10 results found
Zeifman R, Spriggs M, Kettner H, et al., 2023, From Relaxed Beliefs Under Psychedelics (REBUS) to Revised Beliefs After Psychedelics (REBAS), Scientific Reports, ISSN: 2045-2322
Objectives: This was a cross sectional study aimed at describing chest x-ray findings among children hospitalised with clinically diagnosed severe pneumonia and hypoxaemia (SpO2<92%) in three tertiary facilities in Uganda.Methods: We studied chest x-rays of 375 children aged 28 days to 12 years enrolled into the Children’s Oxygen Administration Strategies Trial (COAST)(ISRCTN15622505). Radiologists blinded to the clinical findings reported chest x-rays using the standardized World Health Organization methodology for paediatric chest Xray reporting. We summarised clinical data and chest x-ray findings using descriptive statistics. Chi-square and proportion tests were used to compare proportions and quantile regression compared medians. Results: We found 172, (45.8%) children had radiological pneumonia, 136 (36.3%) normal chest radiographs while 123 (32.8%) non-pneumonia findings, the major one being cardiovascular abnormalities,106 (28.3%); 56 (14.9%) chest radiographs had both pneumonia and other abnormalities. There was no difference in the prevalence of radiological pneumonia, cardiovascular abnormalities, and mortality between the group with severe hypoxaemia (SpO2<80%) and that with mild hypoxaemia (SpO280 to <92%), (95% CI: -13.2,7.1, -6.1,15.9) and -37.2, 20.4) respectively. Conclusion: This study highlights a relatively high prevalence of cardiovascular abnormalities in children who fulfill the WHO clinical criteria for severe pneumonia and have hypoxaemia. We recommend that chest x-ray examinations be routinely done for all children in this population because information concerning cardiovascular and respiratory systems can be obtained in one sitting and guide management better. We hope that these findings can prompt discussions into refining the clinical criteria used to classify and manage pneumonia in children in limited resource settings.
Spriggs MJ, Giribaldi B, Lyons T, et al., 2022, Body mass index (BMI) does not predict responses to psilocybin, Journal of Clinical Psychopharmacology, Vol: 37, Pages: 107-116, ISSN: 0271-0749
Background:Psilocybin is a serotonin type 2A (5-HT2A) receptor agonist and naturally occurring psychedelic. 5-HT2A receptor density is known to be associated with body mass index (BMI), however, the impact of this on psilocybin therapy has not been explored. While body weight-adjusted dosing is widely used, this imposes a practical and financial strain on the scalability of psychedelic therapy. This gap between evidence and practice is caused by the absence of studies clarifying the relationship between BMI, the acute psychedelic experience and long-term psychological outcomes.Method:Data were pooled across three studies using a fixed 25 mg dose of psilocybin delivered in a therapeutic context to assess whether BMI predicts characteristics of the acute experience and changes in well-being 2 weeks later. Supplementing frequentist analysis with Bayes Factors has enabled for conclusions to be drawn regarding the null hypothesis.Results:Results support the null hypothesis that BMI does not predict overall intensity of the altered state, mystical experiences, perceptual changes or emotional breakthroughs during the acute experience. There was weak evidence for greater ‘dread of ego dissolution’ in participants with lower BMI, however, further analysis suggested BMI did not meaningfully add to the combination of the other covariates (age, sex and study). While mystical-type experiences and emotional breakthroughs were strong predictors of improvements in well-being, BMI was not.Conclusions:These findings have important implications for our understanding of pharmacological and extra-pharmacological contributors to psychedelic-assisted therapy and for the standardization of a fixed therapeutic dose in psychedelic-assisted therapy.
