty-five healthy adults were enrolled and 43 analysed, and each received one full-strength session and one placebo presented as a low amount of LSD [16]. One day later the LSD condition gained more on a finger-typing task after a rest period, and one week later perceived stress was lower and one aspect of cognitive flexibility higher. Two tests built to detect plasticity-like change did not show the expected strengthening, and blood BDNF did not change in serum (p = 0.69) or plasma (p = 0.11). The paper states its own limits. Every participant correctly guessed which session contained LSD, so self-report results may partly reflect expectation. Baseline flexibility and stress scores sat near the ceiling and floor of their scales, neither the learning gain nor the questionnaire changes tracked any brain measure, and the gain could reflect motivation, attention or arousal, leaving plasticity unproven. Volunteers reported more fatigue and low mood the day after LSD, and one possibly treatment-related serious adverse event resolved within the study period [16].

A biomarker with a mixed record

For several years blood BDNF, a protein some scientists treated as a sign of brain plasticity, was proposed as a window into plasticity after psychedelics, but the record is mixed. Plasma BDNF rose at the highest amount in the Basel dose-response study, without correction for multiple comparisons [5]. It also rose from baseline in the ketanserin study, and the blocker did not stop the rise, but with no placebo session for LSD the change cannot be separated from time of day or setting [6]. A Maastricht study of three very small amounts reported higher BDNF at two of the three, analysing 8 to 10 of 24 volunteers per amount because blood sampling often failed, and its authors called it preliminary [17]. Larger controlled work did not support these findings: the comparison with psilocybin found no rise with either substance [11], the three-substance comparison found no change in plasma BDNF [12], and the Fribourg trial found none in serum or plasma [16]. A 2025 meta-analysis of 29 studies of psychedelics and related drugs found no overall rise in peripheral BDNF (pooled effect size 0.024, where 0 means no difference, p = 0.64), and the seven LSD studies alone gave 0.01 (p = 0.93), with larger effects in studies at higher risk of bias [18]. Blood BDNF is therefore not a useful marker of what these drugs do in the brain.

Creativity

In a crossover with 24 healthy volunteers, LSD near the peak of a moderate session raised novelty, surprise, originality and symbolic thinking and lowered utility and convergent thinking, finding the single best answer [19]. It shows a shift in thinking style, not whether it helps with real problems or lasts.

Very small repeated amounts

"Microdosing" has attracted far more public belief than evidence. The controlled studies come mostly from Chicago, Maastricht and Auckland.

At Chicago, 20 young adults with prior psychedelic experience received single very small amounts. Subjective effects scaled with the amount, other mood and thinking measures did not change, and systolic blood pressure rose at the middle and highest amounts, although the paper's abstract says physiological measures were unaffected. Only 6 of 20 identified the highest amount as a hallucinogen [20]. A follow-up randomized 56 healthy adults with some prior experience to placebo or one of two very small amounts, and the higher amount caused mild stimulant-like effects and little else, with no mood improvement, no lasting change at follow-up, and symptom scores falling in every group, placebo included. Two small effects appeared without correction for multiple comparisons, and as fewer than half identified the higher amount, blinding held better than in the full-strength Fribourg trial [21].

In Auckland, 80 healthy men took 14 very small amounts over six weeks, in a Bayesian analysis. Daily ratings of creativity, connectedness, energy, happiness and wellness were better on dosing days, even after adjusting for expectation, yet no questionnaire or thinking task changed between the start and the end, and four people in the LSD group withdrew because of anxiety [22].

Maastricht produced mixed results. Three single very small amounts in 24 volunteers gave better mood, friendliness and attention at some amounts and more confusion and anxiety at others [23]. A placebo-controlled trial of four small amounts randomized 53 and analysed 47 and found lower brain-wave power on dosing days and a lower visual P200 plasticity response at the fourth session, which the authors read as a dulled induction of plasticity, with one week of follow-up [24]. In 24 experienced volunteers the highest of three very small amounts raised cold-pain tolerance by about 20 percent and also raised blood pressure, which may account for part of the result [25]. A parallel-group trial that randomized 53 and analysed 48 found no effect on pain tolerance, 42 percent reached the 180-second ceiling of the test, and an unplanned analysis of the 28 who did not hinted at a difference explained mainly by the follow-up visit, when the placebo group also improved. The amount may have been lower than in [25], so this is not a direct failed replication [26].

