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Psychedelic Science Newsletter
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Science in Sixty Seconds
Blocking Psychedelic Activity with an Antagonist
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Classic psychedelics like LSD and psilocin (from psychedelic mushrooms) elicit their effects by activating the serotonin 5-HT2A receptor.
A receptor (a biological lock) can be opened by different keys (e.g. drugs and neurotransmitters), with differing ease to have an effect.
LSD, psilocin and serotonin are all agonists and activators of the 5-HT2A receptor.
A receptor can also be jammed by a key that does not turn. We call molecules that bind to a receptor without causing activation, antagonists. Antagonists can reduce receptor activity by preventing other molecules (keys) from interacting with the receptor.
For example, kentanserin is an antagonist of 5-HT2A because it binds to the receptor but does not activate it. In fact, a recent study showed that giving participants kentanserin 1 hour after giving them LSD reduced the duration of LSD's subjective effects from around 8.5 hours to 3.5 hours. In theory, kentanserin might have use for reducing or terminating a psychedelic experience.
This is also how naloxone (an opioid receptor antagonist) is able to block further activation of opioid receptors and rescue people from an opioid overdose. |
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RESEARCH UPDATES
Psychedelic Clinical Research
- ⭐ Paper of the month: Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. NEJM
- The COMPASS Pathways phase 2 double-blind trial was the largest psilocybin trial to date.
- People with treatment-resistant depression received a single dose of either 25 mg (high dose), 10 mg (moderate dose), or 1 mg (control; very low dose) or psilocybin with psychological support (N=233).
- Psilocybin-assisted psychotherapy reduced depressive symptoms in a dose-dependent manner. But only the high dose reduced depression scores significantly more than the control for 3 weeks, but the effect was not maintained at 12 weeks.
- All doses were associated with adverse side effects: mainly headache, nausea, and dizziness but also suicidality or self-injury.
- 🛑 Ketanserin (an inhibitor of the psychedelic 5-HT2A receptor) reverses the acute response to LSD. When given 1 h after LSD, Ketanserin significantly reduced the duration of subjective effects from 8.5 h to 3.5 h. Results from in a randomized, double-blind, placebo-controlled, crossover study in healthy subjects (N=24). Int J Neuropsychopharmacol *See the Science in Sixty Seconds section at the top of the newsletter for an explainer.
- ⚖ Body mass index (BMI) does not predict responses to psilocybin | BMI did not predict intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during psychedelic use. Data were pooled across three studies using a fixed 25 mg dose of psilocybin (N=77). Interestingly, mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being. J Psychopharmacol
- 🍏 Lifetime psychedelic use associated with healthier behaviours | Having used classic psychedelic at least once was associated with more healthy tobacco-related and diet-related behavior (N = 2822). Self-reported psychological insight during a classic psychedelic experience was associated with higher odds of having a healthy body mass index (BMI) and healthier exercise-related behaviour, but a causal link cannot be drawn from this data. - Ther Adv Psychopharmacol
- 👨⚕️ Attitudes of cancer health-care practitioners towards psychedelics | A sample of cancer health-care practitioners in New Zealand and the USA considered research investigating the potential for psychedelic-assisted therapies to be important and may be more open to studies that start in palliative and end-of-life contexts. Palliat Support Care
- 👨⚕️ Psychiatrists, but not psychologists or researchers showed more hesitancy in recommending trials of MDMA-assisted therapy | A study of the attitudes of mental health professionals (Psychiatrists, psychologists and researchers) towards trials of either MDMA-assisted psychotherapy or an unkown, neutrally labelled pharmacotherapy (N=94). “Research into, and implementation of, MDMA-AP may face barriers with certain MH professionals” BMJ Open
