Blossom Pulse Archive
What happened in psychedelic research in 2017
224 events from 2017, 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 25 December 2017
Open-label single-group MRI study (n=25) assessing IV ketamine 0.5 mg/kg (40-min infusion) in patients with major depressive disorder to examine brain predictors of antidepressant response.
KetamineThis review article (2018) looks at the pre- and post-prohibition clinical studies on psychedelics and offers strategic advice on the legal and regulatory hurdles.
Alcohol Use Disorder (AUD)SchizophreniaSafety & Risk ManagementSet & SettingSubstance Use Disorders (SUD)
Week of 18 December 2017
The meetings took place in Virginia and Maryland, with 17 FDA staff attending the December 20 session under the Breakthrough Therapy Designation programme. MAPS Public Benefit Corporation had completed 11 of 14 site initiation visits for an open-label training study across the US and Canada. Phase 3 trials planned for the US, Canada and Israel will compare MDMA with placebo over 12 weeks, using CAPS-5 as the primary endpoint.
MDMAPTSD
Week of 11 December 2017
This non-randomised trial (n=25) investigates the effects of ketamine on anxiety ratings in patients with anxiety disorders, specifically Generalized Anxiety Disorder (GAD) or Social Phobia (SP).
KetamineUsing connectome-harmonic decomposition, the authors show that LSD selectively alters the energy and power of harmonic brain states, expanding the repertoire of active states and increasing non-random cross-frequency co‑activation. The frequency distribution of these active states follows power laws, indicating a reorganisation of brain dynamics towards the edge of criticality.
LSDNeuroimaging & Brain MeasuresThis study evaluates the effects of Salvinorin A (SA). SA is the active ingredient of the plant Salvia divinorum that is known to have been used by Mexican Indians as part of religious rituals. The purpose of this project is to understand what people experience when they consume Salvinorin A.
Salvia Divinorum
Week of 4 December 2017
The programme is scheduled to begin in the first quarter of 2018, with clinical sites in the Czech Republic, Finland, Germany, the Netherlands, Norway, Portugal, Spain and the UK. Worldwide Clinical Trials will act as the clinical research organisation for the randomised, controlled trial, following COMPASS Pathways’ pre-clinical work and GMP manufacturing readiness.
PsilocybinDepressive DisordersTreatment-Resistant Depression (TRD)Also covered by Newscientist
This rodent study (2017) suggests that the hallucinatory effects of 5-MeO-DMT may be due to simultaneous alteration of prefrontal and visual brain activities. The authors point to 5-HT1A receptor antagonists as a potential treatment for visual hallucinations.
5-MeO-DMTDepressive DisordersAnxiety DisordersSchizophreniaPublic Health, Prevention & Behaviour Change
Week of 27 November 2017
Randomized, parallel-group study (n=154 actual) testing intravenous subanesthetic ketamine with or without adjunctive computer-based cognitive training for treatment-resistant depression; mechanistic outcomes (fMRI, IAT, cognitive flexibility) and clinical outcomes (MADRS acute; QIDS over 12-month follow-up).
KetamineRandomized, double-blind crossover Phase II–III study (n≈46) comparing IV ketamine (0.5 mg/kg, 40 min) to active control midazolam (30 µg/kg, 40 min) in treatment-resistant major depressive disorder, with escalation to repeated infusion schedules to assess durability.
KetamineOpen-label single-arm clinical study (J Psychopharmacol 2019 Apr; Zheng W, Zhou YL, Liu WJ, Wang CY; Affiliated Brain Hospital of Guangzhou Medical University, China; PMID 30789302). Enrolled Nov 2016 – Dec 2017. Participants: adults 18–65 with DSM-5 MDD (confirmed by two psychiatrists), HAMD-17 ≥17, and either suicidal ideation (SSI-part 1 ≥2) or TRD (≥2 failed adequate antidepressant trials in current episode). No control arm, no randomisation. Intervention: six IV ketamine infusions (0.5 mg/kg in 40 mL saline, 40 min infusion pump) on Mon/Wed/Fri over 12 days; concomitant psychotropics continued at stable dose. Co-primary outcomes: MADRS response (≥50% reduction) and remission (MADRS ≤10) at 24 hours after sixth infusion. ITT analysis with SPSS v.24. Methods state registration in the Chinese Clinical Trial Registry (ChiCTR); registration number not reported in paper text or PubMed XML DataBankList.
KetamineAlcohol use disorders remain a significant public health problem. The pharmacological facilitation of behavioral treatment represents a promising strategy for addressing disordered drinking. Alcohol use disorders are recognized to be associated with various vulnerabilities that complicate the course of treatment and that may be amenable to glutamate modulators. The purpose of this randomized, double-blind, controlled trial is to test various glutamate modulators in conjunction with motivational enhancement therapy (MET) for alcohol use disorders.
KetamineThis double-blind, placebo-controlled study (n=22) only used MDMA as a control condition and found that modafinil, although often used as a cognitive enhancer, may show some adverse effects regarding emotion processing.
MDMADepressive DisordersAnxiety DisordersNeuroimaging & Brain MeasuresHealthy VolunteersInterpersonal Functioning & Social ConnectednessThe 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.
LSD
Week of 20 November 2017
This study (2017) reviews the clinical and preclinical data concerning cannabinoids and ketamine as they relate to possible reconsolidation processes of maladaptive memories.
KetaminePTSDSubstance Use Disorders (SUD)This study is designed to investigate whether low-dose ketamine administered during cesarean delivery can decrease the incidence of postpartum depression in parturients with prenatal depression.
Ketamine
Week of 13 November 2017
This article (2017) reviews the history of the regulation of LSD research through the 1962 Kefauver-Harris Amendments (making it harder to do psychedelic research) and their implementation over the course of the ensuing decade.
LSDDepressive DisordersSchizophreniaEquity and EthicsThis mouse study (2017) examined the hippocampi of mice treated with ketamine in order to ascertain which pathways the drug affected. The researchers found, among other things, that ketamine tended to downregulate the ATP/ADP metabolite ratio.
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersThis 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.
MDMA
Week of 6 November 2017
In a large international self‑selecting online survey (n = 96,901), past‑year ayahuasca users (n = 527) reported greater well‑being than both classic psychedelic users and non‑psychedelic drug users, and less problematic alcohol use than classic psychedelic users. Ayahuasca’s acute subjective effects typically lasted about six hours and were strongest around one hour after consumption.
AyahuascaLSDDMTSubstance Use Disorders (SUD)Neurocognitive DisordersThis open-label study (n=20) expands on earlier work by Carhart-Harris and colleagues on the use of psilocybin-assisted therapy for treatment-resistant depression (TRD).