A company-run safety trial, by authors affiliated with Eleusis, gave six small amounts over 21 days to 48 healthy adults aged 55 to 75. Adverse events were common in every group, placebo included (67 to 83 percent), but headaches were more frequent in the active groups (17, 50 and 25 percent against 8 percent). There were no serious adverse events, and the trial tested safety and not benefit [27].

A self-blinding citizen-science study had volunteers prepare their own capsules, active or placebo, over ten weeks. Of 1,630 who registered, 191 finished, and no scale differed significantly between groups after the four dosing weeks or at follow-up. Small mood, energy and creativity advantages on active-capsule days disappeared after adjusting for what each person guessed they had taken. Most used LSD, the capsule contents were not checked, and the study may have been underpowered [42].

Taken together, the controlled and self-blinding studies agree on modest, short-lived effects and little that lasts, and where blinding held up better than in full-strength trials, guesses still shaped the ratings.

Patient trials and the Phase 3 program

The studies above were in healthy volunteers. The clinical program concerns patients with diagnosed disorders and is described here because it shapes public perception. Metanoia does not treat any condition.

A Phase 2b trial in generalized anxiety disorder randomized 198 adults and analysed 194. Its main outcome was whether anxiety fell in step with the amount given, so the differences against placebo come from that model. Single sessions at the two higher amounts reduced anxiety scores by 5.0 and 6.0 points against placebo at four weeks, while the two lower amounts did not differ. Scores fell by about 14 points in the placebo group too, and about 85 percent of participants correctly guessed they had received an active treatment. Other analyses give different gaps, so the figure depends on the method. The paper was peer-reviewed in JAMA, and many of its authors were employees of the company then called MindMed [28].

The Phase 3 program is run by Definium Therapeutics (formerly Mind Medicine, or MindMed), whose drug is called DT120. The company changed its name on 12 January 2026, as its record at the US Securities and Exchange Commission shows (checked 4 October 2026), and the registry record of the Phase 2b trial (NCT05407064) now lists Definium as sponsor [43]. Three Phase 3 readouts have been announced, and a PubMed search on 4 October 2026 and the company's investor page found no journal publication of any, though the search was not exhaustive. The figures below come from the trial registry (grade 1) and company press releases (grade 3).

Emerge tested DT120 in major depressive disorder. The ClinicalTrials.gov record, NCT06941844, lists a Phase 3, randomized, double-blind, placebo-controlled trial with 149 participants and a primary outcome of change in a clinician-rated depression score (MADRS) at week 6. Healthy volunteers were not eligible, and a first-degree relative with psychosis or bipolar disorder was an exclusion. The record names the sponsor as Definium Therapeutics US, Inc., posts no results, and showed the trial as active, not recruiting, last updated 27 August 2026, unchanged on 4 October 2026 [29]. On 22 June 2026 the company announced that Emerge met its primary endpoint, with a placebo-adjusted difference of 8.1 points at week 6 (75 people on drug, 74 on placebo) and 7.3 points at week 12, and 35 percent responders on drug against 7 percent on placebo at week 6, using an orally disintegrating tablet, a different formulation from the Phase 2b trial [30]. On 8 September 2026 it announced a breakthrough therapy designation from the FDA, which speeds development and review but is not an approval or a finding that the drug works, and here rests on the company's own data [31].

Three limits matter. First, Emerge compared one drug with a placebo, with no antidepressant arm, and neither the registry record nor the company releases claim a head-to-head comparison, so a statement that the effect is larger than that of existing antidepressants cannot be drawn from this design. Second, the results are unpublished and have not been through peer review. Third, functional unblinding, where people can tell which arm they are in, is the standing objection to every psychedelic trial, and neither the registry record nor the June release describes a control for it. The anxiety trial Panorama (245 participants) added a lower-amount arm to help with unblinding, though the company says it was not designed or powered for comparisons, and the second depression trial, Ascend, is described as including one [32] [30].

