Blossom Pulse Archive
What happened in psychedelic research in 2021
504 events from 2021, dated by when they happened rather than when we logged them. Papers as they published, trials starting and finishing, programme milestones, and the news coverage around them, grouped by week.
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Week of 27 December 2021
The primary objective of this Phase 1 double-blind, randomized, placebo-controlled study in healthy non-smoking volunteers is to assess safety and tolerability of single-day (SAD) and multiple-day (MAD) oral dosing of 18-MC HCl.
IbogaineUsing dynamic causal modelling of resting‑state fMRI in 25 healthy adults given 100 mg LSD or placebo, the study shows that at peak LSD the normally inhibitory effective connectivity from the salience network to the default mode network becomes excitatory and the inhibitory influence from the default mode to the dorsal attention network is reduced, indicating a diminution of anticorrelation between canonical resting‑state networks. These connectivity changes implicate disruption of the hierarchical balance of intrinsic networks as a neural mechanism of LSD‑induced ego dissolution and link anticorrelation alterations to psychosis and psychedelic therapeutic outcomes.
LSDNeuroimaging & Brain MeasuresSchizophreniaHealthy VolunteersThis preprint (2021) review is one of the most comprehensive reviews on microdosing to date. The reviewers report effects across six categories; mood and mental health; wellbeing and attitude; cognition and creativity; personality; changes in conscious state; and neurobiology and physiology. Studies showed a wide range in risk of bias and argue that the idea that the effects of microdosing are due to expectancy is possibly wrong.
Chronic PainMicrodosingCreativity
Week of 20 December 2021
Using computational cortical-network models, the authors show that partial NMDA-receptor blockade that preferentially affects inhibitory interneurons paradoxically increases gamma oscillations and overall network responsiveness. This hyperexcitable state provides a mechanistic explanation for ketamine- and schizophrenia-associated increases in gamma power and exaggerated responses to sensory input, consistent with hallucinations.
KetamineDepressive DisordersSchizophreniaDouble-blind, randomised Phase II trial (n=44) comparing single oral low doses of psilocybin (5 mg, 10 mg) versus placebo to assess effects on pain tolerance and painfulness in fibromyalgia patients and healthy volunteers.
PsilocybinMindMed said the U.S. Food and Drug Administration placed a clinical hold on its IND submission for a Phase 2b LSD trial in generalised anxiety disorder. The company expects additional detail on the decision within 30 days. Generalised anxiety disorder affects approximately 6% of U.S. adults over their lifetimes, according to the National Institute of Mental Health.
LSDMDMADMTIbogainePsilocybinAnxiety DisordersInterviews with 19 palliative care clinicians found existential distress to be common and often inadequately treated within current, largely non‑medicalised frameworks. Providers regarded psychedelic‑assisted therapies as a promising option for refractory existential distress but emphasised the need for larger trials, clinician education, adapted care models that integrate spiritual and mental‑health expertise, and measures to ensure safety and equitable access.
Depressive DisordersAnxiety DisordersPalliative & End-of-Life DistressPersonality & Trait FactorsThis chemistry paper (2021) outlines a four-step process for synthesizing up to 5kg of MDMA with fully validated cGMP. MDMA is commonly synthesized with safrole, a highly controlled substance. The presented method uses uncontrolled substances achieving results in excess of 99% purity.
MDMAPTSDAnxiety DisordersAlcohol Use Disorder (AUD)Autism Spectrum Disorder (ASD)Substance Use Disorders (SUD)
Week of 13 December 2021
This study measures the safety and efficacy of repeated low dose MM-120 as treatment for ADHD in adults: a multi-center, randomized, double-blind, placebo-controlled trial.
LSDThis review (2021) uses the Research Domain Criteria (RDoC) as a template to analyse the multimodal mechanisms underlying the transdiagnostic therapeutic effects of psychedelic therapy, covering molecular, cellular and network levels. This is the first review to use the RDoC to explore psychedelic therapies and may facilitate a precise-personalized psychedelic therapy paradigm.
Major Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersPTSDAnxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Eating DisordersIn a preregistered double-blind, placebo-controlled within-subject crossover study, psilocybin microdosing over three weeks did not alter emotion processing, self-reported interoceptive awareness or symptoms of anxiety and depression compared with placebo. Exploratory analyses showed reductions in depression and stress in the first block and participant unblinding in the second, indicating possible expectancy or sample effects and the need for further trials in substance-naïve clinical populations.
PsilocybinAnxiety DisordersDepressive DisordersMicrodosingThis rodent study (2021) assessed whether if female rats escalate self-administration of the entactogens MDMA, methylone and pentylone, and investigated the impact this has on GABAA receptor and kappa-opioid receptor (KOR) signalling in the amygdala. It was found that GABA transmission increased in pentylone and MDMA rats compared to those administered saline while pentylone and MDMA disrupted KOR signalling. These findings suggest that GABA and KOR mechanisms play a critical role in entactogen self-administration like those observed with escalation of alcohol or cocaine self-administration.
MDMASubstance Use Disorders (SUD)Double-blind, placebo-controlled randomized crossover (n=46) testing two single-dose LSD 200 µg sessions versus two placebo sessions in patients with anxiety with or without life-threatening illness.
LSDThis meta-analysis (2021) assessed the literature regarding the possibilities of using ketamine to treat anxiety disorders. Six RCTs investigating various disorders were included. Ketamine was associated with treatment response for social anxiety disorder but not for PTSD. Doses of >0.5 mg/kg were associated with a greater reduction in scores of anxiety and these anxiolytic effects could be sustained.
KetamineTreatment-Resistant Depression (TRD)Depressive DisordersPTSDAnxiety DisordersObsessive-Compulsive Disorder (OCD)Safety & Risk ManagementThis academic book chapter (2021) outlines the potential mechanisms of action of psychedelics in the treatment of substance use disorder (SUD).
Alcohol Use Disorder (AUD)Tobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Neuroimaging & Brain MeasuresInterpersonal Functioning & Social ConnectednessPublic Health, Prevention & Behaviour ChangeNuminus common shares will trade on the TSX under NUMI, while warrants will trade under NUMI.WT, NUMI.WT.B and NUMI.WT.C. No shareholder action is required, and founder and CEO Payton Nyquvest will join senior managers to ring the TSX opening bell in Vancouver.
The appointments took effect on 14 December 2021. Barrow, previously MindMed’s interim chief executive officer and chief development officer, led drug development and discovery at Usona Institute and helped obtain Breakthrough Therapy Designation for psilocybin in Major Depressive Disorder. Perry Dellelce stepped down as director and chair.
PsilocybinDepressive DisordersIn an open-label study of 19 people with treatment-resistant depression in Ireland and the United States, 8 patients were responders at week three and all 8 were remitters. The mean MADRS score reduction was 14.9, compared with 12.0 in COMPASS’s phase IIb trial, where SSRI use was stopped. COMPASS expects to begin phase III in Q3 2022.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)Also covered by GlobeNewswire
Effects of single intravenous arketamine dose as an adjunctive therapy for treatment-resistant unipolar… (UMIN000038347, ketamine)
KetamineThis theory-building paper (2021) presents a new model of how psychedelic drugs may act in the brain. The new model, the cortico-clasustro-cortical model (CCC model), proposes that psychedelics disrupt 5-HT2A-mediated network coupling between the claustrum (a region of the brain where 5-HT2A receptors are densely expressed) and the cortex, leading to attenuation of canonical cortical networks. This model is discussed in relation to two previously described models, the CSTC and REBUS.