- 🎭 Race and ethnicity moderate the associations between lifetime psychedelic use (MDMA/ecstasy and psilocybin) and major depressive episodes | For White participants, psychedelic use was associated with better mental health. For Hispanic participants, the association was not as strong, while for Non-Hispanic Racial Minority participants, psychedelic use was not associated with a lower chance of major depressive episodes. Data from the National Survey on Drug Use and Health (2005-2019) (unweighted N = 596,187). J Psychopharmacol
- 💡 An Assessment of Psychedelic Knowledge Among People Using Psychedelics Naturalistically | This study assessed basic knowledge of psychedics-related legal status, therapeutic potential, and side effects of psychedelics among people reporting psychedelic use (N = 1435). Respondents who had used greater numbers of different psychedelics, with higher levels of education, lower age, greater frequency of psychedelic use, identifying as male, used high doses (vs. microdosing only), identifying as Caucasian/White, and with greater annual household income answered more questions correctly. “Most respondents exhibited high knowledge of psychedelics, though there is also a demonstrated need for education and outreach, especially in under-represented communities.” J Psychoactive Drugs
- 🌈 [Preprint] Interest in psilocybin, psychedelic therapy and antidepressant-related search interest increased after declaration of pandemic, but interest in cannabis or cocaine did not. Data from Google Trends - Preprint
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Psychedelic Preclinical Research
- 🧪 Serotonin-releasing agents with reduced off-target effects. Certain cathinones showed promise as serotonin-releasing agents in cells and rodents, without releasing dopamine and with reduced off-target activity at vesicular monoamine transporters and 5-HT2B-receptors, indicative of low abuse-liability and low potential for adverse events. Molecular Psychiatry
- 🍄 Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. Exploring the activity of other tryptamines founds in the psilocybe mushrooms at serotonin 5-HT2A and 5HT-1A receptors in cells and mice. ACS Pharmacol Transl Sci
- 🐁🐁 Repeated LSD dosing increased pro-social behaviours in mice. It also altered brain endocannabinoid levels, prostaglandins, and kynurenine levels as well as gut microbiota. BJP
- 🐭Role of 5-HT2A, 5-HT2C, 5-HT1A and TAAR1 Receptors in the Head Twitch Response Induced by 5-Hydroxytryptophan and Psilocybin: Translational Implications - Int J Mol Sci
- 🧠 [Preprint] Psychedelic compounds directly excite 5-HT2A Layer 5 Pyramidal Neurons in the Prefrontal Cortex through a 5-HT2A Gq -mediated activation mechanism – Preprint
Psychedelic Research Reviews
- 🍎 Psychedelic-Assisted Therapy for People with Eating Disorders - Curr Psychiatry Repv
- 🕷The Missing Piece? A Case for Microglia's Prominent Role in the Therapeutic Action of Anesthetics, Ketamine, and Psychedelics - Neurochem Res
- 🎈 Psychedelics and Neural Plasticity: Therapeutic Implications - J Neurosci
- 🧠 [Preprint] Molecular and structural insights into the serotonin 5-HT2C receptor as a therapeutic target for substance use disorders. Preprint
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Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- Consciousness, Psilocybin, and Well-Being (CoPE Pilot) - NCT05592379
- PET Synaptogenesis After Psilocybin In DEpression Recovery (PET-SPIDER) - NCT05601648
- Efficacy and Safety of COMP360 Psilocybin Therapy in Anorexia Nervosa: a Proof-of-concept Study - NCT05481736
- Efficacy, Safety, and Tolerability of a Single Administration of COMP360 in Participants With TRD - NCT05624268
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Michael Pollan is coming to Australia! Tickets
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Other News
- 🍄 COMPASS Pathways published their Phase 2b Psilocybin trial for depression.
