Science in Sixty Seconds
An Update on Psychedelic Clinical Trials
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The number of clinical trials investigating psychedelics has been increasing, with 27% of trials registered since 2004 being registered in 2022. As of October 2022, there were 192 studies registered on clinicaltrials.gov and more than half of all registered trials use psilocybin as the intervention. The psychedelics interventions that are being explored can be categorized as (in order of prevalence):
- Psilocybin
- MDMA*
- LSD
- Multiple psychedelics (e.g. LSD vs psilocybin or psilocybin + MDMA)
- Proprietary products (novel chemical entities or novel formulations)
- DMT
- Salvinorin A
- Ibogaine
- Harmine
- Mescaline
- Ayahuasca
Almost all of the trials are registered as an equal split between Phase 1 and Phase 2 studies, with only two studies registered in the final phase before registration, phase 3.
*MDMA is not a "classic psychedelic" but does activate the serotonin 5-HT2A receptor and has similar therapeutic uses.
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With increasing trials, the potential therapeutic indications are also expanding. Above is a graph showing the top conditions for which the therapeutic potential of psilocybin, MDMA and LSD are being investigated.
The majority of all the registered clinical trials (36%) are "basic science" studies that are conducted with healthy participants to try and understand how these drugs work (not included in the graph above). For efficacy trials, which explore therapeutic potential, different psychedelics are being investigated for different indications.
For example, most of the trials registered with MDMA as the intervention are for post-traumatic disorder (PTSD), but also include trials in people with anxiety disorders, substance use disorders (formerly referred to as addictions), eating disorders and for management of demoralization (psychological distress associated with a life-threatening illness).
Overall, there are more studies registered for psilocybin and across more conditions, including depression, substance use disorders (alcohol, opioid, nicotine, stimulants), demoralization, anxiety, eating disorders, headache disorders and obsessive-compulsive disorders (OCD).
Conditions not included in the graph with fewer trials include:
- Fibromyalgia
- Burnout
- Pain
- Parkinson Disease
- ADHD
- Bipolar II Disorder
- Body Dysmorphic Disorders
- Borderline Personality Disorder
- Diabetes
- Lyme Disease
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RESEARCH UPDATES
Psychedelic Clinical Research
- 🌈 Low doses of LSD increased reward processing in a small feasibility study (n=18) | This may have important implications for the treatment of depressive disorders – Neuropharmacology
- 🍄💊 A Bayesian Reanalysis of a Trial of Psilocybin Versus Escitalopram for Depression | This reanalysis (n=59) provides a more precise and nuanced interpretation that psilocybin did indeed outperform escitalopram in this trial, but not to an extent that was clinically meaningful and psilocybin is almost certainly noninferior to escitalopram.- Psychedelic Medicine.
- 👨🏽🤝👨🏼 MDMA-assisted psychotherapy for PTSD: Inclusion of transgender and gender diverse people - Front Psychiatry
- ⚡ Promising signal that MDMA-assisted therapy is associated with a reduction in chronic pain among people with post-traumatic stress disorder | Promising but not definitive preliminary data from a small subset of participants from the MAPS phase 2 studies (n=32) - Front Psychiatry.
- 🗣 Better understanding the process and outcomes of MDMA-assisted therapy for anxiety associated with life-threatening illness | A qualitative analysis of interviews conducted with a subset of adult participants (n=10) following the MAPS trial who described in detail their experiences from before, during and after the trial - Front Psychiatry.
- 📉 [Preprint] Serotonergic antidepressant use is associated with weaker psilocybin effects | Online survey of individuals with use of psilocybin with an antidepressant and/or within two years of discontinuing an antidepressant (n=595). Serotonergic antidepressants appear to weaken psilocybin’s effects relative to a non-serotonergic antidepressant. This dampening effect on psilocybin effects may last as long as 3 months following antidepressant discontinuation - PsyArXiv Preprints.
- 🧠 Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape | Combining fMRI, diffusion MRI, PET and network control theory, authors suggest that psychedelics flatten the brain’s energy landscape (a flatter energy landscape corresponds to lower barriers to transition between different states of brain activity) and is likely due to 5-HT2A activation- Nat Commun.
- 🔠[Preprint] Psilocybin Therapy for Treatment Resistant Depression: Prediction of Clinical Outcome by Natural Language Processing | Analysis of language from the post-dosing psychological support session (valence and arousal) combined with the Emotional Breakthrough Index was able to predict treatment outcome (as measured by MADRS scores at 6 weeks) with 85-88% accuracy - PsyArXiv Preprints.
