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Psychedelic Science Newsletter
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Science in Sixty Seconds
How Neurons Communicate
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Neurons (brain cells) communicate with each other using electrical and chemical signals (neurotransmitters)..
- When a neuron receives a signal, it generates an electrical impulse called an action potential.
- This action potential travels down the neuron's axon, which is a long, thin fiber that extends from the neuron's cell body. At the end of the axon, there are tiny structures called synapses that connect to other neurons or other cells in the body.
- When the action potential reaches the synapse, it triggers the release of chemicals called neurotransmitters (e.g. serotonin). These neurotransmitters cross the synapse and bind to receptors (e.g. 5-HT2A receptors) on the receiving neuron. Activation of 5-HT2A receptors is ‘excitatory’ and with sufficient excitation, a new action potential is generated.
The process repeats, activating subsequent neurons and spreading signals across the brain, much like lightning. |
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Check out this video to see real neurons firing like lightning!
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RESEARCH UPDATES
Psychedelic Clinical Research
🍄 Single-dose psilocybin-assisted therapy in major depressive disorder: a placebo-controlled, double-blind, randomised clinical trial - EClinicalMedicine
🌍 Psilocybin improves patient-reported depression, anxiety, and function | A single-dose of psilocybin given with psychological support improved measures of patient-reported depression severity, anxiety, affect, and functioning (outcomes that are of importance to patients) three weeks after treatment. This is further analysis from the largest randomised clinical trial of psilocybin for treatment-resistant depression that was recently published by COMPASS - J Affect Disord
🧠 Seeing the effects of DMT on brain activity | The effects of psychedelics on the brain can be observed using electroencephalography (EEG) as suppression of alpha power and increased signal diversity. In this study, DMT altered EEG activity in a concentration-dependent manner - CPT Pharmacometrics Syst Pharmacol
👩⚕️ Two surveys of Australian and NZ psychiatrists and psychiatry trainees about psychedelics:
The prescription of psychedelic therapies in Australia and New Zealand: A brief survey of psychiatrists – Australasian Psychiatry
- Greater than 65% agreed that psychedelic therapies might address the shortfall in effective psychiatric treatments. Many are interested in further training on this topic. About 70% of the sample hold various concerns about psychedelic therapies, and more believe that the prescription of psychedelics should be limited to psychiatrists in the future.
A survey of Australian psychiatrists’ and psychiatry trainees’ knowledge of and attitudes towards psychedelics in the treatment of psychiatric disorders – Australasian Psychiatry
- They had some knowledge of the research and potential benefits. Most respondents perceived psychedelics as risky but most believed psychedelics deserved further research. “Education about the evidence of their efficacy and the risks associated with their use is needed.”
🌈 Personal Psychedelic Use Is Common Among a Sample of Psychedelic Therapists: Implications for Research and Practice – Psychedelic Medicine
- “We found that experiential learning [personal use] is common in psychotherapy but not in psychiatry, meaning psychedelic therapy straddles two different traditions.”