In the anxiety trials, Voyage (214 participants) reported a 5.4-point placebo-adjusted improvement at week 12, a standardized effect size of 0.81 [33], and Panorama 5.1 points, with an effect size of 0.64 [32], both in company announcements about diagnosed patients.

Safety in healthy adults

The safety evidence comes from screened volunteers, in hospital rooms, with trained staff, under protocols that excluded psychiatric illness. It should not be read as the risk profile of the general public.

A pooled analysis of four Basel trials covered 83 healthy volunteers aged 25 to 60 and 131 single administrations. Blood pressure, heart rate and body temperature rose moderately: systolic pressure passed 140 mmHg in about half of the administrations and 160 in about 5 percent but never reached 180, heart rate passed 100 in about 15 percent, and temperature passed 38 degrees Celsius in 14 percent, the highest reading, 38.8, also occurring on placebo. Kidney and liver tests showed no change about a month later [7]. Very small amounts also raised systolic blood pressure slightly in several microdosing trials [20] [25] [26].

Anxiety is the main acute risk. In the same analysis strong anxiety occurred in about 6 percent of administrations, only at the two higher amounts, and settled with verbal support, with no panic attacks or acute suicidality, and looking back 72 percent rated the experience positive and 8 percent disappointing or bad [7].

Some volunteers had drug-like experiences come back after the drug had worn off. In the pooled safety analysis 6 of 83 reported this between 24 and 86 hours after dosing, and none reported lasting perceptual change [7]. Among 142 healthy volunteers from six Basel studies 13 reported them, mostly brief, visual and mild. Two were distressing and passed on their own, one person had pleasant visual changes return over seven months, and none met the criteria for hallucinogen persisting perception disorder. The authors call such returns common in controlled trials, at 9.2 percent. One distressing case was attributed by the participant and investigators to escitalopram, and only people who reported a return were asked again later. Finding no cases among 142 people rules out a true rate above about 3 percent, but a rate of 1 percent would give no cases about a quarter of the time [34]. In the three-substance study five volunteers had severe headaches and two had depressive symptoms lasting days to weeks that cleared [12]. Outside the laboratory, in an online survey of 2,822 US adults from a stratified research panel, 1.3 percent of 613 lifetime psychedelic users said a doctor had told them they had that disorder, against 0.3 percent of non-users, a self-reported figure from a panel that is not a national probability sample, and psychedelic use was linked to recent psychotic symptoms mainly among people with a family history of psychosis or bipolar disorder [35]. In a two-wave online survey in the US and UK (9,732 adults at the start, 7,667 at follow-up), 100 reported psychedelic use in the two-month window and more unusual visual experiences afterward, and 81 percent had used before [36]. These panels do not give prevalence estimates, and surveys cannot show cause.

A 2026 systematic review of 23 studies found rates of euphoria, hypomania or mania after serotonergic psychedelics from 5.8 percent in controlled psilocybin trials for depression to 30 percent in naturalistic studies of people with bipolar disorder, with higher risk in bipolar I disorder, with relatives who had bipolar or psychotic illness, with several substances, and with unsupervised or illegal use. It pools several substances and does not report LSD alone [37], which is why healthy-volunteer trials exclude people with these histories.

Reporting quality limits all of this. A 2024 meta-analysis identified 214 studies of classic psychedelics, but only 114, with 3,504 participants, reported analysable adverse-event data. It found no serious adverse events among healthy participants, and serious events in about 4 percent of participants with neuropsychiatric disorders, some unrelated to the drug. Among healthy people given LSD, non-serious events needing intervention in the early period included one psychotic state in 284 people and two manic episodes in 340. The authors state that the findings cannot be meaningfully generalized to unsupervised use outside clinical settings [38].

Much is still missing. The Basel authors say their 83 volunteers are too few to detect events that occur in one case in a hundred or one in a thousand, and they had no long-term follow-up and few older participants. Two of the four pooled studies used capsules that may have lost potency, so the authors regrouped people by measured blood levels [7]. The screening, calm room and trained person present throughout are part of the safety result and not part of an unsupervised setting.

Legal status

Each entry names the jurisdiction, the official text it rests on and the date checked, 4 October 2026 for all three. The texts are grade 1 sources. They describe the law and grant no permission, and research with a controlled substance requires authorization in each place.

