Blossom Pulse Archive
What happened in psychedelic research in 2015
151 events from 2015, 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 28 December 2015
This single-blind, placebo-controlled crossover trial (n=30), sponsored by Prague Psychiatric Centre, investigated whether mTOR activation differentiates ketamine responders from non-responders in patients with major depression.
KetamineDouble-blind, randomized, placebo-controlled 3-arm trial of low-dose IV ketamine in TRD with FDG-PET neuroimaging (Hum Brain Mapp 2016 Mar; Li CT, Chen MH, Lin WC, Hong CJ, Yang BH, Liu RS; Taipei Veterans General Hospital, Taiwan; PMID 26821769; DOI 10.1002/hbm.23085; UMIN000016985 confirmed via PubMed DataBankList). n=48 adults (aged 21–65) meeting DSM-IV-TR MDD criteria with TRD (failed ≥3 antidepressants including one during the current episode); background medications continued (add-on design). Randomised 1:1:1 to: Group A – ketamine 0.5 mg/kg IV over 40 min; Group B – ketamine 0.2 mg/kg IV over 40 min; Group C – normal saline. 16 subjects per arm. Primary outcome: FDG-PET-derived PFC and amygdala standardised uptake values (SUVs) pre- and post-infusion. HDRS-17 at baseline and 40/80/120/240 min post-infusion. Responder = ≥50% HDRS-17 reduction. BPRS positive subscale and side-effect monitoring for safety. UMIN000016985 registry confirmed.
KetamineThis unregistered trial (n=51) was a pooled analysis of two controlled ketamine infusion studies for major depressive disorder in inpatients, which found that heart rate and heart rate variability could serve as predictive biomarkers for treatment response.
KetamineThis unregistered trial (n=71) was a double-blind, placebo-controlled, randomised parallel-group study of single intravenous ketamine infusions for treatment-resistant depression in patients with recurrent major depressive disorder, which demonstrated significant dose-related antidepressant effects.
KetamineSix-week, randomised, double-blind, parallel-group outpatient trial (IRCT201508201556N80; Imam Hospital, Tehran University of Medical Sciences, Iran; January–December 2015). Participants: 46 adults aged 20–55 with chronic persistent headache (≥6 months requiring analgesia) and mild-to-moderate MDD (DSM-IV-TR, HDRS-17 score <19). Arms: (1) oral ketamine 50 mg three times daily (150 mg/day); (2) oral diclofenac 50 mg three times daily. Capsules were indistinguishable. Primary outcome: change in HDRS from baseline to weeks 3 and 6. Secondary: HADS depression subscale, response/remission rates, pain VAS, adverse events. Randomisation by computer-generated sequence (1:1, blocks of 4); concealed in sequentially numbered sealed envelopes; participants, investigators and raters blinded.
KetamineRetrospective chart review (Western University of Health Sciences IRB, exempt; single residential ibogaine treatment centre, Mexico; calendar year 2015) of adults with DSM-5 opioid use disorder (OUD) who presented primarily for opioid detoxification. Exclusion: primary non-opioid problem, polysubstance users whose primary substance was not opioids, missing Clinical Opioid Withdrawal Scale (COWS) data. Prior to arrival, patients were converted to short-acting opioids and required to discontinue methadone or buprenorphine ≥4 weeks before treatment. Immediate-release (IR) morphine was maintained until ~4 hours before ibogaine. On arrival: physical examination, 12-lead ECG, toxicology, bloodwork. Treatment: oral ibogaine hydrochloride (Voacanga-derived, GMP-certified) at 18–20 mg/kg total dose (100 mg test dose first, remainder within 2 hours; supplemental 1–5 mg/kg permitted at 72h if post-acute withdrawal persisted; clonidine or gabapentin as adjuncts when indicated). Medical supervision throughout (vital signs, telemetry, IV fluids/electrolytes, on-site emergency clinicians). Programme phases: pre-treatment coaching and screening; 4-day inpatient ibogaine detoxification; 3-day residential; optional aftercare. Primary outcome: clinician-administered COWS (0–48) at ~48h and ~24h pre-ibogaine and ~24h and ~48h post-ibogaine. Secondary outcomes: self-reported SOWS (0–64); three-item Brief Substance Craving Scale (BSCS, 0–12). Baseline demographics and Addiction Severity Index (ASI) composite scores described. Analysis: repeated-measures ANOVA, α=0.05, pairwise comparisons. No trial registry entry; exempt IRB; retrospective design.
This systematic review (2015; 19 studies) found no convincing evidence that moderate use of MDMA is associated with significant brain alterations. However, the authors point out that the included studies were very heterogeneous and often of low quality.
MDMANeuroimaging & Brain MeasuresPublic Health, Prevention & Behaviour ChangeThis rodent study (2015) found that long-term administration of ayahuasca can interfere with the contextual association of emotional events in rats.
AyahuascaAnxiety Disorders
Week of 14 December 2015
This meta-analysis (2015) of six randomised, double-blind, placebo-controlled trials (n=101) examined the short-and mid-term efficacy of ketamine (bipolar) to depression. Ketamine effectively reduced symptoms in unipolar depression for seven days, , whereas the maintenance of its efficacy in bipolar depression failed to reach significance after 4 days.
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Bipolar DisorderDepressive Disorders
Week of 7 December 2015
On 4 December 2015, the last of 23 participants received their final treatment in the Boulder, Colorado study. MAPS had raised 94% of the funds needed to complete the trial, with $44,000 remaining and a potential $7,000 matching gift from two donors.
MDMAPTSD
Week of 30 November 2015
Phase I single-group pharmacokinetics study (n=12) of oral psilocybin in healthy adults, ascending doses 0.3 → 0.45 → 0.6 mg/kg with attended dosing and overnight sampling.
PsilocybinThis open-label trial (n=12), also known as PSILODEP-PILOT is the first to test psilocybin in patients in the UK. The study found psilocybin (10-25mg, x2) to be well-tolerated.
PsilocybinRandomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam for depression relapse prevention in persons at high risk. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.
KetamineRandomised, double-blind, parallel study (n=12) testing a single 0.5 mg/kg IV ketamine dose at induction of anaesthesia versus no ketamine in female surgical patients with depressive symptoms.
KetaminePhase II pilot trial (Yale University; PI: Ilan Harpaz-Rotem PhD; NCT02727998). Status: TERMINATED. Participants: n=28 enrolled; adults with PTSD. Intervention: intensive 7-day treatment combining a single IV ketamine infusion with prolonged exposure therapy. Start: December 2015; end: November 2021. CT.gov: 0 refs listed. Linked paper: Duek O, Korem N, Li Y, Kelmendi B (Yale/VA Connecticut) — Neuropsychopharmacology 2023 (PMID 37270621): neural imaging analysis showing long-term structural and functional changes following a single ketamine infusion in participants with PTSD.
KetamineIn this study investigators are studying the effects of a drug called ketamine on the symptoms of Obsessive-compulsive disorder (OCD).