🍺 Psychedelic treatment for co-occurring alcohol misuse and posttraumatic stress symptoms among United States Special Operations Forces Veterans | An ibogaine and 5-MeO-DMT treatment program (Mexico) reduced alcohol use and PTSD symptoms in a subset of Veterans (N=86) in a sustained manner (6 months). However, less than half of the veterans were responders. Veterans who substantially reduced alcohol use (responders) also had greater reductions in trauma symptoms and improvements in cognitive functioning – Military Psychology
⭐ 2C-B vs psilocybin on subjective experience, mood and cognition | 2-CB (20 mg) elicited alterations of waking consciousness of a psychedelic nature, with dysphoria, subjective impairment, auditory alterations, and affective elements of ego dissolution. Its effects were similar to psilocybin (15 mg) but shorter-lasting, largely resolving within 6 hours. Present findings support the categorisation of 2C-B as a subjectively “lighter” psychedelic – BioRxiv
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Psychedelic Preclinical Research
🌱 Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors | This paper suggests the activation of intracellular serotonin 2A receptors (receptors located inside the cell instead of the cell surface) is responsible for the plasticity-promoting and antidepressant-like properties of psychedelic compounds. These results may explain why serotonin does not induce similar plasticity, as it is too ‘polar’ to cross the cell membrane. This study raises the interesting question, what molecule is the natural ligand for these intracellular 5-HT2Ars? – Science
🍄 Acute psilocybin enhances cognitive flexibility in rats | Acute psilocybin robustly improves cognitive flexibility in rats on a specific learning task via 5-HT2A receptors. However, the more potent 2A agonist, DOI, impaired cognitive flexibility in the same task, suggesting that this effect of psilocybin does not generalize to all other serotonergic psychedelics – Neuropsychopharmacology
🧪 Pharmacologic activity of substituted tryptamines at 5-HT2AR, 5-HT2CR, 5-HT1AR, and SERT – J Pharmacol Exp Ther
🐭 Rearing behaviour in the mouse behavioural pattern monitor distinguishes the effects of psychedelics from those of lisuride and TBG – Front Pharmacol
💻 In silico analysis of biased signaling in the serotonin 2A receptor | The knowledge obtained from this study will be used to develop structure-based pharmacophore models to identify high-affinity biased agonists for the 5HT2A receptor – Biophysical Journal
🧠 5-HT2ARs Mediate Therapeutic Behavioral Effects of Psychedelic Tryptamines – ACS Chem Neurosci
Psychedelic Research Reviews
- Possible psychedelic therapeutic mechanism – Science
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment – Neuropharmacology
- Utility of preclinical models in the study of psilocybin – A comprehensive review - Neurosci Biobehav Rev
- Probing the antidepressant potential of psilocybin: integrating insight from human research and animal models towards an understanding of neural circuit mechanisms – Psychopharmacology
- Therapeutic effect of psilocybin in addiction: A systematic review – Front. Psychiatry
- The economics of psychedelic-assisted therapies: A research agenda – Front Psychiatry
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Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- A Phase II, Multicentre, Randomised, Double-blind, Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Efficacy of COMP360 in Participants With Major Depressive Disorder With One Prior Treatment Failure - NCT05733546
- Efficacy, Safety, and Tolerability of a Single Administration of COMP360 in Participants With TRD [treatment-resistant depression] - NCT05624268
- Efficacy, Safety, and Tolerability of Two Administrations of COMP360 in Participants With TRD [treatment-resistant depression] - NCT05711940
- Psilocybin in Functional Neurological Disorder (PsiFUND) - NCT05723276
- Neural and Physiological Correlates of Psychedelic Sub-states (i2) [Psilocybin] - NCT05698511
- Does Psilocybin Require Psychedelic Effects to Treat Depression? (PSI-RIS) - NCT05710237
- Psilocybin for Major Depressive Disorder - NCT05675800
A Dose-Ranging Study of 50 µg to 100 µg LSD in Healthy Volunteers - NCT05674669
- The Effect of LSD on Neural Synchrony, Prosocial Behavior, and Relationship Quality - NCT05670184
- Acute Dose-dependent Effects of DMT-bolus Applications in Healthy Subjects (DMT BDR-Study) - NCT05695495
- Pharmacokinetics, Safety, and Tolerability of Intramuscular 5-MeO-DMT in Healthy Volunteers - NCT05698095