United States (federal). LSD is a Schedule I hallucinogenic substance, listed at 21 CFR 1308.11(d)(22) with DEA code 7315, in the Electronic Code of Federal Regulations text, up to date as of 1 October 2026 (accessed 4 October 2026). The section was last amended on 21 September 2026 [39]. State law is not covered here and is not verified.

United Kingdom. Lysergide and other N-alkyl derivatives of lysergamide are named in Schedule 2, Part I (Class A drugs) of the Misuse of Drugs Act 1971, in the version on legislation.gov.uk marked as revised, in force from 15 January 2025, checked 4 October 2026. Pending amendments were not checked [40].

Canada (federal). Lysergic acid diethylamide (LSD) and its salts are listed in Schedule III of the Controlled Drugs and Substances Act, item 5, in the Justice Laws text, last amended 18 July 2026 (accessed 4 October 2026) [41].

What is not known

Open scientific questions

Does anything last in healthy adults? The best-controlled follow-up of a full session ran one week and could not rule out expectation [16]. None of the studies read for this page followed healthy people with a control group for months. Do repeated very small amounts do anything, for whom, and over what time? Several groups gave partly different answers, and in none could the role of expectation be fully excluded.

What is the right measure? Blood BDNF did not hold up in the larger controlled work, the stimulation-based plasticity tests did not show the expected strengthening in the best-controlled trial, and its authors question whether they can detect plasticity in people at all [16]. Questionnaires are vulnerable to expectation, and there is no agreed set of outcomes for growth in healthy adults.

How much of the experience comes from the person? The prediction studies explain only part of the variation [13]. CYP2D6 was found in a small sample of seven poor metabolizers to change exposure and possibly effect, and no independent study has repeated this [14]. A PubMed search on 4 October 2026 found no study linking variants of the 5-HT2A receptor gene itself to LSD response in healthy volunteers, but a search is not proof, so that gap is unconfirmed.

Will the Phase 3 results survive peer review, replication and a fair look at unblinding? What does the safety picture look like outside a trial site? How do findings in patients with a diagnosed disorder relate to healthy adults, if at all?

What Metanoia asks

Metanoia has not yet run a study of its own, does not provide or direct anyone toward LSD, and does not treat any condition with it. It has a set of questions and an outcome measure still in development, and because LSD is among the more extensively studied substances in healthy volunteers, some questions can be asked more sharply here.

The first question is what a single session of a classic psychedelic does to growth-type outcomes in healthy adults when they are measured for months instead of one week, and how large the placebo and expectation contribution is when blinding fails. The second is whether the substance can be separated from its setting, and the Basel design that compared LSD, psilocybin and mescaline in one study [11] [12] shows how substances can be compared on equal terms. The third is measurement, since an outcome tool addressed to the twelve dimensions of human potential could be checked against the weaknesses that LSD research has exposed. The fourth is the design of healthy-adult research, including screening for bipolar and psychosis histories and the case for active placebos, and a fifth is how differences between people, such as slow metabolizers, should be recorded.

Any future human work by Metanoia would start from four record-keeping standards (what the material was, what exposure occurred, the surrounding context, and the outcome) and an outcome measure, still in development, addressed to the twelve dimensions of human potential the research asks about.

History and tradition

LSD has no traditional use, so this page contains no grade 4 source. Hofmann first synthesized it in 1938 [1] [2] and found its effects in 1943 [2] [3], Sandoz supplied it to researchers [1] [2] [3], and psychiatric work continued until legal controls tightened around 1970 [2] [3] [4]. Controlled research in healthy volunteers resumed in Basel after a gap of more than 40 years [8]. This history validates neither a safety claim nor a benefit claim.

Sources

Grade key: 1 = primary source or any peer-reviewed publication, including narrative reviews, systematic reviews and meta-analyses, together with official legal texts and registry records. 2 = reliable secondary source that is not peer-reviewed, such as an official agency reference profile. 3 = grey or community source, including company press releases and preprints. 4 = traditional text. Grade describes the type of source, not the strength of the design, which is given separately. "Read in full" means the full main text was retrieved and read by Metanoia on 2 or 4 October 2026, with online supplements not read. "Key sections" means the relevant passages or entries of a long document were read, not all of it. "Abstract only" means only the abstract and indexing record were read, because the full text was behind a subscription or could not be retrieved. The verification date for every entry is 4 October 2026.