PsilocybinAnxiety DisordersDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Obsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressThis double-blind, within-subjects design, placebo-controlled study (n=25) found that LSD increased primary process thinking (implicit, associative, automatic, system 1) via serotonin (5HT) 2a receptor activation.
LSDHealthy VolunteersThis commentary (2017) proposes that MDMA can be used as a safe and effective adjunct for psychotherapy in the treatment of alcohol use disorder. Given that alcoholism is often associated with early traumatic experiences, it is argued that MDMA therapy may be applied efficaciously to a wider range of mental disorders beyond that of only PTSD.
MDMAAdolescentsDepressive DisordersPTSDAnxiety DisordersAlcohol Use Disorder (AUD)Substance Use Disorders (SUD)Safety & Risk ManagementThis double-blind, placebo-controlled study (n=20) with psilocybin (10, 20, 30mg/70kg) and DMX (400mg/70kg) finds very similar subjective effects between the two drugs. The visual, mystical, and insightful effects were more pronounced with psilocybin, disembodiment with DMX.
LSDPsilocybinNeurocognitive DisordersHealthy VolunteersPersonality & Trait FactorsThe purpose of this study is to compare the efficacy and safety of switching treatment-resistant depression (TRD) subjects from a prior antidepressant treatment (to which they have not responded) to either intranasal esketamine plus a new oral antidepressant or switching to a new oral antidepressant plus intranasal placebo.
Esketamine
Week of 30 October 2017
This open-label study (n=20) suggests that the effects of compassionate imagery and MDMA may be additive in regards to self-compassion and emotional empathy.
MDMASet & SettingInterpersonal Functioning & Social ConnectednessThe primary purpose of this study is to see if it is safe to give patients with pancreatic or head and neck cancer a low dose of the FDA approved anesthetic drug ketamine at the same time they receive radiation and/or chemotherapy for their cancer treatment to prevent depression and its effects.
KetamineThis trial (n=60) investigated the effect of MDMA (75mg) on the formation of memories. This was tested by simulating a crime (virtual reality). The trial found no significant effect of heightened vulnerability to external suggestions from MDMA.
MDMAThis review (2017) critically disputes the hypothesis that DMT is secreted by the pineal gland at birth, during dreaming, and at near-death to produce out-of-body experiences, in light of evidence that naturally occurring DMT concentrations in the brain are not sufficient to produce any psychoactive effects. More sound explanations for out-of-body experiences include the stress-related release of kappa-opioid receptor affine endorphins (similar to Salvinorin A) or excessive release of glutamate (similar to ketamine).
DMTRandomised, 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.
PsilocybinThis survey study (n=88) found that ibogaine can be an effective treatment against opioid addiction.
IbogaineDepressive DisordersAnxiety DisordersOpioid Use Disorder (OUD)Substance Use Disorders (SUD)Public Health, Prevention & Behaviour ChangeThis interview study (n=22) analyzed the subjective experiences associated with ibogaine treatment for substance dependence, and found both similarities and differences to effects reported for classic psychedelics.
AyahuascaLSDIbogainePsilocybinOpioid Use Disorder (OUD)Substance Use Disorders (SUD)This secondary analysis of the Imperial open-label psilocybin depression pilot found that 17 treatment-resistant depression patients were slower than 16 healthy controls on a dynamic emotional face recognition task at baseline, but this difference was remediated 1 week after the 25 mg psilocybin session. Reaction-time improvement correlated with reduced anhedonia, while clinical symptom rows are treated as mechanism context rather than duplicate efficacy results.
PsilocybinDepressive DisordersSchizophreniaMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Anxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life Distress
Week of 23 October 2017
Open-label, multicentre, single-group Phase III study (n=802) assessing long-term safety and efficacy of intranasal esketamine plus an oral antidepressant in adults with treatment-resistant depression.
EsketamineThe No Objection Letter covers a Phase 2 training study at Canadian sites, with 10 of 14 Study Initiation Visits completed across the US and Canada. Phase 3 trials are planned to assess three MDMA or placebo sessions with psychotherapy in adults with PTSD, using CAPS-5 as the primary endpoint.
MDMAPTSDThis open-label study (n=34) investigated the effects of ketamine (35mg/70kg) on suicidal ideation and sleep rhythm in patients with (bipolar) depression and found that patients with less post-infusion nocturnal wakefulness exhibited an antisuicidal response to ketamine, compared to patients who were wakeful at night and continued suicidal ideation.
KetamineBipolar DisorderDepressive DisordersSuicidalityMajor Depressive Disorder (MDD)Neuroimaging & Brain Measures
Week of 16 October 2017
In a pooled analysis of over 480,000 US adults from the National Survey on Drug Use and Health (2002–2014), lifetime classic psychedelic use — and psilocybin use specifically — was associated with reduced adjusted odds of past‑year larceny/theft, assault, and arrests for property and violent crimes. However, lifetime psychedelic use was also associated with higher odds of past‑year drug distribution and other illicit drugs were generally linked to increased criminal odds, supporting further clinical research of classic psychedelics, including psilocybin, in forensic settings.
PsilocybinInterpersonal Functioning & Social Connectedness
Week of 9 October 2017
This open-label retrospective study (n=41) evaluated the efficacy and safety of intravenous ketamine (35mg/70kg) infusion in a sample of patients who had treatment-resistant depression (TRD) and were being treated in a ‘naturalistic’ clinical context. Low-dose ketamine was efficacious and generally well-tolerated in the sample population, as participants reported improvements in depressive symptoms with a 53.7% response rate 24 hours post-infusion.
KetamineAdolescentsOlder AdultsMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Bipolar DisorderDepressive DisordersAnxiety DisordersSuicidalityImplementation & Service DeliveryPsilocybin with psychological support produced rapid symptom reductions in treatment‑resistant depression and, on fMRI, elicited post‑treatment decreases in temporal cortex cerebral blood flow including the amygdala (the latter correlating with symptom improvement) alongside increased resting‑state functional connectivity within the default‑mode network. Increased vmPFC–bilateral inferior lateral parietal connectivity and decreased parahippocampal–prefrontal connectivity predicted 5‑week response, prompting the authors to propose a post‑acute “reset” therapeutic mechanism distinct from acute psychedelic effects.
PsilocybinDepressive DisordersNeuroimaging & Brain MeasuresTreatment-Resistant Depression (TRD)In a randomised, double-blind trial, high-dose psilocybin administered within a meditation and spiritual-practice programme produced enduring (six-month) increases in prosocial attitudes and behaviours and in healthy psychological functioning (e.g. interpersonal closeness, gratitude, meaning, forgiveness, daily spiritual experiences). Lasting change was predicted by the intensity of the psilocybin-occasioned mystical-type experience and by participants' continued rates of meditation/spiritual practice.
