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Journal articlePalmisano VF, Agnorelli C, Fagiolini A, et al., 2024,
Membrane Permeation of Psychedelic Tryptamines by Dynamic Simulations
, BIOCHEMISTRY, Vol: 63, Pages: 419-428, ISSN: 0006-2960 -
Journal articleBarba T, Kettner H, Radu C, et al., 2024,
Psychedelics and sexual functioning: a mixed-methods study
, Scientific Reports, Vol: 14, ISSN: 2045-2322Do psychedelics affect sexual functioning postacutely? Anecdotal and qualitative evidence suggests they do, but this has never been formally tested. While sexual functioning and satisfaction are generally regarded as an important aspect of human wellbeing, sexual dysfunction is a common symptom of mental health disorders. It is also a common side effect of selective serotonin reuptake inhibitors (SSRIs), a first line treatment for depression. The aim of the present paper was to investigate the post-acute effects of psychedelics on self-reported sexual functioning, combining data from two independent studies, one large and naturalistic and the other a smaller but controlled clinical trial. Naturalistic use of psychedelics was associated with improvements in several facets of sexual functioning and satisfaction, including improved pleasure and communication during sex, satisfaction with one’s partner and physical appearance. Convergent results were found in a controlled trial of psilocybin therapy versus an SSRI, escitalopram, for depression. In this trial, patients treated with psilocybin reported positive changes in sexual functioning after treatment, while patients treated with escitalopram did not. Despite focusing on different populations and settings, this is the first research study to quantitively investigate the effects of psychedelics on sexual functioning. Results imply a potential positive effect on post-acute sexual functioning and highlight the need for more research on this.
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Journal articleTimmermann Slater CB, Zeifman R, Erritzoe D, et al., 2024,
Effects of DMT on mental health outcomes in healthy volunteers
, Scientific Reports, Vol: 14, ISSN: 2045-2322Psilocybin, a serotonergic psychedelic, is being increasingly researched in clinical studies for the treatment of psychiatric disorders. The relatively lengthy duration of oral psilocybin’s acute effects (4–6 h) may have pragmatic and cost-effectiveness limitations. Here, we explored the effects of intravenous (IV) N,N-Dimethyltryptamine (DMT), a closely related, but faster-acting psychedelic intervention, on mental health outcomes in healthy volunteers. Data is reported from two separate analyses: (1) A comparison of mental health-related variables 1 week after 7, 14, 18, and 20 mg of IV DMT versus IV saline placebo (n = 13) and, (2) A prospective dataset assessing effects before versus 2 weeks after 20 mg of IV DMT (n = 17). Mental health outcomes included measures of depression severity (QIDS-SR16), trait anxiety (STAI-T), Neuroticism (NEO-FFI), wellbeing (WHO-5), meaning in life (MLQ), optimism (LOT-R), and gratitude (GQ-6). In both the prospective and placebo-controlled datasets, significant improvements in scores of depression were found 1–2 weeks after DMT administration. Significant reductions in trait Neuroticism were only found for the placebo-controlled sample. Finally, changes in depression and trait anxiety correlated with acute peak experiences (assessed via ‘Oceanic Boundlessness’). While the use of two separate cohorts in pooled analysis limits the generalizability of these correlational findings, these results suggest that DMT may reduce depressive symptomatology by inducing peak experiences. The short half-life of IV DMT and its potential for flexible dosing via controlled infusions makes it an appealing candidate for psychedelic medicine. Further research in clinical samples is needed to corroborate the therapeutic potential of DMT.
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Journal articleMediano PAM, Rosas FE, Timmermann C, et al., 2024,
Effects of external stimulation on psychedelic state neurodynamics
, ACS Chemical Neuroscience, Vol: 15, Pages: 462-471, ISSN: 1948-7193Recent findings have shown that psychedelics reliably enhance brain entropy (understood as neural signal diversity), and this effect has been associated with both acute and long-term psychological outcomes, such as personality changes. These findings are particularly intriguing, given that a decrease of brain entropy is a robust indicator of loss of consciousness (e.g., from wakefulness to sleep). However, little is known about how context impacts the entropy-enhancing effect of psychedelics, which carries important implications for how it can be exploited in, for example, psychedelic psychotherapy. This article investigates how brain entropy is modulated by stimulus manipulation during a psychedelic experience by studying participants under the effects of lysergic acid diethylamide (LSD) or placebo, either with gross state changes (eyes closed vs open) or different stimuli (no stimulus vs music vs video). Results show that while brain entropy increases with LSD under all of the experimental conditions, it exhibits the largest changes when subjects have their eyes closed. Furthermore, brain entropy changes are consistently associated with subjective ratings of the psychedelic experience, but this relationship is disrupted when participants are viewing a video─potentially due to a “competition” between external stimuli and endogenous LSD-induced imagery. Taken together, our findings provide strong quantitative evidence of the role of context in modulating neural dynamics during a psychedelic experience, underlining the importance of performing psychedelic psychotherapy in a suitable environment.