Zeifman R, Spriggs M, Kettner H, et al., 2022, From Relaxed Beliefs Under Psychedelics (REBUS) to Revised Beliefs After Psychedelics (REBAS): preliminary development of the RElaxed Beliefs Questionnaire (REB-Q), Publisher: PsyArXiv
Background: The Relaxed Beliefs Under pSychedelics (REBUS) model proposes that serotonergic psychedelics decrease the precision weighting of neurobiologically-encoded beliefs, and offers a unified account of the acute and therapeutic action of psychedelics. Although REBUS has received some neuroscientific support, little research has examined its psychological validity. We conducted a preliminary examination of two psychological assumptions of REBUS: (a) psychedelics foster acute relaxation and post-acute revision of confidence in mental-health-relevant beliefs; (b) this relaxation and revision facilitates positive therapeutic outcomes and is associated with the entropy of EEG signals (an index of neurophysiological mechanisms relevant to REBUS). Method: Healthy individuals (N=11) were administered 1 mg and 25 mg psilocybin 4-weeks apart. Confidence ratings for personally held negative and positive beliefs were obtained before, during, and 4-weeks after dosing sessions. Acute entropy and self-reported subjective experiences were measured, as was well-being (before and 4-weeks after dosing sessions). Results: Confidence in negative self-beliefs decreased following 25 mg psilocybin and not following 1 mg psilocybin. Entropy and subjective effects under 25 mg psilocybin correlated with decreases in negative self-belief confidence (acute and 4-weeks after dosing). Particularly strong evidence was seen for a relationship between decreases in negative self-belief confidence and increases in well-being at 4-weeks. Conclusions: We report the first empirical evidence that the relaxation and revision of negative self-belief confidence mediates positive psychological outcomes; a psychological assumption of REBUS. Replication within larger and clinical samples remains necessary. We also introduce a new measure, the Relaxed BEliefs Questionnaire (REB-Q), for examining the robustness of these preliminary findings and the utility of the REBUS model.
Peill JM, Trinci KE, Kettner H, et al., 2022, Validation of the psychological insight scale: a new scale to assess psychological insight following a psychedelic experience, Journal of Psychopharmacology, Vol: 36, Pages: 31-45, ISSN: 0269-8811
Introduction:As their name suggests, ‘psychedelic’ (mind-revealing) compounds are thought to catalyse processes of psychological insight; however, few satisfactory scales exist to sample this. This study sought to develop a new scale to measure psychological insight after a psychedelic experience: the Psychological Insight Scale (PIS).Methods:The PIS is a six- to seven-item questionnaire that enquires about psychological insight after a psychedelic experience (PIS-6) and accompanied behavioural changes (PIS item 7). In total, 886 participants took part in a study in which the PIS and other questionnaires were completed in a prospective fashion in relation to a planned psychedelic experience. For validation purposes, data from 279 participants were analysed from a non-specific ‘global psychedelic survey’ study.Results:Principal components analysis of PIS scores revealed a principal component explaining 73.57% of the variance, which displayed high internal consistency at multiple timepoints throughout the study (average Cronbach’s α = 0.94). Criterion validity was confirmed using the global psychedelic survey study, and convergent validity was confirmed via the Therapeutic-Realizations Scale. Furthermore, PIS scores significantly mediated the relationship between emotional breakthrough and long-term well-being.Conclusion:The PIS is complementary to current subjective measures used in psychedelic studies, most of which are completed in relation to the acute experience. Insight – as measured by the PIS – was found to be a key mediator of long-term psychological outcomes following a psychedelic experience. Future research may investigate how insight varies throughout a psychedelic process, its underlying neurobiology and how it impacts behaviour and mental health.