PsilocybinHealthy VolunteersPalliative & End-of-Life DistressInterpersonal Functioning & Social ConnectednessDepressive DisordersAnxiety DisordersUsing shotgun mass spectrometry on human cerebral organoids treated with 5‑MeO‑DMT, the study identified 6,728 proteins of which 934 were differentially expressed, revealing anti‑inflammatory signatures and modulation of proteins linked to long‑term potentiation, dendritic spine formation and cytoskeletal/microtubule dynamics. This provides the first molecular insight into how 5‑MeO‑DMT alters human brain‑like tissue.
5-MeO-DMTDepressive DisordersImmunology & Inflammation
Week of 2 October 2017
This mouse study (n=52) compared the two enantiomers R-MDMA of S-MDMA, and their racemic mixture (5.6 -; 7.8 mg/kg) with respect to their prosocial therapeutic effects and adverse neurotoxicity, in mice. Due to a lower potency to release dopamine, R-MDMA exerted fewer adverse effects than SR/S-MDMA, but increased prosocial behavior to a similar magnitude.
MDMAPTSDInterpersonal Functioning & Social ConnectednessThis double-blind, randomized, psychoactive placebo-controlled trial (n=147) assessed the efficacy and safety of 3 fixed doses (28 mg, 56 mg, and 84 mg) of intranasal esketamine in addition to comprehensive standard of care for rapidly reducing the symptoms of major depressive disorder (MDD), including suicidal ideation, in pediatric subjects.
EsketamineThis systematic review (2018) and meta-analysis (n=176) examined the effects of ketamine on suicidal ideation using patient-level data from various studies that applied a single-dose intravenous administration route to treat any type of psychiatric disorder. Ketamine significantly reduced suicidal ideation for up to one week after the infusion.
KetamineDepressive DisordersSuicidalityPublic Health, Prevention & Behaviour ChangeIn a retrospective analysis of 274 surviving war‑wounded soldiers from Afghanistan, ketamine administration was not independently associated with development of acute or post‑traumatic stress disorder; multivariable regression identified only acute stress disorder and total number of surgical procedures as independent predictors of PTSD. Although a higher proportion of PTSD cases had received ketamine on unadjusted analysis, injury severity and other covariables accounted for that association.
KetamineAnxiety DisordersChronic PainPTSDVeteransDepressive DisordersAutism Spectrum Disorder (ASD)Neurological InjuryIn a double-blind, placebo-controlled crossover study in 18 healthy volunteers, 100 µg LSD impaired response inhibition and reduced activation in right middle temporal, bilateral frontal, anterior cingulate, left postcentral and cerebellar regions, with altered parahippocampal–prefrontal relationships. These results indicate that 5‑HT2A receptor activation disrupts hippocampal–prefrontal inhibitory control, which may facilitate the emergence of LSD-induced visual imagery and hallucinations.
LSDHealthy VolunteersSchizophreniaNeurocognitive DisordersNeuroimaging & Brain Measures
Week of 25 September 2017
This double-blind, placebo-controlled study (n=58) investigated the effect of two doses of psilocybin (11mg-15mg/70kg) on cerebral blood flow. The larger dose led to significantly higher ratings on 4 of 11 scales of altered consciousness. It also showed which specific brain regions became more, and less, active.
PsilocybinNeuroimaging & Brain MeasuresThis cohort study (n=51) found evidence for the hypothesis that ketamine normalizes prefrontal dysconnectivity. The first part of the study showed an increase in activity in the prefrontal global signal regression after ketamine (35mg/70kg) administration (which was lower in those with depression).
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersHealthy VolunteersThis survey study (n=2,974) found that neurotic individuals may be more likely to have a challenging experience with psilocybin.
PsilocybinPersonality & Trait FactorsThis rodent study explores the effects of harmine treatment on chronic unpredictable stress (CUS)-induced depressive-like behaviors and astrocytic dysfunctions. The results demonstrated that the development of depression is critically contributed by astrocytic dysfunction as a potential mechanism and harmine induces antidepressant-like effects likely via restoration of the said astrocytic functions.
Major Depressive Disorder (MDD)Depressive DisordersThis paper (2017) reviews multiple hypotheses for the origin of visionary experiences in psychedelic use. It proposes that normal/ordinary function of the prefrontal cortex and default mode network (DMN) gets disrupted, allowing for thalamic and other 'lower' brain processes (also based in the mirror neuron system) to emerge.
Neuroimaging & Brain MeasuresUsing BOLD fMRI tonality‑tracking in 25 healthy adults given placebo, LSD and LSD pretreated with the 5‑HT2A antagonist ketanserin, the study shows that 5‑HT2A receptor signalling mediates LSD‑induced alterations in neural tracking of dynamic tonal structure in music. These changes occur across auditory, musical, memory, emotion and self‑referential brain regions and likely underlie the increased emotionality, connectedness and perceived meaningfulness of music during psychedelic states.
LSDNeuroimaging & Brain MeasuresHealthy Volunteers
Week of 18 September 2017
The Santa Cruz-based project is seeking FDA approval and is expected to enter its final testing phase in April. MAPS plans to enrol about 300 participants at 15 sites, while previous trials found that around 68% of 107 participants no longer had PTSD one year after two treatment sessions.
MDMAPTSDThis review (2017) summarizes pre/clinical data pertaining to the effects of psychedelics and their pharmacological mechanisms of action and outlines future areas of translational research to investigate how synapse-related gene expression influences the disruption of established neural connectivity patterns, underlying therapeutic effects.
Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Neuroimaging & Brain MeasuresFollowing oral administration of 100 μg LSD to 20 healthy participants, resting‑state fMRI showed increased thalamic functional connectivity to multiple cortical regions, with thalamus–right fusiform and thalamus–insula connectivity correlating with subjective visual and auditory effects. These findings suggest enhanced thalamocortical coupling—likely via 5‑HT2A receptor mechanisms—may underlie LSD‑induced hallucinations by facilitating cortical excitability.
LSDHealthy VolunteersNeuroimaging & Brain MeasuresIn a longitudinal community-based cohort of marginalised women in Metro Vancouver, lifetime psychedelic drug use was associated with a 60% reduced hazard of incident suicidality over 54 months (adjusted HR 0.40), while crystal methamphetamine use and childhood abuse increased risk. These observational, naturalistic findings suggest a potential protective association of psychedelics and support further investigation of their therapeutic utility for mental health.