- 🤏 [Preprint] Evidence for tolerance in psychedelic microdosing from the self-blinding microdose trial | This study found that with each microdose taken, participants were less likely to distinguish placebo from microdose, and suggest this effect indicates that tolerance to microdosing may develop - PsyArXiv Preprints.
Psychedelic Preclinical Research
- 🌵 A novel analogue of mescaline detected in Australia | N,N-Diformylmescaline, which can act as a prodrug of mescaline, was detected in two unrelated seizures in Queensland - Drug Test Anal
- 🧪 A new series of arylpiperazines characterised as serotoninergic ligands | Molecules containing a 5-norbornene-2-carboxamide nucleus, were synthesised and their affinities and functional activity to the 5-HT1A, 5-HT2A, 5-HT2C and dopaminergic (D2) receptors were evaluated. - Molecules
- 💊 Will combining 5-HT2A agonists with opioids increase their abuse liability? | Serotonin 2A subtype receptor agonists enhance some effects of opioids (e.g. nociceptive), but their impact on adverse effects is unknown. In this study, 5-HT2A receptor agonists, DOM and quipazine, did not enhance the reinforcing effects of opioids in rhesus monkeys and are unlikely to enhance the abuse potential of opioids - J Pharmacol Exp Ther.
Psychedelic Research Reviews
- 🧠 The neural basis of psychedelic action - Nature Neuroscience | This provides a fantastic overview of current understanding of how psychedelics elicits their actions, from receptors to neurons, circuits and networks.
- 🧠 Default Mode Network Modulation by Psychedelics: A Systematic Review - Int J Neuropsychopharmacol
- 🧪 Methods of Lysergic Acid Synthesis—The Key Ergot Alkaloid Molecules
- 🐭 Animal Behavior in Psychedelic Research - Pharmacol Rev.
- 🌱 Ibogaine/Noribogaine in the Treatment of Substance Use Disorders: a Systematic Review of the Current Literature - Curr Neuropharmacol
- 👩🦳 The Safety and Efficacy of Psychedelic-Assisted Therapies for Older Adults: Knowns and Unknowns - Am J Geriatr Psychiatry
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Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- Standardized Natural Psilocybin-assisted Psychotherapy for Tapering of Opioid Medication - NCT05585229
- Effect of SSRIs on Response to Psilocybin Therapy - NCT05594667
- MDMA-assisted Therapy for Adjustment Disorder (AD) in Dyads of Patients With Cancer and a Concerned Significant Other - NCT05584826
- Safety and Tolerability of Psilocybin in Post-Traumatic Stress Disorder - NCT05562973
- Consciousness and Psilocybin Effects on Well-Being: Pilot Phase (CoPE Pilot) - NCT05592379
- Psilocybin-assisted Interpersonal and Social Rhythm Therapy for Depression - NCT05581797
- The Role of Personal Experience for the Therapeutic Attitude in the Context of Substance-assisted Therapy Training - NCT05570708
- Single and Repeat Doses of DMT in Healthy Subjects - NCT05559931
- Clinical Study of DMT in Healthy Adults - NCT05573568
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Other News
- 🚭 NIH-funded psychedelic trial will study whether hallucinogen can help smokers quit - NBC News, 26 October 2022
- 🌈 Why scientists want to create psychedelics that give better trips - National Geographic, 20 October 2022
- 🧠 How do psychedelics work? This brain region may explain their effects - PBS NOVA, 20 October 2022
- 📺 [watch] Can Psychedelics Cure? - PBS NOVA, Season 49 Episode 15 | 53m 47s
- 🤝 To Standardize Psychedelic Therapy, A New Organization Launches - Forbes, 11 October 2022
- 🍄 The magic mushroom experience: Taking psilocybin for science - Monash Lens, 10 October 2022
- 🍄 Psilocybin: a revolution in psychedelic medicines in the US? - BMJ, 06 October 2022
- ⚕ Transforming Psychedelics into Approved Medicines - Genetic Engineering and Biotechnology News, 06 October 2022
- 📈 Interest Grows in Treatment of Mood Disorders by Classic Psychedelics - Psychiatric Times, 05 October 2022
- 🌈 These LSD-based drugs seem to help mice with anxiety and depression - without the trip - NPR Shots, 05 October 2022
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Psylo announces oversubscribed seed round! Read about it in the AFR. |
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Josh Ismin (CEO) and Sam Banister (CSO) gave a highly engaging presentation to a full crowd at the Purpose Conference main stage on the potential of novel medications inspired by psychedelic mushrooms.
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Josh, Sam and Dilara presented at the AusBiotech. conference in Perth, 26th-28th of October. Photographed here with Dr Chris Bladen (Zymedyne).
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