scholarly journals A Phase 1, Dose-Ranging Study to Assess Safety and Psychoactive Effects of a Vaporized 5-Methoxy-N, N-Dimethyltryptamine Formulation (GH001) in Healthy Volunteers

2021 ◽  
Vol 12 ◽  
Author(s):  
Johannes Reckweg ◽  
Natasha L. Mason ◽  
Cees van Leeuwen ◽  
Stefan W. Toennes ◽  
Theis H. Terwey ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Dose Escalation ◽  
Mystical Experience ◽  
Phase 1 ◽  
Vital Signs ◽  
Well Being ◽  
Rapid Onset ◽  
Psychoactive Effects ◽  
The Impact ◽  
Experience Questionnaire

5-Methoxy-N,N-Dimethyltryptamine (5-MeO-DMT) is a tryptamine with ultra-rapid onset and short duration of psychedelic effects. Prospective studies for other tryptamines have suggested beneficial effects on mental health outcomes. In preparation for a study in patients with depression, the present study GH001-HV-101 aimed to assess the impact of four different dose levels of a novel vaporized 5-MeO-DMT formulation (GH001) administered via inhalation as single doses of 2 (N = 4), 6 (N = 6), 12 (N = 4) and 18 mg (N = 4), and in an individualized dose escalation regimen (N = 4) on the safety, tolerability, and the dose-related psychoactive effects in healthy volunteers (N = 22). The psychedelic experience was assessed with a novel Peak Experience Scale (PES), the Mystical Experience Questionnaire (MEQ), the Ego Dissolution Inventory (EDI), the Challenging Experience Questionnaire (CEQ), and the 5-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). Further aims were to assess the impact of 5-MeO-DMT on cognitive functioning, mood, and well-being. Higher doses of 5-MeO-DMT produced significant increments in the intensity of the psychedelic experience ratings as compared to the lowest 2 mg dose on all questionnaires, except the CEQ. Prominent effects were observed following single doses of 6, 12, and 18 mg on PES and MEQ ratings, while maximal effects on PES, MEQ, EDI, and 5D-ASC ratings were observed following individualized dose escalation of 5-MeO-DMT. Measures of cognition, mood, and well-being were not affected by 5-MeO-DMT. Vital signs at 1 and 3 h after administration were not affected and adverse events were generally mild and resolved spontaneously. Individualized dose escalation of 5-MeO-DMT may be preferable over single dose administration for clinical applications that aim to maximize the experience to elicit a strong therapeutic response.

scholarly journals High dose psilocybin is associated with positive subjective effects in healthy volunteers

2018 ◽  
Vol 32 (7) ◽  
pp. 770-778 ◽  
Author(s):  
Christopher R Nicholas ◽  
Kelsey M Henriquez ◽  
Michele C Gassman ◽  
Karen M Cooper ◽  
Daniel Muller ◽  
...  
Keyword(s):  
Mystical Experience ◽  
Subjective Effects ◽  
Vital Signs ◽  
Well Being ◽  
High Dose ◽  
Moderate Increase ◽  
Time And Space ◽  
Significant Difference ◽  
Composite Scores ◽  
Experience Questionnaire

Aim: The aim of the current study was to investigate the relationship between escalating higher doses of psilocybin and the potential psilocybin occasioned positive subjective effects. Methods: Healthy participants ( n=12) were given three escalating doses of oral psilocybin (0.3 mg/kg; 0.45 mg/kg; 0.6 mg/kg) or (18.8–36.6 mg; 27.1–54.0 mg; 36.3–59.2 mg) a minimum of four weeks apart in a supervised setting. Blood and urine samples, vital signs, and electrocardiograms were obtained. Subjective effects were assessed using the Mystical Experience Questionnaire and Persisting Effects Questionnaire. Results: There was a significant linear dose-related response in Mystical Experience Questionnaire total score and the transcendence of time and space subscale, but not in the rate of a complete mystical experience. There was also a significant difference between dose 3 compared to dose 1 on the transcendence of time and space subscale, while no dose-related differences were found for Mystical Experience Questionnaire total scores or rate of a mystical experience. Persisting Effects Questionnaire positive composite scores 30 days after completion of the last dose were significantly higher than negative composite scores. Persisting Effects Questionnaire results revealed a moderate increase in sense of well-being or life satisfaction on average that was associated with the maximum Mystical Experience Questionnaire total score. Pharmacokinetic measures were associated with dose but not with Mystical Experience Questionnaire total scores or rate of a mystical experience. Conclusions: High doses of psilocybin elicited subjective effects at least as strong as the lower doses and resulted in positive persisting subjective effects 30 days after, indicating that a complete mystical experience was not a prerequisite for positive outcomes.

