Discover how a therapeutic dose of psilocybin compares to psychedelic mushrooms in Science in Sixty Seconds before reading a summary of the latest breakthroughs in the rapidly growing field of psychedelic research. There have been at least 17 new clinical trials registered in the last month!
Sam Banister and I (Dilara Bahceci) will be heading to Burning Man next week. If you are also heading to the dust, reach out or come say hi, we are camping with Burning Sky at 5 & H.
I hope you enjoy this edition of Psylo's Psychedelic Science Newsletter 🍄🧪🧠
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Last week we delved into The Heroic Dose of Psychedelics, which is a high dose of psilocybin being used for therapeutic purposes. Most of the therapeutic research into psychedelics uses pure, synthetic psilocybin and was inspired by the traditional use of psilocybin mushrooms. Currently, in the US, psychedelic mushrooms are decriminalised in Denver and can be accessed via clinics in Oregon, and community use of psychedelics is increasing.
Common questions from the community relate to how clinical use compares to traditional use. While there are many factors that differ between these, today we will keep it simple and discuss dosage. At least that was what I originally thought…
Psilocybin mushrooms, also known as "magic mushrooms", are fungi known for eliciting psychedelic effects when ingested. The major psychoactive compounds found in these mushrooms are psilocybin and psilocin.
- Psilocybin turns into psilocin upon ingestion and psilocin is the actual compound that causes psychedelic effects.
Psilocybin mushrooms have been found on all continents. Many psilocybin mushrooms are in the genus Psilocybe, but there are species across several other genera that contain psilocybin. For reference, lions, tigers, and leopards are from the same genus but are different species. There are estimated to be 144 species of psilocybin-containing Psilocybe mushrooms around the world!
Variation in psilocybin concentrations
The concentrations of psilocybin from multiple studies of different Psilocybe species grown in various conditions ranged from 0% to nearly 2%; which equates to 0 mg to 20 mg of psilocybin per gram of dried mushroom.
The concentration of psilocybin found in these mushrooms has been found to differ between species, between flushes of fruiting bodies from the same mycelium, and between individual mushrooms from the same flush.
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🍄 Species
There are hundreds of species of psilocybin mushrooms but Psilocybe cubensis is the most common mushroom used for inducing psychedelic experiences due to its ease of cultivation. In the wild, it is commonly found on cow dung but can also be found on horse and buffalo dung
Cubensis is reported to be “moderately potent,” with analytical reports ranging from 0.7 to 13.3 mg per gram (mg/g) of dried mushroom. Bigwood and Beug1 found “that the level of psilocybin and psilocin varies by over a factor of four among various cultures of Psilocybe cubensis grown under rigidly controlled conditions, while specimens from outside sources varied tenfold.”
- For the data nerds, the ranges for individual reports were 0.7-6.2 mg/g1; 3.2-13.3 mg/g2; 11.5 ± 2 mg/g3; 0.7-3.5 mg/g4; 6.2-15.1 mg/g5; 5 mg/g, 6.3 mg/g, 1.5 mg/g and 1.5 mg/g6.
Psilocybe cyanescens (“wavy cap”), Psilocybe serbica, and Psilocybe azurescens are some of the more potent species with regular reports of psilocybin concentrations of over 15 mg per gram and up to 17.8 mg/g!4,6
Psilocybe subaeruginosa is a species of moderate-to-high potency found in Australia and New Zealand that has been reported to have from 4.5 to 11.2 mg of psilocybin per gram of dried mushroom.7,8
- Note: these values are for dried mushrooms which are the most common way they are consumed. Mushrooms have reliably been reported to contain about 90% water.
Other factors that influence concentrations
Growing conditions, the mushrooms growth stage, how the mushrooms were processed and prepared, age of the preparations and storage method all influence the concentrations of psilocybin. For example:
- Heat: Psychoactive compounds begin to break down rapidly at temperatures exceeding 100 °C (212 °F).