Buchborn T, Lyons T, Song C, et al., 2020, The serotonin 2A receptor agonist 25CN-NBOH increases murine heart rate and neck-arterial blood flow in a temperature-dependent manner., Journal of Psychopharmacology, Vol: 34, Pages: 786-794, ISSN: 0269-8811
BACKGROUND: Serotonin 2A receptors, the molecular target of psychedelics, are expressed by neuronal and vascular cells, both of which might contribute to brain haemodynamic characteristics for the psychedelic state. AIM: Aiming for a systemic understanding of psychedelic vasoactivity, here we investigated the effect of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine - a new-generation agonist with superior serotonin 2A receptor selectivity - on brain-supplying neck-arterial blood flow. METHODS: We recorded core body temperature and employed non-invasive, collar-sensor based pulse oximetry in anesthetised mice to extract parameters of local blood perfusion, oxygen saturation, heart and respiration rate. Hypothesising an overlap between serotonergic pulse- and thermoregulation, recordings were done under physiological and elevated pad temperatures. RESULTS: N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine (1.5 mg/kg, subcutaneous) significantly increased the frequency of heart beats accompanied by a slight elevation of neck-arterial blood flow. Increasing the animal-supporting heat-pad temperature from 37°C to 41°C enhanced the drug's effect on blood flow while counteracting tachycardia. Additionally, N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine promoted bradypnea, which, like tachycardia, quickly reversed at the elevated pad temperature. The interrelatedness of N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine's respiro-cardiovascular effects and thermoregulation was further corroborated by the drug selectively increasing the core body temperature at the elevated pad temperature. Arterial oxygen saturation was not affected by N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine at either temperature. CONCLUSIONS: Our findings imply that selective serotonin 2A receptor activation modulates systemic cardiovascular functioning in orchestration with thermoregulation and with immediate relevance to brain-imminent
Lyons T, Carhart-Harris RL, 2018, More realistic forecasting of future life events after psilocybin for treatment-resistant depression, Frontiers in Psychology, Vol: 9, ISSN: 1664-1078
Background: Evidence suggests that classical psychedelics can promote enduring changes in personality, attitudes and optimism, as well as improvements in mental health outcomes.Aim: To investigate the effects of a composite intervention, involving psilocybin, on pessimism biases in patients with treatment-resistant depression (TRD).Methods: Patients with TRD (n = 15) and matched, untreated non-depressed controls (n = 15) performed the Prediction Of Future Life Events (POFLE) task. The POFLE task requires participants to predict the likelihood of certain life events occurring within a 30-day period, after which the actual rate of event occurrence is reported; this gives an index of potential pessimism versus optimism bias. Psilocybin was administered in two oral dosing sessions (10 and 25 mg) one week apart. Main outcome measures were collected at baseline and one week after the second dosing session.Results: Patients showed a significant pessimism bias at baseline [t(14) = -3.260, p = 0.006; 95% CI (-0.16, -0.03), g = 1.1] which was related to the severity of their depressive symptoms (rs = -0.55, p = 0.017). One week after psilocybin treatment, this bias was significantly decreased [t(14) = -2.714, p = 0.017; 95% CI (-0.21, -0.02), g = 0.7] and depressive symptoms were greatly improved [t(14) = 7.900, p < 0.001; 95% CI (16.17, 28.23), g = 1.9]; moreover, the magnitude of change in both variables was significantly correlated (r = -0.57, p = 0.014). Importantly, post treatment, patients became significantly more accurate at predicting the occurrence of future life events [t(14) = 1.857, p = 0.042; 95% CI (-0.01, 0.12), g = 0.6] whereas no such change was observed in the control subjects.Conclusion: These findings suggest that psilocybin with psychological support might correct pessimism biases in TRD, enabling a more positive and accurate outlook.