KetamineThis cell study investigates the receptor binding profiles of NBOMe drugs compared to their 2C drug analogues and LSD. It finds that NBOMe drugs exhibit high affinity for 5-HT2A receptors, suggesting strong hallucinogenic effects similar to LSD, but with potentially more stimulant properties due to interactions with α1 receptors.
2C-XThis study examines the specific roles and activities of noribogaine at the opioid receptors in relation to physiological outputs in order to characterize noribogaine to the mu (OPRM) and the kappa (OPRK) opioid receptors. The study observed that the biased agonist/antagonist pharmacology is distinctive to noribogaine in comparison to other ligands including ibogaine, nalmefene, 18-MC, and 6′-GNTI. It predicted that noribogaine promoted some analgesic effects and anti-addictive response.
IbogaineAnxiety DisordersChronic Pain
Week of 23 November 2015
This observational study (n=25) found that ayahuasca intake led to significant increases in mindfulness comparable to those obtained after extensive mindfulness practice. The authors argue that this effect may be the mediating factor responsible for ayahuasca's observed therapeutic potential.
AyahuascaTreatment-Resistant Depression (TRD)Depressive DisordersSubstance Use Disorders (SUD)This survey study (n=496) found that indoleamine hallucinogens such as psilocybin and LSD are reportedly comparable to or superior in efficacy against cluster headaches than conventional treatments. Importantly, infrequent and non-hallucinogenic doses of these substances were reported to suffice for this effect to occur.
AyahuascaLSDPsilocybinChronic PainHeadache Disorders (Cluster & Migraine)Public Health, Prevention & Behaviour Change
Week of 9 November 2015
Double-blind, randomised Phase II pilot study (n=14; includes 2-person open-label lead-in) comparing two MDMA-assisted psychotherapy sessions (125 mg vs 30 mg active placebo) plus 10 non-drug psychotherapy sessions in Australian war veterans with chronic, treatment-resistant PTSD.
MDMAThis 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).
Ketamine
Week of 2 November 2015
Phase I double-blind, placebo-controlled, randomised study (n=48) of very low-dose LSD (5, 10, 20 µg) or placebo given six times over 21 days in healthy volunteers aged 55–75.
LSD
Week of 26 October 2015
Randomised, triple-blind, placebo-controlled parallel trial (n=37) of IV ketamine infusions (6 infusions over 3 weeks, twice weekly) versus saline in treatment-resistant major depressive disorder.
KetamineSingle-group proof-of-concept IV ketamine study (n=5) testing a single 0.5 mg/kg (40 min) infusion in patients with comorbid major depressive episode and alcohol dependence.
Ketamine
Week of 19 October 2015
This 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 5 October 2015
Prospective double-blind placebo-controlled RCT (Shenzhen Maternity and Child Healthcare Hospital) testing whether a single intra-operative bolus of ketamine 0.25 mg/kg IV (vs 0.9% saline) after umbilical cord clamping during elective caesarean section reduces postpartum depression. Enrolled: 330 ASA I–II parturients (screened 448, analysed 325). Primary outcome: EPDS at 3 days and 6 weeks postpartum. Secondary: NRS pain. Conducted October 2015 – March 2016.
KetamineThis meta-analysis (2015) validates the Mystical Experience Questionnaire (MEQ30) using data from five experimental studies (n=184) with controlled doses of psilocybin (20mg/70kg).
PsilocybinThis commentary (2015) analyses emerging research on psychedelic drugs for therapeutic purposes that involve humans and considering both the potential benefits and the possible harmful effects of using psychedelics in combination with psychotherapy or counselling for mental disorders illness.
Depressive DisordersPTSDAnxiety DisordersSubstance Use Disorders (SUD)Equity and EthicsThe paper reviews early 1920s–30s clinical trials and the pharmacology of Banisteriopsis caapi and its harmala alkaloids (notably harmine), and argues that—despite historical abandonment—harmine merits reevaluation as a potential rapidly acting anti‑Parkinsonian agent.
AyahuascaDepressive DisordersNeurocognitive Disorders
Week of 28 September 2015
Randomized, quadruple-masked Bayesian adaptive dose-finding trial in 33 veterans with late-life treatment-resistant depression, comparing single-infusion IV ketamine 0.1, 0.25, or 0.5 mg/kg with active-control midazolam 0.03 mg/kg.
KetamineRandomised, 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.
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 review (2015) discusses data from controlled laboratory studies that highlight MDMA altering social feelings, information processing, and behavior in humans, and social behavior in rodents. The findings are consistent with earlier studies that show that laboratory administration of MDMA strongly alters social processing in humans and increases social approach in humans as well as animals and that neurobiologically complex prosocial effects contribute towards its recreational use.
MDMAPTSDInterpersonal Functioning & Social ConnectednessThis double-blind, placebo-controlled, balanced-order, within-subjects study (n=25) investigated how the subjective effects of MDMA are related to its neural effects .fMRI scans during MDMA use showed changes in cerebral blood flow in the right medial temporal lobe, thalamus, inferior visual cortex, somatosensory cortex, right amygdala and hippocampus, as well as decreased resting-state functional connectivity (RSFC) between midline cortical regions, the medial prefrontal cortex, and the medial temporal lobe, and increased RSFC between the amygdala and hippocampus.
MDMAHealthy VolunteersNeuroimaging & Brain MeasuresThis double-blind, placebo-controlled, fMRI study (n=25) found that a moderate dose of psilocybin (11.2mg/70kg) lowered amygdala (which is hyperactive in those with major depression) reactivity to negative and neutral (visual) stimuli. The decrease in emotional processing was correlated with an increase in positive mood.
PsilocybinHealthy VolunteersMajor Depressive Disorder (MDD)Depressive DisordersAnxiety DisordersNeuroimaging & Brain MeasuresThis systematic review (2015) and meta-analysis (n=147) investigates ketamine and other N-methyl-d-aspartate (NMDA) receptor antagonists in the treatment of major depression. It highlighted the antidepressant efficacy of ketamine, and D-cycloserine and rapastinel for future glutamate-modulating strategies but also noted the ineffectiveness of other NMDA antagonists. It underlined the need for a greater understanding of ketamine’s mechanism of action.
KetamineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersSuicidalityThis double-blind, placebo-controlled study (n=16) described the effects of LSD (200 μg) in healthy subjects. It inhibited prepulse inhibition (startle reflex), increased blood pressure, elicited a positive mood, and had no adverse effect after 72 hours.
LSDHealthy VolunteersSchizophreniaPersonality & Trait FactorsThis double-blind, placebo-controlled trial (n=180) investigated the potential benefits of ketamine augmentation during electroconvulsive treatment (ECT) to improve outcomes in depression (MDD).
KetamineOpen-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.
