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Journal articleAngyus M, Osborn S, Haijen E, et al., 2024,
Validation of the imperial psychedelic predictor scale
, PSYCHOLOGICAL MEDICINE, ISSN: 0033-2917 -
Journal articleErritzoe D, Barba T, Greenway KT, et al., 2024,
Effect of psilocybin versus escitalopram on depression symptom severity in patients with moderate-to-severe major depressive disorder: observational 6-month follow-up of a phase 2, double-blind, randomised, controlled trial
, EClinicalMedicine, Vol: 76, ISSN: 2589-5370Background Psilocybin therapy (PT) produces rapid and persistent antidepressant effects in major depressive disorder (MDD). However, the long-term effects of PT have never been compared with gold-standard treatments for MDD such as pharmacotherapy or psychotherapy alone or in combination. Methods This is a 6-month follow-up study of a phase 2, double-blind, randomised, controlled trial involving patients with moderate-to-severe MDD. Participants were recruited from a hospital in the UK. Inclusion criteria: major depressive disorder (DSM-IV), moderate to severe depression (HAM-D ≥ 17), no MRI or SSRI contraindications, confirmed diagnosis by a GP or mental healthcare professional, aged 18-80, both genders, and competent in English. Patients were randomly assigned (1:1) to receive either two 25 mg doses of the psychedelic drug psilocybin administered orally combined with psychological support (‘psilocybin therapy’ or PT) and book-ended by further support or a 6-week course of the selective serotonin reuptake inhibitor (SSRI) escitalopram (administered daily at 10 mg for three weeks and 20 mg for the subsequent three weeks) plus matched psychological support (‘escitalopram treatment’ or ET). The primary outcome measure was change from baseline in the score on the 16-item Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR-16) at week 6, which has been reported previously. Herein, we present results at the 6-month follow-up time point. Measures of social functioning, connectedness, and meaning in life constituted the study’s secondary outcomes during follow-up. Safety in the follow-up period was not assessed. This trial is registered at ClinicalTrials.gov, NCT03429075.Findings Between January 15th, 2019 and March 20th , 2020, 59 patients were enrolled and 30 (11 females (37%) and 19 males (63%)) were assigned to the psilocybin group and 29 (9 females (31%) and 20 males (69%)) to the escitalopram group. 25 participants
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Journal articleMurphy RJ, Sumner RL, Godfrey K, et al., 2024,
Multimodal creativity assessments following acute and sustained microdosing of lysergic acid diethylamide
, PSYCHOPHARMACOLOGY, ISSN: 0033-3158 -
Journal articleDeco G, Sanz Perl Y, Johnson S, et al., 2024,
Different hierarchical reconfigurations in the brain by psilocybin and escitalopram for depression
, Nature Mental Health, Vol: 2, Pages: 1096-1110Effective interventions for neuropsychiatric disorders may work by rebalancing the brain’s functional hierarchical organization. Here we directly investigated the effects of two different serotonergic pharmacological interventions on functional brain hierarchy in major depressive disorder in a two-arm double-blind phase II randomized controlled trial comparing psilocybin therapy (22 patients) with escitalopram (20 patients). Patients with major depressive disorder received either 2 × 25 mg of oral psilocybin, three weeks apart, plus six weeks of daily placebo (‘psilocybin arm’) or 2 × 1 mg of oral psilocybin, three weeks apart, plus six weeks of daily escitalopram (10–20 mg; ‘escitalopram arm’). Resting-state functional magnetic resonance imaging scans were acquired at baseline and three weeks after the second psilocybin dose (NCT03429075). The brain mechanisms were captured by generative effective connectivity, estimated from whole-brain modeling of resting state for each session and patient. Hierarchy was determined for each of these sessions using measures of directedness and trophic levels on the effective connectivity, which captures cycle structure, stability and percolation. The results showed that the two pharmacological interventions created significantly different hierarchical reconfigurations of whole-brain dynamics with differential, opposite statistical effect responses. Furthermore, the use of machine learning revealed significant differential reorganization of brain hierarchy before and after the two treatments. Machine learning was also able to predict treatment response with an accuracy of 0.85 ± 0.04. Overall, the results demonstrate that psilocybin and escitalopram work in different ways for rebalancing brain dynamics in depression. This suggests the hypothesis that neuropsychiatric disorders could be closely linked to the breakdown in regions orchestrating brain dynamics from the top of the h
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Journal articleKettner H, Roseman L, Gazzaley A, et al., 2024,
Effects of Psychedelics in Older Adults: A Prospective Cohort Study.
, Am J Geriatr Psychiatry, Vol: 32, Pages: 1047-1059OBJECTIVE: Affective symptoms such as anxiety, low mood, and loneliness are prevalent and highly debilitating symptoms among older adults (OA). Serotonergic psychedelics are currently investigated as novel interventions for affective disorders, yet little is known regarding their effects in OA. We investigated the mental health effects and psychological mechanisms of guided psychedelic group experiences in OA and a matched sample of younger adults (YA). METHODS: Using a prospective observational cohort design, we identified 62 OA (age ≥60 years) and 62 matched YA who completed surveys two weeks before, a day, two weeks, four weeks, and six months after a psychedelic group session. Mixed linear regression analyses were used to investigate longitudinal well-being changes, as well as baseline, acute, and post-acute predictors of change. RESULTS: OA showed post-psychedelic well-being improvements similar to matched YA. Among baseline predictors, presence of a lifetime psychiatric diagnosis was associated with greater well-being increases in OA (B = 6.72, p = .016 at the four-week key-endpoint). Compared to YA, acute subjective psychedelic effects were less intense in OA and did not significantly predict prospective well-being changes. However, relational experiences before and after psychedelic sessions emerged as predictors in OA (r(36) = .37,p = 0.025). CONCLUSIONS: Guided psychedelic group sessions enhance well-being in OA in line with prior naturalistic and controlled studies in YA. Interestingly, acute psychedelic effects in OA are attenuated and less predictive of well-being improvements, with relational experiences related to the group setting playing a more prominent role. Our present findings call for further research on the effects of psychedelics in OA.
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Journal articleMartial C, Carhart-Harris R, Timmermann C, 2024,
Within-subject comparison of near-death and psychedelic experiences: acute and enduring effects
, NEUROSCIENCE OF CONSCIOUSNESS, Vol: 2024 -
Journal articleBrouwer A, Carhart-Harris RL, Raison CL, 2024,
Psychotomimetic compensation versus sensitization.
, Pharmacol Res Perspect, Vol: 12It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.
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Journal articleLynskey MT, Thurgur H, Athanasiou-Fragkouli A, et al., 2024,
Suicidal Ideation in Medicinal Cannabis Patients: A 12-Month Prospective Study
, ARCHIVES OF SUICIDE RESEARCH, ISSN: 1381-1118 -
Journal articleLuppi AI, Mediano PAM, Rosas FE, et al., 2024,
A synergistic workspace for human consciousness revealed by Integrated Information Decomposition
, eLife, Vol: 12<jats:p>How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a ‘synergistic global workspace’, comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brain’s default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.</jats:p>
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Journal articleSiegel JS, Subramanian S, Perry D, et al., 2024,
Psilocybin desynchronizes the human brain
, NATURE, ISSN: 0028-0836
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