SuicidalityDepressive DisordersPTSDSubstance Use Disorders (SUD)Equity and EthicsPublic Health, Prevention & Behaviour ChangeMAPS reached agreement with the FDA on the design of two Phase 3 trials through a Special Protocol Assessment and selected Montrium’s eTMF Connect to support them. The cloud platform will manage trial documents, data and clinical activities, while MAPS joins Montrium’s Customer Advisory Program.
MDMAPTSDAlso covered by BioSpace
Week of 11 September 2017
This double-blind cross-over trial (n=16) found that LSD (200μg) led to positive well-being/life-satisfaction scores up to 12 months later. The subjects experienced it as one of the top 10 most meaningful experiences (70%) in their lives.
LSDMescalineAnxiety DisordersHealthy VolunteersPersonality & Trait FactorsRandomised, 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 qualitative study (n=100) examined the pleasurable aspects of recreational psychedelics (LSD, psilocybin mushrooms) use reported on the Erowid trip database. The author argues that although pleasurable experiences are regarded as irrelevant within therapeutic contexts, it is a key reason why most people use psychedelics, to facilitate a mode of ‘purposeless play’ that transgresses rules, meanings, and boundaries of the normalized everyday.
DMTThis interview study (n=16) suggests that ayahuasca may hold promise as a treatment for eating disorders (EDs). The interviewees (who used ayahuasca) indicated shifts in body perception, reduction or cessation of ED and mental health symptoms.
AyahuascaEating Disorders
Week of 4 September 2017
Randomised, quadruple-blind, parallel-group pilot trial (n=25) of four once-weekly IV ketamine infusions (0.05 mg/kg) versus midazolam infusions (0.045 mg/kg) as adjunctive treatment for inpatients with acute depressive episodes to assess trial processes and preliminary outcomes.
KetamineThis qualitative study (2017) examined self-reports from online forums about psychoactive substance use for treating migraines and cluster headaches, and found that psychedelic tryptamines, primarily LSD and psilocybin, were frequently reported to lessen both their frequency and intensity of pain at sub-psychoactive doses.
LSDPsilocybinSubstance Use Disorders (SUD)Chronic PainHeadache Disorders (Cluster & Migraine)Safety & Risk Management
Week of 28 August 2017
Randomised, parallel-group trial (n=62) comparing high-intensity daily IV ketamine (0.50 mg/kg for 8 days; HIKER) versus ECT with ketamine anaesthesia (EAST; 8 sessions) for treatment-resistant depression.
KetamineThis theory-building article (2017) argues that the serotonin (5-HT) 2a receptor (psychedelics) is responsible for active coping (plasticity) of adversity, whereas the 5-HT1a receptor (SSRIs) only leads to passive coping (stress reduction). The theory offers an explanation for the different pathways and outcomes of psychedelics and more traditional medications/ways of coping.
Depressive DisordersAnxiety DisordersNeuroimaging & Brain MeasuresMedicinal Chemistry & Drug DevelopmentThis review (2017) summarizes the history of the US military's attempt to operationalize psychotropic drugs, first scopolamine, and mescaline then later on MDMA and other derivatives, as a truth serum. These attempts were largely futile because scopolamine induced a delirium-like state of mind which raised doubt over the validity of the extracted information, whereas psychedelic substances produced excessive hallucinations, thought disturbance, and confusion, which hindered the interrogation process.
MDMAMescalineVeteransThis double-blind, placebo-controlled crossover trial (n=18) investigated the effects of intravenous ketamine (35 mg/70 kg) in adults with social anxiety disorder. It finds that ketamine resulted in a significantly greater reduction in anxiety symptoms compared with placebo on clinician-rated measures, although self-reported anxiety scores did not show a significant difference.
KetamineAnxiety DisordersDepressive DisordersPTSDObsessive-Compulsive Disorder (OCD)Neuroimaging & Brain MeasuresThis review (2017) studied research literature on psychedelics and dreaming to systematically compare these two states of consciousness. It highlighted the broad overlap between dreaming and psychedelic states supporting the perception that psychedelics acutely affect dreamlike subjective experiences that may show long-term beneficial responses to psychosocial functioning and well-being.
AyahuascaLSDPsilocybin
Week of 21 August 2017
This review (2017) examines synaptic deficits associated with chronic stress and persisting symptoms of PTSD and characterizes the rapid efficacy of ketamine via mechanisms that open up a window of increased neuroplasticity and enable cognitive and behavioral therapies to treat patients more effectively.
KetaminePTSDThis randomised, double-blind placebo-controlled, between-subjects study (n=60) investigated the effects of MDMA (70mg/70kg) on the retrieval and encoding of emotional memories and found that it diminished both faculties. These results support the notion that MDMA alters the recollection of details associated with emotional events but not memory for the occurrence of the event, which may help patients re-encoding these memories with novel, less emotional associations in the context of therapy.
MDMAPTSDHealthy VolunteersInterpersonal Functioning & Social Connectedness
Week of 14 August 2017
On 16 August 2017, the FDA designated MDMA a Breakthrough Therapy for PTSD, citing preliminary evidence of potential substantial improvement over existing treatments. The designation includes close FDA collaboration on development, while a 28 July agreement confirmed the Phase 3 protocol, endpoints, conduct and statistical analyses could support regulatory approval.
MDMAPTSDThe primary objective of this study is to determine the effectiveness of serial infusions of intravenous (IV) ketamine in adults with treatment-resistant depression (TRD).
KetamineOpen-label, single-group study (n=9) assessing low-dose IV ketamine (0.5 mg/kg over 40 minutes) on cortical neurophysiological function in treatment-resistant depression.
Ketamine
Week of 7 August 2017
Randomised, parallel delayed‑treatment trial (n=27) evaluating two moderately high oral psilocybin sessions for people with Major Depressive Disorder.
PsilocybinRandomized, double-blind, active-controlled Phase III study (n=139) in elderly participants with TRD testing intranasal esketamine (flexible 28–84 mg, twice weekly for 4 weeks) plus a new oral antidepressant versus intranasal placebo plus a new oral antidepressant.
EsketamineAn open-label, single-arm study at four Chinese hospitals investigating repeated subanesthetic ketamine infusions (0.5 mg/kg IV over 40 min, 6 sessions thrice weekly for 2 weeks) in patients with treatment-resistant depression. Registered prospectively in 2017 and funded by China’s National Key R&D Programme for Precision Medicine.