EsketamineThis study examines the effects of ayahuasca on brain activity with respect to the temporal metabolism of its active compounds and found that DMT (97.3mg/70kg) and harmine (320.6mg/70kg) are related to the early phase of the experience, measured as reduced power in the alpha band after 50 minutes, while harmaline (52.5mg/70kg) and tetrahydroharmine (380.1mg/70kg) are more strongly associated with the later phase of the experience, measured as gamma-band increases after 75 minutes from ingestion. The present results reveal acute biphasic effects of ayahuasca in the brain.
AyahuascaNeuroimaging & Brain MeasuresMedicinal Chemistry & Drug Development
Week of 21 September 2015
This population-based study (2015) extended previous analyses of US adult data to evaluate the specific association between lifetime psilocybin use and mental health outcomes. It aims to determine whether psilocybin use is uniquely associated with reduced psychological distress and suicidality to inform future regulatory decisions.
PsilocybinAnxiety DisordersSuicidalityPublic Health, Prevention & Behaviour Change
Week of 14 September 2015
This rodent study appraises the psychotherapeutic gains facilitated by MDMA and investigates its effects on fear extinction learning, which is a key process in exposure-based therapies for PTSD. The authors propose that MDMA improves fear memory extinction via a BDNF-dependent mechanism. The study highlighted the potential of MDMA as a useful adjunct to exposure-based therapies for PTSD and other anxiety disorders marked by altered fear learning.
MDMAAnxiety DisordersPTSD
Week of 7 September 2015
Randomised, two-period crossover fMRI study (n=24) in healthy volunteers comparing single oral LSD (100 µg) with placebo to assess neuronal correlates of altered consciousness.
LSD
Week of 31 August 2015
The study, led by Phil Wolfson, M.D., with co-therapist Julane Andries, LMFT, aims to treat 18 participants with anxiety linked to ongoing or remitted life-threatening disease that may recur. MAPS Public Benefit Corporation staff reported positive early impressions from therapists’ sessions and said data from the first participant group was forthcoming.
MDMAAnxiety DisordersKetamine has been proposed as a novel approach to induce rapid antidepressant response. In this pilot study (n=10) a single IV subanaesthetic ketamine infusion (0.5 mg/kg) was administered to treatment-resistant patients with major depressive disorder to assess clinical and brain-functional effects.
KetamineRandomised, triple-blind, parallel Phase I trial (n=10) comparing ketamine versus placebo for patients with major depressive disorder and inadequate response to antidepressants.
KetamineInterventional study in MDD (n≈12–13) assessing SEPs/MEPs as markers of cortical plasticity after a single IV ketamine infusion (0.5 mg/kg over 40 minutes); includes an initial open-label cohort and a randomized, double-blind, placebo-controlled cohort.
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 study (n=60) of randomised, placebo-controlled, crossover clinical trials appraises suicidal ideation (SI) with ketamine infusion in persons with treatment-resistant depression (TRD). The results indicated improvement in suicidal thoughts after ketamine infusion and the measures are sensitive to these changes.
KetamineAnxiety DisordersDepressive DisordersSuicidalityTreatment-Resistant Depression (TRD)
Week of 24 August 2015
This review (2015) examines the neurobiology of ketamine’s potential to treat suiciadility and proposes that its working mechanism functions via the suppression of pro-inflammatory cytokines and by restoring tryptophan/serotonin production via inhibition of the kynurenine pathway. It notes that this hypothesis requires further validation via replicated randomised control research with larger samples.
KetamineDepressive DisordersSuicidalityImmunology & InflammationPublic Health, Prevention & Behaviour Change
Week of 17 August 2015
This study further analyzed fMRI data (BOLD signals) using dynamic causal modeling and found that psilocybin decreased top-down connectivity from the amygdala to visual cortex.
PsilocybinAnxiety DisordersNeuroimaging & Brain MeasuresRandomized, 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.
Esketamine
Week of 10 August 2015
This within-subjects, placebo-controlled, single-blind study (n=10) found that LSD enhanced music-evoked emotions, which may have implications for psychedelic-assisted psychotherapy.
LSDHealthy VolunteersSet & SettingRandomized, double-blind, active-controlled Phase III study (n=346) comparing fixed-dose intranasal esketamine (56 mg or 84 mg) plus a newly initiated oral antidepressant versus intranasal placebo plus a newly initiated oral antidepressant in adults with treatment-resistant depression.
Esketamine
Week of 3 August 2015
The session took place on 31 July 2015 among veterans, firefighters and police officers. Data from this and other Phase 2 studies was to support a request to the FDA for Breakthrough Therapy Designation, while long-term follow-ups continued. A crowdfunding campaign also raised $69,406 from 437 donors in 33 countries to expand Zendo Project services.
MDMAPTSDThe 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.
EsketamineThis study measures biological and psychological processes that might help researchers to better understand what is taking place during low or medium dose and full dose MDMA-assisted psychotherapy treatment in people with PTSD.
MDMA
Week of 27 July 2015
In this proof of concept study, the investigators plan to administer iv ketamine interleaved with Electroconvulsion Therapy days.
KetamineThis double-blind, placebo-controlled, within-subjects study (n=50) investigated the psilocybin-induced spiritual experiences and insightfulness in healthy humans to understand the state of consciousness-related neuronal mechanisms using high-density electroencephalogram (EEG) recordings. The results identified a correlation between the intensity levels of psilocybin-induced spiritual experience and EEG measures. The study proposed that the identified mechanism may help find a way for modulating mental health considering that spiritual experiences improve well-being and psychological resilience.
PsilocybinNeuroimaging & Brain MeasuresHealthy VolunteersThis randomised, double-blind, placebo-controlled, four-way, cross-over study (n=37) investigated the acute dissociative effects of MDMA (25, 50, and 100 mg), cannabis (THC 21mg/70kg), and cocaine (300 mg) and compared them to data of schizophrenia patients, Special Forces soldiers, and ketamine users. Results indicate that MDMA, cannabis, and (to a lesser extent) cocaine can produce dissociative symptoms that are similar to dissociative pathology.
MDMASchizophreniaHealthy VolunteersThis randomised, placebo-controlled, crossover trial study (n=17) investigates concurrent neurochemical effects of ketamine on glutamate-glutamine and gamma-aminobutyric acid in obsessive-compulsive disorder (OCD). It suggested that models of OCD pathology should examine the role of GABAergic abnormalities in OCD symptomatology.
KetamineObsessive-Compulsive Disorder (OCD)In a prospective longitudinal UK cohort of 28 MDMA‑exposed and 68 unexposed infants followed to two years with multiple covariates controlled, prenatal MDMA exposure was associated with persistent fine and gross motor delays across the first two years and showed a dose‑dependent relation to motor deficits at 12 months. No other differences at birth were found except that MDMA‑exposed infants were more likely to be male.
MDMAAdolescents
Week of 13 July 2015
This placebo-controlled, cross-species, translational comparison study (n=24: humans; n=18: male rats) examines the acute effects of ketamine (rats: 10 mg/400g; humans: 35 mg/70kg) on resting-state functional connectivity and found a robust increase in the coupling between the hippocampus and the prefrontal cortex in both species. The authors believe this to reflect increased levels of excitatory neurotransmitters, such as glutamate, acetylcholine, and histamine and the disinhibition GABAergic interneurons via ketamine.