Substance Use Disorders (SUD)Headache Disorders (Cluster & Migraine)Neuroimaging & Brain MeasuresChronic PainIn an open‑label study of 14 participants with alcohol use disorder, clinically administered MDMA produced no post‑acute mood declines ('Blue Mondays'); participants maintained positive mood in the week after dosing, reported improved sleep at 3‑ and 6‑month follow‑ups, and none sought illicit MDMA. These results support the safety and tolerability of therapeutic MDMA and suggest previously reported come‑downs are likely due to illicit sourcing and recreational settings rather than clinical use.
MDMAPTSDAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)
Week of 6 December 2021
This paper (2021) explores the ability of psychedelics to alter political beliefs or religious beliefs. Contrary to the popularized idea that psychedelic use is linked to increased environmental concern and liberal politics, it is argued that the psychedelic experience can lead to a shift in any direction of political belief. Case studies are used to support the idea of psychedelics as politically pluripotent.
Set & SettingPersonality & Trait FactorsInterpersonal Functioning & Social ConnectednessNuminus Wellness reported Q4 2021 revenue of C$0.5 million, FY2021 revenue of C$1.5 million and cash of C$59.2 million. It completed the Neurology Centre of Toronto acquisition, received conditional approval to graduate to the TSX and prepared a Phase 1 trial of a proprietary psilocybe extract and a MAPS-partnered Phase 3 extension study of MDMA for PTSD.
This paper (2021) makes a case for broadening our conceptualization of substance use in order to develop more effective drug policy and education. It is argued that we need to move beyond our current framing of substance use as a pathological issue and that research on recreational drug use would be beneficial. Incorporating perspectives on positive drug use would enhance prevention and harm reduction strategies.
Substance Use Disorders (SUD)Safety & Risk ManagementImplementation & Service DeliveryPublic Health, Prevention & Behaviour ChangeZylorion Health announced the committees and appointed five members, including Allan Young, Trisha Suppes and Pierre Chue. The advisers bring expertise in psychiatry, psychopharmacology, clinical trials and digital health, with Young and colleagues at King’s College London involved in psychedelics research.
This supportive care single-group study (n=200) will test whether regular use of the Apollo wearable (TVS) improves sustained remission rates from PTSD following MDMA-assisted psychotherapy.
A lab funded through NIDA’s Addiction Treatment Discovery Program will assess Delix-7’s pharmacology, pharmacokinetics and toxicity. If results from preclinical and animal studies are favourable, Delix plans to apply to the FDA for human clinical trials, although NIDA says psychedelic treatments remain theoretical and unproven.
IbogaineAlso covered by PR Newswire
In a double‑blind placebo‑controlled study of 34 individuals who planned to microdose with 0.5 g dried Psilocybe cubensis, acute subjective effects were stronger with active doses (likely due to unblinding) but most objective measures showed no benefits and instead a trend toward cognitive impairment and reduced EEG theta power. The results suggest that expectation/placebo effects may account for many of the anecdotal benefits attributed to psilocybin microdosing.
PsilocybinMicrodosingNeurocognitive DisordersNeuroimaging & Brain MeasuresCreativityThis paper presents a newly optimised Contextual Behavioural Science (CBS)/Acceptance and Commitment Therapy (ACT) model — the Spectrum of Selves — that adapts psychological flexibility processes to the unique challenges of psychedelic-assisted therapy by integrating varied self-models, biological mechanisms and evolutionary principles. It offers a practical, theory-driven framework (with intervention examples, a case study and an integration checklist) to align guided experiences with target behaviours and maintenance strategies, aiming to broaden treatment benefits and reduce relapse.
MDMAPsilocybinDepressive DisordersPTSDMajor Depressive Disorder (MDD)Anxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life DistressSet & SettingClinical concentrations of psilocin do not cause significant inhibition of the human ether-a-go-go-related gene (hERG) potassium channel. Therefore hERG channel blockade is unlikely to explain reported psilocybin-associated QT prolongation or other cardiotoxic effects.
MDMAMescalinePsilocybin
Week of 29 November 2021
The authors propose that psychedelic‑inspired treatments, acting primarily via the 5‑HT2A receptor to enhance neurotrophic signalling, neuronal growth and immune modulation, could rescue cortical atrophy common to neurodegenerative diseases. They further suggest these compounds may help treat behavioural and psychological symptoms of dementia and warrant targeted preclinical and clinical investigation.
Depressive DisordersPTSDSubstance Use Disorders (SUD)Neurocognitive DisordersImmunology & InflammationIn a randomised double-blind placebo-controlled study comparing 5, 10 and 20 μg LSD with placebo, there was no evidence that microdoses affected working memory recall or differentially influenced the balance between distractor resistance (ignoring) and updating on a modified delay‑match‑to‑sample task. These null findings are preliminary due to a small sample and larger studies are needed to confirm whether low-dose LSD influences short-term recall.
LSDMicrodosingOlder AdultsThe Regenerative Financing Vine, a special purpose vehicle, will fund patient-access infrastructure and Phase 3 MDMA-assisted therapy trials. In return, funders will receive 6.1% of North American MDMA revenue for eight years after initial sales, while MAPS remains 100% non-profit-owned and MAPS PBC oversees drug development and post-approval activities.
MDMAPTSDAlso covered by Lucid News
The authors review unique methodological challenges in psychedelic clinical trials—particularly pronounced subjective drug effects, strong media-driven expectancies and frequent unmasking—that heighten susceptibility to placebo and nocebo bias. They provide practical recommendations on study design, recruitment and selection, disclosure strategies, choice of active placebo and measurement of expectations and masking efficacy to reduce bias and better isolate treatment‑specific effects.
Medicinal Chemistry & Drug DevelopmentRandomised, double-blind factorial trial (n=24) testing three repeated microdoses of LSD (20 µg; three dosing days) versus placebo in healthy volunteers to assess effects on mood, sleep, neuroplasticity and related biomarkers.
LSDRandomised, parallel-group prevention trial (n=80) testing a single low-dose IV esketamine infusion (0.3 mg/kg over 40 min) versus saline to prevent postoperative depression after cardiac surgery.
EsketaminePhase I randomised, triple‑blind, placebo‑controlled 5‑period crossover in healthy volunteers (n=23) comparing single oral MDMA, MDA, lysine‑MDMA, lysine‑MDA and placebo.
MDMADouble-blind, randomised, placebo-controlled crossover Phase I study (n=17) comparing single oral methylone 200 mg, MDMA 100 mg, and placebo in healthy volunteers to assess abuse potential, subjective and physiological effects, and pharmacokinetics.