KetamineOpen-label single-arm clinical study (J Psychopharmacol 2019 Apr; Zheng W, Zhou YL, Liu WJ, Wang CY; Affiliated Brain Hospital of Guangzhou Medical University, China; PMID 30789302). Enrolled Nov 2016 – Dec 2017. Participants: adults 18–65 with DSM-5 MDD (confirmed by two psychiatrists), HAMD-17 ≥17, and either suicidal ideation (SSI-part 1 ≥2) or TRD (≥2 failed adequate antidepressant trials in current episode). No control arm, no randomisation. Intervention: six IV ketamine infusions (0.5 mg/kg in 40 mL saline, 40 min infusion pump) on Mon/Wed/Fri over 12 days; concomitant psychotropics continued at stable dose. Co-primary outcomes: MADRS response (≥50% reduction) and remission (MADRS ≤10) at 24 hours after sixth infusion. ITT analysis with SPSS v.24. Methods state registration in the Chinese Clinical Trial Registry (ChiCTR); registration number not reported in paper text or PubMed XML DataBankList.
KetamineThis randomised, double-blind, placebo-controlled crossover study (n=15) investigated changes in endogenous plasma metabolites following a single intake of MDMA (125 mg) and found an overall increase in oxidative stress indicated by the metabolic ratio of methionine-sulfoxide over methionine.
MDMAHealthy VolunteersThis systematic review (2018) examines the long-term effects of MDMA on neurocognitive performance amongst abstinent ecstasy users and found evidence of hemodynamic and electrophysiological changes in the prefrontal brain regions that is reflective of increased cognitive effort to maintain performance levels during executive functions.
MDMAPalliative & End-of-Life DistressNeurocognitive DisordersNeuroimaging & Brain MeasuresDepressive DisordersAnxiety DisordersAnalysis of resting‑state fMRI using complex‑network methods shows that Ayahuasca increases the Shannon entropy of the brain functional network degree distribution and produces greater local but reduced global integration. These network changes support the entropic brain hypothesis and are discussed in relation to users’ reports of “mind‑expansion.”
AyahuascaNeuroimaging & Brain MeasuresDepressive DisordersSubstance Use Disorders (SUD)
Week of 31 July 2017
MAPS, the Multidisciplinary Association for Psychedelic Studies, began accepting Ethereum and Litecoin alongside Bitcoin. DecentraNet and HSW will host a cocktail cruise and art auction on 13 August to support Phase 3 trials of MDMA-assisted psychotherapy for PTSD, which MAPS estimates will cost $25 million.
MDMAPTSDRandomised, placebo-controlled trial in active-duty military patients hospitalised for suicidal thinking (planned n=40) comparing a single IV bolus of ketamine 0.2 mg/kg versus placebo, with acute monitoring and follow-up to 10 weeks.
KetamineThis commentary paper (2017) proposes that connectedness is the key to its therapeutic potential.
Treatment-Resistant Depression (TRD)Depressive DisordersNeuroimaging & Brain MeasuresThis randomised, quadruple-blind, crossover study (n=67) tests a single 35 mg/70 kg IV ketamine infusion (40 min) versus placebo for rapid antidepressant effects in major depressive disorder.
KetamineThis study is designed to compare the effectiveness of two medications, Ketamine and Midazolam, for rapidly relieving suicidal thoughts in people suffering from depression.
Ketamine
Week of 24 July 2017
This systematic review (2017) examined the reported side-effects of ketamine treatment for depression across 288 published reports and identified that headache, dizziness, dissociation, elevated blood pressure, and blurred vision were the most common in response to intravenous infusion. The most common acute psychiatric side-effect was anxiety, but there was no conclusive evidence about long-term side effects from the currently available studies.
KetamineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Chronic PainHeadache Disorders (Cluster & Migraine)Safety & Risk ManagementThis review (2017) shifts the usual focus from psychedelics as a potential treatment for mental health problems to psychedelics as a potential enhancer of well-being in healthy individuals. The author argues that the relatively low risk and high potential benefit of psychedelic drugs are incongruent with the stringent drug laws seen around the world.
Anxiety DisordersHealthy VolunteersEquity and EthicsThis survey study (n=10) asked experienced psilocybin therapists and research staff to recommend music that best supports the lead-up to and peak of psilocybin sessions aiming to elicit mystical experiences. It finds that peak-period music is typically regular, predictable and gradually building with a continuous forward motion and relatively low perceptual brightness, offering practical guidance for selecting or composing music to optimise peak psychedelic experiences in research and therapy.
Substance Use Disorders (SUD)Set & SettingThis mouse study (n=360) investigated the role of serotonergic neurotransmission in MDMA's (7.8 mg/kg) ability to extinguish fearful memories in mice and found that the selective inhibition of serotonin release via 5-HTT and the inhibition of neurotransmission via 5-HT2A receptors diminished this effect.
MDMAPTSDInterpersonal Functioning & Social Connectedness
Week of 17 July 2017
This placebo-controlled study (n=20) found that individuals under the acute influence of MDMA (75mg) were less sensitive to negative sounds. The authors also found evidence that this may be related to the 5-HT2A receptor.
MDMAInterpersonal Functioning & Social ConnectednessThis review (2017) discusses the isolation of mushroom-derived indole alkaloids.
PsilocybinThis Phase I study explored the safety, tolerability, pharmacokinetics, and pharmacodynamics of low doses of Lysergic Acid Diethylamide (LSD) ranging from 50 µg to 100 µg in healthy volunteers (n=32).
LSD
Week of 10 July 2017
This randomised, double-blind, active placebo‑controlled Phase II pilot (n=10) compared low (25 mg) versus full (125 mg) MDMA‑assisted psychotherapy across two experimental sessions in people with chronic, treatment‑resistant PTSD.
MDMAThis in vitro study investigated the neurogenic properties of alkaloids found in Banisteriopsis caapi, the vine component of ayahuasca. It finds that harmine, tetrahydroharmine, and harmaline stimulated the proliferation, migration, and differentiation of adult neural stem cells, suggesting a mechanism for the antidepressant effects of ayahuasca.
AyahuascaDepressive DisordersThis placebo-controlled study (n=20) found that the 5-HT2A receptor does not mediate the dissociative effects of MDMA (75mg) nor correlate with cortisol levels or MDMA blood concentrations. A correlation with heart rate was observed but didn't appear causally linked to the dissociative effects.
MDMA
Week of 3 July 2017
The study involves Catholic, Orthodox and Presbyterian priests, a Zen Buddhist and several rabbis, with sessions at Johns Hopkins and New York University in controlled, living room-like settings. Participants receive two doses one month apart, while a one-year follow-up will assess outcomes. Preliminary observations suggest a deeper appreciation of participants’ religious heritage and other faiths.
PsilocybinThis article (2017) examines the history of LSD experiments within the US army and their frequent short and long-term side effects and complications that have, according to the author, not received enough attention in the recent resurgence of interest in psychedelics.
LSDVeteransEquity and EthicsThis article (2017) presents a case study of a physician who attempted to self-medicate with DMT in order to treat their bipolar depression (BD). However, the paper goes beyond the case study to discuss DMT in general terms, as well.