- Storage: Psychoactive compounds were reported to degrade to about half of the original concentration9. However, another study analysed samples that were decades old and found considerable concentrations10.
This is all before factors like methods of consumption (e.g. capsule, in food, tea, Lemon Tek) and individual variation impact the experience.
Finally, I only included psilocybin for simplicity but these mushrooms contain psilocin and other compounds that are bioactive and can influence the effect. But we’ll get into that next time…
Conclusions:
- The only consistent finding was that psilocybin concentrations are highly variable.
- Based on the reported analyses, there can be anywhere between 0 and 18 mg of psilocybin per gram of dried mushroom.
- Luckily the median lethal dose of psilocybin is 280 mg/kg, which equates to 19.6 kg of psilocybin(!), or a lot of mushrooms, for a 70 kg (155 lb) person.
1. Bigwood and Beug 1982a, 2. Bigwood and Beug 1982b, 3. Laussmann and Giebing 2010, 4. Gotvaldova et al 2022a, 5. Gotvaldova et al 2022b, 6. Stamets 1996 Psilocybin Mushrooms of the World: An Identification Guide, 7. Anastos 2006, 8. Picker and Rickards 1969, 9. Gotvaldová 2020, 10. Bradshaw 2022.
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Psychedelic Clinical Research
- 👶🧒👨👴 Risk of developing a mental disorder across the lifespan | About half of the population can expect to experience at least one mental disorder by the age of 75 found a study of 156 331 respondents from 32 surveys in 29 countries. These disorders usually emerge during childhood, adolescence, or young adulthood, emphasizing the need for timely detection and care tailored to these stages of life. The Lancet
- 🗣 Predicting treatment response to psilocybin using natural language processing | Analyzing the conversations between patients and therapists after receiving psilocybin in the COMPASS phase 2 trials, using Advanced language analysis and machine learning, was able to predict long-term patient response. Psychopharmacology
- 👩🦽 Serotonin-Like Syndrome in People with Spinal Cord Injury After Use of Serotonergic Psychedelics | Individuals with spinal cord injuries using serotonergic psychedelics reported a distinctive syndrome of heightened muscle and autonomic sensitivity resembling peripheral-dominant serotonin syndrome - anecdotal online reports. Neurotrauma Reports
- ⚡ Psychedelics reported to improve some pain conditions symptoms in survey | People with chronic pain self-reported that psychedelics led to better pain relief compared to conventional medication for fibromyalgia, arthritis, migraine, tension-type headache but not sciatica in a survey (N = 170) European Pain Federation
- 💜🌈 MDMA and psychedelics: a joyful combination | Combining psilocybin/LSD with a self-reported low (but not medium–high) dose of MDMA was associated with less challenging and more positive psychedelic experiences in a small, self-reported survey study (N=27). Scientific Reports
- 🍄 Psychedelics reported to improve OCD symptoms in survey | Reported symptom reduction was associated with the intensity of the psychedelic experience and the duration of benefits varied from weeks to months (N = 174). Scientific Reports
- 🧠 Insights into how d-amphetamine, LSD, and MDMA alter communication between different brain regions | Each drug influenced the interactions between brain regions in unique ways, shedding light on the intricate workings of psychedelics in the brain - fMRI data from a controlled, double-blind, placebo-controlled, crossover study in healthy subjects (N = 25). Biological Psychiatry