KetamineNeuroimaging & Brain MeasuresSchizophreniaHealthy VolunteersThis review (2015) describes the immunomodulatory potential of classical serotonergic psychedelics (DMT, LSD, MDMA, etc) from a perspective of molecular immunology and pharmacology. With a particular focus on functional interaction of serotonin and sigma-1 receptors and cross-talk with toll-like and RIG-I-like pattern-recognition receptor-mediated signalling.
PsilocybinLSDAyahuascaDepressive DisordersSchizophreniaNeurocognitive DisordersImmunology & Inflammation
Week of 6 July 2015
This review (2015) discusses research developments regarding therapeutic compounds that exert their antidepressant efficacy via the glutamatergic, cholinergic, and opioid systems. The authors encourage innovative research strategies for improving the efficacy of treatments such as ketamine, whose effects are rapid but not long-lasting.
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive Disorders
Week of 29 June 2015
On 2 July 2015, the study site passed a routine inspection by the U.S. Drug Enforcement Administration. Sponsored by MAPS and conducted with Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center and Stanford University, the study is assessing whether MDMA combined with therapy can improve functional skills and quality of life. Recruitment was progressing, with several treatment sessions planned for the following month.
MDMAAnxiety DisordersRandomized, 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.
KetamineThe investigators of this study plan to investigate the feasibility and efficacy of repeated doses of intranasal ketamine in severely depressed patients who are at least 65 years of age and experiencing suicidal ideation. The results of the study could lead to development of new strategies for treating depression.
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.
KetamineRepeated drug consumption may progress to problematic use by triggering neuroplastic adaptations that attenuate sensitivity to natural rewards while increasing reactivity to craving and drug cues. Converging evidence suggests that glutamate modulation may work to correct these adaptations and rapidly restore motivation for delayed non-drug rewards relative to immediate drug use. Using an established laboratory model aimed at evaluating behavioral shifts in the salience of cocaine now vs. money later, the investigators will test the effect of CI-581a on cocaine self-administration as compared to the active control.
KetamineThis double-blind, placebo-controlled, within-subjects proof-of-concept study (n=20) investigated the antidepressant efficacy of inhaled nitrous oxide (50/50 nitrous oxide/oxygen vs. 50/50 nitrogen/oxygen) in patients with treatment-resistant depression (TRD). Nitrous oxide resulted in treatment response in 20% of patients and symptom remission in 15%, an effect size comparable to that of ketamine.
Nitrous OxideDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Safety & Risk ManagementThis review (2015, pre-print) of the psychedelics literature on creativity argues that creativity is too elusive/inconsistent a measure that is confounded by other changes.
LSDMescalineCreativityPhase I double-blind, placebo-controlled, randomised study (n=48) of very low-dose LSD (5, 10, 20 µg) or placebo given six times over 21 days in healthy volunteers aged 55–75.
LSD
Week of 22 June 2015
This double-blind, placebo-controlled, within-subjects study (n=16) evaluated the pharmacokinetic profile of oral LSD (200 μg) in humans. The analysis found that the acute subjective and sympathomimetic effects of LSD lasted for up to 12 hours and were closely linked to the plasma concentrations over time and showed no acute tolerance. This is the first such study and can act as a potential reference for the assessment of intoxication with LSD.
LSDPalliative & End-of-Life DistressHealthy VolunteersMedicinal Chemistry & Drug DevelopmentDepressive DisordersAnxiety DisordersIn a double-blind, placebo-controlled within-subjects study of 1.5 mg/kg oral MDMA in healthy volunteers, MDMA produced a prosocial syndrome characterised by increased feelings of authenticity, reduced concern about negative evaluation, and greater comfort disclosing emotional memories, despite some stimulant- and sedative-like effects and increased self-reported anxiety.
MDMAAnxiety DisordersHealthy VolunteersPTSDInterpersonal Functioning & Social Connectedness
Week of 8 June 2015
This theory-building article examines the psychedelic state (and the entropic brain theory) from the perspective of Integrated Information Theory (IIT) and attributes the diversity of psychedelic-induced brain correlates to a loss of cause-effect information represented within the brain dynamics, which leads to a more flexible, but less predictable form of perception and cognition.
Neurological InjuryNeuroimaging & Brain MeasuresCreativityEquity and Ethics
Week of 1 June 2015
Double-blind, randomised, parallel pilot study (n=20) comparing a 100-hour IV ketamine infusion plus clonidine versus a 40-minute IV ketamine infusion (plus clonidine and a 100-hour saline infusion) in adults with treatment-resistant major depressive disorder.
KetamineThis randomised controlled parallel group Phase IV trial (n=145) evaluated the safety and efficacy of ketamine for depression delirium postoperative cognitive dysfunction using 35mg/70kg ketamine.
KetamineThis double-blind, randomised placebo-controlled, within-subjects study (n=8) investigated the effects of vaporized salvinorin-A (0.25, 0.50, & 1 mg) on interoception and the sense of body-ownership in healthy volunteers, who reported an increase of bodily sensations at moderate doses, and an almost complete loss of body ownership and out-of-body experiences at the highest. These effects were rapid and intense but short-lived and included perceptual modifications in the visual domain and commonly entailed auditory hallucinations that are not typical for serotonergic hallucinogens by contrast. This implicates that the Kappa opioid system plays a significant role in the regulation of sensory perception, interoception, and the sense of body ownership.
Salvia DivinorumHealthy VolunteersRandomised controlled trial (n=30) assessing IV ketamine 0.5 mg/kg (2 weekly infusions) versus IV scopolamine 4 µg/kg and saline placebo as add-on treatment in patients with major depressive disorder.
KetamineUsing the Welfare Trade-Off Task (WTT), the authors show MDMA produces context-dependent prosocial effects: 1.0 mg/kg increased generosity toward friends, while 0.5 mg/kg produced a slight increase in generosity toward strangers, particularly in women. Baseline WTT generosity correlated with household income and trait Agreeableness, and the study proposes the WTT as a novel tool to quantify generosity, with underlying neural mechanisms yet to be determined.
MDMAHealthy VolunteersInterpersonal Functioning & Social ConnectednessIn a double‑blind, within‑subjects study of 35 experienced volunteers, a single 1.5 mg/kg oral dose of MDMA increased social, sexual and emotional word use during five‑minute conversations about close relationships, as identified by both LIWC dictionary analysis and machine‑learning classifiers. This indicates that MDMA acutely alters speech content and that analysing speech may reveal drug effects on socio‑emotional states.
MDMAHealthy VolunteersPTSDInterpersonal Functioning & Social Connectedness
Week of 18 May 2015
This single-blind placebo-controlled fMRI study (n=15) details the neural correlates of ego-dissolution. A correlation was found between decreased functional connectivity (FC), between the medial temporal lobe and high-level cortical regions, and ego dissolution.