DMTBipolar DisorderDepressive DisordersSchizophreniaThis study aims to determine whether ketamine could improve the depressive symptom of perioperative patients. It will also examine the safety for administrating ketamine as an antidepressant intraoperatively and effects on anxiety, postoperative pain, and delirium (n=84).
KetamineThis retrospective follow-up study (n=151) assessed the case material of 151 patients who applied for financial compensation for harms elicited by psychedelic treatments administered between 1959 to 1973 and re-evaluated in 1986. It found that one-third of the patients experienced a transient improvement in their mental state independent of the diagnosis, while the mental state of another third of the patients deteriorated with treatment.
LSDPsilocybinPTSDAnxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressDepressive Disorders
Week of 26 June 2017
Single-group pilot study (n=13) assessing neural and emotional processing changes after a single oral psilocybin dose (25 mg/70 kg) in healthy volunteers to evaluate mechanisms related to potential abuse liability.
PsilocybinDouble-blind, randomised, parallel pilot study (n≈31) comparing ketamine (1–2 mg/kg IV) versus methohexital (0.5–1 mg/kg IV) anesthesia during ECT for depressive episodes to assess speed of remission and cognitive side effects.
KetamineThis randomised controlled parallel group Phase I trial (n=24) evaluated the safety and efficacy of ketamine for major depressive disorder post traumatic stress disorder obsessive compulsive disorder generalized anxiety disorder social phobia using 70mg/70kg ketamine.
KetamineThis opinion paper (2017) argues that ego-dissolution experiences induced by psychedelic substances offer insight into the nature of the self. The authors argue that self-awareness results from hierarchical predictive models tied to an unchanging entity and, ultimately, that the self is merely a useful fiction.
This article is the first review to compile core competencies for psychedelic therapists, identifying six: empathetic abiding presence; trust enhancement; spiritual intelligence; knowledge of the physical and psychological effects of psychedelics; therapist self‑awareness and ethical integrity; and proficiency in complementary techniques. It also delineates 12 fundamental curricular domains for training these competencies and argues such guidelines are urgently needed as psilocybin‑ and MDMA‑assisted therapies progress to Phase 3 trials and possible wider clinical availability.
MDMAPsilocybinEquity and EthicsThis double-blind, placebo-controlled crossover study (n=15) investigated whether a single dose of LSD (100 µg) alters gene expression in whole blood as a marker of tolerance. Results show no significant changes in the expression of the 5-HT2A receptor gene or early growth response genes (EGR1-3) at 1.5 or 24 hours post-administration.
LSDHealthy Volunteers
Week of 19 June 2017
In 16 healthy participants, acute LSD (75 µg) markedly altered cortical and subcortical responses to naturalistic music, with the strongest effects tied to the music’s timbral complexity. These timbre-related activity and connectivity changes occurred in established music‑perception and emotion networks and correlated with increased music‑evoked feelings of wonder, supporting a neurobiological basis for the use of music in psychedelic therapy.
LSDHealthy VolunteersNeuroimaging & Brain MeasuresSet & SettingDouble-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.
LSDIn a randomised trial of MDMA-assisted psychotherapy for chronic, treatment-resistant PTSD, participants showed long-term increases in Openness and decreases in Neuroticism, and increased Openness (but not reduced Neuroticism) moderated the relationship between MDMA treatment and reductions in PTSD symptoms. These findings suggest MDMA-assisted psychotherapy can produce enduring personality change—particularly heightened Openness—that may act as a mechanism for therapeutic improvement.
MDMAPTSDAnxiety DisordersPersonality & Trait FactorsInterpersonal Functioning & Social ConnectednessThis retrospective chart review (n=27) investigates the efficacy and safety of rapid infusion of esketamine in patients with treatment-resistant depression (TRD) and bipolar depression (BD). The study found that rapid infusion of esketamine is not the best choice for treatment-resistant depression due to tolerability issues. Additionally, patients reported dissociative symptoms ranging from mild to severe and found them to be disturbing.
KetamineEsketamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Bipolar DisorderDepressive DisordersSafety & Risk ManagementIn a large-scale (N = 1,487) online study using structural equation modelling, lifetime experience with classic psychedelics uniquely predicted greater self-reported pro-environmental behaviour. This association was statistically mediated by increased nature relatedness and remained robust to controls for other drug use and personality traits, though the data are correlational.
LSDMescalinePsilocybinSubstance Use Disorders (SUD)Personality & Trait FactorsInterpersonal Functioning & Social ConnectednessSix months after an open‑label trial, patients with treatment‑resistant depression reported that psilocybin shifted them from disconnection (from self, others and the world) and emotional avoidance towards increased connectedness and acceptance. This suggests psilocybin may relieve depression via mechanisms opposite to those of conventional antidepressant medications and some short‑term talking therapies.
PsilocybinAnxiety DisordersDepressive DisordersTreatment-Resistant Depression (TRD)Neuroimaging & Brain Measures
Week of 12 June 2017
This placebo-controlled study (n=56) investigated the acute effect of psilocybin (15mg/70kg) on empathy and moral decision-making in healthy human subjects. The results found the first such evidence that psilocybin has distinct effects on social cognition by enhancing emotional empathy but not moral behavior. It also supports previous findings, indicating that psilocybin may promote emotional empathy presumably through activation of serotonin 2A/1A receptors, showing that focusing on serotonin 2A/1A receptors has the potential to treat dysfunctional social cognition.
PsilocybinMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersHealthy VolunteersBorderline Personality Disorder (BPD)Personality DisordersInterpersonal Functioning & Social ConnectednessThis 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.
EsketamineInterpretative phenomenological analysis of interviews with 13 adults given a single supervised dose of psilocybin identified ten themes indicating that psilocybin-assisted psychotherapy produced profound shifts—reconciliation with death, acknowledgement of cancer’s place in life, emotional uncoupling from cancer, spiritual meaning‑making, and a renewed presence and confidence facing recurrence. These psychological mechanisms likely underlie reported reductions in cancer-related anxiety and improvements in quality of life.
PsilocybinAnxiety DisordersDepressive DisordersPTSDPalliative & End-of-Life DistressHealthy VolunteersThis open-label study (n=16) investigated neurometabolic and connectivity modifications after a single ayahuasca use and their association with mindfulness measures. The results support the involvement of glutamate neurotransmission in the effects of ayahuasca. Furthermore, changes in the posterior cingulate cortex (default network) and connection of the posterior cingulate cortex and the medial temporal lobe (emotion & memory) may contribute to the effects of ayahuasca.