Lyons T, Carhart-Harris RL, 2018, Increased nature relatedness and decreased authoritarian political views after psilocybin for treatment-resistant depression, Journal of Psychopharmacology, Vol: 32, Pages: 811-819, ISSN: 1461-7285
Rationale:Previous research suggests that classical psychedelic compounds can induce lasting changes in personality traits, attitudes and beliefs in both healthy subjects and patient populations.Aim:Here we sought to investigate the effects of psilocybin on nature relatedness and libertarian–authoritarian political perspective in patients with treatment-resistant depression (TRD).Methods:This open-label pilot study with a mixed-model design studied the effects of psilocybin on measures of nature relatedness and libertarian–authoritarian political perspective in patients with moderate to severe TRD (n=7) versus age-matched non-treated healthy control subjects (n=7). Psilocybin was administered in two oral dosing sessions (10 mg and 25 mg) 1 week apart. Main outcome measures were collected 1 week and 7–12 months after the second dosing session. Nature relatedness and libertarian–authoritarian political perspective were assessed using the Nature Relatedness Scale (NR-6) and Political Perspective Questionnaire (PPQ-5), respectively.Results:Nature relatedness significantly increased (t(6)=−4.242, p=0.003) and authoritarianism significantly decreased (t(6)=2.120, p=0.039) for the patients 1 week after the dosing sessions. At 7–12 months post-dosing, nature relatedness remained significantly increased (t(5)=−2.707, p=0.021) and authoritarianism remained decreased at trend level (t(5)=−1.811, p=0.065). No differences were found on either measure for the non-treated healthy control subjects.Conclusions:This pilot study suggests that psilocybin with psychological support might produce lasting changes in attitudes and beliefs. Although it would be premature to infer causality from this small study, the possibility of drug-induced changes in belief systems seems sufficiently intriguing and timely to deserve further investigation.
Buchborn T, Lyons T, Knopfel T, 2018, Tolerance and Tachyphylaxis to Head Twitches Induced by the 5-HT2A Agonist 25CN-NBOH in Mice, Frontiers in Pharmacology, Vol: 9, ISSN: 1663-9812
The serotonin (5-HT) 2A receptor is the primary molecular target of serotonergic hallucinogens, which trigger large-scale perturbations of the cortex. Our understanding of how 5-HT2A activation may cause the effects of hallucinogens has been hampered by the receptor unselectivity of most of the drugs of this class. Here we used 25CN-NBOH (N-(2-hydroxybenzyl)-2,5-dimethoxy-4-cyanophenylethylamine), a newly developed selective 5-HT2A agonist, and tested it with regard to the head-twitch-response (HTR) model of 5-HT2A activity and effects on locomotion. 25CN-NBOH evoked HTRs with an inverted u-shape-like dose-response curve and highest efficacy at 1.5 mg/kg, i.p. HTR occurrence peaked within 5 min after agonist injection, and exponentially decreased to half-maximal frequency at ~11 min. Thorough habituation to the experimental procedures (including handling, saline injection, and exposure to the observational boxes 1 day before the experiment) facilitated the animals' response to 25CN-NBOH. 25CN-NBOH (1.5 mg/kg, i.p.) induced HTRs were blocked by the 5-HT2A antagonist ketanserin (0.75 mg/kg, 30 min pre), but not by the 5-HT2C antagonist SB-242084 (0.5 mg/kg, i.p., 30 min pre). SB-242084 instead slightly increased the number of HTRs occurring at a 3.0-mg/kg dose of the agonist. Apart from HTR induction, 25CN-NBOH also modestly increased locomotor activity of the mice. Repeated once-per-day injections (1.5 mg/kg, i.p.) led to reduced occurrence of 25CN-NBOH induced HTRs. This intermediate tolerance was augmented when a second (higher) dose of the drug (3.0 mg/kg) was interspersed. Short-interval tolerance (i.e., tachyphylaxis) was observed when the drug was injected twice at intervals of 1.0 and 1.5 h at either dose tested (1.5 mg/kg and 0.75 mg/kg, respectively). Inducing ketanserin-sensitive HTRs, which are dependent on environmental valences and which show signs of tachyphylaxis and tolerance, 25CN-NBOH shares striking features common to serotonergic hallucinogens. Gi
Fagan SG, Rispin-Dureuil C, Lyons T, et al., 2016, The involvement of PANX-1 in amyloid-induced neurodegeneration and the protective effect of the endocannabinoid system, Publisher: SPRINGER LONDON LTD, Pages: S179-S179, ISSN: 0021-1265
O'Hare E, Jeggo R, Kim E-M, et al., 2016, Lack of support for bexarotene as a treatment for Alzheimer's disease, NEUROPHARMACOLOGY, Vol: 100, Pages: 124-130, ISSN: 0028-3908
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