MDMAThree-arm double-blind RCT at three Swiss psychiatric hospitals (J Psychiatr Res 2024; Colla M, Offenhammer B, Scheerer H, Kronenberg G; PMID 38522166; April 2019 – December 2021, with COVID-19 recruitment hiatus). Study code: KET01. Registered on Swiss National Clinical Trials Portal (SNCTP); registration number not recoverable from methods. Participants: adults 18–70, ICD-10 major depressive episode, MADRS ≥19, failed ≥2 adequate antidepressant trials, BMI 18–30; exclusions: psychosis/dementia, active suicidality, substance dependence, serious medical comorbidity. 1:1:1 block randomisation (block size 6, stratified by age/sex/weight) to: placebo vs KET01 160 mg/day (80 mg BID) vs KET01 240 mg/day (120 mg BID) for 14 days. Ongoing antidepressants maintained without washout. Target: n=33/arm (n=99 total); recruitment curtailed before target. Primary outcome: MADRS change baseline to day 15; MADRS also assessed days 1, 2, 4, 7, 11. CT.gov: 0 hits.
KetamineThis review (2021) explores the anti-inflammatory properties of ketamine and how they relate to its antidepressant effects. A case is made for using ketamine for psychiatric emergencies due to its dual effect on both inflammation and depressive symptoms. Ketamine may be a successful and personalized treatment of inflammatory-induced TRD and suicidal thoughts and behaviour.
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersSuicidalityImmunology & InflammationThis protocol paper describes the PsiDeR study, a single-centre, randomised, placebo-controlled feasibility trial of psilocybin-assisted therapy in up to 60 people with treatment‑resistant depression (TRDD), testing a single 25 mg psilocybin dose plus psychological support with primary feasibility outcomes at a 3‑week primary endpoint and 6‑week follow‑up. The protocol also collects optional neuroimaging and omics data for mechanism and biomarker analyses and offers an open‑label 25 mg psilocybin extension.
PsilocybinTreatment-Resistant Depression (TRD)Major Depressive Disorder (MDD)Depressive DisordersNeuroimaging & Brain MeasuresSafety & Risk ManagementEquity and EthicsThis paper proposes that there are synergies to be found between psychedelics for substance use disorders and the twelve-step facilitation (TSF) program, specifically Alcoholics Anonymous (AA). Although controversial, as total abstinence is often promoted, the founder of AA (Bill Wilson) did have positive experiences with psychedelics.
PsilocybinAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Retrospective real-world analysis (15 US states; January–November 2021; institutional review board approved as exempt) of de-identified routine clinical and quality-management data from a telemedicine ketamine-assisted therapy (KAT) service. Patients completed online eligibility screening followed by a video-based intake with a prescribing psychiatric clinician confirming diagnosis and at-home safety. Inclusion: age ≥18, reliable internet access, clinician-assigned diagnosis of depression (PHQ-9 ≥10) and/or anxiety (GAD-7 ≥10). Exclusion: ketamine allergy, current substance dependence, history of opioid use disorder, active/past psychosis or mania, uncontrolled cardiac disease, pregnancy/nursing, recent suicidal intent or attempt. N=1,247 patients with sufficient outcome data identified from a chart review of approximately 2,848–4,334 records (discrepancy noted in the paper text). Treatment: 300–450 mg rapidly dissolving sublingual ketamine tablets (initial dose ~5 mg/kg, adjusted for dissociative response), mailed to patients; administered at home with a physically present peer monitor and real-time guide support via text during each 8-hour session. Guides provided 30-minute pre- and post-session video calls plus daily text check-ins. Clinicians conducted follow-up video consultations 1–2 days after the first session. Outcomes: PHQ-9 (depression) and GAD-7 (anxiety) assessed at baseline, after Session 2 (week 2), and after Session 4 (week 4). Safety outcomes: C-SSRS suicide screening (baseline), AUDIT, DAST-10, plus real-time vital sign monitoring. Dissociation measured with a 3-item adaptation of the Clinician Administered Dissociative States Scale. Primary analyses included response rate (≥50% score reduction), remission (follow-up score <5 with baseline ≥10), and clinically significant change (≥5-point reduction below clinical threshold). Growth Mixture Modelling (Mplus 8, parallel PHQ-9 and GAD-7 processes) identified latent trajectory classes.
atai Life Sciences remains COMPASS Pathways’ largest shareholder after raising its ownership to 20.8%. COMPASS’s 233-patient Phase 2b trial found that a single 25 mg dose of COMP360, combined with psychological support, reduced MADRS scores by 6.6 points at week three versus 1 mg (p<0.001). COMP360 has FDA Breakthrough Therapy Designation for treatment-resistant depression.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)Using text mining of over 2,000 first‑person trip reports and psychometric data from a large survey (N = 1,424), this mixed‑methods study finds that recreational psychedelic users commonly report complete mystical experiences — incidence varying by drug type and dose — and that such experiences are strongly associated with improved psychological wellbeing.
Set & Setting
Week of 22 November 2021
Phase II pilot trial (Yale University; PI: Ilan Harpaz-Rotem PhD; NCT02727998). Status: TERMINATED. Participants: n=28 enrolled; adults with PTSD. Intervention: intensive 7-day treatment combining a single IV ketamine infusion with prolonged exposure therapy. Start: December 2015; end: November 2021. CT.gov: 0 refs listed. Linked paper: Duek O, Korem N, Li Y, Kelmendi B (Yale/VA Connecticut) — Neuropsychopharmacology 2023 (PMID 37270621): neural imaging analysis showing long-term structural and functional changes following a single ketamine infusion in participants with PTSD.
KetamineSingle-group Phase II study (n=22) of intranasal ketamine (three doses on Days 1, 4, 7; 50 mg → 50–100 mg → 50–150 mg) for treatment of moderate–severe major depressive disorder in cancer patients receiving palliative care.
KetamineThis randomized Bayesian adaptive dose-finding trial compared single-infusion IV ketamine 0.1, 0.25, and 0.5 mg/kg with active-control midazolam in 33 veterans with late-life treatment-resistant depression. Ketamine 0.5 mg/kg had the strongest day-7 MADRS response signal and better day-28 response durability among day-7 responders.
KetamineDepressive DisordersVeteransOlder AdultsTreatment-Resistant Depression (TRD)SuicidalityNeurocognitive DisordersSafety & Risk ManagementThis pilot mixed-methods study of psychiatrists in one NHS mental health trust found widespread familiarity with and majority support for controlled therapeutic use of psychedelics, with trainees better informed than non‑training-grade psychiatrists. Despite positive attitudes, clinicians across grades reported low preparedness to deliver psychedelic-assisted psychotherapy and identified substantial training needs and wider societal and professional uncertainties as barriers to implementation.
Depressive DisordersAnxiety DisordersAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressPersonality & Trait FactorsIn a naturalistic online sample, prospective assessments before and after psychedelic use showed reduced Neuroticism alongside increases in Agreeableness and perceived social connectedness, with reductions in Neuroticism covarying with Agreeableness increases consistent with shared emotion‑regulation processes. These changes—largely independent of demographics, setting and acute factors but modestly amplified by baseline trait levels—suggest psychedelics may help address interpersonal aspects of personality pathology and loneliness.
Depressive DisordersSubstance Use Disorders (SUD)Set & SettingPersonality & Trait FactorsInterpersonal Functioning & Social ConnectednessIn a phase 1 dose-ranging study in 22 healthy volunteers, inhaled GH001 (5‑MeO‑DMT) was well tolerated and produced dose-related increases in psychedelic intensity, with individualized dose escalation yielding the largest mystical and ego‑dissolution effects (PES, MEQ, EDI, 5D‑ASC) while cognition, mood, well‑being, vitals and adverse events remained largely unaffected or mild. These findings indicate individualized dose escalation may be preferable to single fixed doses when aiming to maximise therapeutic psychedelic experiences.