AyahuascaDepressive DisordersHealthy VolunteersInterpersonal Functioning & Social Connectedness
Week of 5 June 2017
The revision followed a 11 May 2017 Type A meeting with the FDA and meeting minutes received on 30 May. MAPS was seeking $25 million, with $10 million raised, to conduct the Phase 3 studies required for FDA approval by 2021.
MDMAPTSDDouble-blind, randomised, placebo-controlled Phase III trial (n=226) testing intranasal esketamine 84 mg twice weekly for 4 weeks plus standard of care versus intranasal placebo plus standard of care for rapid reduction of MDD symptoms including suicidal ideation in adults at imminent suicide risk.
EsketamineThis review (2017) evaluates the therapeutic research into psilocybin as a treatment for addiction, treatment-resistant depression, and mood and anxiety disorders. The authors also analyse the safety data from these clinical trials.
PsilocybinTreatment-Resistant Depression (TRD)Depressive DisordersAnxiety DisordersSubstance Use Disorders (SUD)Palliative & End-of-Life Distress
Week of 29 May 2017
Single-arm, Phase IV biomarker study (n=75) of three IV ketamine infusions (0.5 mg/kg over 100 minutes) for adults with treatment-resistant unipolar or bipolar depression to develop blood-based predictive and change biomarkers.
KetamineThis rat study (n=160) investigated the effects of ketamine (125 mg/kg) on the formation of traumatic memories in rats and found that it increased the retention of fearful memories when administered in close proximity to stress exposure.
KetaminePTSDThis interview (ethnographic) study finds that the caregiving context of ritual ayahuasca use plays a key role in the treatment of addiction. This offers an contrasting narrative to the more 'standard' or 'medical' model in which addiction is often framed.
AyahuascaSubstance Use Disorders (SUD)Randomised, triple-blind, parallel Phase III ED trial (n=5) comparing IV ketamine 0.3 mg/kg + ondansetron 4 mg to prochlorperazine 10 mg + diphenhydramine 25 mg for benign headache; terminated.
KetamineCompared with 30 attendees of peer‑support groups, 30 people who had taken ayahuasca scored lower on the Present Feelings Scale of the Texas Revised Inventory of Grief and showed benefits on some psychological and interpersonal measures. Qualitative reports described emotional release, recall of biographical memories and experiences of contact with the deceased, providing preliminary evidence that ayahuasca may have therapeutic potential in grief treatment.
Ayahuasca
Week of 22 May 2017
This placebo-controlled, double-blind, cross-over study (n=24) compared the acute autonomic, subjective, endocrine, and emotional effects of single doses of MDMA (125 mg), methylphenidate (60 mg), modafinil (600 mg) in healthy subjects using psychometric scales, the Facial Emotion Recognition Task (FERT), and the Sexual Arousal and Desire Inventory (SADI). It found that while all active drugs induced comparable hemodynamic and adverse effects, MDMA induced subjective, emotional, sexual, and endocrine effects that were distinctive from those of methylphenidate and modafinil with the doses used.
MDMAHealthy VolunteersPTSDAnxiety DisordersInterpersonal Functioning & Social ConnectednessPhase I randomized, double-blind crossover study (n=150) of IV ketamine (0.5 mg/kg; crossover with saline placebo) in patients with MDD and healthy volunteers; includes a metabolites substudy (single 0.5 mg/kg IV infusion) and a Phase III randomised repeated-dose comparison (0.5 vs 0.1 mg/kg twice weekly).
KetamineThis observational field study (n=30) investigated the effects of ibogaine on opioid detoxification amongst individuals who sought addiction treatment at a private clinic and found that the treatment had a substantiative effect of reducing drug use up to 1 month, or even up to 12 months amongst select individuals.
IbogaineOpioid Use Disorder (OUD)Substance Use Disorders (SUD)This theory-building article (2017) explores the phenomenological, neurophysiological and philosophical significance of drug-induced ego dissolution with classical psychedelics, dissociative anesthetics, and kappa-opioid receptor agonists and highlights their relevance for investigating the neurophysiological mechanisms underlying the representation and the sense of self.
SchizophreniaNeuroimaging & Brain MeasuresHealthy Volunteers
Week of 15 May 2017
Using data from the Global Drug Survey, the authors found that users of LSD analogues (AL‑LAD, 1P‑LSD, ETH‑LAD)—most of whom had also used LSD—reported similar time‑to‑peak (~2 hr) and duration (~8 hr) but significantly weaker subjective effects (pleasurable high, strength, comedown, urge to reuse), lower value for money and lower perceived risk than LSD; many obtained analogues online and almost all used them orally. The paper recommends chemical confirmation and dose measurement in future studies to validate these self‑report findings.
LSDEquity and EthicsThe pledge will provide $1 million annually for five years towards Phase 3 studies, projected to cost $25 million to $35 million for FDA and EMA approval. MAPS said it had $10 million available and received a further $197,000 in donations and pledges from 268 supporters in April 2017.
MDMAPTSD
Week of 8 May 2017
This observational study analysed over eight million reports from the FDA Adverse Effect Reporting System to evaluate the antidepressant effects of ketamine. It finds that pain patients who received ketamine reported significantly lower frequencies of depression and opioid-induced side effects compared with patients taking other pain medications.
KetamineAdolescentsTreatment-Resistant Depression (TRD)Depressive DisordersChronic PainSuicidalitySafety & Risk ManagementEquity and EthicsThis double-blind, randomised, parallel-group, placebo-controlled trial study (n=71) examines adjunctive ketamine's dose-related effects in Taiwanese patients with treatment-resistant depression (TRD). This first such report showing the dose-related efficacy of ketamine for TRD, and characterized ketamine effects in a genotyped Chinese group in which 83% of patients had at least one copy of the BDNF gene's lower functioning Met allele.
KetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Medicinal Chemistry & Drug DevelopmentThis review (2017) examines studies on psilocybin-assisted therapy to treat psychiatric disorders related to depression, anxiety, and substance abuse. In contrast to conventional paradigms, psilocybin-assisted therapy consists of only a few six-hour medication therapy sessions that may significantly improve symptoms and help patients achieve response or remission within weeks with support from integrative psychotherapy sessions.
PsilocybinDepressive DisordersAnxiety DisordersTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Neuroimaging & Brain MeasuresMedicinal Chemistry & Drug Development
Week of 1 May 2017
At Psychedelic Science 2017 in Oakland, California, researchers presented Phase II results from 107 people with PTSD. More than a year after two or three MDMA-assisted therapy sessions, about 67% no longer met PTSD criteria, compared with about 23% of the psychotherapy-plus-placebo group. MAPS is training therapists at 14 clinics in North America and Israel ahead of Phase III trials.