PsilocybinSchizophreniaNeuroimaging & Brain MeasuresHealthy VolunteersRandomised, triple-blind (participant, investigator, outcomes assessor), active-placebo-controlled pilot trial (NCT02397889; Icahn School of Medicine at Mount Sinai). Participants: 30 adults with chronic PTSD. Intervention: repeated IV ketamine vs IV midazolam (active control). Status: COMPLETED. Start: May 2015. Primary results published: Feder A et al., Am J Psychiatry 2021 (PMID 33397139). Secondary neuroimaging sub-study: Danböck SK et al., Psychopharmacology 2024 (PMID 37872291) — fMRI resting-state fronto-limbic connectivity, 28 enrolled, 26 completed.
KetamineRecreational MDMA use and a compassion-focused imagery exercise produced similar sociotropic effects, increasing self-compassion and reducing self-criticism, with additive benefits of the combined interventions in participants higher in attachment-related avoidance. These preliminary, non-blinded findings with uncontrolled MDMA dose/purity suggest MDMA may enhance intrapersonal pro-social attitudes relevant to psychotherapy, but require replication with pharmaceutical-grade MDMA in controlled trials.
MDMAInterpersonal Functioning & Social Connectedness
Week of 11 May 2015
This Phase II pilot study is a randomized, double-blind, placebo-controlled study in 18 participants comparing the effects of MDMA-assisted therapy vs. placebo with therapy.
MDMAThe subsidiary will complete Phase 2 studies and prepare Phase 3 trials of MDMA-assisted psychotherapy for PTSD, while MAPS continues education, harm reduction and fundraising. If approved, prescription sales could help fund further research and reduce MAPS’ long-term reliance on donations, while complying with IRS rules.
MDMAAnxiety DisordersPTSD
Week of 4 May 2015
This open-label study (n=52) investigated the effects of ketamine (35mg/70kg) with regard to the neural correlates related to the remission of anhedonia in major depressive disorder (MDD). Ketamine infusion rapidly reduced anhedonia, a trend that was sustained for three days and correlated with increased glucose metabolism in the hippocampus and dorsal anterior cingulate cortex (dACC) and decreased metabolism in the inferior frontal gyrus and orbitofrontal cortex (OFC).
KetamineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersSuicidalityNeuroimaging & Brain Measures
Week of 27 April 2015
Randomised, double-blind, parallel-group Phase II trial (n=40) comparing a single oral psilocybin dose (0.36 mg/kg) versus diphenhydramine 100 mg with CBT-based preparation and integration in adults seeking to stop cocaine use; includes MRI assessments.
PsilocybinThe purpose of this study is to see whether ketamine, when given as repeated infusions, can produce quick and sustained improvement in depression and PTSD symptoms for individuals who have not had their symptoms effectively treated by current treatments.
KetamineThis Phase IV, randomised, double-blind, placebo-controlled, parallel-group trial (n=72) evaluated intranasal ketamine vs placebo for suicidality in patients with severe major depression awaiting ECT.
KetamineThis study (n=10) investigated the brain's directed functional connectivity (FC) under the influence of ayahuasca, and found that neural hierarchies were temporarily disrupted with decreased top-down control and increased bottom-up information transfer.
AyahuascaNeuroimaging & Brain MeasuresThis double-blind, placebo-controlled, cross-over, within-subjects study (n=22) investigated the effects of ketamine (30mg/70kg) on whole-brain functional connectivity in healthy male participants while attenuating pre-synaptic glutamate release directly via pretreatments with the sodium-channel modulator lamotrigine (300 mg), and indirectly via pretreatment with the 5-HT2A receptor antagonist risperidone (2mg). Ketamine induced robust changes in the functional connectivity pattern and produced a shift from a cortically-centered to a sub-cortically-centered brain state. Pre-treatment with risperidone, but not lamotrigine, resulted in a strong modulation of the ketamine-induced hub changes, which suggests that these changes are likely a result of NMDA blockade and possible serotonergic modulation rather than purely modulation of glutamate release.
KetamineSchizophreniaNeuroimaging & Brain MeasuresHealthy Volunteers
Week of 20 April 2015
In an Italian online survey of 54 cluster headache patients, a substantial proportion reported using illicit drugs—most commonly cannabinoids, but also cocaine, heroin and psychedelics such as psilocybin, LSA and LSD—for self‑medication after dissatisfaction with conventional treatments. Many sourced recommendations online, often ceased medical care, underestimated legal and safety risks and did not inform their physicians.
LSDPsilocybinOpioid Use Disorder (OUD)Headache Disorders (Cluster & Migraine)Substance Use Disorders (SUD)Chronic PainThis open-label trial (n=12), also known as PSILODEP-PILOT is the first to test psilocybin in patients in the UK. The study found psilocybin (10-25mg, x2) to be well-tolerated.
PsilocybinParallel Phase II study (n=247) comparing neural-exosomal miRNAs in three MDD groups (recent attempt, suicidal ideation, no ideation) given a single IV ketamine infusion (0.5 mg/kg) and healthy controls with one-time blood draw.
Ketamine
Week of 13 April 2015
This double-blind, randomised, placebo-controlled, within-subjects crossover study (n=30) investigated the effects of esketamine (23.1mg/70kg) on the modulation of thalamocortical circuitry during resting state in healthy volunteers, to investigate whether their brain connectivity exhibits a similar profile as patients with schizophrenia. They found that a subanesthetic dose of ketamine leads to significantly higher functional connectivity in the thalamus hub network, and the strengthening of functional cortico-thalamic connectivity for the somatosensory and temporal seed regions but not for prefrontal, occipital, and parietal regions, in accordance with the connectivity profile of schizophrenia.
KetamineHealthy VolunteersSchizophreniaThis review (2015) provides a comprehensive overview of a broad class of serotonergic hallucinogens known as tryptamines, concerning<br />their evolution, prevalence, patterns of use and legal status, chemistry, toxicokinetics, toxicodynamics, and their physiological and toxicological effects on animals and humans. Although classical psychedelics are generally considered to be physiologically safe molecules, there is a lack of information on new tryptamine derivatives, regarding their acute and long-term effects, interactions with other substances, toxicological risk, or addictive potential.
AdolescentsPublic Health, Prevention & Behaviour ChangeThis review (2014) examines ketamine as a prospective treatment option for patients with depression and provides an overview of its role within the glutamate system, its antidepressant mechanisms of action, safety profile, and evidence from clinical studies that investigated the efficacy of single or multiple infusions. Furthermore, it compares alternative modes of ketamine administration and highlights fundamental research on other types of NMDA agonists that may have less psychotomimetic effects.
KetamineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersSuicidalitySafety & Risk Management
Week of 6 April 2015
This meta-analysis (2015; n=437) examined the antidepressant effects of ketamine, with regard to its efficacy over short and long-term periods, across single or repeated infusions, moderating variables related to the experimental design, and efficacy amongst patients with depression (MDD) or bipolar disorder (BD). Results conveyed that ketamine is an effective and rapid treatment for depression in the short term, with large antidepressant effects emerging after 4 hours and lasting up to 2 weeks post-infusion in participants with a primary diagnosis of MDD or BD. Repeated infusion showed larger effect sizes but did not extend the duration of antidepressant effect.
KetamineMajor Depressive Disorder (MDD)Bipolar DisorderDepressive DisordersSuicidality
Week of 30 March 2015
Randomised, wait-list controlled pilot (n=12) testing two psilocybin sessions (20 mg/70 kg then 20 or 30 mg/70 kg) in professional religious leaders to assess psychological, spiritual and prosocial changes.
PsilocybinRandomised, placebo-controlled, double-blind crossover pilot study (n=21) testing up to 50% nitrous oxide in oxygen versus placebo (50% nitrogen/50% oxygen) for one hour in patients with major depressive disorder.
Nitrous OxideRandomised, triple-blind, parallel pilot trial (n=6) comparing once-weekly IV ketamine 0.5 mg/kg vs midazolam 0.045 mg/kg for up to four weeks to prevent relapse after successful ECT in adults with major depressive disorder.
KetamineRandomised, parallel RCT (n=62) in Veterans with treatment‑resistant depression comparing six IV ketamine infusions (0.5 mg/kg) over 12 days versus a single IV ketamine infusion (0.5 mg/kg) preceded by five midazolam infusions (0.045 mg/kg) as an active comparator.
KetamineThis case report (n=3) examines patients who developed manic symptoms and diagnosed with Bipolar-I disorder in response to ibogaine use. None of the patients had a prior diagnosis or family history of bipolar disorder, but all of them were poly-drug users or recovering from addiction. Manic symptoms which often included grand delusions that lasted up to two weeks after using ibogaine.
IbogaineBipolar DisorderOpioid Use Disorder (OUD)Substance Use Disorders (SUD)Safety & Risk ManagementDepressive DisordersThis study (n=44) investigated the long-term effects of regular ayahuasca use on the human brain. Structural MRI showed that regular ayahuasca users had significantly different cortical thickness (with thinning in the posterior cingulate cortex) when compared to non-users. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation.
AyahuascaNeuroimaging & Brain MeasuresPersonality & Trait Factors
Week of 23 March 2015
This article documents a Zurich psychotherapist’s years-long underground provision of MDMA-, LSD- and 2‑C‑B‑assisted individual and group psycholytic psychotherapy, ending with her 2009 arrest, and reports on clinical outcomes and practice details. It situates these findings in the context of expanding medical research on psychedelics and highlights the attendant psychopharmacological, moral, ethical and legal tensions for regulation and clinical adoption.
LSDMDMAEquity and Ethics
Week of 9 March 2015
On 13 March 2015, the 22nd participant received their first experimental treatment, while the 23rd had enrolled and the potential final participant was being screened. Principal Investigator Michael Mithoefer will discuss preliminary results at the American Psychiatric Association Annual Meeting in Toronto from 16 to 20 May 2015, where MAPS will host an educational booth.
MDMAPTSDVeterans
Week of 2 March 2015
In a nationally representative sample of 135,095 US adults (19,299 lifetime psychedelic users), lifetime use of LSD, psilocybin or mescaline was not associated with increased odds of past‑year serious psychological distress, mental‑health treatment, suicidal thoughts/plans/attempts, depression or anxiety after adjusting for sociodemographics, other drug use and childhood depression. The authors conclude psychedelics are unlikely to be independent risk factors for mental health problems and question the public‑health rationale for their prohibition.
LSDMescalinePsilocybinAnxiety DisordersDepressive DisordersSuicidalitySubstance Use Disorders (SUD)Safety & Risk ManagementPublic Health, Prevention & Behaviour Change
Week of 23 February 2015
Randomised, double-blind, placebo-controlled crossover fMRI study (n=25) testing single 100 µg oral LSD vs placebo and ketanserin (40 mg pretreatment) in healthy volunteers to probe 5-HT2A receptor contributions to self and personal meaning.
LSDRandomised, triple-blind, parallel Phase I trial (n=10) comparing ketamine versus placebo for patients with major depressive disorder and inadequate response to antidepressants.
KetamineThe current protocol is a pilot study of the effects and possible utility of psilocybin-facilitated experiences for professional religious leaders.
PsilocybinThis meta-analysis (2015) of open-label studies (n=97) examined the safety, tolerability, and acceptability of intravenous ketamine (35mg/70kg) infusion for patients with depression. They found that it was safe and well-tolerated with little to no psychotomimetic effects, adverse medical effects, or any increase in long-term substance abuse.
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersSubstance Use Disorders (SUD)SchizophreniaSafety & Risk ManagementThis meta-analysis (n=129) evaluated the relation between long-term treatment with ketamine and the frequency of psychotic and mood disorders, amongst patients located in Hong Kong, China. According to standardized diagnostic criteria, psychosis and/or depression were very common amongst these patients, which raises the issue of safety when considering ketamine for long-term treatment of depression.
KetamineDepressive DisordersSubstance Use Disorders (SUD)SchizophreniaThis open-label study (n=6) found that a single dose of ayahuasca has fast-acting anxiolytic and antidepressant effects (up to 21 days later, MADRS) in patients with a current depressive episode.
AyahuascaAnxiety DisordersBipolar DisorderDepressive DisordersMajor Depressive Disorder (MDD)Turing Pharmaceuticals launched with three drugs acquired from Retrophin, including an experimental intranasal ketamine formulation for treatment-resistant depression. The company also plans to develop intranasal oxytocin and Vecamyl, while pursuing ketamine’s re-approval for lactation indications. Johnson & Johnson is developing a competing ketamine treatment, amid concerns about abuse and safety.
KetamineDepressive DisordersThis review (2015) summarizes the clinical effects of ketamine and its neurobiological underpinnings and mechanisms of action that may provide insight into the neurobiology of depression, relevant biomarkers, and treatment targets, and directions for future research.
KetamineAdolescentsDepressive DisordersPTSDThis open-label study (n=21) investigated the pharmacokinetics of a single dose of ibogaine (20mg) in response to inhibiting its metabolism via pretreatment with the antidepressant paroxetine in a placebo-controlled manner. Results indicate that the dose was safe and well-tolerated in all subjects, although paroxetine greatly increased the half-life of ibogaine to detectable levels at 72 hours post-infusion.
IbogaineHealthy VolunteersDepressive DisordersMedicinal Chemistry & Drug DevelopmentPersonality & Trait FactorsThis case report describes the clinical profile of a man from Argentina with a family history of bipolar disorder who participated in a four-day Ayahuasca ceremony that led to the eruption of a hypomanic episode two days after, consisting of mystical and paranoid delusional ideas, auditory hallucinations, racing thoughts, disorganized behavior, elevated energy, and manic euphoria. Given that the remission of psychotic symptoms was immediately followed by an onset of depressive symptoms, the authors theorize that antidepressant effects of harmine may have occasioned the manic shift of his bipolar disorder.