5-MeO-DMTPsilocybinDepressive DisordersHealthy VolunteersSafety & Risk ManagementThe double-blind, placebo-controlled retreat took place on Mt. Rigi under the collaboration of Zen teacher Vanja Palmers and neuroscientist Franz Vollenweider of the University of Zurich. The study found that psilocybin increased meditation depth and produced positive self-dissolution without anxiety, according to the provided description.
PsilocybinAnxiety DisordersThis review (2021) presents a framework to understand the basis for using psilocybin to treat individuals with suicidal behaviours. The positive effects psilocybin has on suicidal behaviours are discussed, specifically its role as a 5-HT2A receptor agonist and its ability to increase neuroplasticity and suppress inflammation.
PsilocybinAdolescentsMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersSuicidalityImmunology & InflammationInterpersonal Functioning & Social ConnectednessPublic Health, Prevention & Behaviour ChangeRandomised, double-blind, placebo-controlled parallel trial (n=51 actual) testing repeated IV ketamine infusions (0.5 mg/kg, six 40-minute infusions) for depression in people with Parkinson's disease.
KetamineDrawing on ethnographic fieldwork at a shamanic centre in the Peruvian Amazon, the paper shows that psychedelics induce a state of hypersuggestibility that powerfully facilitates the ritual transmission of beliefs, yet they also provoke doubt, ambivalence and reflexivity so that enculturation hinges on the recipient’s active experiential testing rather than on “brainwashing”. The author further examines the sustainability of the resulting social affiliation and the attendant ethical challenges of globalising these practices.
Equity and EthicsRandomized, double-blind, placebo-controlled single-dose and open-label multiple-dose Phase I study in healthy volunteers (n=46) assessing inhaled GH001 (5‑MeO‑DMT) at 6, 12 and 18 mg for pharmacokinetics, safety and psychoactive effects.
5-MeO-DMTDouble-blind, placebo-controlled crossover trial (n=23) assessing oral ketamine given twice daily for 5 days (cohort doses 0.75 mg/kg and 1.5 mg/kg) vs placebo in females aged 6–12 with Rett syndrome.
KetamineIn an open‑label pilot in chronic cluster headache, intranasal ketamine did not meet the predefined 50% pain reduction at 15 minutes but produced a significant mean 59% reduction at 30 minutes (69% of evaluable patients ≤4/10) with no serious adverse events. These results indicate intranasal ketamine may be an effective acute treatment at 30 minutes and warrant larger controlled trials, with caution regarding ketamine’s abuse potential.
KetamineChronic PainHeadache Disorders (Cluster & Migraine)Safety & Risk ManagementIn a randomised, double-blind, placebo-controlled crossover study in healthy volunteers, 14 days of escitalopram pretreatment attenuated psilocybin-induced bad drug effects, anxiety and adverse cardiovascular effects while not reducing positive mood effects. Escitalopram also did not alter psilocin pharmacokinetics, QTc, circulating BDNF or HTR2A/SLC6A4 expression, and the authors note further work is needed with longer pretreatment and clinical populations.
PsilocybinAnxiety DisordersDepressive DisordersHealthy VolunteersMedicinal Chemistry & Drug Development
Week of 15 November 2021
This review (2021) explores the use of ketamine to treat Anorexia Nervosa (AN). The ability of ketamine to induce neuroplasticity, neurogenesis and synaptogenesis is discussed in relation to AN. Furthermore, the known antidepressant effects of ketamine may be beneficial to people with AN as depression is often experienced comorbidly.
KetamineDepressive DisordersEating DisordersSet & SettingRandomised, parallel-group Phase II trial (n=30) comparing immediate vs delayed point-of-care psilocybin for treatment-resistant depression; single dosing with up to two repeat doses permitted for relapse.
PsilocybinThis open-label Phase II feasibility study (n=12) of manualized MDMA-assisted psychotherapy for moderate-to-severe depression (MDD) included up to two experimental oral MDMA sessions (supplemental dose allowed) and used clinician-rated MADRS change at ~12 weeks as the primary outcome.
MDMAParallel randomized double-blind trial of a single IV infusion of ketamine 0.5 mg/kg vs midazolam 0.045 mg/kg (active placebo) in adults 20–65 with treatment-resistant depression and prominent suicidal ideation. Target enrollment: 48. Primary outcome: rate of reduction in suicide symptoms post-infusion. Conducted at Taipei Veterans General Hospital, Taiwan. Funded by the Ministry of Science and Technology.
KetamineIn a large mobile-app survey of 8,703 adults, psilocybin was the most commonly reported microdose and users described diverse dosing and “stacking” practices with predominantly health and wellness motives. Compared with non-microdosers, microdosers—despite more often reporting a history of mental‑health concerns—reported lower levels of depression, anxiety and stress, suggesting perceived mental‑health benefits that merit longitudinal study.
PsilocybinAnxiety DisordersDepressive DisordersMicrodosingThis rat study demonstrated a causal link between reduced prefrontal mGluR2 receptor function and both impaired executive control and alcohol craving. It finds that psilocybin restored mGluR2 expression and reduced alcohol relapse behaviour, identifying a potential biomarker strategy for treating alcohol dependence.
PsilocybinAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Neurocognitive DisordersNeuroimaging & Brain MeasuresThis observational cohort study (n=30) evaluated the safety and efficacy of Ibogaine-Magnesium Therapy in veterans with sequelae of repeated blast exposure.
Ibogaine
Week of 8 November 2021
Semi‑structured interviews with 11 people who self‑medicated chronic pain with classic psychedelics revealed substantial subjective reductions in pain and identified two recurrent processes—Positive Reframing and Somatic Presence—alongside adjunct practices (mindfulness, breathwork, movement) that participants credited with improving wellbeing and pain experience. Although qualitative and not causal, these patient‑involvement findings were used to inform the design of a forthcoming controlled trial of psychedelic therapy for chronic pain.
Chronic PainDepressive DisordersThis theoretical paper synthesises neurobiological, neurochemical and psychobehavioural evidence to propose mechanisms—such as increased empathy, communication, attachment security and social bonding, and reduced avoidance—by which MDMA-assisted couple therapy may facilitate interpersonal and systems-level healing. The authors introduce a clinical model for MDMA-assisted couple therapy and outline implications for intervention development, delivery and future research.
MDMAPTSDPersonality & Trait FactorsInterpersonal Functioning & Social ConnectednessRandomised, double-blind, placebo-controlled crossover Phase II trial (n=34) comparing repeated low oral doses of psilocybin (5 mg) and ketamine (35 mg) versus placebo in people with Parkinson’s disease to assess effects on affect, cognition and biological markers.
PsilocybinKetamineThe randomised, controlled, double-blind trial involved 233 patients across 10 countries, with psychological support provided alongside a single dose. The 25mg dose significantly outperformed the 1mg comparator at week three, with responses sustained up to week 12, while the 10mg dose did not show a significant difference. COMPASS expects to begin a phase III programme in 2022.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)Also covered by Psychedelic Alpha
Open-label observational study (n=36) collecting EEG and genetic data from patients with treatment-resistant MDD receiving intramuscular ketamine as standard of care.