MDMAPTSDRandomized, multiple-crossover ICU study (n=10) evaluating whether continuous ketamine infusion (basal ~0.1 mg/min, titrated) suppresses cortical spreading depolarizations compared with other sedation regimens.
KetamineThis review (2017) examines ketamine's rapid antidepressant efficacy with respect to evidence that it can neurochemical/physiological disturbances, such as abnormalities in excitatory and/or inhibitory neurotransmission in association with altered brain levels of glutamate and gamma-aminobutyric acid. It highlights neuroimaging studies to support the notion that glutamatergic modulation may be a viable biomarker for investigating depression in future studies.
KetamineDepressive DisordersMajor Depressive Disorder (MDD)Bipolar DisorderNeuroimaging & Brain MeasuresThis review (2016) examines the psychoactive properties and therapeutic potential of Salvinorin A, a kappa-opioid receptor agonist that is the bioactive constituent of the indigenous plant Salvia divinorum. Next to highly potent psychoactive properties as a dissociative hallucinogen, preliminary scientific evidence also indicates it may have broad-range therapeutic applications for treating addiction, inflammation, pain, and depression.
Salvia DivinorumDepressive DisordersTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Chronic PainImmunology & InflammationMedicinal Chemistry & Drug Development
Week of 24 April 2017
This double-blind, randomized, placebo-controlled exploratory pilot study assessed the safety and feasibility of 3,4-methylenedioxymethamphetamine (MDMA)-assisted therapy for social anxiety in MDMA-naïve adults on the autism spectrum.
MDMAThis placebo-controlled, double-blind crossover trial (n=40) explores the potential therapeutic effects of a low dose (30–70 mg) of MDMA for treating tinnitus.
MDMAThis first qualitative interpretative phenomenological analysis of 13 cancer patients receiving psilocybin-assisted psychotherapy identified consistent themes — relational embeddedness, broadened emotional range, music- and vision-mediated meaning‑making, movement from separateness to interconnectedness, and revised life priorities — alongside transient distress and integration challenges. The findings indicate psilocybin-assisted psychotherapy may be a promising treatment for psychological distress in people with cancer and highlight experiential mechanisms relevant to theory and clinical practice.
PsilocybinAnxiety DisordersAdolescentsOlder AdultsTreatment-Resistant Depression (TRD)Depressive DisordersPalliative & End-of-Life DistressSet & SettingPersonality & Trait FactorsIn a pilot randomised, midazolam‑controlled trial of 16 people with bipolar depression and suicidal ideation, a single sub‑anaesthetic ketamine infusion produced a larger reduction in suicidal ideation at day 1 than midazolam (mean difference ≈5.8 points, P=0.074), demonstrating feasibility and preliminary efficacy. Memory improvement on the Selective Reminding Test and reductions in serum BDNF correlated with suicidal‑ideation decreases after ketamine, but the findings require replication in a fully powered trial.
KetamineBipolar DisorderDepressive DisordersSuicidalityNeurocognitive DisordersThis review (2017) presents the findings from all six modern clinical studies using LSD in the previous 25 years, detailing the effects and suggested mechanism of action in both healthy participants and those with end-of-life anxiety.
LSDAnxiety DisordersPalliative & End-of-Life DistressSchizophreniaNeuroimaging & Brain MeasuresHealthy VolunteersPersonality & Trait FactorsInterpersonal Functioning & Social ConnectednessDepressive DisordersThis review (2017) looks at the potential of psychedelics to be used in treatment of mental disorders, with a focus on psilocybin for depression.
PsilocybinMajor Depressive Disorder (MDD)Depressive DisordersObsessive-Compulsive Disorder (OCD)Alcohol Use Disorder (AUD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressNeuroimaging & Brain MeasuresAnxiety DisordersThis retrospective survey study (n=893) investigated the relationship between psychedelics use, ego dissolution, personality traits, political perspectives, and nature relatedness, and found that psychedelic use was associated with liberal and anti-authoritarian political views, openness to new experiences, and nature-relatedness.
SuicidalityPersonality & Trait FactorsThis ascending single-dose study (n=12) evaluates the dose-related effects of ketamine (18-70mg/70kg) on patients with anxiety symptoms with treatment-resistant anxiety disorders. Ten of the twelve participants (83%) found relief for up to seven days. The results support ketamine as a potential therapeutic alternative for patients with anxiety disorders.
KetamineAdolescentsTreatment-Resistant Depression (TRD)Depressive DisordersPTSDAnxiety DisordersObsessive-Compulsive Disorder (OCD)Neuroimaging & Brain MeasuresSafety & Risk Management
Week of 17 April 2017
This randomised, double-blind, placebo-controlled, between-subjects study (n=39) assessed the effects of MDMA (35mg and 70mg/70kg) or placebo on physiological and subjective responses to a public speaking task under stressful and non-stressful conditions. Contrary to their initial hypothesis of dampening stress reactions, MDMA produced stress-like effects on both physiological (heart rate, blood pressure, cortisol) and subjective (ratings of stress, tension, and insecurity) ratings on both the stress and no-stress sessions.
MDMAAnxiety DisordersPTSDHealthy VolunteersInterpersonal Functioning & Social ConnectednessUsing magnetoencephalography, the authors show that spontaneous neural signal diversity (entropy and Lempel–Ziv complexity) increases reliably under psilocybin, ketamine and LSD—most strongly for single-channel (temporal) LZ—and that these changes correlate with reported intensity of the psychedelic experience. This first application of such measures to the psychedelic state suggests that sustained psychedelic phenomenology corresponds to an elevated level of consciousness as indexed by neural signal diversity.
LSDKetaminePsilocybinEquity and Ethics
Week of 10 April 2017
The trial gave 14 people ayahuasca and 15 a placebo, with 64% of the ayahuasca group reporting at least a 50% reduction in depression severity after seven days, compared with 27% of the placebo group. David Mischoulon of Massachusetts General Hospital said the findings suggest a short-term antidepressant benefit, but longer follow-up is needed.
AyahuascaDepressive DisordersThis open-label study (n=14, 8 at follow-up) found that treatment with ibogaine resulted in lower addiction (ASI-Lite) and depression (BDI-II) scores up to 12 months later.
IbogaineDepressive DisordersOpioid Use Disorder (OUD)Substance Use Disorders (SUD)This review (2017) examines treatment strategies for depression based on neuroplasticity induction via non-invasive brain stimulation and NMDA receptor and glutamatergic modulation via ketamine. The authors raise concerns over the long-term antidepressive efficacy and safety of ketamine and highlight other MDA receptor and glutamate modulators, such as sarcosine, which show antidepressive effects in small-scale studies.
KetamineMajor Depressive Disorder (MDD)Depressive Disorders
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