- 🩺 [Preprint] Hallucinogen-related hospital visits rose in California from 2016–2021 | A study analyzed emergency department (ED) visits and hospitalizations related to hallucinogen use in California from 2016 to 2021. Rates of ED visits associated with hallucinogen increased by 69% between 2016 and 2021, whereas ED visits associated with alcohol and cannabis decreased by 24% decrease and 1.9%, respectively. However, the absolute rates for hallucinogens admissions were still very low compared to alcohol and cannabis: 3.8 (hallucinogens) vs 256.5 (alcohol) vs 118.6 (cannabis) per 10,000 ED visits in 2021. As there has been an increase in psychedelic use (see July’s Science in Sixty Seconds), future research should assess hospitalization in relation to use. - MedRxiv
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Psychedelic Preclinical Research
- 🧠🧠 Psychedelics and dissociatives cause brain regions to hyper-synch | A study in rats explored how different types of psychedelic drugs impact the brain. 5-HT2AR psychedelics (LSD and DOI) and NMDAR psychedelics (ketamine, PCP) caused different firing patterns at the neuronal level but resulted in similar patterns of high-frequency oscillations that were extremely synchronized across various brain regions. This hypersynchrony is suggested to be a key mechanism for the changes in perception and cognition during psychedelic drug use. Communications Biology
- 🐭 Glucocorticoids mediate psilocybin’s anti-anxiety effects in mice | Psilocybin reduced anxiety behavior in mice and this effect appears to be mediated through a transient increase in glucocorticoid hormones, providing insight into psilocybin’s downstream effects. ACS Pharmacol Transl Sci
- 🧫 Anti-inflammatory effects of psychedelics and drugs target TRP receptors | Some of the tested compounds, including psilocybin, curcumin, and eugenol, reduced inflammation in human small intestinal cells without causing harm to the cells. This research suggests that these compounds could be promising for developing treatments for inflammatory bowel diseases and other inflammation-related conditions. Curr Issues Mol Biol
- 🐀 Psychedelic receptor linked to compulsive behavior and cognitive inflexibility in rats | The study investigated compulsive behavior in rats and found that those with high compulsivity showed cognitive inflexibility, reduced serotonin 2A (5-HT2A) receptor binding levels and Htr2a (5-HT2A), Grin1, and Bdnf gene expression in the frontal cortex, a region critical for executive brain function. Mol Neurobiol
- 🧪 Indazole as a phenol replacement for NMDA receptor antagonists | The study explored using indazole as a replacement for the phenol group in NMDA receptor antagonists, which can lead to enhanced neuroprotective effects. By replacing the phenol with indazole, the new compounds showed high affinity for GluN2B receptors and reduced glucuronidation, offering potential benefits for neuroprotection. J Med Chem
- 💻 Identifying serotonin receptor modulators using computational chemistry | The study created a diverse compound library inspired by natural alkaloids to find compounds that can affect serotonin receptors. By combining different fragments, they discovered potential new compounds that were then confirmed to have significant agonist or antagonist activity against 5-HT2A and/or 5-HT2C. Subsequent optimization of one of these delivered a lead dual 5-HT2B/C antagonist with a highly promising selectivity profile. J Med Chem
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Psychedelic Reviews and Commentaries
Patent Highlights
- Exploring Next-Generation Therapeutics: Morphic Mixtures and Specified Salts for the Treatment of Mental Disorders and CNS Modulation - ACS Medicinal Chemistry Letters
- The Synergistic Effects of 5-HT2A and TRP Agonism/Antagonism in Reducing Inflammation for Enhanced Mental and Physical Health - ACS Medicinal Chemistry Letters
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Listen to Future Medicine to hear Dr Dilara Bahceci (Head of Communications) share why psychedelics are changing the future of mental health treatments and how Psylo is working to make them more accessible, on Humans of Purpose podcast, 7 August 2023