KetamineThis open-label, randomized study will assess the comparative effectiveness of two versus three active MDMA-assisted sessions in U.S. military veterans with at least moderate chronic PTSD treated in an outpatient VA treatment clinic (n=26 actual enrollment); MDMA 120 mg + supplemental 60 mg with manualized psychotherapy.
MDMAIn an open‑label study of 24 patients with major depressive disorder, psilocybin therapy produced an enduring increase in cognitive flexibility for at least four weeks and altered anterior cingulate cortex (ACC) biochemistry (reduced glutamate and N‑acetylaspartate) alongside increased ACC–posterior cingulate cortex dynamic functional connectivity (dFC). Paradoxically, larger post‑treatment ACC–PCC dFC increases were associated with smaller cognitive gains, while greater baseline ACC dFC predicted better baseline flexibility but less subsequent improvement, suggesting a nuanced relationship between neural and cognitive flexibility in therapeutic response.
PsilocybinDepressive DisordersMajor Depressive Disorder (MDD)Neuroimaging & Brain Measures
Week of 1 November 2021
The aim of the study is to investigate the safety of GH001 (containing 5-methoxy-dimethyltryptamine; 5-MeO-DMT), and to investigate its effects on severity of depressive symptoms, and its dose-related psychoactive effects in patients with Treatment-Resistant Depression (TRD).
5-MeO-DMTAustralian clinicians and researchers identify five categories of challenges—inherent risks, poor clinical practice, inadequate infrastructure, problematic perceptions and divisive relationships—that could impede translation of psychedelic-assisted therapies from trials to community clinics. They propose strategies including public-sector support for research and training, funding for equitable access, and the creation of a broadly endorsed multidisciplinary advisory body to guide policy, implementation and professional cohesion.
PTSDAnxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Implementation & Service DeliveryThis theory-building paper (2021) makes a case for using psychedelics to treat Alzheimer's Disease (AD). The effects psychedelics have on neuroplasticity, inflammation and brain functional connectivity are discussed in relation to the pathophysiology of AD. Additionally, results from animal studies have shown psychedelics positively impact learning and memory which could have implications for the treatment of AD.
Anxiety DisordersDepressive DisordersNeurocognitive DisordersNeuroimaging & Brain MeasuresImmunology & InflammationIn a prospective online survey of 321 people, concomitant cannabis use during a serotonergic psychedelic experience was associated with dose-dependent increases in acute subjective effects — linear increases in mystical experiences, visual phenomena and ego dissolution, and a quadratic increase in challenging experiences, with no effect on emotional breakthrough. However, the observational design and self-report measures limit causal inference and the clinical implications of these interactions.
PsilocybinSet & SettingThe multicentre, open-label COMP201 study will begin at King’s College London’s Institute of Psychiatry, Psychology & Neuroscience, led by Principal Investigator Dr James Rucker. Participants will be followed for 12 weeks, with safety as the primary endpoint and PTSD symptoms, functionality and quality of life assessed as secondary endpoints.
PsilocybinPTSDHart, an advocate for evidence-based drug policy and humanising people who use drugs, will support MAPS’ strategic growth and participate in its events. His work will include contributing to MAPS’ Phase 3 research into MDMA-assisted therapy for PTSD.
MDMAPTSDFilament Health extracts psilocybin and psilocin from magic mushrooms and has developed PEX010, PEX020 and PEX030, its leading botanical drug candidates. The company says its technology controls compound levels and helps prevent psilocin degradation, supporting direct administration of the active compound. US FDA authorisation permits these study drugs to be administered in a phase 1 clinical trial.
PsilocybinThis study is a biomarker study designed to characterize how MDMA impacts the reward circuits of the human brain.
MDMAThis double-blind, parallel-group trial (n=78) compared the effects of intravenous ketamine versus midazolam on neurocognition in depressed patients with significant suicidal ideation. While ketamine rapidly reduced suicidal ideation and improved reaction time and cognitive control, these neurocognitive improvements were independent of changes in depression or mood.
KetamineSuicidalityDepressive DisordersNeurocognitive DisordersHealthy VolunteersThis open-label trial (n=30) examined the effects of weekly oral ketamine treatment over six weeks on functional recovery in adults with chronic suicidality. It finds that while depression and suicidality scores improved, effect sizes for social functioning and wellbeing were smaller, suggesting that symptom reduction alone may not restore full functioning.
KetamineAnxiety DisordersDepressive DisordersSuicidalityMajor Depressive Disorder (MDD)
Week of 25 October 2021
Randomised, double-blind, crossover study (n=14) comparing low (0.0143 mg/kg) and high (0.143 mg/kg) oral psilocybin versus placebo in adults with migraine.
PsilocybinThe KARE protocol, licensed by Awakn from the University of Exeter and validated in a completed Phase IIa/b trial, will be distributed through MINDCURE’s iSTRYM platform across its North American clinical partner network. Awakn plans to deploy the protocol in its UK and European clinics under consultant psychiatrist leadership.
KetamineAlcohol Use Disorder (AUD)Interventional, sequential Phase II dose-escalation study (n=37) assessing safety and EEG biomarkers of RL-007 (cohorts 10–80 mg, TID) with within-cohort placebo sequences in adults with schizophrenia.
KetamineThe paper argues that Indigenous and biomedical frameworks for ayahuasca are ontologically incommensurate: Indigenous efficacy is understood as correct communication with non‑human powers mediated by ritual, whereas modern medicine explains effects via MAO inhibition and dimethyltryptamine‑triggered neuropsychological processes, so one cannot legitimately be used to validate the other. It also highlights the colonial dynamics in neo‑shamanic and recreational appropriation and calls for these issues to be questioned and resolved in any application of ayahuasca.
AyahuascaDMTSet & SettingThis systematic review (2021) entails a meta-analysis of the current literature on MDMA-assisted therapy for the treatment of PTSD. It was found that MDMA significantly reduced CAPS scores and is generally safe and well tolerated although side effects such as headache and nausea are commonly reported.
MDMADepressive DisordersPTSDAnxiety DisordersSubstance Use Disorders (SUD)Headache Disorders (Cluster & Migraine)Safety & Risk ManagementChronic PainThis randomised, double-blind, placebo-controlled crossover study (n=24) investigated the effects of LSD (50 μg) on the stream of thought in healthy participants. It finds that LSD significantly altered mind-wandering and free association by increasing facets of chaos, meaning, sensation, and abstract flow, particularly between two and six hours post-dosing.
LSDHealthy VolunteersThis review (2021) summarizes the current state of research regarding the use of ketamine and esketamine for depression. Across 11 studies it was found that ketamine alleviated symptoms of depression 40 min to 1 week while esketamine improved symptoms at 2 hours to 4 weeks. The methodological quality of most reviews was described as critically low.
KetamineEsketamineDepressive DisordersSuicidalitySafety & Risk ManagementThis open-label pilot trial (n=25) will assess the safety, tolerability, and clinical effects of intranasal ketamine (IN) treatment in patients with Ultra-Resistant Depression (URD) who have not responded to convulsive therapy.
KetamineThis multilevel meta-analysis of 27 placebo-controlled studies (54 effect sizes, N = 592) found that MDMA produces a moderate-to-large increase in self-reported sociability-related feelings (d = 0.86, 95% CI 0.68–1.04; r = .39). The authors conclude this effect size suggests MDMA could meaningfully enhance social connection in both social and clinical contexts and discuss possible mechanisms and directions for future research.
