Psylo Newsletter - May 2022

psylo_newsletters

26 May

Science in sixty seconds

This graph shows which indications psilocybin therapies (drug alone and with psychotherapy) are being investigated for, and the number of trials for that indication.

Psilocybin therapies are showing remarkable promise for the treatment of depression, evidenced by the 27 clinical trials. But early-stage research suggests psilocybin might be useful in treating a range of conditions.

Studies in healthy participants explore factors including underlying mechanisms, consciousness, cognition, pharmacokinetics and spirituality.

Substance Use Disorders include alcohol, opioids, amphetamine-related drugs (methamphetamine and cocaine) and nicotine. Health-related distress includes trials exploring the use of psilocybin for managing the distress associated with cancer, hospice care and AIDS.

Psilocybin’s therapeutic potential is also being investigated for headache disorders, anxiety conditions, obsessive-compulsive disorder (OCD) and fibromyalgia.

While it is too early to determine psilocybin’s benefits for these indications, it is remarkable that one compound could have such a broad range of applications.

Is there a common mechanism underling these conditions that psilocybin addresses?

RESEARCH UPDATES

Psychedelic Clinical Research

LSD reduces anxiety suggest preliminary results | MindMed Dr. Matthias Liechti and Dr. Friederike Holze present top-line data from Phase 2 trial at the PSYCH Symposium.

LSD was reported to produce rapid and long-lasting reductions in anxiety and comorbid depression symptoms up to 16 weeks post-treatment. Interestingly, an acute positive or mystical experience correlated with long-term therapeutic outcomes. Note: These results have not been peer-reviewed. [Psychedelic Alpha twitter].
Psilocybin broken heart | The first case report of psilocybin-induced takotsubo cardiomyopathy (heartbreak syndrome). [case study]
How LSD, MDMA and d-amphetamine alter the mind | Despite having distinct pharmacology and subjective effects, all 3 drugs increased connectivity between the thalamus and sensorimotor cortices; LSD caused a global increase, while MDMA and amphetamine induced more nuanced changes. Connectivity was measured with resting-state functional magnetic resonance imaging in 28 healthy volunteers. [study]

Ayahuasca adverse effects | A case study of psychological adverse effects after ayahuasca administration in a clinical setting and recommendations for its management. [case reports]
Does psilocybin open depressed minds? | In last month’s newsletter, we reported on a study led by Carhart-Harris, which suggested the neural mechanisms for psilocybin therapy’s antidepressant effects (Nature Medicine).
This study has since come under serious scrutiny from other researchers who question the methods and statistics that were used to determine psilocybin’s efficacy.
Critics have published their concerns as a preprint (not peer-reviewed article) in PsyArXiv titled, “Skepticism About Recent Evidence that Psilocybin Opens Depressed Minds” [preprint].
A detailed recount of the events was published by Vice.

Psychedelic Preclinical Research

A new LSD | A novel LSD analogue (lysergamide 1P-AL-LAD) was analytically characterised in vitro and in vivo, and shown to have similar activity to LSD and psilocybin. [study]
Exploring the underlying mechanisms of MDMA treatment for PTSD | MDMA treatment was effective in attenuating stress responses in a rat model of PTSD only when paired with memory reactivation by a trauma-cue, not on its own. The HPA axis and serotonergic systems were implicated as the underlying mechanisms. [study]
“Psychedelic” 5-HT2A receptor implicated in spinal cord injury recovery | Overexpression of nerve growth factors (NT-3 and IGF-1) in a rat model of spinal cord injury improved recovery of motor function and spasticity. The animals that had better function had higher expression of 5-HT2A receptors in the spinal cord (along with other proteins). [study]

