Blossom Pulse Archive
What happened in psychedelic research in 2019
202 events from 2019, 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 30 December 2019
Open-label, single-group pilot (n=30) testing one oral psilocybin session combined with ten-session manualised group psychotherapy for demoralization in long-term AIDS survivors.
Psilocybin
Week of 23 December 2019
The study’s data collection ended across sites in the United States and Canada after co-therapy teams completed training and supervision with one participant with PTSD. The research team will analyse the data and prepare a manuscript for peer-reviewed publication, while developing a 12-month follow-up protocol.
MDMAPTSDDouble-blind, placebo-controlled study (n=40) using single or repeated all-day oral psilocybin sessions to examine acute and persisting effects on meditation, spirituality, well-being, prosocial attitudes and brain function in long-term meditators.
Psilocybin
Week of 16 December 2019
Randomized, triple-blind Phase IV trial (n=200) testing a single IV ketamine 0.5 mg/kg infusion plus computer-based cognitive training versus sham training and treatment-as-usual in medically hospitalized suicidal patients.
KetamineIn a phase 1 double‑blind, placebo‑controlled trial in 48 healthy older volunteers (mean age 62.9), oral low doses of LSD (5, 10 and 20 μg) given every fourth day for 21 days produced undetectable plasma levels at 5 μg and 30‑minute peak concentrations at 10 and 20 μg. The regimen was well tolerated with adverse event rates similar to placebo and no detectable impairment of cognition, balance or proprioception, supporting further evaluation of LSD for prevention or treatment of Alzheimer’s disease.
LSDHealthy VolunteersNeurocognitive DisordersMicrodosingSafety & Risk ManagementImmunology & InflammationMedicinal Chemistry & Drug DevelopmentPublic Health, Prevention & Behaviour ChangeThis double-blind, placebo-controlled trial (n=1, terminated) aimed to determine whether perioperative ketamine (bolus 1 mg/kg + infusion 0.20 mg/kg/hr) increases postoperative pain tolerance and reduces opioid consumption in opioid-dependent patients undergoing spinal laminectomy/fusion.
KetamineIn a prospective online study of 654 people planning a psychedelic experience, nature relatedness increased at 2 weeks, 4 weeks and remained elevated 2 years after the event. The increase was linked to improved psychological well‑being and depended on state factors (ego‑dissolution) and the perceived influence of natural surroundings, indicating a context‑ and state‑mediated causal effect.
Psilocybin
Week of 9 December 2019
Results of the study and of 5 years follow up of depressed patients who participated in the study during 2014-2015. We will locate the participants and will interview them will use the same questionnaires to evaluate their depressive symptoms. We will also measure the time to relapse.
The randomised, double-blind, placebo-controlled study assigned 89 participants to 10 mg COMP360, 25 mg COMP360 or placebo. No serious adverse events occurred, and most adverse events involved expected psychedelic effects such as sensory changes and positive mood alteration, without negative cognitive or emotional effects. Up to six six-hour sessions ran simultaneously, with a 12-week follow-up.
PsilocybinHealthy VolunteersAlso covered by Kcl, Newsweek, Psychologytoday, Psychologytoday
In a prospective study of 11 volunteers, inhalation of vaporised synthetic 5‑methoxy‑N,N‑dimethyltryptamine produced immediate increases in salivary cortisol and decreases in IL‑6, alongside improvements in affect and mindful non‑judgment that persisted to one week. These biomarker changes were not correlated with ratings of mental health or the psychedelic experience, suggesting a dissociation between subjective effects and acute neuroendocrine/immune responses.
5-MeO-DMTAnxiety DisordersDepressive DisordersHealthy VolunteersSubstance Use Disorders (SUD)Immunology & Inflammation
Week of 2 December 2019
Open-label naturalistic study (n≈80) assessing repeated IV (0.5 mg/kg), intranasal, and oral (2.0–2.5 mg/kg) ketamine twice weekly for 4 weeks in patients with treatment-resistant mood disorders.
KetamineRetrospective chart review (n=891) of adults treated with IV ketamine for MDD, bipolar disorder, PTSD, or OCD at a Canadian clinic to characterise outcomes and safety.
KetamineThis literature review (2019) discusses controlled experimental studies on the effects of psychedelics (e.g. LSD, psilocybin, MDMA) on social cognition and behavior to treat disorders characterized by social dysfunctions such as depression, post-traumatic stress disorder (PTSD), anxiety, and autism spectrum disorders (ASD). It also discusses persisting knowledge gaps into sex-specific drug effects and objective data on social behavior within the framework of MDMA- and hallucinogen-assisted therapy. The study suggests hallucinogen-based treatment methods and the development of novel medication for trans-diagnostic dysfunction in social cognition and noted that entactogens and hallucinogens have consistently shown prosocial effects and have identified alterations in social processing and behavior as major factors for the efficacy of treatments involving them.
MDMALSDPsilocybinDepressive DisordersPTSDAnxiety DisordersAutism Spectrum Disorder (ASD)Neurocognitive DisordersPersonality & Trait FactorsInterpersonal Functioning & Social Connectedness
Week of 25 November 2019
The SevereBD study will test the hypothesis that NRX-101 is superior to lurasidone alone in maintaining remission from symptoms of depression, clinical relapse, and suicidal ideation/behavior over a six-week period of twice-daily oral dosing in patients stabilized with ketamine (n=72; 2:1 randomization).
This review (2019) investigates psychedelics (and other medications) as promising treatments for anxiety and anxiety-related disorders. In combination with talk or exposure therapy, these new drugs can increase the effectiveness of treatments.
PTSDAnxiety DisordersObsessive-Compulsive Disorder (OCD)This synthesis article (2019) explains the gram-scale production of psilocybin in E. coli (a prokaryotic host), which is a 32-fold improvement over earlier techniques. However, it's still much more expensive than growing it in mushrooms/truffles.
PsilocybinDepressive DisordersPTSDAnxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life DistressHealth Economics & ReimbursementThis literature review and hypothesis paper (2019) proposes that the enduring improvements in well-being following psychedelic therapy are mediated by a reduction in death anxiety. It integrates existential psychology with psychedelic science to suggest that addressing this fundamental anxiety is central to the therapeutic process.
Anxiety DisordersAnalysis of YouTube self‑reports and comments found that users predominantly describe therapeutic and enhancement benefits from psychedelic microdosing (mainly LSD and psilocybin), with notable improvements for depression and outcomes shaped by intentions and peer‑shared strategies. The study suggests microdosing may offer some benefits similar to full‑dose treatments with fewer acute adverse reactions, but repeated long‑term exposure could introduce additional risks.
