The "Heroic Dose" is a very high dose of psychedelics that challenges you and changes you. We explore this concept in Science in Sixty Seconds. Then we deliver the latest and greatest psychedelic science and news in this edition of the Psylo Psychedelic Science Newsletter
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The Heroic Dose of Psychedelics
The term "heroic dose" was popularized by the American psychologist and psychonaut, Terence McKenna, who advocated for exploring altered states of consciousness through the use of psychedelic substances. Historically, it was described as consuming 5 grams of dry mushrooms (Psilocybe Cubensis) alone, in the dark, in silence, and with eyes closed.
However, the psychedelic field has since evolved.
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A great description of the "heroic dose" comes from Prof Matt W. Johnson, a Professor of Psychiatry and psychedelics at Johns Hopkins University, and can be viewed here.
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The specific dosage that qualifies as a heroic dose can vary depending on an individual's tolerance, body weight, and sensitivity to psilocybin. Generally, a heroic dose is considered to be at the upper end of the dosage spectrum — typically around or more than 5 grams of dried psilocybin mushrooms or anywhere from 25 to 40 mg of pure psilocybin. Such quantities can lead to profoundly altered states of consciousness, intense visual and auditory hallucinations, a dissolution of the ego, and potentially transformative and spiritual experiences.
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Sam Harris, who is a neuroscientist, philosopher, author, and podcast host, delivers a well articulated recount of a high-dose psychedelic experience.
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Are psychedelics legal?
Before delving further, it is important to address the legal status of psychedelics. Psychedelics remain illegal in most countries. However, some types of psychedelics are decriminalized or not illegal in certain parts of the world, including the US, Australia, Austria, Brazil, Portugal, the Netherlands, Jamaica, the Bahamas, Spain, Mexico, Nepal, Peru, Ecuador and Costa Rica.
In Australia, accessing psilocybin has strict and specific requirements — it can only be prescribed for the treatment of treatment-resistant depression by authorized psychiatrists. In the US, psilocybin and/or natural psychedelics have been legalized and/or decriminalized in Oregon and Colorado, and it is predicted that a majority of states will legalize psychedelics by 2033–2037.
👉 For detailed information about the regulatory landscape in the US, explore Psychedelic Alpha’s highly acclaimed Psychedelic Legalization & Decriminalization Tracker
Psychedelic use is increasing but it’s not all rainbows
With these regulatory changes, the evolving public image, and the growing acceptance of psychedelics being discussed and portrayed in the news and media, it is no surprise that the use of psychedelics has been increasing in adults [1, 2, 3]. It's important to distinguish recreational use from therapeutic use, with the latter being administered in controlled settings, supervised by trained therapists, and alongside psychological therapy.
Though there is debate about whether therapy is necessary to derive the benefits of psychedelics, most researchers and experts in the field emphasize the importance of set and setting, along with psychotherapy, to enhance the safety and efficacy of high-dose psychedelic treatments. More evidence is required to settle the debate. Meanwhile, it is unlikely that psychedelics inducing strong subjective effects will be clinically administered without psychotherapy due to ethical and safety concerns. Notably, psychedelic-assisted psychotherapy will likely cost more than US$10,000 or AUD$25,000 per patient, making access challenging for many individuals until reimbursement and access pathways are arranged.
The inability to access a "revolutionary" treatment might tempt individuals to turn to self-medication. Six percent of those who completed the 2020 Global Drug Survey said they used recreational drugs to deal with mental health issues, mostly LSD, MDMA (ecstasy) and psilocybin (magic mushrooms). While the percentage of people who sought emergency medical treatment after using psychedelics recreationally was low (1%), this was four-fold higher (4%) for people who were self-medicating with psychedelics.
How individuals respond to psychedelics is highly variable
A recent survey of people who had difficult psychedelic experiences revealed a diverse spectrum of accounts, ranging from "Truly Worth It" to "I need help. My life has been destroyed." The survey also highlighted the variability within the experiences of the same person. For example, one respondent shared, “I had 4 prior experiences with no effect but the fifth destroyed my life.”
Research indicates that most recreational users possess a good level of knowledge about psychedelic use, which can protect against challenging experiences. However, the study also highlights the “need for education and outreach, especially in under-represented communities.” In fact, a study included in last month’s newsletter shows racial disparity, with Black people not experiencing the same health benefits from psychedelics as their White counterparts.
While psychedelics can offer transformative insights, the reality is that most people don’t know what they’re signing up for – they can’t. The nature of the psychedelic is to alter perception, increase entropy and “rearrange” the mind to unveil connections that have remained unexplored or suppressed. They also facilitate the changing of the mind through the formation of new connections between neurons, but a recent article describing the dark side of neuroplasticity suggests that the "changes aren't necessarily all good."
Proceeding with Caution
There is still much work to be done in determining how best to use psychedelics in our societies. In the meantime, respect the 5-HT2A agonist and if you choose to explore, proceed with caution.
Psychedelics are powerful tools, and their effects can be profound and unpredictable. As Matt Johnson aptly stated in the video, "I think the only bet you can make is if you have the dose high enough, something really interesting is going to happen."
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Psychedelic Clinical Research
- 🚺 Psilocybin therapy safe for females with anorexia nervosa: a small phase 1, open-label feasibility study (N=10) - Nature Medicine
- 🧘♀️ Altered states of leadership: mindfulness meditation and insights during psychedelic use were associated with positive leadership development - Front. Psychol.
