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Overview of clinical trials
As of October 2023, 257 trials have been registered on clinicaltrials.gov for classic psychedelics (5-HT2A agonists), MDMA and related compounds. The number of trials for each intervention are shown below (total count, percentage):
- Psilocybin (131, 51%)
- MDMA (59, 23%)
- LSD (27, 11%)
- DMT (19, 7%)
- 5-MeO-DMT (8, 3%)
- Ibogaine (4, 2%)
- Salvinorin A (4, 2%)
- Ayahuasca (2, 1%)
- 2C-B (1, 0.4%)
- Mescaline (1, 0.4%)
Phases
Almost all of these trials are evenly split between Phase 1 or Phase 2 studies, and there are six studies (2%) registered as Phase 3, the final phase before seeking regulatory approval. This time last year there were only two Phase 3 trials.
Status
Most of these registered trials have been completed (89, 35%), with the next largest proportion currently recruiting (69, 27%), followed by studies that are not yet recruiting (45, 18%) and active but not recruiting (27, 11%).
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As the number of trials increases, so do the potential conditions for which these substances may be beneficial.
Like last year, most trials were for "basic science" studies, which are conducted with healthy participants to try and understand how these drugs work (not included in the graph above). However, last year trials for PTSD were the most common. This year, there are more trials for depression than any other condition. A breakdown of the number of trials for each condition can be found below and the graph above shows the distribution of the major compounds being investigated for each condition.
- Basic science (84, 33%)
- Depression (50, 19%)
- PTSD (34, 13%)
- Substance use disorder (29, 11%)
- Demoralization or health-related psychological distress (14, 5%)
- Chronic pain (12, 5%)
- Anxiety (9, 4%)
- Eating disorders (6, 2%)
Conditions not shown on the graph include:
- ADHD
- Autism
- Bipolar II Disorder
- Body Dysmorphic Disorders
- Borderline Personality Disorder
- Burnout
- Diabetes Insipidus
- Fragile X Syndrome
- Functional Neurological Disorder
- Lyme Disease
- Obsessive-compulsive Disorder
- Schizophrenia
- Stroke
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Psychedelic Clinical Research
- SSRI Antidepressant Increases Neuroplasticity Over Weeks | The study reveals a time-dependent effect of the SSRI antidepressant escitalopram on cerebral synaptic plasticity over 3-5 weeks; a randomized controlled trial involving healthy participants (N=32). It provides the first in vivo evidence supporting neuroplasticity as a mechanism of action for SSRIs in humans and offers a plausible biological explanation for the delayed treatment response commonly observed in patients treated with SSRIs. Molecular Psychiatry
- Neurocognitive Mechanisms of Psychedelics | This study demonstrates that repeated ayahuasca use can lead to structural differentiation in certain cortical areas, and such changes are related to dysregulation of 5-HT2A gene expression and possibly, to the broader effects of psychedelics at a molecular level; neuroimaging data from 24 members of an ayahuasca-using church vs case-matched controls. Frontiers in Neuroscience
- Understanding Psilocybin's Effects and Impact on Blood Flow | The study reveals a connection between psilocybin-induced changes in brain blood flow, individual baseline characteristics, and the subjective experiences during a psychedelic state; data from a clinical trial with healthy participants (N=70). Scientific Reports
- Ketamine vs Placebo for depression when masked by surgical anesthesia | A single dose of intravenous ketamine administered during surgical anesthesia did not significantly reduce the severity of depressive symptoms compared to a placebo in adults with major depressive disorder; randomized, placebo-controlled trial (N=40). Nature Mental Health
- Extended DMT Administration: Effects and Safety | The study explored a novel method of administering DMT by combining a bolus injection with a 30-min infusion. The method was tolerable and participants experienced extended subjective effects, low anxiety ratings, and heart rate habituation within 15 minutes; a within-subjects, placebo-controlled study of healthy volunteers (N=11). Journal of Psychopharmacology
- Predicting the Intensity of Psychedelic Experiences | The study identified higher doses of psilocybin as a strong predictor of intense mystical and challenging experiences, as well as younger age and neurotic personality traits being associated with challenging experiences at higher doses; a post-hoc analysis of a Phase 1, placebo-controlled, between-groups clinical trial of healthy volunteers (N=89). Neuropsychiatric Disease and Treatment
- LSD Use Trends Among Adults with Depression | The study found a disproportionate increase in LSD use among US adults with major depression from 2008 to 2019, particularly among younger adults and those with lower incomes. JAMA Psychiatry
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Psychedelic Preclinical Research
- Non-Hallucinogenic 5-HT2A Agonist Shows Anti-Depressant Effects in mice | The non-hallucinogenic 5-HT2A agonist Lisuride was shown to produce anti-depressant-like effects as reduced immobility times in tail suspension and promoted a preference for sucrose without inducing head-twitch response in mice. Frontiers in Molecular Biosciences