AyahuascaBipolar DisorderDepressive DisordersSchizophrenia
Week of 16 February 2015
This follow-up study (n=15) to an open-label pilot-study of psilocybin-facilitated smoking addiction treatment found that the mystical experience (MEQ) but not the intensity of the experience was predictive of smoking abstinence (80% at 6-month follow-up).
PsilocybinAnxiety DisordersAlcohol Use Disorder (AUD)Opioid Use Disorder (OUD)Tobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Palliative & End-of-Life DistressHealthy VolunteersPersonality & Trait FactorsDepressive DisordersThis review (2014) examines the historic transformation of LSD, from a psychoactive drug that exhibited great promise for the treatment of addiction, to an illicit substance affiliated with counterculture without a medical purpose. This review outlines aspects of its psychopharmacology that are still relevant for the treatment of addiction, which may warrant a renewed interest to continue research in this domain.
LSDSubstance Use Disorders (SUD)SchizophreniaMedicinal Chemistry & Drug DevelopmentThis open-label study (n=9) investigated the effects of ayahuasca (123,2mg DMT, 32,34mg Harmine) on the functional brain connectivity of experienced users, and found a decrease in the activity of core structures of the Default Mode Network (DMN).
AyahuascaNeuroimaging & Brain MeasuresThis open-label between-subjects fMRI study (n=38) investigated the antidepressant effects of ketamine (35mg/70kg) with regard to changes in the neural correlates of emotional processing, 24 hours after infusion, in patients with major depression (n=18) compared to baseline measures from healthy volunteers (n=20). They found that ketamine rapidly increases brain responses to positive emotion, which correlated with increased connectivity of the right caudate during and improvement in depression severity.
KetamineDepressive DisordersMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Neuroimaging & Brain MeasuresHealthy Volunteers
Week of 9 February 2015
This review (2015) looks at the influence of subjective (therapeutic) effects on the (treatment) outcomes of psychedelic experiences. This is put in context of the neuronal mechanism of psychedelics, but that relationship is still something that we know little about.
Anxiety DisordersObsessive-Compulsive Disorder (OCD)Substance Use Disorders (SUD)Headache Disorders (Cluster & Migraine)Palliative & End-of-Life DistressSchizophreniaNeuroimaging & Brain MeasuresChronic PainDepressive Disorders
Week of 2 February 2015
The study could enrol up to 12 people with chronic, treatment-resistant PTSD. It aims to train co-therapists, collect outcome data and prepare for a potential Phase 3 site, marking Canada’s first Health Canada-approved clinical psychedelic research in over 40 years.
MDMAPTSDAlso covered by MAPS
Week of 26 January 2015
Randomized, double-blind, placebo-controlled study (n=5) testing a single oral dose of ketamine 0.5 mg/kg versus placebo for depression and anxiety in patients with cancer.
KetamineRandomised, 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.
KetamineSingle-group Phase I study (n=16): four IV ketamine infusions (twice weekly over 2 weeks) combined with 16 CBT sessions over 8 weeks for depressive episodes.
KetamineThis review (2015) provides an overview of the antidepressant mechanism of ketamine, clinical studies with ketamine, and its use in shaping the development of next-generation treatments, which include better tolerated non-ketamine NMDA antagonists and other non-NMDA glutamatergic modulators.
KetamineMajor Depressive Disorder (MDD)Treatment-Resistant Depression (TRD)Depressive DisordersSuicidalityThis review (2015) examines how the anti-addictive drug ibogaine affects the heart and the cardiovascular system and outlines a sequence of deleterious events that lower heart rate and selectively block cardiac ion channels which pave the way for life-threatening arrhythmias. Due to the longevity of noribogaine-ibogaine’s active metabolite-in human plasma, cardiac adverse events may also occur several days after, which highlights the need for developing less toxic variants of ibogaine such as 18-MC.
IbogaineTobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Safety & Risk ManagementMedicinal Chemistry & Drug DevelopmentThis observational field study (n=176) evaluated the efficacy of a natural setting-based crisis intervention program aimed at festival attendees who encountered challenging experiences while using psychoactive substances. While many of the care-seekers resolved their crises in response to onsite interventions, unresolved crises were more often related to outbursts of mental health episodes that were either brought on by psychoactive substance use or not.
Substance Use Disorders (SUD)CreativitySafety & Risk ManagementThis interview study (n=15) investigated the phenomenology of individuals under the acute influence of psilocybin (intravenously injected -; quicker onset) in an fMRI scanner.
PsilocybinNeuroimaging & Brain Measures
Week of 12 January 2015
This mouse study investigated the effects of the highly selective 5-HT₂ receptor agonist (R)-DOI (0.01-1mg/kg) in a mouse model of allergic asthma. They demonstrate that inhaled (R)-DOI has potent anti-inflammatory effects and blocks the development of allergic asthma through the activation of the serotonin 5-HT2A receptor subtype.
Immunology & InflammationIn a single-group proof-of-concept study of 10 participants with DSM‑IV alcohol dependence, psilocybin administered alongside motivational enhancement therapy produced a significant increase in abstinence after dosing that was largely maintained to 36 weeks, with the intensity of the first session strongly predicting subsequent reductions in drinking, craving and increased abstinence self‑efficacy. There were no significant treatment‑related adverse events, supporting the need for larger controlled trials to evaluate efficacy and mechanisms.
PsilocybinAnxiety DisordersAlcohol Use Disorder (AUD)Tobacco/Nicotine Use Disorder (TUD)Substance Use Disorders (SUD)Safety & Risk ManagementPooled analysis of over 190,000 US adults (NSDUH 2008–2012) found lifetime classic psychedelic use was associated with reduced odds of past‑month psychological distress and past‑year suicidal thinking, planning and attempts, whereas illicit use of other drugs was generally linked to increased risk. These findings suggest classic psychedelics may hold promise for suicide prevention and warrant further clinical research and reconsideration of their highly restricted legal status.
SuicidalityAnxiety DisordersPersonality & Trait FactorsPublic Health, Prevention & Behaviour Change
Week of 29 December 2014
* Social Anxiety Disorder (SAD) is common and causes significant impairment. * First-line treatments for Social Anxiety Disorder are only partially effective. Many SAD patients experience little or inadequate symptom relief with available treatments. * Ketamine is a potent NMDA receptor antagonist. Ketamine represents an agent with a potentially novel mechanism of action for the treatment of anxiety disorders. * Ketamine has demonstrated efficacy in the treatment of psychiatric disorders closely related to Social Anxiety Disorder including Major Depression, Bipolar Depression and possibly Obsessive-Compulsive Disorder. Ketamine represents the possibility to provide rapid symptom relief to patients with SAD and may provide the mechanism for future drug development to treat SAD more rapidly and effectively.