- MDMA Plus Exposure Therapy for PTSD - NCT05746572
- Preliminary Effectiveness of Individual and Group MDMA-assisted Therapy for Israeli Veterans With PTSD and Moral Injury - NCT05732155
- Developing Optimal Psychedelic Assisted Psychotherapy for Obsessive-Compulsive Disorder [MDMA] - ACTRN12622001525774p
- A study of the psychological, cognitive and physiological effects of Psychedelic Medicines (ASSESS) [MDMA] - ACTRN12622001535763p
- MDMA-assisted Prolonged Exposure Therapy for Comorbid Alcohol Use Disorder and Post-traumatic Stress Disorder (MPATHY) - NCT05709353
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Other News
- 🌈 Wall Street Gets Behind Next Wave of Mental Health Treatment: Psychedelics – Investopedia, 23 Feb
- 🍄 [Podcast] The Promise and Perils of Psychedelics - “Intention to Treat,” a podcast from the New England Journal of Medicine, 23 Feb
- 🥽 Virtual reality plus psychedelics are being trialled in therapy. Are they effective? An article including out friends at Enosis – ABC News, 20 Feb
- 🌵 Psychedelics Are a Promising Therapy, but They Can Be Dangerous for Some – The New York Times, 10 Feb
- ❓ Experts question timing of psychedelics approval – NewsGP, 9 Feb
- ✅ The TGA has approved certain psychedelic treatments: the response from experts is mixed – The Conversation, 8 Feb
- 🩺 Prescribing MDMA and psilocybin: who will get the drugs and how will they help? – The Guardian, 7 Feb
- 🔜 Australian approval of MDMA and psilocybin a ‘baby step in the right direction’, medical experts say – The Guardian, 4 Feb
- 🟪 TGA approves psilocybin and MDMA for use in treating depression and PTSD – ABC News, 3 Feb
- 🦘 Australia becomes first country to recognise psychedelics as medicines – Sydney Morning Herald, 3 Feb
- 💚 MDMA and Psilocybin Are Approved as Medicines for the First Time – Wired, 3 Feb
- 🪁 [Podcast] How Psychedelics Helped a Paralyzed Athlete Walk Again – Outside podcast, 1 Feb
- ☀ [Video] The “heroic dose” of psychedelics, according to Johns Hopkins – BigThink
- 🧠 [Listen] Psychedelic drugs may launch a new era in psychiatric treatment, brain scientists say – “Shots” Health News from NPR, 27 Dec
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We’ve been busy growing the team, forming an Advisory Board, gathering data, filing patents, advancing our drug candidates with new experiments and partnerships, and making new psychedelics that have never-before existed! And it is only March... 2023 is going to be a HUGE year for Psylo! Watch this space 👀
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A Sponsored Computational Chemistry PhD Opportunity in Psychedelics
Psylo is co-supervising a PhD candidate at RMIT University with Jessica Holien's lab. The selected applicant will use molecular modelling to predict hallucinogenic properties of novel compounds, contributing to the company's In-Psylico platform development. This project will deliver better psychedelic-inspired medicines, faster! The position has a stipend and a top-up scholarship.
Contact Jessica Holien for more info jessica.holien@rmit.edu.au
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Sam Banister, CSO, visited the US and caught up with many Hamilton Morris and Jason Wallach, Lars Wilde, Michael Baumann and Grant Glatfelter, Graham Pechenik, and Gregory Dwulet.
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Meet our chemistry interns! It was a real pleasure for Psylo to host Jacob Cameron from The University of Queensland as our very first chemistry intern, and we're super excited to welcome Emil Kurt Dziedzic from Freie Universität Berlin as our next!
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Psylo had a very successful Strategy Day in early January where we reviewed our progress in 2022 and strategic priorities for 2023.
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Psylo and Sam Banister on Nine News describing our cutting-edge research being conducted at UNSW to develop new treatments for mental disorders, as part of the UNSW Founders SynBio10X program, 10 Jan
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Psylo in the Media
Upcoming
- Josh Ismin, CEO, will be presenting at World Science Festival in Brisbane, 24 – 25 March 2023
- Sam will be hosting a webinar with psychedelic pharmacologists, Charles and David E. Nichols, as part of the Collaborative Drug Discovery Scientific Webinar Series.
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This is Psylo's Psychedelic Science Newsletter, delivering curated research right to your inbox. Join the revolution.
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