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Rational Psychedelic Drug Design
Dr Alexander Shulgin, the "Godfather" of MDMA, developed hundreds of new psychoactive agents throughout his career, and discovered their effects through self-experimentation.
His work highlights that very small changes in chemical structure can have profound effects on the dose, duration, and subjective experience of a psychedelic drug. In medicinal chemistry, this "tweaking" of chemical structure is known as rational design.
For example, Shulgin hypothesised that modifying mescaline to form TMA would change its metabolism. Indeed, TMA was found to be about 3 times as potent as mescaline, and lasted ~30% longer.
Then, modifying TMA to TMA-2 increased potency by 5-fold, and extended duration by another 50%. While adding a bromine atom to TMA-2 formed DOB - an incredibly potent psychedelic with a dose of just 1 mg lasting up to 30 hours. 🤯
At Psylo we are using these, and other medicinal chemistry, techniques to develop next-generation psychedelics!
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RESEARCH UPDATES
Psychedelic Clinical Research
- 🍄 Psilocybin microdosing associated with greater improvements in mood and mental health | Mild-moderate improvements in mood and mental health were observed in those who microdose psilocybin (n = 953) compared to non-microdosers (n = 180) after 30 days found a naturalistic, observational study. Controlled studies are needed to better understand the relationship. [Scientific Reports]
- 🌱 Preliminary data supports rapid anti-depressant effects of DMT | A small study of 10 people found i.v. DMT to be mostly safe and suggested to have next-day antidepressant effects in patients with treatment-resistant depression [Neuropsychopharmacology]
- 🧡 MDMA-assisted therapy reduced PTSD symptoms in diverse ethnoracial groups | Secondary analysis of data from 2 Phase 2 open-label trials and a Phase 3 randomized, blinded placebo-controlled trial. There was a trend towards increased placebo effect in the Black, Indigenous, and People of Color group. Future studies should recruit culturally representative populations. [J Psychopharmacol]
- 🌈 LSD has low reported incidence of adverse events and request for emergency care | Only 1% of 10,293 past-year LSD users reported seeking emergency medical treatment in the 2017 Global Drug Survey. The most common symptoms were psychological, while younger age, comorbid mental health conditions and higher frequency of LSD use were associated with increased risk of emergency care. [J Psychopharmacol]
- 🍄 Psilocybin use was associated with reduced odds of nicotine dependence | Conversely, LSD use was associated with increased nicotine dependence. More research is needed to establish whether these associations are causal. Data from 214,505 participants in the National Survey on Drug Use and Health (2015–2019). [Scientific Reports]
Psychedelic Preclinical Research
- 🦟 Psilocybin's long-lasting antidepressant-like effects observed in flies | A test used to model depressive symptoms (the forced swim test) was validated in Drosophila flies and used to demonstrate psilocybin's long-lasting antidepressant effects. The Drosophila model holds potential for the study psychedelic drug neuropharmacology. [Scientific Reports]
- 🐀👨🧠 LSD suggested to have nootropic (brain performance enhancing) effects | LSD enhanced memory performance in rats and humans, and enhanced neural plasticity pathways (including via mTOR) in human brain organoids. [Experimental Neurology]
- 🐭 DMT's antidepressant effects in mice | DMT-containing extract of Mimosa tenuiflora had antidepressant-like effects in mice via 5-HT2A/2C receptors and [J Psychopharmacol]
- 🐭 LSD reduced binge-like alcohol drinking in mice | LSD did not impact sucrose-binging or direct intracranial self-stimulation and is not suspected to generally attenuate reward effects. [J Psychopharmacol]
- 🐟 Novel psychedelics screened in zebrafish | N-benzyl-2-phenylethylamine (NBPEA) derivatives altered zebrafish behaviour to suggest neuroactivity and potentially hallucinogenic activity. [ACS Chemical Neuroscience]
- 🧪 “Psychedelics and Neurochemistry” - Special issue of the Journal of Neurochemistry. A focus on the basic science of psychedelics with reviews on fundamental cellular, molecular, and genetic mechanisms.