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Journal articleMurphy RJ, Godfrey K, Shaw AD, et al., 2024,
Modulation of long-term potentiation following microdoses of LSD captured by thalamo-cortical modelling in a randomised, controlled trial
, BMC NEUROSCIENCE, Vol: 25, ISSN: 1471-2202 -
Journal articleErritzoe D, Timmermann C, Godfrey K, et al., 2024,
Exploring mechanisms of psychedelic action using neuroimaging
, Nature Mental Health, Vol: 2, Pages: 141-153Modern psychedelic research and clinical development is at a crucial inflection point, with great potential for the treatment of many mental illnesses demonstrated but significant questions that remain unresolved. Neuroimaging has been pivotal in the modern era of psychedelic research, providing crucial insights into the acute effects of these drugs that revealed translational, clinical potential. Here we review this evidence from functional magnetic resonance imaging, positron emission tomography and magnetoencephalography/electroencephalography studies and describe how these findings inform computational models of both the acute action of psychedelics and their longer-term therapeutic effects. This approach, based on multi-modal neuroimaging, provides a solid evidence base for these therapies as they move forwards, as well as a fuller understanding of the powerful effects of psychedelics on the phenomenology of human consciousness.
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Journal articleBarbut Siva J, Barba T, Kettner H, et al., 2024,
Interactions between classic psychedelics and serotonergic antidepressants: Effects on the acute psychedelic subjective experience, well-being and depressive symptoms from a prospective survey study
, JOURNAL OF PSYCHOPHARMACOLOGY, Vol: 38, Pages: 145-155, ISSN: 0269-8811 -
Journal articleSzigeti B, Weiss B, Rosas FE, et al., 2024,
Assessing expectancy and suggestibility in a trial of escitalopram v. psilocybin for depression
, PSYCHOLOGICAL MEDICINE, ISSN: 0033-2917 -
Journal articleJames E, Erritzoe D, Benway T, et al., 2024,
Safety, tolerability, pharmacodynamic and wellbeing effects of SPL026 (dimethyltryptamine fumarate) in healthy participants: a randomized, placebo-controlled phase 1 trial
, FRONTIERS IN PSYCHIATRY, Vol: 14, ISSN: 1664-0640 -
Journal articleWeiss B, Ginige I, Shannon L, et al., 2024,
Personality change in a trial of psilocybin therapy vs escitalopram treatment for depression
, Psychological Medicine, Vol: 54, Pages: 178-192, ISSN: 0033-2917Background:Psilocybin Therapy (PT) is being increasingly studied as a psychiatric intervention. Personality relates to mental health and can be used to probe the nature of PT's therapeutic action.Methods:In a phase 2, double-blind, randomized, active comparator controlled trial involving patients with moderate-to-severe major depressive disorder, we compared psilocybin with escitalopram, over a core 6-week trial period. Five-Factor model personality domains, Big Five Aspect Scale Openness aspects, Absorption, and Impulsivity were measured at Baseline, Week 6, and Month 6 follow-up.Results:PT was associated with decreases in neuroticism (B = −0.63), introversion (B = −0.38), disagreeableness (B = −0.47), impulsivity (B = −0.40), and increases in absorption (B = 0.32), conscientiousness (B = 0.30), and openness (B = 0.23) at week 6, with neuroticism (B = −0.47) and disagreeableness (B = −0.41) remaining decreased at month 6. Escitalopram Treatment (ET) was associated with decreases in neuroticism (B = −0.38), disagreeableness (B = −0.26), impulsivity (B = −0.35), and increases in openness (B = 0.28) at week 6, with neuroticism (B = −0.46) remaining decreased at month 6. No significant between-condition differences were observed.Conclusions:Personality changes across both conditions were in a direction consistent with improved mental health. With the possible exception of trait absorption, there were no compelling between-condition differences warranting conclusions regarding a selective action of PT (v. ET) on personality; however, post-ET changes in personality were significantly moderated by pre-trial positive expectancy for escitalopram, whereas expectancy did not moderate response to PT.
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