LSDPsilocybinDepressive DisordersMicrodosing
Week of 18 November 2019
The designation supports an efficient development programme and recognises major depressive disorder as an area of unmet medical need. Usona’s Phase 2 PSIL201 trial planned to enrol about 80 participants across seven US sites, with two recruiting and the remainder expected to be active by early 2020.
PsilocybinDepressive DisordersMajor Depressive Disorder (MDD)Also covered by Medscape
The authors developed and validated a simple, low‑cost SPE–LC method with UV diode‑array detection for quantifying N,N‑dimethyltryptamine, tryptamine and β‑carbolines in ayahuasca, showing good linearity (r>0.9902), excellent repeatability (RSD<0.8%) and an LOD of 0.12 mg/L. Applied to 20 samples from a Fortaleza religious group's brew, the method found target compound concentrations ranging widely from 0.3 to 36.7 g/L.
AyahuascaDMTThis study is conducted as a feasibility study for a pivotal Phase IIb/3 clinical trial and the primary outcomes for this Phase II study were blood levels of NRX-101, in order to confirm pharmaco-kinetics with remission from depression, as measured by BISS-derived MADRS and relapse as secondary outcomes.
KetamineThis secondary analysis of a double-blind, parallel-arm, randomised placebo-controlled trial (n=29) investigates the impact of ayahuasca on suicidality (SI) in individuals with treatment-resistant depression (TRD). It found that ayahuasca may show potential as a fast-acting and innovative intervention for SI, but didn't find significant results (only a trend with a large effect size). This is the first study to investigate the use of ayahuasca for SI.
AyahuascaTreatment-Resistant Depression (TRD)SuicidalityBorderline Personality Disorder (BPD)Depressive DisordersPersonality DisordersMajor Depressive Disorder (MDD)Public Health, Prevention & Behaviour ChangeIntravenous DMT markedly reduced alpha and beta oscillatory power and robustly increased spontaneous EEG signal diversity, with emergent delta/theta activity correlating with the peak, eyes‑closed visual component of the experience. These oscillatory and diversity changes closely tracked subjective reports and plasma drug levels, linking specific EEG signatures to immersive DMT states of consciousness.
DMTNeuroimaging & Brain Measures
Week of 11 November 2019
In a randomised, double-blind, cross-over study in 28 healthy subjects, single doses of LSD (0.1 mg), MDMA (125 mg) and d-amphetamine (40 mg) produced similar autonomic responses but clearly distinct subjective and endocrine profiles. LSD caused the strongest alterations of consciousness, ego dissolution, cognitive impairment and anxiety; MDMA produced the most positive/empathetic effects and increased plasma oxytocin; d-amphetamine primarily raised blood pressure and enhanced activity and concentration, while none of the drugs altered plasma BDNF — results that can inform dose-finding in substance-assisted psychotherapy.
LSDMDMAAnxiety DisordersHealthy VolunteersNeurocognitive DisordersMedicinal Chemistry & Drug DevelopmentThe 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-DMT
Week of 28 October 2019
Randomised, double-blind, active-placebo-controlled Phase II trial (n=60) of two-session LSD-assisted psychotherapy (100 µg → 100/200 µg) versus low-dose LSD (25 µg ×2) for Major Depressive Disorder.
LSDIn an observational study of 30 combat veterans, six high‑dose 1‑hour ketamine infusions targeting a transpersonal dissociative experience produced large, statistically significant reductions in depressive (PHQ mean 18.9→9.5) and PTSD symptoms (PCL‑5 mean 56.2→31.3), while self‑reported substance use did not significantly change. These results suggest high‑dose ketamine infusion therapy may be a promising treatment for combat‑related PTSD and warrant controlled trials to confirm efficacy and clarify mechanisms.
KetamineAnxiety DisordersDepressive DisordersPTSDVeteransSubstance Use Disorders (SUD)This double-blind, placebo-controlled study (n=55) investigated the use of ketamine (35mg/70kg) versus midazolam (an anesthetic), plus mindfulness-based therapy (5-week program) for cocaine dependence. The ketamine group scored significantly better and were 53% less likely to relapse.
KetamineDepressive DisordersSubstance Use Disorders (SUD)Safety & Risk ManagementPublic Health, Prevention & Behaviour ChangeThis double-blind, placebo-controlled, within-subject study (n=20) found that a microdose of LSD (up to 26μg; 3x) elicited dose-dependent subjective effects during the 'peak' of the experience but not at the follow-up (48 hours).
LSDMicrodosingDepressive DisordersHealthy Volunteers
Week of 21 October 2019
The study is being conducted to evaluate the safety and pharmacokinetics of HR071603 (ketamine nasal spray) in healthy subjects.
KetamineIn a double-blind trial giving psilocybin or placebo to meditators during a 5-day mindfulness retreat, psilocybin deepened meditation and produced positively experienced self-dissolution without increased anxiety, with openness, optimism and emotional reappraisal predicting the acute response. Greater acute self-dissolution under psilocybin predicted larger improvements in mindfulness and psychosocial functioning at four months, suggesting meditation enhances psilocybin’s positive effects and that emotion/attention regulation and transient selflessness modulate longer-term outcomes.
PsilocybinAnxiety DisordersPersonality & Trait FactorsThe South Florida and South Carolina research network will use its Schedule I DEA licence to study psilocybin’s safety and efficacy in major depressive disorder. Its new Miami Lakes facility supports early-phase, inpatient and outpatient trials in psychiatric, neurological and general medical conditions, with 29 research beds.
PsilocybinDepressive Disorders
Week of 14 October 2019
The primary aim of this study is to investigate the role of acute serotonin release in the effects of fear extinction. MDMA will be used as pharmacological tool to induce serotonin release in this study.
MDMARandomised, double-blind, placebo-controlled ED trial (n=29) testing a single low-dose IV ketamine infusion (0.5 mg/kg over 40 minutes) for acute depression or suicidal ideation.
KetamineOpen-label, non-randomised Phase II study (n=40) of weekly supervised oral ketamine (start 0.5 mg/kg, titrate to 3.0 mg/kg) over six weeks for patients with chronic suicidal ideation.
KetamineResearchers Roland Griffiths and Matthew Johnson discussed Johns Hopkins trials in which psilocybin was associated with reduced depression and anxiety among cancer patients, while a participant reported quitting smoking after 46 years. Johns Hopkins plans to establish a Center for Psychedelic and Consciousness Research, supported by $17 million from private donors including Tim Ferriss, Matt Mullenweg, Blake Mycoskie and Craig Nerenberg.
PsilocybinAnxiety DisordersDepressive Disorders
Week of 7 October 2019
On 11 October 2020, MAPS submitted a detailed request addressing the FDA’s concerns about Study MT2’s risk-benefit ratio and investigator qualifications. MAPS also offered self-reported survey data from participants in the earlier Study MT1 therapist training study on perceived benefits and harms.