- ⛰ Veterans’ psychedelic trip to Peru banished the demons of war - The Times, 28 Nov
- 💊 I Tried Ibogaine, the Psychedelic Anti-Addiction Drug - Vice, 25 Nov
- 🏃♀️ Sports and Psychedelics: Opening up about personal experiences, pro athletes are changing the perception of psychedelics - Fitt Insider, 22 Nov
- ❤ Doctoral student’s goal: Access to psychedelics for Indigenous peoples - Berkley News, 22 Nov
- ✅ Second MAPS-Sponsored Phase 3 Trial of MDMA-assisted Therapy for PTSD completed - MAPS, 18 Nov
- 🧠 Psychedelic drugs may reopen critical learning periods in the brain - New Scientist, 17 Nov
- “In adult mice, psychedelic drugs including LSD, ketamine and psilocybin have been shown to reopen the brain to a critical window for social learning usually only seen in adolescents”
- 📊 Interview with Elliot Marseille on the health economics of psychedelics - Psychedelics Alpha, 14 Nov
- 🚭 New psychedelic trial to test whether hallucinogenic drug can help cure smoking addiction - 7 News, 13 Nov
- 🗣 Psychedelic guides trained in first-ever UC Berkeley program - Berkley News, 10 Nov
- ⚖ Psychedelic research: balancing trippyness with a new scientific rigor – The Conversation Weekly podcast transcript, 10 Nov. Interview with Robin Carhart-Harris, Wayne Hall and Josjan Zijlmans
- 🎭 [Watch, 11m] Researchers experiment with psychedelics to treat post-traumatic stress disorder - ABC News, 9 Nov
- 👩🦽 Jim Harris Was Paralyzed. Then He Ate Magic Mushrooms. – Outside, 9 Nov
- 🍎 [Listen, 11m] Psychedelics to treat eating disorders? - ABC News, 6 Nov
- 🌈 Nature Biotechnology’s academic spinouts 2021 feat. Delix creating psychedelics without the trip - Nature Biotechnology, 3 Nov
- 💻 Virtual Screening's Latest: an attempt to find new subtype-selective serotonin receptor ligands de novo – Science, 31 0ct
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Meet the newest members of Psylo. We are thrilled to have Joanna Hare join as Operations Manager and Lachlan Whish (not pictured) and Bilqees Sameem join as Chemistry Research Assistants. Welcome to the team! 🍄💕
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Psylo was short-listed for two of the UNSW Founders Awards - 'Startup Of the Year' and 'Research Making Impact' |
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We have been selected as one of the Hello Tomorrow Deep Tech Pioneers!
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Psylo at the UNSW Founders 2022 10x Accelerator Demo Day
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In November, we hit over 1000 subscribers for the newsletter, over 2000 followers on LinkedIn and over 1000 followers on Twitter! Thank you for all your support 🍄💓
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Dilara is working on a survey to support of a clinical trial being led by A/Prof Jonathan Brett from St. Vincent's Hospital Sydney that is looking for participants.
Researchers at UNSW are conducting a project about the effects of psychedelics and methamphetamine (meth/ice) and you are being invited to take part. Taking part in this research study is optional and you may choose not to take part.
If you are interested the research project is looking for people in the US and Australia who want to take part in this research and who:
- Have used meth at least once per month during the last 3 months AND
- Have also used a psychedelic (psilocybin mushrooms, LSD, DMT, ayahuasca, or mescaline) at least once during the past three months.
If you decide to take part in the research, a full description of the research is included at the beginning of the on-line survey which can be accessed here:
Participation in this survey will take approximately 20 minutes. We will not collect any information that can be used to identify you in the future. If you would like to enter a prize draw for a first prize of a AUD$300 gift voucher, along with a second prize of a AUD$100 gift voucher, please enter your email address at the end of the survey.
If you would like more information or are interested in being part of the research study, please contact Jonathan.Brett@svha.org.au
If you know of anyone else who may be interested in participating in this survey, please feel free to forward this information on to them.
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We are still looking for a VP of
drug development
Is working with Psylo in sunny Sydney your next big adventure?
Help advance our portfolio of psychedelic medicines
for mental health conditions into clinical studies.
More information and application details here.
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