The Bloom #166 Free Edition Meow meow

Before we answer the question if psychedelics are effective, researchers have to establish safety.

Yes, you may say that millions of experiences speak for themselves. Yet research can help us determine precisely what (obscure) risks exist and at what dosages things go sideways.

This applies to psychedelics that have been around for centuries and novel compounds alike. Researchers gave a variety of dosages of mescaline (up to 800mg) to participants and found the administration to be generally safe (though nauseating at high dosages). Another research team published the first safety study (afaik) on 3-MMC - a well-known designer drug - and in the dosages (and one-time use (not chronic use)) up to 100 mg found no significant adverse events (and improvements in neurocognitive task performance).

For the final featured article, we look at a meta-analysis of 29 studies on 'psychoplastogens'. When initially reading the title, my mind went to 'non-hallucinogenic' psychedelics (or psychedelic-inspired novel molecules). This isn't the case here, as the authors look at classical psychedelics, MDMA, ketamine, and two other molecules. Contrary to (my) expectations they find no significant changes in BDNF (a protein involved in the growth and differentiation of new neurons and synapses). The analysis hints that BDNF is likely not a reliable marker of neuroplasticity (in humans - the correlation has been found in animal studies).

Black Friday Sale: If you're on the fence about paying for full summaries of research articles and supporting Blossom - now is the time to pull the trigger. Use the code BF30 to get a 30% discount on a lifetime Blossom Pro membership.

Floris - Founder of Blossom

ps The BF30 discount code is valid until midnight coming (Cyber) Monday. Use it here.

pps In less than two weeks (Dec 11th), we're diving into psychedelics and design. Check out the virtual conference here.

Latest Psychedelic Research

1 Safety and cognitive pharmacodynamics following dose escalations with 3-methylmethcathinone (3-MMC): a first in human, designer drug study​

This pre-print cross-over, placebo-controlled trial (n=14) assesses the effects of escalating doses of 3-MMC (25, 50, 100mg) on vital signs, neurocognitive function, state of consciousness, appetite, and drug desire. Results show dose-dependent increases in heart rate and blood pressure (not clinically significant), enhanced neurocognitive task performance, and mild dissociative and psychedelic effects. Participants reported decreased appetite and transient increases in liking and wanting 3-MMC. Low to moderate doses were well tolerated and safe, with potential risks associated with high doses.

2 Safety pharmacology of acute mescaline administration in healthy participants​

This pooled analysis of two RCTs (n=48) investigates the safety of mescaline in single oral doses of 100–800 mg (96 administrations). Positive subjective effects increased dose-dependently, while autonomic effects were moderate. Adverse effects, including nausea (dose-limiting), were recorded, but no significant issues with liver/kidney function or blood cell counts occurred. "Flashbacks" were reported in 2% of administrations. Mescaline doses up to 800 mg were deemed safe in a controlled clinical setting for healthy participants.

3 Effects of psychoplastogens on blood levels of brain-derived neurotrophic factor (BDNF) in humans: a systematic review and meta-analysis​

This meta-analysis (s=29) examines the effects of psychedelics (including ketamine and MDMA) and two other 'psychoplastogens' on peripheral BDNF levels in humans. It finds no significant changes in BDNF levels post-administration (SMD=0.024, p=0.64), regardless of drug, dose, participant age, or psychiatric condition. Studies with better-controlled designs report smaller effect sizes, and later timepoints show minimal increases in BDNF. The authors conclude that peripheral BDNF is likely not a reliable marker of rapid neuroplasticity and recommend neuroimaging or stimulation-based methods for future research.

Pair it with this new publication: Structural neural plasticity evoked by rapid-acting antidepressant interventions​

More Research

• ​MDMA pharmacokinetics: A population and physiologically based pharmacokinetics model-informed analysis​
• ​Reconsidering evidence for psychedelic-induced psychosis: an overview of reviews, a systematic review, and meta-analysis of human studies​
• ​Psilocybin-Assisted Psychotherapy for Treatment-Resistant Depression in Bipolar II Disorder​
• ​Major life changes following psychedelic use: A retrospective survey among people using psychedelics naturalistically​
• ​Strategies for resolving challenging psychedelic experiences: insights from a mixed-methods study​
• ​The conceptual framework for the therapeutic approach used in phase 3 trials of MDMA-assisted therapy for PTSD​
• ​Oxytocin and the Role of Fluid Restriction in MDMA-Induced Hyponatremia: A Secondary Analysis of 4 Randomized Clinical Trials​

New on Blossom

1 Psychedelics and Creativity​

Written in collaboration with Dilara Oexemann.

• Psychedelics may increase creative thinking by disrupting the Default Mode Network (DMN), enhancing cognitive flexibility and openness to new ideas.
• Flexible, divergent thinking, fostered by psychedelics, can help treat mental health disorders such as anxiety and depression, according to research on these substances’ potential therapeutic effects.
• More research is needed to understand the long-term effects of psychedelics on creativity, with implications for both therapeutic and recreational uses.

2 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 Why Psychedelic Research is Booming: Current Trends and Hurdles (Podcast)

Psychedelic research is booming, and a recent podcast episode explored how we can keep up with this explosion of information. I was interviewed on Psychedelics Today about the challenges and trends in the field. My platform, Blossom, catalogs research papers, trials, courses, and companies, showcasing the rapid growth of psychedelic science. I shared how the number of studies has increased dramatically, from barely enough for a weekly newsletter to almost daily additions.

We discussed what's fueling this research boom and the roadblocks that remain. I offered insights into the trends I've observed, highlighting how research can change public opinion about psychedelics. We also touched on the importance of real-world data, and how retreat centers and underground communities contribute valuable knowledge.

The conversation also covered the culture around psychedelics in the Netherlands, where psilocybin truffles are legal. I discussed drug development, including tweaking existing molecules, and the regulatory landscape, referencing the Lykos and FDA situation. We also considered the economics of psychedelic therapy, predicting that insurance coverage will be a major topic soon. Finally, I discussed my work with FLO coaching and how coaching, ACT, and psilocybin can work together.

2 Psychedelics Design Conference (Event)

My good friend Alex—a brilliant designer—and your humble psychedelic research enthusiast have put together an exiting event: the Psychedelics Design Online Conference on December 11, 2024. This unique gathering will explore the intersection of art, science, design, and engineering, shedding light on the transformative potential of psychedelics.

We aim to connect like-minded individuals, share groundbreaking insights, and build a collaborative community that benefits society and the planet.

Join us to engage with renowned speakers and immerse yourself in innovative discussions that promise to inspire and provoke thought. Don’t miss this opportunity to be part of a movement at the forefront of psychedelic exploration and design.

Use code BLOSSOM15 for a 15% discount.

Molenvaart 76, Anna Paulowna, NH 1761AL
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