KetamineDouble-blind, placebo-controlled crossover trial (n=24) testing the role of the 5-HT2a receptor in MDMA-induced effects on social behaviour (MDMA 75 mg; ketanserin 40 mg; combination; placebo).
MDMAThe investigators will compare 3 groups (ketamine + naltrexone vs ketamine alone vs placebo) in an 8-week randomised, double-blind, placebo-controlled trial (n=65) of repeated IV ketamine (0.5 mg/kg weekly x4) for comorbid MDD and AUD.
KetamineThe purpose of this study is to determine whether subanesthetic dose of ketamine combined with propofol is superior to propofol anesthesia alone in improving cognitive function in depressive patients undergoing ECT
KetamineRandomised, crossover neuroimaging study (n=10) comparing IV S-ketamine 0.25 mg/kg versus saline placebo in adults 20–60 to investigate glutamatergic mechanisms relevant to MDD.
KetamineThis unregistered trial (n=30) was an open-label, uncontrolled pilot study of psilocybin for treatment-resistant depression in patients and healthy controls, which found that psilocybin reduced pessimism bias and improved depressive symptoms.
PsilocybinProspective within-subject ascending-dose study (J Psychopharmacol 2017; Glue P, Medlicott NJ, Harland S, Neehoff S, Anderson-Fahey B, Le Nedelec M, Gray A, McNaughton N; University of Otago, Dunedin, New Zealand; DOI 10.1177/0269881117705089). Registered with the Australian New Zealand Clinical Trial Registry (ANZCTR); number not reported in extracted methods text, PubMed DataBankList, or CrossRef. Participants: 12 adults (4 male, 8 female; mean age 31 yr) with treatment-refractory DSM-IV GAD and/or SAD (HAM-A ≥20 and/or LSAS ≥60; failed ≥2 antidepressant courses; MADRS <20). No control arm (within-subject design). Intervention: subcutaneous ketamine at three ascending dose levels (0.25, 0.5, 1.0 mg/kg) plus an active control (midazolam 0.01 mg/kg) administered once weekly; doses given in fixed ascending order with midazolam randomly inserted. Participants continued stable ongoing medications. Primary outcomes: HAM-A and Fear Questionnaire (FQ). Companion papers: anxiety symptoms (Glue P et al. J Psychopharmacol 2017) and EEG (Glue P et al. Int J Neuropsychopharmacol 2018, PMID 29718262).
KetamineSix-week, randomised, double-blind, parallel-group outpatient trial (IRCT201508201556N80; Imam Hospital, Tehran University of Medical Sciences, Iran; January–December 2015). Participants: 46 adults aged 20–55 with chronic persistent headache (≥6 months requiring analgesia) and mild-to-moderate MDD (DSM-IV-TR, HDRS-17 score <19). Arms: (1) oral ketamine 50 mg three times daily (150 mg/day); (2) oral diclofenac 50 mg three times daily. Capsules were indistinguishable. Primary outcome: change in HDRS from baseline to weeks 3 and 6. Secondary: HADS depression subscale, response/remission rates, pain VAS, adverse events. Randomisation by computer-generated sequence (1:1, blocks of 4); concealed in sequentially numbered sealed envelopes; participants, investigators and raters blinded.
KetamineRetrospective chart review (Western University of Health Sciences IRB, exempt; single residential ibogaine treatment centre, Mexico; calendar year 2015) of adults with DSM-5 opioid use disorder (OUD) who presented primarily for opioid detoxification. Exclusion: primary non-opioid problem, polysubstance users whose primary substance was not opioids, missing Clinical Opioid Withdrawal Scale (COWS) data. Prior to arrival, patients were converted to short-acting opioids and required to discontinue methadone or buprenorphine ≥4 weeks before treatment. Immediate-release (IR) morphine was maintained until ~4 hours before ibogaine. On arrival: physical examination, 12-lead ECG, toxicology, bloodwork. Treatment: oral ibogaine hydrochloride (Voacanga-derived, GMP-certified) at 18–20 mg/kg total dose (100 mg test dose first, remainder within 2 hours; supplemental 1–5 mg/kg permitted at 72h if post-acute withdrawal persisted; clonidine or gabapentin as adjuncts when indicated). Medical supervision throughout (vital signs, telemetry, IV fluids/electrolytes, on-site emergency clinicians). Programme phases: pre-treatment coaching and screening; 4-day inpatient ibogaine detoxification; 3-day residential; optional aftercare. Primary outcome: clinician-administered COWS (0–48) at ~48h and ~24h pre-ibogaine and ~24h and ~48h post-ibogaine. Secondary outcomes: self-reported SOWS (0–64); three-item Brief Substance Craving Scale (BSCS, 0–12). Baseline demographics and Addiction Severity Index (ASI) composite scores described. Analysis: repeated-measures ANOVA, α=0.05, pairwise comparisons. No trial registry entry; exempt IRB; retrospective design.
This review connects serotonin signaling to stress coping, especially how different serotonin pathways shape active or passive responses to aversive situations. It matters here because receptor theories of psychedelics often draw on the same stress-coping framework used to compare 5-HT1A and 5-HT2A function.
This comprehensive review (2015) summarizes the chemical characterization, pharmacology, and toxicity of New Psychoactive Substances from the published literature, as well as information gathered from non-peer-reviewed sources, such as drug forums. They provide an overview of useful information, such as reported death cases, for public health workers.
Medicinal Chemistry & Drug DevelopmentPublic Health, Prevention & Behaviour ChangeThis commentary (2015) examines how inappropriate, non-evidence-based, legislative restrictions of MDMA have failed to mitigate the harms of recreational ecstasy use but have effectively halted clinical research for therapeutic use. They urge the regulatory authorities to re-schedule MDMA and promote research for therapeutic uses within psychiatry.
MDMAPTSDOpioid Use Disorder (OUD)Safety & Risk ManagementSubstance Use Disorders (SUD)This case study discusses the LSD-linked “Alice in Wonderland Syndrome”(AIWS) or Todd’s syndrome in a patient with a history of sporadic and recreational cannabis, alcohol, and LSD use. The observation suggests that AIWS only manifested during LSD use and continued post LSD suspension, namely, Hallucinogen Persisting Perception Disorder (HPPD). While this did not result in a major functional impairment, it induced considerable worry and concern because of its persistent continuation.
LSDHeadache Disorders (Cluster & Migraine)Chronic PainThis article (2015) examines the advantages and applications of intranasal drug delivery, with a particular focus on the potential of intranasal ketamine for the acute and maintenance therapy of refractory depression. The article contrasts intranasal delivery to oral and sublingual delivery methods, which are less effective with regards to their bioavailability, crossing of the blood-brain-barrier, and rapid onset of drug effects.
KetamineEsketamineDepressive DisordersChronic PainHeadache Disorders (Cluster & Migraine)SchizophreniaAutism Spectrum Disorder (ASD)Neurocognitive DisordersPersonality & Trait Factors
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