Extended difficulties following the use of psychedelic drugs: A mixed methods study.

Long-term adverse experiences following psychedelic use can persist for weeks, months, or even years, and are relatively unexplored in psychedelic research. Our convergent mixed-method study gained quantitative and qualitative data from 608 participants who reported extended difficulties following psychedelic experiences. Data was gathered on the context of use, the nature and duration of the challenges they experienced (including a written description of these), plus a range of possible risk factors and perceived causes. The most common forms of extended difficulty were feelings of anxiety and fear, existential struggle, social disconnection, depersonalization and derealization. For approximately one-third of the participants, problems persisted for over a year, and for a sixth, they endured for more than three years. It was found that a shorter duration of difficulties was predicted by knowledge of dose, drug type and lower levels of difficulty reported during the psychoactive experience, while a narrower range of difficulties was predicted by taking the drug in a guided setting. Implications for psychedelic harm reduction are discussed.

Psychedelic therapy in the treatment of addiction: the past, present and future.

Psychedelic therapy has witnessed a resurgence in interest in the last decade from the scientific and medical communities with evidence now building for its safety and efficacy in treating a range of psychiatric disorders including addiction. In this review we will chart the research investigating the role of these interventions in individuals with addiction beginning with an overview of the current socioeconomic impact of addiction, treatment options, and outcomes. We will start by examining historical studies from the first psychedelic research era of the mid-late 1900s, followed by an overview of the available real-world evidence gathered from naturalistic, observational, and survey-based studies. We will then cover modern-day clinical trials of psychedelic therapies in addiction from first-in-human to phase II clinical trials. Finally, we will provide an overview of the different translational human neuropsychopharmacology techniques, including functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), that can be applied to foster a mechanistic understanding of therapeutic mechanisms. A more granular understanding of the treatment effects of psychedelics will facilitate the optimisation of the psychedelic therapy drug development landscape, and ultimately improve patient outcomes.

Heterogeneity in major depressive disorder: The need for biomarker-based personalized treatments.

Major Depressive Disorder (MDD) or depression is a pathological mental condition affecting millions of people worldwide. Identification of objective biological markers of depression can provide for a better diagnostic and intervention criteria; ultimately aiding to reduce its socioeconomic health burden. This review provides a comprehensive insight into the major biomarker candidates that have been implicated in depression neurobiology. The key biomarker categories are covered across all the "omics" levels. At the epigenomic level, DNA-methylation, non-coding RNA and histone-modifications have been discussed in relation to depression. The proteomics system shows great promise with inflammatory markers as well as growth factors and neurobiological alterations within the endocannabinoid system. Characteristic lipids implicated in depression together with the endocrine system are reviewed under the metabolomics section. The chapter also examines the novel biomarkers for depression that have been proposed by studies in the microbiome. Depression affects individuals differentially and explicit biomarkers identified by robust research criteria may pave the way for better diagnosis, intervention, treatment, and prediction of treatment response.