MDMAHealthy VolunteersNon-randomised, crossover Phase I study (n=15 actual) in healthy volunteers assessing the effect of a 2 g kratom tea on CYP3A4 (midazolam) and CYP2D6 (dextromethorphan) probe pharmacokinetics.
Week of 30 September 2019
The aim of the study is to investigate the safety of GH001 (containing 5-methoxy-dimethyltryptamine; 5-MeO-DMT), and its dose-related psychoactive effects in healthy volunteers.
5-MeO-DMTRandomised, placebo‑controlled, triple‑blind Phase II study (n=38) testing single IV ketamine doses (0.1–0.5 mg/kg) with MRI to measure glutamate and GABA in major depressive disorder; optional second 0.5 mg/kg infusion offered to non‑responders.
KetamineRandomised, early-phase diagnostic parallel study (n=11) comparing ketamine versus methohexital induction during ECT, using dcEEG to examine infra-slow/slow-wave characteristics in patients with major depressive episodes.
KetamineThis theoretical paper (2019) proposes Contextual Behavioural Science (CBS) as an ideal framework for understanding psychedelic experiences and therapeutic change. The authors argue that CBS-based therapies, such as Acceptance and Commitment Therapy (ACT), are uniquely positioned to deepen and maintain the acute effects of psychedelic-assisted therapy.
Depressive DisordersAnxiety DisordersObsessive-Compulsive Disorder (OCD)Palliative & End-of-Life DistressThis study (n=48) found that there is significant overlap in the neural correlates of classic serotonergic psychedelics (psilocybin, LSD) and ketamine, even though the mechanism of action is not the same.
LSDPsilocybinNeuroimaging & Brain MeasuresThis historic review (2019) examines cellular mechanisms underlying the antidepressant effects of the R(-) and S(+) ketamine enantiomers and their norketamine and hydroxynorketamine metabolites. Although S(+) ketamine exhibits greater affinity to the NMDAR, which is believed to be the mediator of its antidepressant effect, preclinical evidence from animal models suggests that (R)-ketamine exerts greater potency and longer-lasting antidepressant effects with less detrimental side-effects. Given that the phase I clinical studies on R(-)ketamine and hydroxynorketamine are now underway, future studies will be able to perform a direct comparison of their efficacy to treat patients with depression.
KetamineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersSuicidalityThis experiment measured brain states (fMRI) under psilocybin infusion, and found more general coherence (communication) and lower frontoparietal network activity.
PsilocybinNeuroimaging & Brain MeasuresThis digital ethnographic study investigates how online health communities use self-experimentation to determine their treatment protocols by examining the case study of clusterbusters, a platform that came into being when a self-experimenter reported that LSD had prevented his usual cluster headache cycles on an internet forum. This example typifies how a rare disease being responded to with an even rarer form of intervention is cultivated through the collective experimentation of patient communities embedded in social networks who engage in collective forms of knowledge production.
LSDHeadache Disorders (Cluster & Migraine)Chronic PainRandomised, double-blind, placebo-controlled parallel trial (n=67) of six IV ketamine infusions (0.5 mg/kg) over 3 weeks in veterans with comorbid PTSD and MDD to probe neuroanatomy and executive functioning.
KetamineThe Psychedelics and Wellness Study (PAWS) is an anonymous cross-sectional online survey of adults (18+) who have taken a psychedelic at least once, assessing relationships between past psychedelic use and measures of mental wellness (planned n=5,000; actual enrolled=3,234).
This review of recent fMRI studies finds that acute LSD produces widespread alterations in functional brain connectivity — predominantly increases and most consistently heightened thalamocortical coupling — supporting models of reduced cerebral filtering of external and internal information, though results are tempered by neuroimaging limitations and potential biases.
LSDAnxiety DisordersDepressive DisordersNeuroimaging & Brain MeasuresSchizophreniaSubstance Use Disorders (SUD)Healthy VolunteersPersonality Disorders
Week of 23 September 2019
Double-blind, randomised 2×2 crossover study in healthy adults (n=22) testing IV Delta-9-THC (0.015 mg/kg) and IV ketamine (0.2 mg/kg) alone and combined with EEG and psychotomimetic outcomes.
Ketamine
Week of 16 September 2019
The multi-site study also operates in Boulder, Colorado, and Charleston, South Carolina, with sites led by Marcela Ot’alora and Zhenya Gelfand. Invitation-only enrolment is for therapists training to work on MAPS-sponsored MDMA-assisted psychotherapy trials for PTSD. The Phase 1 study has enrolled 81 healthy volunteers examining MDMA’s psychological effects in a therapeutic setting.
MDMAHealthy VolunteersPTSDRandomised, double-blind, parallel-group Phase I/II study (n=19 actual) comparing IV ketamine 0.5 mg/kg weekly ×4 versus placebo in patients with major depressive disorder and advanced cancer receiving palliative care.
KetamineThe FDA-regulated trials combine 12 weeks of preparatory and integration psychotherapy with three day-long sessions using MDMA or placebo, alongside psychotherapy. Efficacy and safety will be assessed using CAPS-5 ratings from blinded independent raters, informing potential approval as a prescription treatment for PTSD.
MDMAPTSDAlso covered by MAPS
Mind Medicine, Inc. acquired the 18-MC drug development programme from Savant HWP Inc., whose leadership team will join Mindmed. Previously funded by the National Institute on Drug Abuse, 18-MC is designed to retain ibogaine’s anti-addictive properties without its hallucinogenic effects and is being prepared for a Phase II FDA trial targeting opioid use disorder.
IbogaineAlso covered by BioSpace
The training events took place in Louisville, Kentucky, from 10 to 17 August 2019, with 53 of the 55 trainees identified as clinicians and researchers of colour from across the US. MAPS PBC had submitted an MDMA-assisted psychotherapy protocol for PTSD to the FDA and expected to hear about its Expanded Access application the following month. The next retreat was scheduled for 1 to 8 October in Asheville, North Carolina, with registration already full.
MDMAPTSDThis open-label, non-randomised feasibility study (n=32) investigates low-dose individually-tailored subcutaneous ketamine infusions (0.1–0.4 mg/kg over 2 hours) given weekly by response for depression in palliative care patients with advanced life-limiting illnesses.
Ketamine
Week of 9 September 2019
This survey study (n=410) showed that those with mental & physical health problems self-rated the effectiveness of microdosing as higher than conventional treatments in regards to ADHD/ADD and anxiety. They rated it as less effective than a high dose of psychedelics.
Anxiety DisordersDepressive DisordersMicrodosingChronic PainHeadache Disorders (Cluster & Migraine)CreativityThis review (2019) details the potential superiority of MDMA-assisted psychotherapy as a treatment for PTSD compared to the conventional treatment options paroxetine and sertraline.
