The Bloom #145 Free Edition catching up

Welcome to all the new readers of The Bloom. This newsletter usually goes out every week, but due to several circumstances it's only hitting your inbox now.

This means there is a lot to cover, and instead of the top 3 articles from last week, I've featured 8.

Outside of the lab, two more psychedelic companies have received FDA Breakthrough Designation (a fast-track for review, like the one Lykos is currently in the final stages of). Cybin is developing a pislocybin analogue for depression (MDD), whilst is in the midst of developing an analogue of LSD for generalized anxiety (GAD).

Both companies have Phase III studies in the works and by the end of the year I expect half a dozen to be ongoing (including the just launched Phase III by the non-profit Usona).

These developments, including new funding rounds, give hope to the development of psychedelics as medicines. Yet, a new report by ICER is critical of the rigour and viability of MDMA-assisted therapy for PTSD (see the spotlight).

Without further ado, here is the latest in psychedelic research.

Floris - Founder of Blossom

ps My friend Carly is hosting a 'Psychedelic Professionals Networking Club' later today (4pm PST / 7pm EST) and you can register with the discount BLOSSOM here.​

pps I'll be speaking and moderating at the Psychedelics and Design Conference in two weeks, get at 15% discount with the code FLORIS15.

Latest Psychedelic Research

1 Unique Psychological Mechanisms Underlying Psilocybin Therapy Versus Escitalopram Treatment in the Treatment of Major Depressive Disorder​

This reanalysis of a trial (n=59) investigates the mechanisms underlying the efficacy of Psilocybin Therapy (PAT) versus Escitalopram Treatment in patients with depression (MDD) over a 6-week trial period. Acute psychological experiences such as "mystical experience" and "ego dissolution" were found to mediate the effect of treatment condition on depressive response, suggesting a mechanistic role of these experiences in the treatment of depression via PAT.

Related: Effects of discontinuation of serotonergic antidepressants prior to psilocybin therapy versus escitalopram for major depression​

Both studies re-analyse data from the Escitalopram vs Psilocybin trial from 2021.​
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2 Adolescent Psychedelic Use and Psychotic or Manic Symptoms​

This observational study (n=16.255) investigates the association between naturalistic psychedelic use and self-reported psychotic or manic symptoms in adolescents, utilizing a genetically informative design. Results suggest that psychedelic use may be associated with reduced psychotic symptoms after adjusting for other drug use, while associations with manic symptoms seem to be linked to genetic vulnerability to schizophrenia or bipolar I disorder.

3 The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder​

This randomized, waiting list-controlled clinical trial (n=24) for depression (MDD) assessed the therapeutic alliance between participants and intervention facilitators in psilocybin-assisted therapy (PAT). Therapeutic alliance significantly increased from the final preparation session to one-week post-intervention, with a stronger alliance predicting depression scores at various post-intervention time points. Stronger alliances were correlated with peak ratings of mystical experiences and psychological insight, which in turn were correlated with depression scores.

4 Brain substates induced by DMT relate to sympathetic output and meaningfulness of the experience​

This pre-print single-blind study (n=14) used multimodal neuroimaging techniques (fMRI + EKG) to investigate brain activity and autonomic physiology during DMT (20mg) altered state of consciousness. Results reveal unique brain activity substates, with increased superior temporal lobe activity and hippocampal deactivation under DMT, correlating with auditory distortions and meaningfulness of the experience, respectively. Moreover, increased heart rate under DMT correlates with hippocampal and medial parietal deactivation, suggesting a potential link between sympathetic regulation and positive mental health outcomes following psychedelic administration.

5 Safety pharmacology of acute psilocybin administration in healthy participants​

This pooled analysis (n=85; doses=113) of three randomized crossover studies evaluates the safety pharmacology of psilocybin (15-30mg). Psilocybin induced stronger effects at higher doses, with 25 mg and 30 mg doses showing increased anxiety. However, overall, psilocybin was found to be safe in terms of acute psychological and physical harm, with no serious adverse reactions reported, suggesting its potential safety for controlled research settings.

6 Salience, Sensemaking, and Setting in Psilocybin Microdosing: Methodological Lessons and Preliminary Findings of a Mixed Method Qualitative Study​

This pre-print (n=13) investigates the subjective experiences of individuals engaging in psilocybin microdosing in their daily lives. Combining momentary ecological assessments and retrospective interviews, participants reported varied effects, including loosening of mental structures, increased salience of external stimuli, flexible cognition, and ego-dystonic contents.