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Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- 5 MeO-DMT | Healthy Subjects | Dose-finding PKPD Trial for RE02 [5 MeO-DMT, Reconnect Labs] in Healthy Subjects - NCT05979727
- 5-MeO-DMT | Healthy Subjects | Functional, cognitive and behavioural effects of 5-MeO-DMT administered by intramuscular injection - ACTRN12623000884606
- Ketamine | Existential Distress | Ketamine-assisted Psychotherapy (KAP) for Patients With Existential Distress Associated With Non-operable GI Cancers (TREK) - NCT06001372
- Ketamine | Treatment-Resistant Depression | Ketamine versus Ketamine plus Behavioural Activation Therapy for Adults with Treatment Resistant Depression - ACTRN12623000817640
- LSD | Healthy Subjects | LSD-Perceptual-Choice-Study (LUCY) - NCT05976698
- LSD + Ketanserin, Olanzapine, Lorazepam | Healthy Subjects | Effect of Ketanserin, Olanzapine, and Lorazepam After LSD Administration on the Acute Response to LSD in Healthy Subjects (LBL) - NCT05964647
- MDMA | Posttraumatic Stress Disorder | A study to investigate the safety and feasibility of delivering MDMA-assisted psychotherapy to patients with posttraumatic stress disorder - ACTRN12623000838617
- MDMA | PTSD | MDMA-assisted Brief Cognitive Behavioral Conjoint Therapy for PTSD (MDMA-bCBCT) - NCT05979844
- MDMA | Veterans with PTSD | Group MDMA-therapy for Veterans With PTSD (Group-MVP) - NCT05961527
- Psilocybin | Alcohol Use Disorder | Psilocybin-Assisted Psychotherapy for Alcohol Use Disorder (PAP-AUD) - NCT05995769
- Psilocybin | Cancer Pain | Psilocybin in Cancer Pain Study - NCT06001749
- Psilocybin | Chronic PTSD | Psilocybin-assisted massed cognitive processing therapy for chronic posttraumatic stress disorder: an open-label trial - 276390
- Psilocybin | Healthy Subjects | Pairing Psilocybin With Transauricular Vagus Nerve Stimulation (ENHANCE) - NCT05866471
- Psilocybin | Opioid Use Disorder | Inpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder (BIPOD-In) - NCT06005662
- Psilocybin | Prolonged Grief | PARTING: Psilocybin-Assisted suppoRtive psychoTherapy IN the treatment of prolonged Grief - ACTRN12623000827639
- Psilocybin | Treatment-Resistant Depression | Psilocybin-assisted psychotherapy for treatment-resistant depression: a randomized phase ii clinical trial comparing one versus two psychedelic doses of psilocybin (psi-1v2) - 276629
- Psilocybin | Treatment-Resistant Depression | Treatment Resistant Depression Intervention with Psilocybin-assisted Psychotherapy - ACTRN12623000832673
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The Sydney Psylo team, based at UNSW
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Other News
- 🌈 One way to heal a brain injury? Let LSD open your mind—literally - National Geographic, 23 Aug
- 🥼 Non-Hallucinogenic Drug Inspired by Psychedelics Enters First-in-Human Study - Technology Networks, 21 Aug
- 🏃♀️ Q&A: Could psychedelics be used to help manage athletes' mental health? - Medical Xpress, 21 Aug
- ❓ Is the therapeutic potential of hallucinogens risky and overhyped? - The Guardian, 19 Aug
- ⚖ Psychedelics are hot on the Hill. Washington is getting hip to the promise of psychedelic medicine. - Politico, 18 Aug
- 💰 COMPASS Pathways to advance psilocybin therapy with up to $285M in new financing - Tech EU, 18 Aug
- 💜 MDMA Is One of the Safer Illegal Drugs. But There Are Risks - New York Times, 18 Aug
- 👁🗨 Woman With No Mind’s Eye Develops One After Taking Magic Mushrooms - IFLScience, 17 Aug
- 💊 Study Indicates Take-at-Home, Oral Ketamine is an Effective Option for Treatment-Resistant Depression - Pharmacy Times, 16 Aug
- 🍺 Four Yale Psychiatry Researchers Awarded Grants to Study Alcohol Use Disorder, including a trial of DMT - Yale Medicine, 16 Aug
- 🍷 I Went to Rehab for Alcoholism 18 Times. Only Psychedelics Helped - Vice, 16 Aug