MDMAAnxiety DisordersPTSDSuicidalitySingle-blinded, randomised, crossover trial (n=17) in treatment-resistant depression comparing etomidate- vs ketamine-general anaesthesia with ECT and ketamine alone; ketamine ~2 mg/kg IV across six treatment sessions per participant.
KetamineIn adults with treatment-resistant depression receiving intravenous ketamine, clinically significant childhood sexual and physical abuse and greater cumulative maltreatment predicted larger reductions in depressive symptoms after single and repeated infusions and higher remission rates after repeated treatment. This suggests ketamine may be especially effective in TRD patients with high childhood trauma burden, perhaps by blocking trauma-associated behavioural sensitisation, in contrast to poorer responses seen with conventional antidepressants.
KetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Bipolar DisorderPTSDRandomised, crossover Phase II study (n=1) testing single IV ketamine infusions 0.5 mg/kg and 0.2 mg/kg in postpartum depression to assess safety, pharmacokinetics and antidepressant efficacy.
Ketamine
Week of 2 September 2019
Qualitative interviews with 11 Indigenous participants of ayahuasca‑assisted ceremonial retreats indicated reductions in substance use and cravings, with eight reporting complete cessation of at least one substance at six‑month follow‑up. Participants attributed benefits to increased connectedness with self, others and nature/spirit, suggesting ayahuasca may offer therapeutic mechanisms distinct from conventional addiction treatments and merits further study.
AyahuascaSubstance Use Disorders (SUD)Private donors have funded the centre’s first five years, including the Steven & Alexandra Cohen Foundation and philanthropists Tim Ferriss, Matt Mullenweg, Blake Mycoskie and Craig Nerenberg. Researchers will investigate psychedelics’ effects on brain function, mood, learning and memory, and study potential treatments for addiction, depression, anorexia nervosa and other conditions. The centre will support six faculty neuroscientists, psychologists and clinicians, five postdoctoral scientists, and student training.
PsilocybinAnxiety DisordersDepressive DisordersEating Disorders
Week of 26 August 2019
Randomised, quadruple-blind, crossover adolescent trial (n=17 actual) assessing single IV ketamine (0.5 mg/kg) versus active midazolam (0.045 mg/kg) for medication-refractory MDD or anxiety disorders with 2-week washout.
KetamineThis qualitative interview and diary study (n=14) investigated the context in which romantic couples use MDMA and found that it occasioned shared experiences which could modulate and enhance existing feelings of closeness in the process of being subsumed into things that couples enjoyed doing together, to the effect that it refreshed and revitalized their relationship.
MDMASafety & Risk ManagementInterpersonal Functioning & Social ConnectednessThis case study (2019) explores repeated intravenous (IV) ketamine in synergy with antidepressants to treat refractory depression (TRD). It found that high-dose IV ketamine may stably enhance depressive symptoms and cognitive function in patients with TRD who do not tend to respond to a rapid intravenous dose of standard-dose ketamine.
KetamineAdolescentsMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersSubstance Use Disorders (SUD)Neurocognitive DisordersSafety & Risk ManagementUsing semistructured interviews with 30 microdosers and the sociology of accounts, the authors show that participants offered no excuses but instead deployed six justificatory strategies—denial of injury, self-sustaining, self-fulfilment, appeal to normality, appeal to loyalties and knowledgeableness—when describing their practice. The study highlights how these justifications reveal microdosers’ subjective experiences and their attempts to align the practice with societal expectations.
LSDPsilocybinMicrodosingCreativityThis double-blind placebo-controlled clinical trial (n=12) examined the effects of naltrexone and ketamine on suicidal ideation (SI) and found that naltrexone attenuates (blocks) the effects of ketamine. It's proposed, just as with the antidepressant effect of ketamine, that it requires opioid receptor activation.
KetamineAnxiety DisordersSuicidalityDepressive DisordersOpen-label, single-group Phase I pilot (n=22) testing up to four oral psilocybin sessions (initial 20 mg, titratable to 30 mg) in adults with chronic anorexia nervosa to assess safety and preliminary efficacy.
Psilocybin
Week of 19 August 2019
Double-blind, randomised clinical trial (n=45) comparing intraoperative ketamine infusion (0.5 mg/kg over 40 minutes) versus saline in patients with major depressive disorder undergoing non-cardiac surgery.
Ketamine
Week of 12 August 2019
Open‑label, single‑arm Phase II proof‑of‑concept study (n=20) evaluating intranasal ketamine spray (sub‑anesthetic doses, product up to 75 mg) for acute treatment of chronic cluster headache in adults.
Ketamine
Week of 5 August 2019
This multi-site, open-label, Phase II lead-in study (n=38) assesses safety and efficacy of three sessions of MDMA-assisted therapy (flexible MDMA dosing 80–120 mg with optional supplemental half-dose) in participants with at least severe PTSD.
MDMAPatients who suffer from MDD received ketamine (2014-15) in open study will be addressed and there depression mood will be evaluated using the rating scale that were used in the original research. In addition time of relapse and questions about their medications and drug use will be performed.
KetamineRandomized, triple-blind, crossover study (n=22) testing single oral MDMA 1.5 mg/kg versus placebo on affective touch responses across a range of autistic traits.
MDMA
Week of 29 July 2019
Randomised, parallel-group non-inferiority trial (n=198) comparing racemic ketamine IV infusions (0.5 mg/kg over 40 minutes, thrice weekly) with ECT in inpatients with severe MDD.
KetamineRandomized, double-blind, parallel study (withdrawn) testing IV ketamine 0.5 mg/kg infusion over 40 min in adults with treatment-resistant major depressive disorder (actual n=0).
KetamineSingle-group, Phase I study (n=60) assessing IV ketamine infusions (0.5 mg/kg over 40 minutes, up to 4 sessions) in adults with major depression to identify neuroimaging and blood biomarkers of rapid response and relapse.
KetamineThis double-blind, placebo-controlled study (n=38) found that psilocybin (22mg/70kg) in combination with mindfulness training elicited changes in the default mode network (DMN) that are associated with ego loss. These changes predicted positive outcomes four months later.
PsilocybinNeuroimaging & Brain MeasuresSet & SettingThis interview study (n=30) reviewed the experiences of subjects who have used psychedelics (e.g. LSD, psilocybin) in small quantities (microdosing) to understand their reasons and how they perceived themselves in their conventional lives in the context of their narrative identity. The study opined that the acute use of such psychedelics in small quantities allowed the subjects to rationalize their reasons due to their procurement and administration practices as well as health reasons. This helped them normalize their drug use, facilitated persistence and saw themselves as conventional citizens with middle-class values. This reasoning ultimately allows them to distance themselves from those who abuse psychedelics.
LSDPsilocybinAnxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life DistressMicrodosingCreativityDepressive DisordersThis long-term follow-up (n=28) found that transcranial magnetic stimulation (TMS) combined with ketamine infusions, for those suffering from depression (TRD) was effective up to two years later. The administration of ketamine during TMS allowed for higher intensities than would otherwise be tolerated by patients.
KetamineDepressive DisordersSchizophreniaMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)This animal study (n=15) investigated the efficacy of ayahuasca (0.6mg DMT, 3.1mg harmine, 0.4mg harmaline, and 0.34mg tetrahydroharmine /300g) to treat depressed marmoset monkeys exposed to 8 weeks of social isolation. They found that ayahuasca reduced scratching and depression-like behaviors, increased the feeding rate, and restored body weight and fecal cortisol to baseline levels, particularly within male monkeys.
AyahuascaDepressive DisordersAdolescentsMajor Depressive Disorder (MDD)
Week of 22 July 2019
Single-group, open-label Phase I study (n=9 actual) assessing tolerability and efficacy of low-dose IV ketamine infusions for Levodopa-Induced Dyskinesia in Parkinson's disease.
KetamineThe study analysed National Survey on Drug Use and Health data from about 394,415 people surveyed between 2011 and 2017. Summer accounted for 34% of new LSD use, 30% of new marijuana and ecstasy use, and 28% of new cocaine use, prompting calls for seasonal prevention and education.
LSDThirteen clinical trial sites across the UK, Netherlands, USA, Spain, Ireland and Canada were active, with 65 therapists and assisting therapists trained. Compass Pathways also said it was collaborating with 20 research teams, providing GMP psilocybin without charge in exchange for safety data rights, and expected full healthy-volunteer study results later in 2019.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)
Week of 15 July 2019
Randomised, double-blinded, placebo-controlled Phase II trial (n=60) testing intravenous ketamine (Ketamin Inresa) with CBASP versus placebo+CBASP and ketamine+treatment-as-usual for chronic, treatment-resistant depression in Germany.
KetamineDouble-blind, randomised, parallel-group RCT (n=24 adolescents) comparing six 0.5 mg/kg IV ketamine infusions (2/week for 3 weeks) versus six midazolam infusions; primary outcome CDRS at Day 18; 6-month open extension offers ketamine to midazolam non-responders.
KetamineIn this open‑label proof‑of‑concept study, the first four participants with alcohol use disorder tolerated an 8‑week MDMA‑assisted psychotherapy programme (two MDMA sessions each) with no MDMA‑related serious adverse events or clinically significant physiological, ECG or laboratory changes, supporting safety and informing plans for a randomised placebo‑controlled trial.
MDMADepressive DisordersPTSDAnxiety DisordersAlcohol Use Disorder (AUD)Safety & Risk ManagementSubstance Use Disorders (SUD)
Week of 8 July 2019
We don't know much about the effects of microdosing or have even defined it rigorously. Kuypers and colleagues (2019) ask the questions and take the first step in building a framework for a more scientific microdosing study. Microdosing is defined as the 1) use of a low dose below the perceptual threshold that does not impair ‘normal’ functioning of an individual, 2) a procedure that includes multiple dosing sessions, and 3) with the intention to improve well-being and enhance cognitive and emotional processes.
LSDPsilocybinMicrodosingMedicinal Chemistry & Drug DevelopmentThe FDA responded to MAPS regarding its submitted protocol for an expanded access programme involving MDMA-assisted psychotherapy for post-traumatic stress disorder. The response marked a regulatory update in MAPS’ efforts to extend the therapy beyond clinical trials, but no further details are provided.
MDMAPTSDThe present randomised crossover study (n=16) in healthy volunteers used escalating single oral doses of LSD (25–200 µg) with a placebo arm and a ketanserin (40 mg) pre-treatment to probe the role of the 5-HT2A receptor in LSD-induced altered states.
LSDThe authors validate a six‑item Emotional Breakthrough Inventory (Cronbach’s α=0.932), demonstrating that emotional breakthrough is a distinct, dose‑dependent component of the acute psychedelic experience that is more likely with therapeutic planning and intent. In a low‑well‑being subsample (n=75) emotional breakthrough and mystical-type experiences independently predicted subsequent increases in well‑being, whereas challenging experiences predicted smaller improvements.
Substance Use Disorders (SUD)This survey study (n=278) aimed to develop a codebook of benefits and challenges associated with microdosing. The authors found, among other things, that many parallels exist between the effects reported as benefits and those reported as challenges.
LSDPsilocybinMicrodosingDepressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Safety & Risk Management
Week of 1 July 2019
Randomised, triple-masked, two-period crossover healthy volunteer study (n=27) comparing 14-day escitalopram pretreatment versus placebo before a single oral psilocybin 25 mg session to assess subjective, physiological and gene-expression effects.
PsilocybinRandomised, parallel Phase III trial (n=140) of low-dose subcutaneous ketamine (starting 0.6 mg/kg, titrated up to 0.9 mg/kg; weekly ×4) versus low-dose midazolam in 16–25-year-olds with moderate-to-severe major depressive disorder.
KetamineThis study will explore whether the use of a medication, ketamine, can help patients who come to the ER with thoughts of suicide by improving their mood and reducing thoughts of suicide.
KetamineRandomized, double-blind, placebo-controlled, parallel-group pilot (University of São Paulo, Brazil; conducted September 2015 – July 2019) of a single oral dose of ayahuasca (2 mL/kg; prepared by a Santo Daime church and stored refrigerated; alkaloid concentrations verified by UPLC-MS) versus placebo (2 mL/kg; mineral water, glycerin, propylene glycol, methylparaben; organoleptic match) in 17 undergraduate volunteers (15 women) meeting DSM-5 Social Anxiety Disorder criteria confirmed by SCID-5-CV (SPIN ≥19 or excessive social fear on screening). From 894 screened, 17 met criteria and were randomised: 9 to ayahuasca, 8 to placebo. Key exclusions: current SAD treatment, major medical or other psychiatric disorders (except comorbid anxiety), psychoactive medications, recurrent illicit drug use, prior ayahuasca use (>2 lifetime hallucinogen uses), pregnancy/lactation. Primary outcome: Self-Statements During Public Speaking Scale (SSPS) state version during a Simulated Public Speaking Test (SPST; anticipatory, preparation and speech phases) administered 300–355 minutes post-dose. Secondary outcomes: Visual Analogue Mood Scale (VAMS; anxiety, sedation, cognitive impairment, discomfort factors) at 11 time points from baseline to 355 minutes; Bodily Symptoms Scale (BSS); Beck Anxiety Inventory (BAI; baseline, 240 min, follow-ups); Recognition of Emotions in Facial Expressions (REFE) task; cardiovascular measures. Follow-up at days 7, 14, and 21. Analysis: two-way repeated-measures ANOVA (time × group), Bonferroni correction, α=0.05, η² effect sizes. No formal sample size calculation (pilot feasibility study). All 17 completed the experimental session and three follow-ups; equipment failure reduced some outcome analyses to 14 participants (7 per group). No trial registry number reported.