  1. European Union Drugs Agency. Drug profile: Lysergide (LSD). https://www.euda.europa.eu/publications/drug-profiles/lsd_en. Grade 2. Official agency reference profile, not peer-reviewed. Read in full. It calls LSD semi-synthetic and dates the first synthesis to 1938, and it gives no year for the discovery of the effects.
  2. Passie T et al. CNS Neurosci Ther 2008, 14(4):295-314. PMID 19040555. DOI 10.1111/j.1755-5949.2008.00059.x Grade 1. Narrative review. Read in full.
  3. Nichols DE. ACS Chem Neurosci 2018, 9(10):2331-2343. PMID 29461039. DOI 10.1021/acschemneuro.8b00043 Grade 1. Historical review. Abstract only (full text behind a subscription).
  4. Nichols DE. Pharmacol Rev 2016, 68(2):264-355. PMID 26841800. DOI 10.1124/pr.115.011478 Grade 1. Narrative review. Key sections: abstract, history, safety and receptor-activity sections, about 16 percent of the text.
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  6. Becker AM et al. Int J Neuropsychopharmacol 2023, 26(2):97-106 (online 2022). PMID 36342343. DOI 10.1093/ijnp/pyac075 Grade 1. Double-blind crossover with LSD in both sessions and no LSD-free placebo session, n = 24. Read in full.
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  9. Dolder PC et al. Neuropsychopharmacology 2016, 41(11):2638-2646. PMID 27249781. DOI 10.1038/npp.2016.82 Grade 1. Pooled analysis of two placebo-controlled crossover studies, n = 24 and n = 16, each at a different amount. Read in full. Note: LSD more weakly impaired recognition of sad faces.
  10. Holze F et al. Front Pharmacol 2021, 12:711255. PMID 34326773. DOI 10.3389/fphar.2021.711255 Grade 1. Report from the same placebo-controlled crossover as item 5, n = 16. Read in full.
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  12. Ley L et al. Neuropsychopharmacology 2023, 48(11):1659-1667. PMID 37231080. DOI 10.1038/s41386-023-01607-2 Grade 1. Randomized double-blind placebo-controlled crossover, n = 32. NCT04227756. Read in full. Note: mean durations were about 11 hours for mescaline, 8 for LSD and 5 for psilocybin, and no substance was identified correctly in every case.
  13. Vizeli P et al. Transl Psychiatry 2024, 14:357. PMID 39231959. DOI 10.1038/s41398-024-03074-9 Grade 1. Pooled analysis of nine crossover studies, n = 213. Read in full. Note: openness, mood before the session and prior psychedelic experience also predicted the experience.
  14. Vizeli P et al. Sci Rep 2021, 11:10851. PMID 34035391. DOI 10.1038/s41598-021-90343-y Grade 1. Pooled analysis of four trials, n = 81, of whom 7 were poor metabolizers. Read in full.
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  16. Calder AE et al. Neuropsychopharmacology 2026, 51(9):1577-1587. PMID 42315644. DOI 10.1038/s41386-026-02454-7 Grade 1. Randomized double-blind crossover, 45 enrolled and 43 analysed. University of Fribourg. Read in full. Note: the finger-typing improvement in the second test block was 348 milliseconds for LSD against 262 for placebo, a 32.8 percent larger improvement. One test used repeated tones with EEG and one paired magnetic pulses with nerve stimulation. During the session LSD reduced some auditory brain responses and made muscle responses to magnetic pulses larger and faster, and the authors could not say whether this was central or muscle tension. A change in one auditory response a week later was labelled exploratory.
  17. Hutten NRPW et al. ACS Pharmacol Transl Sci 2021, 4(2):461-466 (online 2020). PMID 33860175. DOI 10.1021/acsptsci.0c00099 Grade 1. Placebo-controlled within-subject study of three very small amounts, 24 enrolled and 8 to 10 analysed per amount. Read in full.
  18. Calder AE, Hase A, Hasler G. Mol Psychiatry 2025, 30(2):763-776 (online 2024). PMID 39613915. DOI 10.1038/s41380-024-02830-z Grade 1. Systematic review and meta-analysis, 29 studies. Read in full. Note: 17 of the 29 studies were of ketamine, and effects were smaller in studies controlled against both placebo and baseline.
