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Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study

Lucas F. Borkel, Jaime Rojas-Hernández, Luis Alberto Henríquez-Hernández, Ángelo Santana Del Pino & Domingo J. Quintana-Hernández (2023) Set and setting predict psychopathology, wellbeing and meaningfulness of psychedelic experiences: a correlational study, Expert Review of Clinical Pharmacology, DOI: 10.1080/17512433.2023.2295997

Background: In psychedelic therapy, the importance of set and setting is a fundamental but under-researched assumption. The aim of this study is to correlate variables of set (psychedelic use motivation) and setting (psychedelic use location and type of companion) with psychopathology, wellbeing and personality variables.

Research design and methods: A sample of 1022 participants of the Spanish-speaking population was collected through an online survey. A novel instrument, the Psychedelic Use Scale (PUS), was developed to measure substance use variables of LSD, mescaline, psilocybin, DMT, 5-Meo-DMT, ketamine, Salvia divinorum, ibogaine and MDMA. Various personality, well-being and psychopathology instruments were implemented to measure outcome variables.

Results: Growth motivations, natural settings and presence of significant others predicted less psychopathology, greater wellbeing and meaningfulness of psychedelic experiences, whereas problematic motivations predicted greater psychopathology, lower wellbeing and did not predict meaningfulness of psychedelic experiences.

Conclusions: Based on these results, we suggest experimental hypotheses for future clinical trials and longitudinal studies with potential clinical implications.





Hofmann vs. Paracelsus: Do Psychedelics Defy the Basics of Toxicology?—A Systematic Review of the Main Ergolamines, Simple Tryptamines, and Phenylethylamines

Henríquez-Hernández, L. A., Rojas-Hernández, J., Quintana-Hernández, D. J., & Borkel, L. F. (2023). Hofmann vs. Paracelsus: do psychedelics defy the basics of toxicology?—a systematic review of the main ergolamines, simple tryptamines, and phenylethylamines. Toxics, 11(2), 148.

Psychedelics are experiencing a strong renaissance and will soon be incorporated into clinical practice. However, there is uncertainty about how much harm they can cause at what doses. This review aimed to collect information on the health-hazardous doses of psychedelic substances, to be aware of the risks to which patients may be subjected. We focused on ergolamines, simple tryptamines, and phenylethylamines. We reviewed articles published in major medical and scientific databases. Studies reporting toxic or lethal doses in humans and animals were included. We followed PRISMA criteria for revisions. We identified 3032 manuscripts for inclusion. Of these, 33 were ultimately useful and gave relevant information about effects associated with high psychedelics doses. Despite having different molecular structures and different mechanisms of action, psychedelics are effective at very low doses, are not addictive, and are harmful at extremely high doses. For LSD and psilocybin, no dose has been established above which the lives of users are endangered. In contrast, MDMA appears to be the most dangerous substance, although reports are biased by recreational missuses. It seems that it is not only the dose that makes the poison. In the case of psychedelics, the set and setting make the poison.

Mindfulness Prevents Depression and Psychopathology in Elderly People with Mild to Moderate Alzheimer’s Disease: A Randomized Clinical Trial

Quintana-Hernández, D. J., Rojas-Hernández, J., Santana-del Pino, A., Céspedes Suárez, C., Pellejero Silva, M., Miró-Barrachina, M. T., ... & Borkel, L. F. (2023). Mindfulness prevents depression and psychopathology in elderly people with mild to moderate Alzheimer’s disease: a randomized clinical trial. Journal of Alzheimer's Disease, (Preprint), 1-11.
DOI: 10.3233/JAD-220889

Background: This longitudinal study addressed whether mindfulness practice prevents psychological and behavioral symptoms, especially mood disorders, in Alzheimer’s disease (AD).

Objective: To assess the incidence of depression in the course of AD and to determine which non-pharmacological treatment (NPT) is most effective in preventing psychopathological symptoms.

Methods: We conducted a longitudinal, non-inferiority and equivalence randomized clinical trial, repeated-measures design, with a control group and three experimental treatments: mindfulness, cognitive stimulation, and relaxation. Each experimental group performed three weekly sessions for two years. The pharmacological treatment of all participants was donepezil (10 mg). Participants were patients with probable AD without diagnosed depression from the public neurology services of the Canary Health Service, Spain. Psychological evaluation was performed using the Geriatric Depression Scale (GDS), Hamilton Depression Rating Scale (HDRS), and Neuropsychiatric Inventory (NPI-Q). The statistical analysis included only patients who attended at least 75% of the sessions. A nonparametric, repeated-measures analysis was performed with Kruskal-Wallis H test and between-group differences with Mann-Whitney U test with Bonferroni correction (p < 0.008). Effect size was calculated with partial eta-squared.

Results: The results showed significant differences with large effect sizes (η2p>0.14) between mindfulness and the rest of the experimental groups as well as the control in the GDS, HDRS, and NPI-Q scales.

Conclusion: Compared to the other experimental groups, only mindfulness prevented the onset of depression and other psychopathologies in early-stage AD. Based on its effectiveness in maintaining cognitive functions and preventing psychopathology, we recommend mindfulness as the first-choice NPT for mild to moderate AD.

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