Stable, high-level biosynthesis of complex natural products requires precise control of heterologous pathway expression, yet transcriptional architectures optimized on plasmids often fail when transferred to the chromosome. Here, we present ePathIntegrate, a genome-centric pathway engineering strategy that leverages CRISPR-associated transposases (CASTs) to ...
The Redefine Study (COMP202) is testing COMP360 to see if it may reduce post-traumatic stress disorder (PTSD) symptoms when administered alongside monitoring and support from a trained study team. COMP360 is a lab-made form of the naturally occurring chemical compound psilocybin.
Efficacy, Safety, and Tolerability of two administrations of COMP360 in participants with treatment-resistant depression (TRD) This is a phase III, international, multi-centre, randomised, parallel group, fixed repeat dose, double-blind, controlled study. The study population will include participants aged ≥18 years with TRD. Overall, 568 participants are to...
Psilocybin, a naturally occurring tryptamine alkaloid found in over 200 species of fungi, has emerged as a focal point in the modern revival of psychedelic science. Once relegated to the margins of psychopharmacology due to its association with counterculture and strict legal restrictions, psilocybin is now undergoing a scientific renaissance. This transform...
Efficacy, Safety, and Tolerability of a single administration of COMP360 in participants with treatment-resistant depression (TRD) This is a phase III, international, multi-centre, randomised, parallel group, fixed single-dose, double-blind, placebo-controlled study. The study population will include participants aged ≥18 years with TRD. Overall, 255 partici...
Safety, Tolerability, pharmacokinetics and efficacy of a single administration of COMP360 in participants with recurrent Major Depressive Disorder. This is a phase II, multi-centre, randomised, double-blind, controlled study. The study population will include participants aged ≥18 years with recurrent Major Depressive Disorder (MDD) with up to four prior tre...
The Safety and Tolerability of COMP360 in Participants with Post-traumatic Stress Disorder The Safety and Tolerability of COMP360 administered under supportive conditions in participants with Post-traumatic Stress Disorder
Mental health disorders and associated economic impact continue to rise domestically and globally. In 2023, to expand treatment options for individuals suffering Treatment Resistant Depression (TRD), the Therapeutic Goods Administration (TGA) of Australia has permitted psychiatrist lead psilocybin-assisted psychotherapy. Psilocybin, a psychedelic tryptamine ...
Naturally occurring psychoactive compounds have been used for cultural and ethnomedical purposes for centuries. Several more such molecules continue to be chemically synthesized, exhibiting a wide range of potency, therapeutic, and hallucinogenic effects. Promising clinical data and a renewed interest in understanding the cellular mechanisms of action have i...
Efficacy and Safety of COMP360 Psilocybin therapy in Anorexia Nervosa: a Proof-of-concept Study This study aims to explore the efficacy and safety of COMP360 25 mg as compared to COMP360 1 mg (control condition) administered with psychological support in participants with Anorexia Nervosa
The recent relaxation of psychedelic drug regulations has prompted extensive clinical investigation into their potential use to treat diverse mental health conditions including anxiety, depression, post-traumatic stress, and substance-abuse disorders. Most clinical trials have relied on a small number of known molecules found in nature, such as psilocybin, o...
The Safety and Efficacy of Psilocybin as an Adjunctive Therapy in Participants with Treatment-Resistant Depression A recent open label study of the effects of psilocybin in participants with treatment-resistant depression (TRD) showed rapid significant decrease of depressive symptoms after treatment with psilocybin coupled with psychological support. Over 40...
The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression The Safety and Efficacy of Psilocybin in Participants with Treatment Resistant Depression - a dose-ranging study
The primary objective of this study is to assess the long-term efficacy of psilocybin with respect to use of new antidepressant treatment, hospitalisations for depression, suicidality, and depressive severity rated using the Montgomery and Asberg Depression Rating Scale (MADRS) over a total of 52 weeks (compared across the 1 mg, 10 mg and 25 mg psilocybin gr...
Therapeutic use of psilocybin has become a focus of recent international research, with preliminary data showing promise to address a range of treatment-resistant mental health conditions. However, use of psilocybin as a healing entheogen has a long history through traditional consumption of mushrooms from the genus Psilocybe. The forthcoming adoption of new...
It is well established that a wide range of drugs of abuse acutely boost the signaling of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis, where norepinephrine and epinephrine are major output molecules. This stimulatory effect is accompanied by such symptoms as elevated heart rate and blood pressure, more rapid breathing, in...
Metabolic regulation strategies have been developed to redirect metabolic fluxes to production pathways. However, it is difficult to screen out target genes that, when repressed, improve yield without affecting cell growth. Here, we report a strategy using a quorum-sensing system to control small RNA transcription, allowing cell-density-dependent repression ...
Abstract The psychotropic effects of Psilocybe “magic” mushrooms are caused by the l -tryptophan-derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other l -tryptophan-derived β-carbolines as their ...
Heterologous expression of multi-gene biosynthetic pathways in eukaryotic hosts is limited by highly regulated individual monocistrons. Dissimilar to prokaryotes, each eukaryotic gene is strictly controlled by its own regulatory elements, such as promoter and terminator. Consequently, parallel transcription can occur only when a group of genes is synchronous...