  19. Wießner I et al. J Psychopharmacol 2022, 36(3):348-359. PMID 35105186. DOI 10.1177/02698811211069113 Grade 1. Randomized double-blind placebo-controlled crossover, n = 24. Abstract only (full text not retrieved).
  20. Bershad AK et al. Biol Psychiatry 2019, 86(10):792-800. PMID 31331617. DOI 10.1016/j.biopsych.2019.05.019 Grade 1. Randomized double-blind crossover, n = 20. Read in full. Note: vigor rose at the highest amount, positive images were rated slightly less positively, and heart rate and temperature were unchanged.
  21. de Wit H et al. Addict Biol 2022, 27(2):e13143. PMID 35106880. DOI 10.1111/adb.13143 Grade 1. Randomized placebo-controlled study with three groups, n = 56. Read in full. Note: the two small effects were fewer false alarms for fearful faces and less distress during a simulated social rejection. Heart rate and blood pressure did not change, and the authors concluded that the study gave little support for benefits to mood or thinking.
  22. Murphy RJ et al. Biol Psychiatry 2023, 94(6):511-521. PMID 36997080. DOI 10.1016/j.biopsych.2023.03.013 Grade 1. Randomized placebo-controlled trial, 80 men. Abstract only (full text not retrieved). Note: the placebo was inactive, only men were enrolled, and the analysis was Bayesian.
  23. Hutten NRPW et al. Eur Neuropsychopharmacol 2020, 41:81-91. PMID 33082016. DOI 10.1016/j.euroneuro.2020.10.002 Grade 1. Placebo-controlled within-subject study, n = 24. Abstract only (full text not retrieved).
  24. Hutten NRPW et al. Transl Psychiatry 2024, 14:288. PMID 39009578. DOI 10.1038/s41398-024-03013-8 Grade 1. Randomized placebo-controlled trial, 53 randomized and 47 analysed. Read in full. Note: volunteers' guesses about their group were no better than chance.
  25. Ramaekers JG et al. J Psychopharmacol 2021, 35(4):398-405 (online 2020). PMID 32842825. DOI 10.1177/0269881120940937 Grade 1. Randomized placebo-controlled, n = 24. Read in full.
  26. Cavarra M et al. Br J Pain 2025, 19(6):434-445. PMID 40917239. DOI 10.1177/20494637251371626 Grade 1. Randomized placebo-controlled parallel-group trial, 53 randomized and 48 analysed. Read in full.
  27. Family N et al. Psychopharmacology (Berl) 2020, 237(3):841-853 (online 2019). PMID 31853557. DOI 10.1007/s00213-019-05417-7 Grade 1. Phase 1 randomized double-blind trial, n = 48 older volunteers, company-affiliated authors (Eleusis). Read in full. Note: at the lowest amount LSD was below the limit of detection in blood. There was no change on thinking tests, and ratings of reduced alertness and bad drug effect rose with the amount.
  28. Robison R et al. JAMA 2025, 334(15):1358-1372. PMID 40906494. DOI 10.1001/jama.2025.13481 Grade 1. Phase 2b randomized trial in generalized anxiety disorder, 198 randomized and 194 analysed. NCT05407064. Clinical population. Company-affiliated authors. Read in full.
  29. ClinicalTrials.gov. NCT06941844, Phase 3 trial of DT120 in major depressive disorder (Emerge). https://clinicaltrials.gov/study/NCT06941844. Grade 1. Registry record read in full on 4 October 2026. Status: active, not recruiting, last updated 27 August 2026. No results posted. Note: the record lists a 12-week blinded phase followed by a 40-week open extension, participants aged 18 to 74, and two interventions, DT120 and placebo.
  30. Definium Therapeutics. Press release, 22 June 2026, Phase 3 Emerge topline results. https://ir.definiumtx.com/news-events/press-releases/detail/232. Grade 3. Company statement, not peer-reviewed. Read in full.
  31. Definium Therapeutics. Press release, 8 September 2026, Breakthrough Therapy designation in major depressive disorder. https://ir.definiumtx.com/news-events/press-releases/detail/247. Grade 3. Company statement. Read in full.