MDMAPTSD
Week of 18 October 2021
This single-blind, placebo-controlled study (n=111) assessed the cognitive effects of six ketamine infusions (35 mg/70 kg) in patients with unipolar or bipolar depression. Results indicate that ketamine improved processing speed independently of its antidepressant effects, while improvements in verbal learning were mediated by reductions in depressive symptoms.
KetamineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersSuicidalityThis review evaluates preclinical and early clinical evidence that psychedelic tryptamines, particularly psilocybin, could be repurposed from psychiatry to neurology as prospective therapeutics for brain injury and neurodegenerative disorders. It highlights findings that psychedelics promote neuroplasticity, synaptogenesis and neural progenitor proliferation and reduce pro‑inflammatory cytokines (e.g. IL‑1β, IL‑6, TNF‑α), while emphasising that the precise molecular mechanisms and neural–glial interactions remain to be determined.
PsilocybinDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)PTSDSubstance Use Disorders (SUD)Neurological InjuryNeurocognitive DisordersImmunology & InflammationPublic Health, Prevention & Behaviour ChangeThis commentary paper (2021) explores what led to the abandonment of psychedelic research post-1970 in North America. Although the War on Drugs played a role, it was concluded that tighter regulation of the pharmaceutical industry, failure of psychedelic experiments to live up to expectations, and a lack of interest from the pharmaceutical industry to fund trials were all contributing factors.
Depressive DisordersAnxiety DisordersAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressRandomized, double-blind, active-placebo crossover imaging trial (n=56) comparing IV ketamine 0.5 mg/kg vs active placebo midazolam 0.045 mg/kg (three infusions per treatment period) in adults 18–55 with treatment-resistant depression.
KetamineUS Patent No. 11,149,044 was granted to COMPASS Pathways on 19 October 2021. It covers an alternative crystalline form of psilocybin, pharmaceutical formulations containing it and methods of treating major depressive disorder, expanding the company’s portfolio beyond the anhydrate form used in COMP360. COMP360 is being developed for treatment-resistant depression in a phase IIb trial at 22 sites across Europe and North America.
PsilocybinDepressive DisordersThis Phase I, randomised, double-blind, placebo-controlled single ascending dose trial (n=56) evaluated oral psilocybin in healthy adults to identify a safe, non-psychedelic threshold dose and to assess safety, tolerability, pharmacodynamic effects and pharmacokinetics. Participants received single doses of psilocybin from 0.5 mg up to 5 mg, with matching placebo, in a parallel-group design. The study enrolled up to 10 cohorts of 8 subjects, with 6 assigned to psilocybin and 2 to placebo in each cohort. Dosing took place during a 3-day/2-night inpatient treatment phase, with safety monitoring and pharmacodynamic assessments collected through 24 hours after dosing and follow-up about 7±2 days later. Outcome measures included adverse events, vital signs, ECGs, laboratory tests, the 5D-ASC, STAI, reaction time, rapid visual information processing, spatial working memory, and multiple visual analogue scales for perceived drug effects, alongside blood sampling for pharmacokinetic analysis and possible pharmacogenetic testing.
PsilocybinThe paper argues that communal traditional rituals involving psychoactive plants should be recognised, protected and integrated as complementary, community-level mental health interventions within the Global Mental Health movement because they foster social engagement, respect local meaning-making and are relatively affordable. The authors further contend that biomedical explanations and recent clinical trials support their therapeutic potential, so international practitioners and advocates should consider these practices alongside conventional treatments.
This narrative review synthesises preclinical, epidemiological and pharmacological literature on 5‑MeO‑DMT, identifying it as a short‑acting serotonergic agonist with highest affinity for 5‑HT1A that produces profound alterations of consciousness (including mystical experiences) but lacks controlled clinical human studies. Given its short duration, relative paucity of visual effects and reportedly high rates of ego‑dissolution, the authors conclude 5‑MeO‑DMT merits further clinical investigation with the same safeguards used for other classic psychedelics.
5-MeO-DMTMedicinal Chemistry & Drug DevelopmentIn a 5-year follow-up of 16 treatment‑resistant patients given intravenous ketamine alongside stable antidepressants, the five patients receiving quetiapine had a significantly longer time to relapse (mean 965.8 vs 80.5 days) and three remained in remission at 5 years. These results suggest that adjunctive quetiapine may substantially prolong the antidepressant effect of ketamine.
KetamineAnxiety DisordersDepressive DisordersSchizophreniaMajor Depressive Disorder (MDD)Public Health, Prevention & Behaviour ChangeIn 42 patients with treatment‑resistant depression, eight adjunctive ketamine infusions produced a statistically significant reduction in anhedonia (SHAPS), and this antianhedonic change mediated ketamine’s antidepressant effect, with one‑week post‑treatment benefits observed only in patients not taking benzodiazepines. These preliminary results require replication in a larger randomised placebo‑controlled trial.
KetamineAnxiety DisordersDepressive DisordersSchizophreniaSuicidalityTreatment-Resistant Depression (TRD)
Week of 11 October 2021
This open-label trial (n=84) will evaluate the efficacy of ayahuasca-assisted constructivist therapy in reducing the severity of grief.
AyahuascaIn a naturalistic replication with 73 ceremony attendants, a single ayahuasca session produced sub‑acute increases in life satisfaction and awareness and, at four weeks, reduced stress, anxiety and somatisation and increased non‑judging, with stronger psychedelic (e.g. ego‑dissolution) experiences predicting sub‑acute mental‑health gains and no differences between first‑time and experienced users. No reduction in depression was found, and the authors note placebo‑controlled trials are required to confirm therapeutic effects.
AyahuascaAnxiety DisordersDepressive DisordersHealthy VolunteersIn a survey of 5,618 adults during the COVID‑19 pandemic, lifetime psychedelic use was associated with higher positive affect and personality traits favouring plasticity and resilience (increased openness and a higher beta factor), alongside decreased conscientiousness. No link was found between lifetime psychedelic use and impaired mental health, whereas some other psychoactive drugs were associated with worse indicators.
Anxiety DisordersDepressive DisordersPersonality & Trait FactorsThis mouse study investigated the development of immunopharmacotherapies to generate antibodies against ketamine and its metabolites. It finds that specific hapten designs successfully elicited antibody responses with high affinity for ketamine or 6-hydroxynorketamine, offering a potential pathway for treating overdose or restricting metabolite access to the brain.
KetamineTreatment-Resistant Depression (TRD)Depressive DisordersTobacco/Nicotine Use Disorder (TUD)Chronic PainImmunology & InflammationSubstance Use Disorders (SUD)This mixed-methods study (interviews N=38; survey N=319) shows that challenging psychedelic “bad trips” have a broader thematic range than previously recognised—fear is near-ubiquitous and confusion is prominent—yet participants typically report positive long-term effects, with meditation practice showing paradoxical associations that merit further study.
Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Set & SettingThis open-label, interventional trial (n=19) explored the effectiveness of 25mg of psilocybin as adjunctive therapy to SSRI use in participants with treatment-resistant depression (TRD).
PsilocybinDouble‑blind, randomised, parallel‑group Phase II trial (n=60) comparing oral ketamine versus oral midazolam in adults (18–64) with a major depressive episode to assess antidepressant efficacy.