AyahuascaThis double-blind, placebo-controlled, crossover study (n=20) analyzes the pharmacodynamic response of the brain under acute MDMA effects to understand its functional connectivity (FC) using a novel multimodal method (REACT). The study showed that FC can be understood through the distribution of its main targets by linking the resting state (rs-)fMRI analysis with molecular data of voxel-wise distribution of the serotonin receptors across the brain, due to the serotonergic effects of MDMA. The conclusion supported the usefulness of this method to define the specificity of the functional response of the brain to MDMA effects linked to serotonergic receptors and the potential of the definition of a new fingerprint in the characterisation of new compounds; and the possibility of further studying the effects of the treatment.
MDMANeuroimaging & Brain MeasuresHealthy VolunteersMedicinal Chemistry & Drug DevelopmentInterpersonal Functioning & Social ConnectednessThis theoretical paper (2019) introduces the ‘REBUS’ (Relaxed Beliefs Under Psychedelics) model, integrating the free-energy principle with the entropic brain hypothesis. It proposes that psychedelics relax the precision weighting of high-level beliefs (priors), thereby liberating bottom-up information flow and enabling the revision of pathological or rigid thought patterns.
This double-blind, placebo-controlled study (n=57) investigated ketamine’s effects on brain activity (BOLD) during an emotional processing task where fMRI of participants with depression (MDD) showed greater activity than healthy participants. After ketamine treatment, the depressed participants showed similar levels of brain activity, suggesting a normalization of function during emotional processing.
KetamineDepressive DisordersMajor Depressive Disorder (MDD)Neuroimaging & Brain MeasuresHealthy Volunteers
Week of 24 June 2019
Open-label, single-group biomarker pilot (n=9) testing intranasal ketamine (40 mg, mucosal atomization) in treatment-resistant depression with MRI and blood assays before and after treatment.
KetamineThis study will test the hypothesis that that NRX-100 is superior to placebo in achieving rapid reduction in symptoms of depression and suicidal ideation in patients with Severe Bipolar Depression and Acute Suicidal Ideation or Behavior within 24 hours of administration.
Ketamine
Week of 17 June 2019
This placebo-controlled, double-blind study (n=69) investigated the dissociated effects of ketamine in young healthy individuals (aged 18-30) and found that men had greater depersonalization and amnestic symptoms than women. The study also found that age was a factor in the overall effect of ketamine on dissociative symptoms with men with rising age being less affected than women. This conclusion links gender and age to the effects of drugs and recommends including them as factors so that psychiatric treatments could be more effective.
KetamineHealthy VolunteersSchizophreniaAdolescentsOlder AdultsDepressive DisordersMedicinal Chemistry & Drug Development
Week of 10 June 2019
This randomised controlled trial (n=70) investigated the effects of ketamine on mentalizing and metacognition in healthy volunteers.
KetamineRandomised, double-blind, placebo-controlled five-site trial (n=51) testing oral brexpiprazole (up to 3 mg/day) versus placebo combined with intranasal ketamine (40 mg, six administrations over 4 weeks) added to stable antidepressant therapy for adults with TRD.
KetamineThis retrospective study (n=183) replicated an earlier model of psilocybin response, which predicts that states of surrender and preoccupation at the time of ingestion are significant variables determining the nature of the experience.
PsilocybinAnxiety DisordersDepressive DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Healthy VolunteersPersonality & Trait FactorsRandomized, parallel-group Phase II study (n=40) comparing nitroprusside versus placebo co-administration with ketamine (0.5 mg/kg IV over 40 minutes) in patients with major depression to assess antidepressant and psychotomimetic effects.
Ketamine
Week of 3 June 2019
This multi-site, open-label, Phase II, lead-in study assesses the safety and effect of 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in participants diagnosed with at least severe posttraumatic stress disorder (PTSD).
MDMAProspective observational cohort (n=20) assessing neurobiological effects of intranasal ketamine in adolescents and adults with Bipolar Disorder — Fear of Harm phenotype; off-dose and 2–3 h post-dose neuroimaging/EEG comparisons.
KetamineThis placebo-controlled, double-blind randomised trial study (n=73) investigated the impact of BDNF (a protein related to the growth of neurons) on patients with depression who were administrated ayahuasca. The trial results observed a potential link between the changes in serum BDNF levels and the antidepressant effects of ayahuasca and also supported using psychedelics as an antidepressant.
AyahuascaDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)
Week of 27 May 2019
This mouse study investigated the mechanisms behind sensitisation to the prosocial effects of MDMA (7.8 mg/kg). It finds that repeated administration led to increased social interaction, a process dependent on social context and 5-HT2A receptor activation during the development, but not the expression, of this sensitisation.
MDMAPTSDAutism Spectrum Disorder (ASD)Interpersonal Functioning & Social ConnectednessThis review article by David Nutt gives an overview of where psychedelics research stands in June 2019.
Treatment-Resistant Depression (TRD)Depressive DisordersPTSDAnxiety DisordersAlcohol Use Disorder (AUD)Tobacco/Nicotine Use Disorder (TUD)Neuroimaging & Brain MeasuresSubstance Use Disorders (SUD)This rodent study (2019) evaluated the acute effects of LSD on intracranial self-stimulation (ICSS), an operant conditioning reward measure. It found that acute LSD treatment did not alter its own ICSS depressant and the likelihood of methamphetamine abuse effects.
MescalinePsilocybinDepressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)MicrodosingThis cell-based (in vitro) study investigated how the cytochrome P450 (CYPs) enzymes contribute to the metabolism of LSD to nor-LSD and 2-oxo-3-hydroxy-LSD and its potential for clinical LSD use. The study found that the human liver converted only small quantities of LSD to nor-LSD and O-H-LSD, however, several CYPs substantially contributed to the process. The review concluded that there is a link between genetic polymorphisms and drug interactions and it could therefore affect the pharmacodynamics and pharmacokinetics of LSD. Also, it was found that nor-LSD potentially may have hallucinogenic activity similar to LSD, while O-H-LSD is inactive.
LSDAdolescentsMedicinal Chemistry & Drug DevelopmentSurveying 1,116 psychedelic users, the study found most microdosed with LSD or psilocybin—typically 2–4 times weekly—primarily to enhance performance and commonly experienced acute psychological side‑effects while under the influence, with many stopping because they perceived no benefit. The authors conclude that placebo‑controlled experimental studies are needed to quantify any performance enhancement and assess longer‑term harms.