  32. Definium Therapeutics. Press release, 14 September 2026, Phase 3 Panorama topline results. https://ir.definiumtx.com/news-events/press-releases/detail/251. Grade 3. Company statement, not peer-reviewed. Read in full.
  33. Definium Therapeutics. Press release, 12 August 2026, Phase 3 Voyage topline results. https://ir.definiumtx.com/news-events/press-releases/detail/243. Grade 3. Company statement, not peer-reviewed. Read in full.
  34. Müller F et al. Psychopharmacology (Berl) 2022, 239(6):1933-1943. PMID 35076721. DOI 10.1007/s00213-022-06066-z Grade 1. Pooled analysis of six crossover trials, n = 142. Read in full.
  35. Simonsson O et al. Psychopharmacology (Berl) 2025, 242(7):1577-1583 (online 2023). PMID 37874345. DOI 10.1007/s00213-023-06478-5 Grade 1. Cross-sectional online survey, stratified research panel, N = 2,822. Read in full.
  36. Simonsson O et al. J Psychopharmacol 2024, 38(1):110-115 (online 2023). PMID 38140891. DOI 10.1177/02698811231218931 Grade 1. Two-wave online survey, US and UK, 9,732 at baseline and 7,667 at follow-up. Read in full.
  37. Eskinazi M et al. Mol Psychiatry 2026, 31(10):5749-5763. PMID 42215638. DOI 10.1038/s41380-026-03657-6 Grade 1. Systematic review and meta-analysis, 23 studies. Abstract only (full text behind a subscription).
  38. Hinkle JT et al. JAMA Psychiatry 2024, 81(12):1225-1235. PMID 39230883. DOI 10.1001/jamapsychiatry.2024.2546 Grade 1. Systematic review and meta-analysis, 214 studies identified and 114 with analysable adverse-event data. Read in full. Note: only 16 of 68 studies published since 2005 assessed adverse events systematically. The serious events were 3.9 percent in psilocybin outpatients and 5.2 percent in LSD outpatients, and included a death from existing illness.
  39. Electronic Code of Federal Regulations. 21 CFR 1308.11, Schedule I, paragraph (d). https://www.ecfr.gov/current/title-21/chapter-II/part-1308/section-1308.11. Grade 1. Official legal text, eCFR up to date as of 1 October 2026, accessed 4 October 2026 through the eCFR API. Key sections: the LSD entry.
  40. Misuse of Drugs Act 1971 (c. 38), Schedule 2, Part I. https://www.legislation.gov.uk/ukpga/1971/38/schedule/2. Grade 1. Official legal text, retrieved as XML. Key sections: the LSD entry.
  41. Controlled Drugs and Substances Act (S.C. 1996, c. 19), Schedule III. https://laws-lois.justice.gc.ca/eng/acts/C-38.8/. Grade 1. Official legal text, Justice Laws XML downloaded 4 October 2026, header showing last amended 18 July 2026. Key sections: the LSD entry.
  42. Szigeti B et al. eLife 2021, 10:e62878. PMID 33648632. DOI 10.7554/eLife.62878 Grade 1. Self-blinding citizen-science study, 1,630 registered and 191 completed. Read in full. Note: four weeks of dosing with a follow-up at week 9. Wellbeing, mindfulness, life satisfaction and paranoia scores improved in the active group, while in the placebo groups mindfulness and paranoia improved but wellbeing and life satisfaction did not change significantly. More than half said the material came from the illegal market, and the authors calculated, at 90 percent power, that 1,392 to 4,918 participants would be needed for the four psychological scales (well-being, mindfulness, life satisfaction, paranoia) and 366 for the composite cognitive score. Psilocybin mushrooms were 57 of the 240 who started, given as 24 percent in the results and 23 percent in the limitations.
  43. U.S. Securities and Exchange Commission. EDGAR submissions record, CIK 0001813814 (Definium Therapeutics, Inc.). https://data.sec.gov/submissions/CIK0001813814.json. Grade 1. Official registry record. The current name and the former-name entry (Mind Medicine (MindMed) Inc., until 12 January 2026) were read, and the company's filings were not.

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