KetamineThis review synthesises fMRI and neuropharmacological evidence that both psychotic and psychedelic states feature thalamocortical dysconnectivity — notably thalamus–sensorimotor hyperconnectivity (linked to altered perception) and, in psychosis, thalamus–prefrontal hypoconnectivity (linked to cognitive deficits). It argues these shared patterns extend into cortico‑striatopallidothalamo‑cortical circuitry and discusses clinical implications and future research directions.
Neuroimaging & Brain MeasuresSchizophreniaNeurocognitive DisordersThis review (2021) summarizes what we know thus far with regards to the ability of serotonergic psychedelics to induce neural plasticity. Proposed mechanisms of action are discussed, as are the questions that need to be addressed as we move forward.
Week of 4 October 2021
In a community sample of lifetime classic psychedelic users (n = 159), psychedelic use predicted greater spirituality, which in turn predicted improved emotion regulation and consequently lower anxiety, depressed mood and disordered eating. The study suggests spirituality and emotion‑processing mediate the relationship between psychedelic use and reduced mental distress.
Anxiety DisordersTreatment-Resistant Depression (TRD)Depressive DisordersPalliative & End-of-Life DistressThis prospective, randomized, double-blinded, parallel-group trial (n≈72) compares intraoperative esketamine 0.2 mg/kg versus saline adjunct to general anaesthesia to assess postoperative depression, gut microbiota, and bispectral index in female breast cancer patients.
EsketamineThis review paper (2021) provides further evidence for the use of psilocybin-assisted therapy for the treatment of end-of-life anxiety in the absence of serious adverse effects.
PsilocybinDepressive DisordersAnxiety DisordersPalliative & End-of-Life DistressSafety & Risk ManagementRandomised, multicentre, parallel-group, quadruple-blind trial (n=345) comparing placebo, low-dose S-ketamine (0.5 mg/kg bolus + 2 µg/kg/min infusion) and high-dose S-ketamine (0.5 mg/kg bolus + 4 µg/kg/min infusion) on intraoperative sufentanil consumption in female breast cancer surgery patients.
EsketamineThis preprint review (2021) surveys the literature on cognition and neuroimaging studies that have investigated functional and structural changes associated with MDMA use. It concludes that the neurocognitive/neurophysiological changes that occur with repeated MDMA use are potentially reversible over time.
MDMASubstance Use Disorders (SUD)Palliative & End-of-Life DistressNeurocognitive DisordersNeuroimaging & Brain MeasuresDepressive DisordersAnxiety DisordersThis double-blind study (n=22) investigated the effects of microdosing LSD (13μg & 26μg) on resting-state electroencephalography (EEG) and event-related potential (ERP) in healthy adults. The study found that microdoses of LSD produced desynchronization patterns similar to those reported with higher doses of psychedelics, leading the authors to believe that microdoses of LSD may produce therapeutic effects in the absence of a full psychedelic experience.
LSDDepressive DisordersAnxiety DisordersObsessive-Compulsive Disorder (OCD)Eating DisordersNeuroimaging & Brain MeasuresHealthy VolunteersMicrodosingA multi-centre, Phase II, randomized, double-blind, active placebo-controlled trial of sub‑anesthetic IV ketamine vs midazolam in patients with Parkinson's disease and levodopa‑induced dyskinesia (n=30).
KetamineThis open-label interventional trial (n=12) explored the feasibility of offering psilocybin therapy in a group setting to patients with cancer. The study aimed to decrease the therapist-to-subject ratio, implementing a 1:1 ratio with a group size of six patients.
PsilocybinThis open-label Phase II trial (n=10) investigates the safety and efficacy of MDMA-assisted Cognitive Processing Therapy (CPT) for Posttraumatic Stress Disorder (PTSD).
MDMA
Week of 27 September 2021
This animal study assesses the effects of tryptamine and phenethylamine psychedelics (psilocin, LSD, mescaline and dimethoxybromoamphetamine (DOB)) using EEG in freely moving rats. The researchers found that all psychedelic's caused a global decrease in EEG activity. The overall results were almost identical to the effects from human EEG studies, proving that the method has robust translational validity.
PsilocybinMescalineLSDNeuroimaging & Brain MeasuresRandomized, triple-blind, parallel trial (n=36) evaluating two IV infusions of ketamine (0.5 mg/kg each) versus placebo in patients with treatment-resistant MDD and suicidality.
KetamineThis Phase I open-label trial (n=14) studied the safety of psilocybin when administered to healthy participants enrolled in a psychedelic-assisted therapy training programme. Participants ingested 25 mg of psilocybin extract, and vital signs, including heart rate, blood pressure, temperature, and ECG, were monitored.
PsilocybinPlacebo-controlled, double-blind randomized naturalistic microdosing study (n=34) testing two 0.5 g dried Psilocybe cubensis sessions versus matched placebo in healthy microdosing volunteers with EEG, cognitive, behavioural and self-report outcomes.
PsilocybinThis historical case study (1959; n=1) describes the treatment of a woman with anorexia nervosa who received two injections of psilocybin. The patient reported immediate and lasting improvement, attributing her recovery to psychodynamic insights gained during the psychedelic experience.
PsilocybinEating DisordersThis rodent study investigated the biological substrates of the enduring effects of the psychedelic DOI on the frontal cortex. It finds that a single dose produced rapid structural changes in dendritic spines and sustained alterations in chromatin organisation related to synaptic plasticity, potentially explaining long-lasting antidepressant actions.
SchizophreniaDepressive DisordersAnxiety DisordersIn a naturalistic study of ayahuasca ceremony attendees, a single ingestion was associated with increases in cognitive and implicit emotional empathy, life satisfaction and decentering, and reduced trait neuroticism persisting up to one week, while divergent creative fluency decreased. These short-term changes suggest potential therapeutic relevance for stress-related psychopathology and warrant controlled clinical trials.
AyahuascaAnxiety DisordersDepressive DisordersCreativityPersonality & Trait FactorsInterpersonal Functioning & Social ConnectednessThis survey study (n=283) examined parental attitudes toward the use of ketamine for treating mood disorders and suicidality in adolescents. It finds high acceptability for the treatment, though parents expressed concerns regarding potential side effects and the lack of FDA approval for paediatric use.
KetamineAnxiety DisordersDepressive DisordersSuicidalityAdolescentsMajor Depressive Disorder (MDD)Bipolar DisorderIn a web-based survey of 200 people with eating disorders, 70% had used complementary treatments and most regarded psychedelic research as worthwhile despite moderate concerns. Participants emphasised the need for education and professional endorsement, plus a safe, monitored setting and strong patient–therapist rapport to address those concerns and support future trials.
Eating DisordersDepressive DisordersAnxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Equity and EthicsDouble-blind, randomised, 2-period crossover in healthy adults (n=24) testing whether ketanserin 40 mg given 1 hour after 100 µg LSD shortens and attenuates acute subjective LSD effects.
LSDThis hypothesis paper (2021) puts forward evidence for a model of the co-evolution and advantages to the consumption of psychedelics by humans in pre-history. Four factors may have contributed to the inclusion of psychedelics in their diet: 1) management of psychological distress, 2) enhanced social interactions, 3) facilitation of collective rituals, and 4) enhanced group decision making.