Psychedelic Research Reviews

Psychedelics in the treatment of headache and chronic pain disorders. [review]
Psychedelics and anti-inflammatory activity in animal models. [review]
A review of pharmacological treatments for anhedonia includes evidence for anti-anhedonic effects of ketamine and psychedelic agents. [review]
Special considerations for evaluating psilocybin-facilitated psychotherapy in vulnerable populations. [review]
A systematic review of neuroimaging studies investigating the effects of psilocybin in adults with major depressive disorder (10 studies) and the general population (3 studies). [review]

Psychedelic Clinical Trials Update

A round-up of the latest registered clinical trials investigating psychedelics:

A Study of a Psilocybin Analog (CYB003) in Participants With Major Depressive Disorder (Cybin) - NCT05385783
Psilocybin Versus Ketamine - Fast Acting Antidepressant Strategies in Treatment-resistant Depression (National Institute of Mental Health, Czech Republic) - NCT05383313
Acute Dose-dependent Effects of DMT in Healthy Subjects: A Placebo-controlled Cross-over Study (University Hospital, Basel, Switzerland) - NCT05384678
The Effects of Psilocybin on Self-Focus and Self-Related Processing in Treatment Resistant MDD (Massachusetts General Hospital) - NCT05381974
Effects of Repeated Dosing of Psilocybin on Obsessive-Compulsive Disorder: A Randomized, Waitlist-Controlled Study (Yale University) - NCT05370911
A Double-blind, Randomized Trial Examining the Preliminary Efficacy of Psilocybin Therapy for People With Chronic Low Back Pain (Joshua Woolley, MD/PhD) - NCT05351541

Other Updates

💰 $2.7M grant from NIDA to find to develop non-hallucinogenic psychedelic analogues for substance use disorders – Mirage News, 25 May 2022
🔬 CSIRO starts work on medicinal psychedelics – CSIRO News, 18 May 2022
How psychedelic mushrooms helped pro surfer Koa Smith overcome depression and trauma: ‘I never slipped back’ – Independent, 11 May 2022
⚖ Direct comparison of the acute effects of lysergic acid diethylamide and psilocybin in a double-blind placebo-controlled study in healthy subjects – Bloom Analysis
🌈 MindMed Collaborators Prof. Liechti and Dr. Holze Announce Positive Topline Data from Phase 2 Trial Evaluating LSD in Anxiety Disorders – PR Newswire, 11 May 2022
👮‍♂️ Peaceful protesters were arrested in front of DEA offices while protesting for psilocybin to be available to terminal patients via ‘The Right to Try act’ – Lucid News, 10 May, 2022
🥉 MAPS Completes Enrollment, as Planned, for the Confirmatory Phase 3 Trial of MDMA-Assisted Therapy for PTSD – PR Newswire, 9 May 2022
🌎 Europe’s first psychedelic drug trial firm to open in London – The Guardian, 9 May 2022
🕵️‍♀️ Probing the antidepressant action of psychedelics – Nature Review Drug Discovery, 9 May 2022
🍄 New species of psychedelic mushroom believed to live in Kakadu National Park – ABC News, 2 April 2022
⭐ Our favourite substack of the month – The Trip report by Zach Haigney. Why do we love it? In-depth analyses of the emerging US psychedelics industry, with a focus on technology and commentary on policy.

PSYLO UPDATES

Psylo was featured in the Cosmos Magazine article, The Aussie startup creating next-generation psychedelics, 20 May 2022
Honey, I shrunk the chemists! Asher Brants and Jin Tan use VR technology with Nanome to go inside the “psychedelic” 5-HT2a receptor and better understand how compounds bind to induce psychedelic effects. [Full video]

Josh and Sam chat with Peter Ostick on the Soma Collective podcast about the evidence behind psychedelics and their potential for mental health. [listen]

Sam and Dilara present on the science of psychedelics to a full house during a sold-out Pint of Science Festival event.

Sam and Josh meet up with Prash & Agnieszka from Enosis Therapeutics to discuss the awesome work they're doing with VR.

Sam and Dilara catch up with talented researchers Vince Polito, Stephen Bright and Liam Engel, who are leading psychedelic clinical trials in Australia.