LSDPsilocybinMicrodosingBEDROC: Phase 2a proof-of-concept two-part study of R-107, an extended-release ketamine tablet, in treatment-resistant MDD. Part 1: open-label R-107 120 mg/day × 5 days (~200 screened). Part 2: responders randomized to placebo or R-107 (30/60/120/180 mg) twice-weekly for 12 weeks (target 150). Primary outcome: MADRS change from baseline to Day 92. Sponsor: Douglas Pharmaceuticals Ltd. Sites: Australia, New Zealand, Singapore, Taiwan.
KetamineThe grant includes $2.9 million for GMP-certified pharmaceutical-grade MDMA production, $1.1 million for EMA-regulated Phase 2 and 3 trials for PTSD, and funding for regulatory advice, staff salaries and a therapy training event for communities of colour in Kentucky. PSFC aims to support regulatory approval and future patient access.
MDMAPTSD
Week of 20 May 2019
MAPS said Yensen and Dryer engaged in an unethical sexual relationship with a participant after treatment sessions ended in 2015, and substantially deviated from the MDMA-assisted Therapy Treatment Manual during the trial. They were barred from MAPS-related activities in 2018, while MAPS notified the FDA, Health Canada, ethics committees and relevant authorities after reopening its review in November 2021.
MDMAAt the APA 2019 Meeting, Janssen presented data on 63,855 adults with MDD and suicide ideation or attempt, finding that fewer than half received an antidepressant in the preceding year. Among 160,343 hospitalised patients, 19.2% had a readmission or subsequent ED visit within six months, with nearly half occurring within 30 days.
Depressive DisordersMajor Depressive Disorder (MDD)SuicidalityThe cost-per-remitter model, based on Phase 3 trial response, remission and relapse rates, predicted savings of at least $20,000 per patient achieving remission with SPRAVATO and an oral antidepressant. Savings increased approximately threefold when lost productivity was included, with similar findings across US payer types.
EsketamineDepressive DisordersTreatment-Resistant Depression (TRD)Also covered by Jnj
In the Flinders Sensitive Line rat model of depression, psilocin and psilocybin produced no antidepressant-like effects in the forced swim test and did not alter locomotor activity, despite FSL rats showing the expected increased immobility versus controls. The authors suggest the FSL model and FST may be inappropriate for translational studies of psilocybin’s antidepressant actions.
PsilocybinDepressive DisordersAdolescentsTreatment-Resistant Depression (TRD)
Week of 13 May 2019
The trials assess MDMA or placebo alongside psychotherapy over 12 weeks, with 12 preparatory and integration sessions and three day-long dosing sessions. The primary endpoint is CAPS-5, assessed by blinded independent raters, and the studies represent the final FDA-required research phase before a decision on prescription use.
MDMAPTSDRandomised, parallel Phase I study (n=8) testing three IV ketamine doses (0.3, 0.5, 0.7 mg/kg) to examine relationships between hydroxynorketamine (HNK) serum levels, depressive symptoms, and glutamate/GABA changes.
KetamineAn anonymous online survey of 343 mostly White male adults with prior severe AUD found that a single naturalistic moderate-to-high dose psychedelic experience (primarily LSD or psilocybin) was associated with marked reductions or cessation in alcohol use, with 83% no longer meeting AUD criteria afterwards. Greater dose and higher ratings of mystical-type, insightful and personally meaningful effects predicted larger reductions, though causality cannot be established and the findings support further clinical investigation of psychedelic-assisted treatment for AUD.
LSDPsilocybinAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Public Health, Prevention & Behaviour Change
Week of 6 May 2019
A pooled analysis of six randomised, double‑blind phase 2 trials found MDMA‑assisted psychotherapy produced large, clinically meaningful reductions in PTSD symptoms versus control (MMRM mean difference −22.0; Cohen’s d = 0.8) with higher remission rates (54.2% vs 22.6%) and acceptable tolerability, providing the rationale and design basis for phase 3 trials and FDA Breakthrough Therapy designation.
MDMADepressive DisordersPTSD
Week of 29 April 2019
The proposed licence could cover intranasal or intravenous scopolamine therapeutics worldwide. The relevant US and international patents, filed or granted between 2006 and 2017, are assigned to the US Government.
Bipolar DisorderDepressive DisordersThe U.S. Food and Drug Administration sent MAPS a formal response regarding the submitted protocol for an Expanded Access programme involving MDMA-assisted psychotherapy for post-traumatic stress disorder. The letter indicated that regulatory progress remained ongoing while MAPS awaited approval to proceed with expanded access studies.
MDMAPTSDObservational prospective cohort (n=7) evaluating change on psychological screening tools before, after, and 30 days following a six-infusion ketamine series in paramedics with work-related PTSD.
KetamineProof-of-concept randomised, placebo-controlled trial (n=48) testing low-dose ketamine (0.2 mg/kg; possible escalation to 0.5 mg/kg) as an adjunct to propofol-based anaesthesia for ECT in adults with major depressive disorder.
KetamineThis comprehensive review (2019) by some of the leading researchers in psychedelics looks at both the epidemiological & clinical studies and the positive (and negative) effect that psychedelics can have.
MescalinePsilocybinDepressive DisordersTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressNeuroimaging & Brain MeasuresHealthy VolunteersInterpersonal Functioning & Social ConnectednessAnxiety DisordersThis randomised, double-blind, placebo-controlled study (n=36) investigated the effects of MDMA (52.5 to 105 mg/kg) and methamphetamine (20 mg) in healthy young adults on behavioral and psychophysiological response to socially relevant, “affective” touch, and visual attention to emotional faces. The tests showed that MDMA positively influenced responses to affective touch, but neither drug influenced ratings of observed touch.
MDMAPTSDAutism Spectrum Disorder (ASD)Interpersonal Functioning & Social ConnectednessThis study characterised the pharmacokinetics of a novel oral LSD solution (100 μg) in 27 healthy subjects, finding first‑order elimination with a geometric mean Cmax ≈1.7 ng/mL at 1.7 h, t1/2 ≈3.6 h, measurable O‑H‑LSD but not nor‑LSD, and no sex differences. The subjective effects lasted about 8.5 h with peak effects at ≈2.5 h and were closely associated with plasma concentrations (EC50 ≈1.0 ng/mL for “good” and ≈1.9 ng/mL for “bad” effects).
LSDHealthy VolunteersMedicinal Chemistry & Drug Development
Week of 22 April 2019
Based at Imperial’s Hammersmith campus, the centre will build on more than a decade of research, including trials comparing psilocybin with an antidepressant for depression and planned work on anorexia. Led by Dr Robin Carhart-Harris, it also aims to develop a research clinic that could inform future licensed psychedelic care facilities.