- 🍄 ‘Society For Neuroscience Meets Burning Man’: Perspectives From The Largest Psychedelic Conference In History - Forbes, 14 Aug
- 🏁 The Neuropsychiatric Pipeline: 10 Late-Stage Therapies to Watch - Biospace, 14 Aug
- ⚖ We’re on the cusp of another psychedelic era. But this time Washington is along for the ride - Politico
- 🏇 New study to investigate psychedelic therapy for gambling addiction - Imperial College London, 11 Aug
- 🚺 Estrogen Impacts the Effects of Psilocybin for Women - Pharmacy Times, 11 Aug
- 📚 Psychotropics help us map our minds. They might also bring us together. - Washington Post, 10 Aug
- ⚡ Early trial results show reduced frequency and intensity of migraine attacks after single dose of psilocybin - Mecial Xpress, 9 Aug
- 🧼 Psychedelic therapy grows as a popular workplace benefit. Dr. Bronner’s says it pays off - Fast Company, 9 Aug
- 🧠 Psychedelics Sync Neurons: A Glimpse into Consciousness & Psychosis - Neuroscience News, 8 Aug
- 💊 atai Life Sciences Announces Results from the Phase 1 IV-to-Subcutaneous Bridging Study of PCN-101 (R-Ketamine) - Global Newswire, 8 Aug
- 📊 Antidepressant-Resistant Depression Biotype Identified in 27% of Study Patients - Psychiatrist, 7 Aug
- 🌏 MDMA and magic mushrooms have arrived: Australia lets psychs find a new way for happy to fight sad - Body & Soul, 4 Aug
- 🤰 For the First Time, There’s a Pill for Postpartum Depression - The New York Times, 4 Aug
- 👸 A patient who tried psychedelic therapy said hallucinations of Disney imagery 'hijacked' her experience, blaming her habit of spending 6 hours a day trading Disney pins online - Insider, 3 Aug
- 🎯 GABA Receptors Unveiled as Potential Antidepressant Targets - Neuroscience News, 3 Aug
- 🌍 Half the population to have a mental health disorder by 75 - UQ News, 31 July
- ☯ This Ivy League researcher says spirituality is good for our mental health - NPR All Things Considered, 30 July
- 🐴 I Was Traumatized After an Accident. Then I Tried Ketamine Therapy. - Outside Online, 26 July
- 🎭 Journeys Beyond: Contrasting Psychedelic Trips and Near-Death Experiences - Neuroscience News, 28 July
- 🍽 Psilocybin Is Safe to Give to Anorexic Patients, Trial Finds - Technology News, 25 July
- 🧪 Psychedelics might revolutionize therapy. What happens if you remove the trip? - Vox, 25 July
- 🥇 Landmark trial to treat grief from cancer loss with psychedelics - New Atlas, 25 July
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Dr Sam Banister (Chief Scientific Officer) attended the Lionheart Ventures summit in Costa Rica last month to connect with other visionaries and discuss tackling the world's leading problems.
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Dr Will Jorgensen (Lead Medicinal Chemist) presented on psychedelic drug development at NeuRA, 16 August and starred in the sold-out Future Science Talks Comedy show, 23 August. |
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Lifting depression: Are hallucinations compulsory? - Cosmos Magazine, 7 August
"On a more practical level, future drugs could simply be more accessible without the hallucinogenic effect and the time required to undergo a monitored treatment, says Sam Banister, chief scientific officer, Psylo"
Sam Banister, CSO and co-founder of Psylo were featured in an article about the therapeutic potential of psychedelics, alongside Martin Williams from Psychedelic Research in Science & Medicine, David E. Olson from Delix Therapeutics and Mike Musker from University of South Australia.
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Catch Josh Ismin, CEO and CO-founder, at TEDxSydney talking about the ground-breaking work being conducted at Psylo, 1 September. This is one not to miss!
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Don't miss Will Jorgensen's science-comedy fusion, "Sex, Psychedelics and Science", at the Sydney Fringe Festival, 14 September. Get your ticket here! 🔥 |
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