7 The pharmacokinetics and pharmacodynamics of ibogaine in opioid use disorder patients​

This pharmacokinetic study (n=14) on ibogaine (700mg/70kg) for opioid use disorder (OUD) finds significant variability in ibogaine clearance, strongly correlated with CYP2D6 genotype. Ibogaine plasma concentrations correlate with QTc prolongation and cerebellar effects, while neither ibogaine nor noribogaine correlate with the severity of opioid withdrawal symptoms.

8 Childhood trauma, challenging experiences, and posttraumatic growth in ayahuasca use​

This observational study (n=231) examines the relationship between childhood trauma, challenging experiences during acute ayahuasca effects, and posttraumatic growth. Results show that individuals with histories of childhood trauma were not at higher risk of adverse experiences during ayahuasca use, nor did they exhibit different levels of posttraumatic growth compared to those without such histories. Additionally, experiencing more challenges during acute ayahuasca effects did not correlate with increased posttraumatic growth.

More new research

• ​Structure-activity relationships of serotonergic 5-MeO-DMT derivatives: insights into psychoactive and thermoregulatory properties​
• ​IV low dose ketamine infusions for treatment resistant depression: Results from a five-year study at a free public clinic in an academic hospital​
• ​Oral esketamine in patients with treatment-resistant depression: a double-blind, randomized, placebo-controlled trial with open-label extension​
• ​Sublingual Ketamine for Depression and Anxiety: A Retrospective Study of Real-World Clinical Outcomes​
• ​Perceived attachment history predicts psychedelic experiences: A naturalistic study​
• ​Conflict monitoring and emotional processing in 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine users - A comparative neurophysiological study​

New on Blossom

1 PieBot - Chat with our Database​

Chat with our database!

Our experimental chat interface goes beyond Claude and ChatGTP, as it has all the research from the database at its fingertips. Please try it out and leave us feedback.

2 Psychedelics in Israel​

We updated our page on the psychedelic research landscape in Israel.

In 2019, Israel became the world’s first country to approve a “compassionate use” program for MDMA-assisted therapy for the treatment of PTSD. MAPS is heavily involved with researchers in the country who are conducting clinical trials exploring the potential of psychedelics.

3 Premenstrual Dysphoric Disorder & Psychedelics​

Psychedelics, psilocybin specifically, has been used by women in the treatment of Premenstrual Dysphoric Disorder (PMDD) symptoms. This topic page covers the background and first research on this topic.

4 Psychedelic Research Links 2024​

All the other papers that have come out this year that don't have a separate entry in the database.

Spotlight

1 ICER Draft Evidence Report on Lykos’ MDMA-Assisted Psychotherapy Deems Clinical Evidence “Insufficient”​
(Article)

PsychedelicAlpha analysed the Institute for Clinical and Economic Review's (ICER) draft evidence report on MDMA-assisted psychotherapy (MDMA-AP) for the treatment of PTSD. The report highlights various concerns regarding the clinical evidence provided by Lykos Therapeutics, ranging from trial design and conduct issues to potential ethical and safety problems. ICER deems the clinical evidence to be of 'low certainty', which is insufficient for determining comparative clinical effectiveness, making their cost-effectiveness analyses exploratory.

The report presents several trial design and delivery-related concerns, such as the choice of CAPS-5 as the primary outcome measure, lack of standardization in assisted psychotherapy, and functional unblinding. Additionally, ICER recounts ethical and safety concerns, including the involvement of individuals with a strong belief in psychedelics' therapeutic potential, pressure to report favourable outcomes and instances of sexual boundary violations.

Despite the concerns, ICER's exploratory cost-effectiveness analysis finds MDMA-AP to be less costly and more effective than placebo. However, the organization emphasizes that the analysis is hampered by the low certainty in the clinical evidence. The report also points to potential logistical challenges in delivering MDMA-AP, such as the substantial therapist time and specialized training required. While ICER does not have a formal role in evaluation or reimbursement, its analyses are increasingly used by private payers to inform price negotiations with pharmaceutical companies.

2 Psychedelics Design Conference (Event)

I'm excited to invite you to the ​Psychedelics Design Conference​ on April 11, 2024. Psychedelics Design and Blossom created a half-day Online Conference featuring well-known experts such as Paul Austin, Michel Rojkind, Jemma Campbell, and yours truly.

Join us to explore the cultural nuances that shape our creative and psychedelic landscapes. Tickets are priced at £20 / $25 and ​available here​. Use code Floris15 for a 15% discount.

Molenvaart 76, Anna Paulowna, NH 1761AL
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