PsilocybinDepressive DisordersEating DisordersThis study investigated serotonin transporter (SERT) complexes with ibogaine to illustrate structure-based mechanisms for transport in serotonin transporter (SERT). The investigation reported that cryo-electron microscopy structures of SERT-ibogaine complexes captured in outward-open, closed and inward-open conformations with ibogaine binding to the central binding site, and the closing extracellular gate with movements of TMs 1b and 6a. The intracellular gate opening had a hinge-like movement of TM1a and the partial unwinding of TM5 that together built a permeation pathway enabling substrate and ion diffusion to the cytoplasm. These structures show the structural rearrangements which occur from the outward-open to inward-open conformations, and give an important insight into the working mechanism of neurotransmitter transport and ibogaine inhibition.
IbogaineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersAnxiety DisordersAutism Spectrum Disorder (ASD)Usona Institute had FDA clearance and central Institutional Review Board approval to launch its first clinical trials of psilocybin for major depressive disorder. The nonprofit aimed to establish five to seven sites, with activity anticipated from autumn 2019, and sought potential FDA approval if results were positive.
PsilocybinDepressive DisordersMajor Depressive Disorder (MDD)This survey study (n=4258) compares natural (non-drug) and psychedelic (LSD, psilocybin, ayahuasca, DMT) reported God encounter experiences and finds very similar descriptions. For half of the participants the experience qualified as a full mystical experience, more than 67% of participants who identified as atheists didn't do so after the experience (e.g. became agnostic).
AyahuascaLSDPsilocybinThis review (s=8) found that psychedelics (LSD, psilocybin) can aid in the recognition of emotions in facial expressions (REFE), which is thought to be a key aspect of social cognition. Psychedelics do this by modulating the activity of the amygdala.
PsilocybinLSDDepressive DisordersAnxiety DisordersEating DisordersInterpersonal Functioning & Social Connectedness
Week of 15 April 2019
This opinion paper (2019) proposes the use of psilocybin on patients with disorders of consciousness, since psilocybin can increase brain complexity, a possible indicator of conscious level.
PsilocybinNeurological InjuryHealthy VolunteersEquity and EthicsTriple-blind, randomised, parallel trial (n=56) testing four repeated very low doses of LSD (13 µg or 26 µg) versus placebo in healthy adults 18–40 to assess mood, cognitive performance and responses to emotional tasks.
LSD
Week of 8 April 2019
This open-label (naturalistic) study (n=42) with 5-MeO-DMT (smoked) found that it significantly reduced ratings of depression, anxiety, and stress. It also increased scores on mindfulness and life satisfaction. These effects correlated with higher ego dissolution and oceanic boundlessness during the acute experience.
5-MeO-DMTAnxiety DisordersDepressive DisordersCreativityPhase IIa, multi-centre, randomized, double-blind, placebo- and active-comparator-controlled study (n=66) evaluating single IV infusions of MIJ821 (multiple dose cohorts) versus ketamine and placebo in adults with treatment-resistant depression; primary outcome MADRS at 24 hours.
KetamineThis double-blind, randomized, placebo-controlled trial (n=226) aimed to assess the efficacy and safety of intranasal esketamine 84 milligrams (mg) in addition to comprehensive standard care for rapidly reducing Major Depressive Disorder (MDD) symptoms, including suicidal ideation, in adults at imminent risk for suicide.
EsketamineThis comprehensive review (2019) compared the efficacy of ketamine treatment for pain and depression within palliative care across administration route and dosing regimen. Efficacy of pain treatment exhibited generally inconclusive and mixed results, but studies that administered ketamine either epidurally or intrathecally demonstrated significant analgesia, in contrast, to subcutaneously or intravenous administration routes. Depression was improved across all relevant studies and was sustained the longest during a daily dosing regimen, whereas a single or a multidose did not exert effects beyond 7 days after administration.
KetamineDepressive DisordersChronic PainPalliative & End-of-Life DistressAnxiety DisordersThis double-blind, placebo-controlled study (n=12) investigated the effects of MDMA elder cousin, MDA. It found the duration to be longer (8 vs 6 hours), and with various characteristics more similar to classical psychedelics.
MDMAHealthy VolunteersMedicinal Chemistry & Drug DevelopmentThis review (2019) examines the lack of efficient treatment options for patients suffering from PTSD and explores the viability of ketamine for patients who do not respond to conventional treatment. It is thought that ketamine might reverse some of the damage caused by chronic stress, by means of upregulating BDNF and antagonizing NMDA. The review also notes that the deterrent of dissociative side-effects may be less common than previously reported and point to early evidence which supports that ketamine may yield a near-complete resolution of traumatic symptoms, albeit only over a short-term of 1-2 weeks.
KetamineVeteransMajor Depressive Disorder (MDD)Depressive DisordersPTSDAnxiety DisordersSubstance Use Disorders (SUD)
Week of 1 April 2019
This review (2019) investigates what research has been done with psychedelic-assisted group therapy. It identifies 12 studies, mostly with LSD (2 with psilocybin), and ranging from surveys to randomised controlled trials.
LSDPsilocybinSet & SettingInterpersonal Functioning & Social ConnectednessThis mice study investigates the restoration/regulation of social reward learning for patients with long-term depression using MDMA. The findings point towards the potential of understanding the pathogenesis of neurodevelopmental diseases, which are defined by social impairments, and of disorders that are effected by social influence or are a consequence of social injury.
MDMADepressive DisordersPalliative & End-of-Life DistressAnxiety DisordersIn April 2019, MAPS PBC sent the U.S. Food and Drug Administration a response concerning its submitted Expanded Access protocol for MDMA-assisted psychotherapy for post-traumatic stress disorder. The clinical hold was expected to delay the proposed research.
MDMAPTSDThree-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 paper presents an alternative hypothesis of how psychedelics work with a focus on sleep (macrodose) and the microbiome (microdose). The author proposes ways of testing this hypothesis.
Treatment-Resistant Depression (TRD)Depressive DisordersMicrodosingCreativityImmunology & Inflammation
Week of 25 March 2019
This diary study (n>100) investigates the safe and beneficial use of psychedelic microdosing (e.g. 10μg LSD) to improve positive moods by evaluating positive and negative emotional states using the PANAS checklist and written reports. The study showed that microdosers perceived improved health habits, increased energy, and improved work effectiveness. Furthermore, smaller samples demonstrated alleviation of symptoms in migraine headaches, traumatic brain injury, pre-menstrual syndromes (PMS), shingles, and other such conditions that have not been previously associated with psychedelic use.
PsilocybinDepressive DisordersMicrodosingHeadache Disorders (Cluster & Migraine)Traumatic Brain Injury (TBI)Neurological InjuryChronic Pain
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