- 🧠 Sub-acute effects of psilocybin on EEG correlates of neural plasticity in major depression: Relationship to symptoms - Journal of Psychopharmacology
- 💊 Psilocybin for treatment resistant depression in patients taking a concomitant SSRI medication | A single 25 mg dose of psilocybin alongside psychological support was given in combination with a selective serotonin reuptake inhibitor (SSRI) in participants with treatment-resistant depression in an open-label trial (N = 19). The treatment seemed safe and a reduction in symptoms was observed, supporting the further investigation with larger trials Neuropsychopharmacology
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- 🔍 The difference between ‘placebo group’ and ‘placebo control’: a case study in psychedelic microdosing - Scientific Reports
- 🧠 The relationship between the default mode network and the theory of mind network as revealed by psychedelics – A meta-analysis - Neurosci Biobehav Rev
- 🥼 Psilocybin for treatment-resistant depression without psychedelic effects: study protocol for a 4-week, double-blind, proof-of-concept randomised controlled trial - BJPsych Open
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Psychedelic Preclinincal Research
- 5-HT2AR and NMDAR psychedelics induce similar hyper-synchronous states in the rat cognitive-limbic cortex-basal ganglia system - Communications Biology
- Antidepressant effects of novel positive allosteric modulators of Trk-receptor mediated signaling - a potential therapeutic concept? - Psychopharmacology (Berl)
- Psychoactive substances 25H-NBOMe and 25H-NBOH induce antidepressant-like behavior in male rats - Eur J Pharmacol
- Automated Detection of Psychedelic-Induced Head-Twitch Response in Mice – Schizophrenia
- Discovery of Novel Oleamide Analogues as Brain-Penetrant Positive Allosteric Serotonin 5-HT2C Receptor and Dual 5-HT2C/5-HT2A Receptor Modulators - J. Med. Chem
- The Synergistic Effects of 5-HT2A and TRP Agonism/Antagonism in Reducing Inflammation for Enhanced Mental and Physical Health - ACS Med. Chem. Lett.
- Neurotoxic effects of hallucinogenic drugs 25H-NBOMe and 25H-NBOH in organotypic hippocampal cultures - Heliyon
- Design, Synthesis, Molecular Docking, and Biological Evaluation of Novel Pimavanserin-Based Analogues as Potential Serotonin 5-HT2A Receptor Inverse Agonists - J. Med. Chem.
- Lysergic acid diethylamide stimulates cardiac human H2 histamine and cardiac human 5-HT4-serotonin receptors Naunyn-Schmiedeberg's Archives of Pharmacology
- Subhallucinogenic Concentrations of Substituted Phenethylamines as a Novel Therapeutic Approach for Inflammatory and Neurological Disorders - ACS Med. Chem. Lett.
- Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System - ACS Chem. Neurosci.
- [Preprint] Lasting dynamic effects of the psychedelic 2,5-dimethoxy-4-iodoamphetamine ((±)-DOI) on cognitive flexibility - bioRxiv
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Watch Dr Sam Banister (Psylo CSO) deliver an entertaining and inspiring talk at the Entheogenesis Australis Meeting last year. He described the rational development of entirely new classes of psychedelic drugs and what these new medicines will mean for the most desperate patients.
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Psychedelic Reviews and Commentary
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Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- LSD Occupancy of the Serotonin 2A Receptor in the Human Brain (dOccLS) - NCT05953038
- A Community of Practice Program With Psilocybin-assisted Therapy for End-of-Life Patients - NCT05958758
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of up to Two Doses of Psilocybin for the Treatment of Major Depressive Disorder in Adults With Cancer - NCT05947383
- Prosocial Effects of MDMA (PEM) - NCT05948683
- MDMA for Alcohol Use Disorder and PTSD Comorbidity (MDMA) - NCT05943665
- A Novel Combined Neuromodulation Therapy to Enhance Balance and Neuroplasticity - NCT05940636
- Ketamine-Assisted Mindfulness-Based Cognitive Therapy for Depression: A Pilot Study - NCT05950711
- Examining Mu Opioid Mechanisms of Ketamine's Rapid Effects in obsessive-compulsive disorder (OCD) (MKET2) - NCT05940324
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A must-see video of Dr Marg Ross, one of the pioneers of psychedelics research in Australia, sharing the learning from the St Vincent’s psilocybin for end-of-life anxiety trial; also from the Entheogenesis Australis meeting. Try not to cry, I dare you.
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We're thrilled to announce that Josh Ismin, CEO and CO-founder, will be giving a talk at TEDxSydney about the ground-breaking work being conducted at Psylo. This year's theme is 'tipping point' and the event will take place on September 1st.
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Dr William Jorgensen (Lead Medicinal Chemist) gave engaging (and probably hilarious) presentations at the University of Sydney Drug Discovery Initiative (USYD DDI) Neurodrug Symposium on the 28th of June and the USYD DDI Early Career Researchers Symposium on the 20th of July.
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Taking Psylo to new heights in Colorado!
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🔥 Don't miss Will at the Future Science Talks Comedy Show in Sydney, 23 August. Get your ticket here!
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- Will Jorgensen will be giving a presentation at NeuRA, Sydney - 16 August
- Will will also be presenting at the Sydney Fringe Festival - 16 September
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