- Microdosing Psilocybin Boosts Stress Resilience in Rats | The study validates a psilocybin microdosing regimen in rats, and reports that repeated low doses of psilocybin increased resilience to stress, reduced compulsive self-grooming behaviors, and enhanced synaptic density and 5-HT7 receptor expression in the paraventricular nucleus of the thalamus in rats, without manifesting signs of anhedonia, anxiety, or altered locomotor activity. Molecular Psychiatry
- Music Alleviates Stress-Induced Depression in Mice | Mice were subjected to chronic unpredictable mild stress (CUMS) during the day and exposed to music at night. Exposure to music significantly prevents stress-induced depression and anxiety-like behaviors in mice. Music is a core component of psychedelic-assisted therapy and may be playing a key therapeutic role. Translational Psychiatry
- Anti-estrogenic and Serotonergic Compounds for Breast Cancer | The synthesized triarylethylene analogs showed promising dual anti-estrogenic and serotonergic activity with potential applications in breast cancer treatment and menopausal symptom relief. Drug Development Research
- Serotonin 2C receptors are also important in head-twitch response | Activation of 5-HT2CR produces a comparable degree of head-twitch responses, with divergent signaling and enhanced neurotoxic properties at a higher dose. Both serotonin 2A and 2C receptors play roles in mediating psychedelic head-twitch responses in male mice. Psychopharmacology (Berl)
- Antidepressant Effects of Psychedelics in Mice | 5-HT2A is implicated in the antidepressant but not the anxiolytic effects of serotonergic psychedelics in mice. Acute psilocin treatment was followed by sustained antidepressant effects for at least three weeks in mice. Naunyn-Schmiedeberg's Archives of Pharmacology
- Arketamine Shows Prophylactic Antidepressant Effects | The study reveals that arketamine, but not DOI or lisuride, exhibits significant prophylactic effects against depression-like behaviors in mouse models. Pharmacology Biochemistry and Behavior
- Antidepressant Potential of Psilocybin And LSD In Rats | Psilocybin produced acute antidepressant-like effects in a rat model of depression but the effects were not sustained at 4 weeks. LSD did not elicit any antidepressant effects in this model. Journal of Psychopharmacology
- Atractylenolide I Eases Depression-like Behavior in Mice | Atractylenolide I (ATR) is a bioactive compound in Atractylodes macrocephala, a traditional medicinal plant utilized in Asian countries. This study reveals that ATR improves depressive-like behaviors in mice by modulating neurotransmitter balance via the 5-HT2A receptor. Phytotherapy Research
- The effects of 5-HT2A Drugs on Visual Attention in Mice | The 5-HT2A receptor agonists, psilocybin and TCB-2, as well as the 2A antagonist, M100907, all impaired performance in a mouse visual attention test, but the impairments might be attributed to drug-induced locomotor changes rather than alterations in visual attention. Psychopharmacology
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Psychedelic Reviews and Commentaries
- Functional imaging studies of acute administration of classic psychedelics, ketamine, and MDMA: Methodological limitations and convergent results | The systematic review analyzed 91 fMRI studies on psychedelics' acute effects, finding consistent brain connectivity alterations with psilocybin, LSD, and ketamine, and highlights methodological challenges requiring improved practices for more accurate findings.
Neuroscience & Biobehavioral Reviews
- Cardiovascular safety of psychedelic medicine: current status and future directions | The review assesses the cardiovascular safety of various psychedelics based on existing experimental and clinical data, indicating a need for further research to elucidate the cardiovascular implications, especially in long-term therapies and in individuals with cardiovascular disease. Pharmacol Rep
- Novel treatments for anorexia nervosa: Insights from neuroplasticity research | The review explores neurobiological changes in Anorexia Nervosa, proposing novel psychopharmacological and psychotherapeutic treatments based on neuroplasticity insights, including psychedelics, to improve treatment outcomes. European Eating Disorders Review
- μ-opioid receptor agonists and psychedelics: pharmacological opportunities and challenges | The review explores the potential of psychedelic 5-HT2AR agonists for treating Opioid Use Disorder, highlighting the cellular and circuitry crosstalk between MOR and 5-HT2AR, and emphasizes the need for further analysis of non-hallucinogenic 5-HT2AR agonists or positive allosteric modulators. Frontiers in Pharmacology.
- Preclinical models of treatment-resistant depression: challenges and perspectives | The review discusses the challenges in diagnosing and treating treatment-resistant depression, and reviews research on novel therapies including psychedelics, indicating the importance of further research using relevant animal models. Pharmacological Reports.
- Promising new pharmacological targets for depression: The search for efficacy | The review discusses the limitations of current serotonergic drugs for MDD and explores the potential of novel targets, including 5-HT2A, for developing more effective antidepressant drugs. Drug Discovery Today.
- Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions | This review outlines the potential association between the host microbiota and neuropsychiatric disorders, emphasizing the need for further research on microbiota-targeted interventions and underlying mechanisms. Molecular Psychiatry.
- Psychedelics and Psychotherapy: Is the Whole Greater than the Sum of its Parts? | The article discusses the potential efficacy and safety of psychedelics in conjunction with psychotherapy, and underscores the need for factorial design trials to further evaluate these aspects for developing safe and cost-effective treatments. Clinical Pharmacology & Therapeutics.
- Intellectual Property of Psychedelics for Addiction Treatment: Enabling Access and Protecting Innovation Opportunities Through Preserving the Public Domain | The perspective highlights the attempts to monopolize psychedelic compounds via patents, and emphasizes the importance of mitigating exclusionary patent practices to ensure access to psychedelic therapeutics for addiction treatment. Journal of Studies on Alcohol and Drugs
- Does MDMA have treatment potential in sexual dysfunction? A systematic review of outcomes across the female and male sexual response cycles Get access Arrow | This systematic review found that MDMA increases sexual desire and intensifies orgasm, with mixed evidence on its impact on sexual arousal, and potentially impairs erectile and ejaculatory functions in men. Sexual Medicine Reviews
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Psychedelic Clinical Trials Update
A round-up of the latest registered clinical trials investigating psychedelics:
- Psilocybin | Cocaine Use Disorder | Safety Profile of Psilocybin for Cocaine Use Disorder - NCT06102434
- Psilocybin + Buprenorphine | Opioid Use Disorder | Outpatient Buprenorphine Induction With Psilocybin for Opioid Use Disorder (BIPOD-Out) - NCT06067737
- Psilocybin, MDMA, Methylphenidate | Pro-social Behavior | Does Serotonin System Stimulation Increase Pro-social Behavior? - A Comparative Pharmacological Neuroscientific Study in Healthy Humans - NCT06081179
- Psilocybin | Neuroimaging, Depression | A Randomized Neuroimaging Trial of Psilocybin in Depression (EMBRACE) - NCT06072898
- DMT | Alcohol Use Disorder | The Potential Therapeutic Effects of Psychedelic, N, N-dimethyltryptamine (DMT), on Alcohol Use Disorder (AUD) - NCT06070649
- DMT | Depression | Safety, Tolerability and Antidepressant Effects of DMT in Patients With Depression - NCT06094907
- MDMA | Fibromyalgia (pain) | MDMA-assisted Therapy for Fibromyalgia - NCT06066853
- MDMA | PTSD in Military Veterans and First Responders | MDMA-assisted therapy for Post-Traumatic Stress Disorder in Military Veterans and First Responders - ACTRN12623000971639
- Ketamine-assisted Therapy | Demoralization | Ketamine-assisted Therapy for Patients With Pancreatic Ductal Adenocarcinoma - NCT06077487
- Ketamine | Multiple Sclerosis-related Fatigue | Ketamine for MS Fatigue - NCT06064162
- Ketamine | Severe Traumatic Brain Injury | Ketamine in Severe Traumatic Brain Injury - NCT06062628
- Ketamine | Depression and Alcohol Use Disorder | Ketamine for Combined Depression and Alcohol Use Disorder (KeDA) - NCT06090422
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Psylo wins gold: Dr Will Jorgensen, Psylo's Director of Medicinal Chemist, took first place in the Hello Tomorrow APAC challenge in Singapore this month. Read coverage of this story in Yahoo Finance.
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SLINGSHOT Singapore: Will's win at Hello Tomorrow APAC secured Psylo a sponsored trip back to Singapore to present at SLINGSHOT 2023.
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SXSW: The Psylo team had a great time at SXSW Sydney. Josh spoke on a panel about ‘Psychedelics and the Future of Mental Health Treatments’ with Agnieszka Sekula from Enosis and Dr Adam Bayes from Black Dog Institute, and Sam presented at the session, “Reimagined Futures” alongside Hon Weng Chong from Cortical Labs.
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Dr Dilara Bahceci, Psylo Head of Communications, is an author on a recent publication that reveals why ketamine is still inaccessible to many with severe depression as a case study to highlight the systemic barriers that are preventing access to affordable treatments. Learn more via The Guardian, UNSW News, ABC news or the original article.
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Inspiring the next generation: Sam presented at the Innovative Leaders Speaker Series, hosted by Macquarie University’s Global Leadership Program, 17 October.
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First Psylo Inc team lunch in Boulder, Colorado.
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- Biotechnology Start-Up Psylo Wins Hello Tomorrow APAC Deep Tech Competition in Singapore - Yahoo Finance, 31 October
- Phil Morle on everything VC Main Sequence Ventures is doing at SXSW (and some other events that caught his eye) - Startup daily, 12 October 2023
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Sam and Dilara will be visiting Australia in November.
If you'd like to meet up, please reach out!
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