Psychedelic Research Reviews
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Applying Lessons From Cannabis to the Psychedelic Highway - JAMA Health Forum
- Serotonergic psychedelic treatment for obesity and eating disorders - J Psychiatry Neurosci
- Sustained effects of single doses of classical psychedelics in humans - Neuropsychopharmacology
- Psychedelics as preventive treatment in headache and chronic pain disorders - Neuropharmacology
- Classic and non‐classic psychedelics for substance use disorder: A review of their historic, past and current research - Addiction Neuroscience
- Novel ethical and policy issues in psychiatric uses of psychedelic substances - Neuropharmacology
Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- Pragmatic Trial of Psilocybin Therapy in Palliative Care - NCT05403086
- Psilocybin in Co-occuring Major Depressive Disorder and Borderline Personality Disorder - NCT05399498
- Psilocybin-assisted Psychotherapy for Treatment of Alcohol Use Disorder - NCT05421065
- ELE-101 Safety & Tolerability Study in Healthy Participants - NCT05434156
- A Dose-Finding Study of MM-120 for the Treatment of Anxiety Symptoms - NCT05407064
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Other News
- 💊 Can microdosing psychedelics improve your mental health? Here's what the science says - ABC News, 3 July 2022. Feat. Dr Vince Polito and Dr Stephen Bright.
- 🌈 The Never-Ending Psychedelic Trip of Michael Pollan - Rolling Stone, 3 July 2022. Pollan speaks about the new Netflix four-part docuseries on psychedelics.
- 🥽 Psychedelics and VR: Exploring New Horizons in Therapeutics and IP - Microdose, 29 June 2022. Feat. Australian medical technology company and friends, Enosis Therapeutics.
- 💜 MDMA and psilocybin are being trialed to enhance therapy for veterans - The New York Times, 24 June 2022
- 💚 VA Studying Psychedelics As Mental Health Treatment For Veterans - Forbes, 24 June 2022
- 💻 Can computers hallucinate? Someone interviews AI on the topic of psychedelics - Psychedelics Spotlight, 22 June 2022
- 💆♀️ Psilocybin-induced mystical experiences linked to lasting positive psychological effects - PsyPost, 12 June 2022
- 🗣 Psychedelics and MDMA can make a real difference to mental health, especially for extreme depression and PTSD. We should take this seriously. - Elon Musk tweets, 10 June 2022
- 🚺 Where Women Fit in the Science of Psychedelics - Dane Magazine, 8 June 2022
- 🧠 How psychedelic drugs might treat depression - BBC Future, 7 June 2022
- 🍄 New Study To Evaluate Psilocybin’s Therapeutic Potential On Autistic Adults - Neuroscience News, 4 June 2022
- 🚵♀️ Can you take the trip out of psychedelics and still treat depression? - NewScientist, 1 June 2022
- 📈 Psychedelics startups are on a long journey to consumer markets, but these 5 VCs are taking the ride - TechCrunch, 5 May 2022
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- 💊 Dr Sam Banister presented to a sold-out crowd on the 'Future of Drugs' during the Sydney Vivid Festival with Dr Margaret Ross and Prof Iain McGregor, 3 June 2022. Watch it here.
- 🧪The lab build at UNSW is complete and we are synthesizing psychedelic-inspired molecules in-house!
- 🥼 We were proud to have Psylo representing at the prestigious QUT Bridge Program for pharmaceutical development. Dr Jin Tan was invited as Bridge Fellow, and alumnus Dr Will Jorgensen as a program Mentor, 30 June 2022
- 🥐 Dr Sam Banister and Dr Dilara Bahceci presented to a full house on the Future of Psychedelics at the Commons in Melbourne, 1 July 2022. Thanks to Garry Williams for organizing the event!
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Psylo in the Media
- 🎧 "This is an interview with the great Samuel D. Banister..." - A remarkable introduction from Hamilton Morris to preface the episode on synthetic cannabinoid chemistry and designing new psychedelics. Now available on Youtube, 18 June 2022
Upcoming
- Dr Sam and Dr Dil will be presenting at the Splendour in the Grass Science Tent, on the benefits and risks of psychedelics and other drugs alongside an all-star host of scientists. Come say hi!
- Dilara spoke with Australian national treasure Dr Karl about the science of medicinal cannabis on his podcast, Shirtloads of Science. Coming out late July.
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