CreativityMedicinal Chemistry & Drug DevelopmentInterpersonal Functioning & Social ConnectednessThis review (2022) explores how psychedelics can be used to treat substance use disorders (SUDs) Specifically, the authors discuss the role of different forms of psychotherapy such as psychodynamic and cognitive behavioural.
Substance Use Disorders (SUD)Public Health, Prevention & Behaviour ChangeThis survey study (n=121) explored the co-occurrence of PTSD in patients with a substance use disorder (SUD). It was found that SUD patients with PTSD were more likely to use MDMA than those without PTSD and MDMA use was associated with avoidance symptoms. The authors conclude that MDMA use might reflect an attempt to self-medicate to deal with avoidance symptoms however, it may also be the case that MDMA use led to more severe avoidance symptoms.
MDMAPTSDAdolescentsSubstance Use Disorders (SUD)This Phase II, randomised, quadruple-blind, parallel-group, dose-ranging trial (n=233) evaluated the safety and efficacy of psilocybin in adults aged 18 and over with treatment-resistant depression (TRD). Sponsored by COMPASS Pathways and conducted across 25 sites in the United States, Canada, and multiple European countries, the study compared three psilocybin dose levels (low, medium, and high) to identify an optimal therapeutic dose for this population.
PsilocybinRandomised, double-blind, quadruple-masked crossover study (n=27) in adults with treatment-resistant depression testing IV ketamine 0.5 mg/kg (40 min) with oral naltrexone 50 mg or placebo pretreatment to assess acute glutamate, functional connectivity and cerebral blood flow effects.
KetamineThis review (2021) explores the potential of MDMA-assisted therapy for treating the various symptoms of social anxiety disorder (SAD). The authors hypothesize how disruptions in neurological, perceptual, receptive, and expressive systems regulating social behavior in SAD may take place as a result of MDMA-assisted therapy, thereby acting as a stimulus for further research.
MDMAAnxiety DisordersAutism Spectrum Disorder (ASD)
Week of 20 September 2021
Dermot Hanley and Dr Duncan Moore will join GH Research’s board and Audit Committee on 24 September 2021, expanding it to five members. The company is studying inhalable 5-MeO-DMT candidate GH001 in Phase 1/2 trials for treatment-resistant depression, with a healthy-volunteer pharmacokinetic study also under way. Cash stood at $292.6 million on 30 June 2021.
5-MeO-DMTDMTDepressive DisordersTreatment-Resistant Depression (TRD)The open-label BIMA study reported a 20% relapse rate within nine months, compared with 75% for traditional treatments. Awakn said the data would support a faster, more efficient phase IIb randomised controlled trial in the UK, as it pursues marketing authorisation for MDMA-assisted alcohol use disorder treatment in the UK and EU.
MDMAAlcohol Use Disorder (AUD)In a nationally representative US online survey (Nov 2020–Mar 2021), adults reporting psychedelic mushroom use—often to self-treat general mental health—had worse mental-health indicators (higher anxiety and depression scores and lower mental-quality-of-life), were less likely to have health insurance, yet used more healthcare services than non-users. The authors highlight this mismatch with positive media and clinical narratives and call for research into drivers of self‑medication and a national harm‑reduction strategy.
PsilocybinAnxiety DisordersDepressive DisordersPTSDSubstance Use Disorders (SUD)Safety & Risk ManagementIn male mice, repeated oral ibogaine (10 or 30 mg/kg) did not produce conditioned place preference but blocked both cue‑ and drug‑induced reinstatement of ethanol‑conditioned place preference in priming‑injection and context‑re‑exposure tests. This indicates ibogaine at non‑rewarding doses may reduce relapse‑like alcohol seeking and warrants consideration as a potential treatment for alcohol use disorder.
IbogaineAdolescentsAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Public Health, Prevention & Behaviour ChangeThis review (2021) examines how the prefrontal cortex and other brain networks influence the variability and stability of mental phenomena, such as executive functions, mind-wandering, and psychedelic experiences. Specifically, they highlight how different brain networks contribute to these dynamics in the short and long term while acknowledging that the stability of conscious experiences are also contingent upon the stability or variability of the internal and external environments. Since most research on psychedelics has mostly focussed on investigating large-scale brain networks, the authors conclude that future research should also study how specific regions contribute to the variability and stability of conscious experiences depending on their functional specialization.
Neurocognitive DisordersNeuroimaging & Brain MeasuresCreativityEquity and EthicsThe paper proposes a critical-period framework for psychedelic‑assisted psychotherapy, hypothesising that psychedelics transiently remove brakes on adult neuroplasticity to create a development‑like state during which psychotherapeutic and environmental input can produce enduring clinical change. It argues that ocular dominance plasticity in the visual system offers a tractable model for identifying the biological ingredients of such critical periods and for translating those insights to limbic circuits relevant to psychiatric disorders.
PTSD
Week of 13 September 2021
Acute administration of salvinorin-A, a highly selective kappa opioid receptor agonist, produced dramatic dissociative psychotomimetic effects without dysphoria and revealed a cortico–subcortical imbalance. Neurophysiologically this was reflected by widespread cortical hypoperfusion and reduced cortical EEG alpha (with increased delta and gamma) alongside increased blood flow in medial temporal regions (amygdala, hippocampal gyrus) and the cerebellum.
Salvia DivinorumDepressive DisordersSubstance Use Disorders (SUD)Chronic PainNeuroimaging & Brain MeasuresHealthy VolunteersThis methodological paper (2021) describes a standardized protocol for freeze-drying ayahuasca and compares its alkaloid composition before and after the procedure.
AyahuascaSingle-group interventional study (n=15 actual) tracking neurobiological targets in unipolar depression with a subsample receiving a single IV ketamine infusion (0.5 mg/kg over 40 min).
KetamineObservational pilot survey (n=~102 actual) collecting anonymous self-reported data on intentions, experiences and demographics from people who attended entheogen therapy centres or retreats in the past five years.
This review paper (2021) investigated the persisting effects of psychedelics on neuropsychological function. There is relatively little reliable data on neuropsychological consequences of psychedelics, especially studies with psilocybin (now most commonly used in trials) are lacking.
DMTMescalineLSDPsilocybinSubstance Use Disorders (SUD)Interviewing 23 practitioners who administered MDMA or psilocybin in underground contexts, the study identifies distinctive relational ethical challenges—such as client nudity, use of non‑sexual touch, and expectations that therapists must have their own psychedelic experiences—and organises these into descriptive themes. It also outlines prescriptive themes (supervision, boundary‑setting, staying within one’s competence) and discusses implications for training and regulation as psychedelic therapies move toward clinical approval.
MDMAPsilocybinMajor Depressive Disorder (MDD)Depressive DisordersPTSDSubstance Use Disorders (SUD)Equity and EthicsThis placebo-controlled, randomised trial (n=90) investigates the efficacy of a single infusion of ketamine combined with magnesium sulphate in treating refractory chronic cluster headache (CCH).
KetamineThe review argues that psychedelics rarely induce wholly new beliefs but instead alter how affective states and social suggestions shape the attribution and updating of beliefs, with individuals’ baseline beliefs moderating both acute and long-term effects. The authors emphasise that these mechanisms must be tested empirically if psychedelics are to be harnessed safely and effectively in clinical and wellbeing contexts.
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