Abstract 2009: ALX-0081 a Novel Anti-Thrombotic: Results of a Single-Dose Phase 1 Study in Healthy Volunteers and Further Development in Patients with Stable Angina Undergoing PCI

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jozef Bartunek ◽  
Emanuele Barbato ◽  
Josefin-Beate Holz ◽  
Kristof Vercruysse ◽  
Hans Ulrichts ◽  
...  
Keyword(s):  
Single Dose ◽  
Healthy Volunteers ◽  
Dose Escalation ◽  
Stable Angina ◽  
Thrombus Formation ◽  
Phase 1 ◽  
Controlled Study ◽  
Double Blind ◽  
Phase Ib ◽  
Wide Range

Background : ALX-0081 is a bivalent Nanobody ® based on the variable domain of naturally occurring heavy-chain only antibodies. It binds with high affinity to the A1 domain of von Willebrand Factor (vWF) and thereby blocks the interactions between platelets and vascular collagen. It selectively prevents thrombus formation under high shear stress conditions. Aim : Test ALX-0081 single IV infusions (60 minutes) dosed from 0.5mg to 12mg total in 40 male healthy volunteers in double-blind, randomized, placebo controlled study and assess pharmacokinetic (PK), pharmacodynamic (PD), safety and immunogenicity. Results : ALX-0081 displayed non-linear pharmacokinetic properties, following a 2 compartment model. Ristocetin induced platelet aggregation (RIPA) was analyzed as marker for PD effect with full inhibition (defined as measured levels dropping <10%) observed at ALX-0081 concentrations of ~ 400ng/ml. All subjects dosed ≥ 2mg achieved full RIPA inhibition at 1h post-dosing for maximum of 12h. ALX-0081 treatment was well tolerated and safe, no signs of bleeding were reported and no immunogenic response was detected. Target related mild and transient reductions of vWF and FVIII plasma levels were observed and all events were fully reversible. Phase Ib study design : double-blind, randomized, placebo controlled, multiple ascending dose study. ALX-0081 added to standard anti-thrombotic regimen (ASA, clopidogrel, UFH) in patients with stable angina undergoing elective PCI. Single-dose escalation will be followed by multiple dosing (up to 4 doses in 24h). Dose escalation will be guided by safety and efficacy marker. Endpoints: safety, pharmacological profile, biomarker (RIPA, RICO and ACT) and early clinical outcome (MACE, IMR, molecular marker). Conclusion : ALX-0081 can be administered safely over a wide range of dose-regimen. First results of the phase Ib study in stable angina patients will be presented.

scholarly journals An evaluation of foundation doctor training: a mixed-methods study of the impact on workforce well-being and patient care [the Evaluating the Impact of Doctors in Training (EDiT) study]

2013 ◽  
Vol 1 (15) ◽  
pp. 1-208 ◽  
Author(s):  
S Mason ◽  
C O’Keeffe ◽  
A Carter ◽  
R O’Hara ◽  
C Stride
Keyword(s):  
Health Care ◽  
Quality Of Care ◽  
Longitudinal Study ◽  
Phase 1 ◽  
Well Being ◽  
Junior Doctors ◽  
Phase 2 ◽  
Adequate Quality ◽  
The Impact

BackgroundA major reform of junior doctor training was undertaken in 2004–5, with the introduction of foundation training (FT) to address perceived problems with work structure, conditions and training opportunities for postgraduate doctors. The well-being and motivation of junior doctors within the context of this change to training (and other changes such as restrictions in working hours of junior doctors and increasing demand for health care) and the consequent impact upon the quality of care provided is not well understood.ObjectivesThis study aimed to evaluate the well-being of foundation year 2 (F2) doctors in training. Phase 1 describes the aims of delivering foundation training with a focus on the role of training in supporting the well-being of F2 doctors and assesses how FT is implemented on a regional basis, particularly in emergency medicine (EM). Phase 2 identifies how F2 doctor well-being and motivation are influenced over F2 and specifically in relation to EM placements and quality of care provided to patients.MethodsPhase 1 used semistructured interviews and focus groups with postgraduate deanery leads, training leads (TLs) and F2 doctors to explore the strategic aims and implementation of FT, focusing on the specialty of EM. Phase 2 was a 12-month online longitudinal study of F2 doctors measuring levels of and changes in well-being and motivation. In a range of specialties, one of which was EM, data from measures of well-being, motivation, intention to quit, confidence and competence and job-related characteristics (e.g. work demands, task feedback, role clarity) were collected at four time points. In addition, we examined F2 doctor well-being in relation to quality of care by reviewing clinical records (criterion-based and holistic reviews) during the emergency department (ED) placement relating to head injury and chronic obstructive pulmonary disease (COPD).ResultsPhase 1 of the study found that variation exists in how successfully FT is implemented locally; F2 lacks a clearly defined end point; there is a minimal focus on the well-being of F2 doctors (only on the few already shown to be ‘in difficulty’); the ED presented a challenging but worthwhile learning environment requiring a significant amount of support from senior ED staff; and disagreement existed about the performance and confidence levels of F2 doctors. A total of 30 EDs in nine postgraduate medical deaneries participated in phase 2 with 217 foundation doctors completing the longitudinal study. F2 doctors reported significantly increased confidence in managing common acute conditions and undertaking practical procedures over their second foundation year, with the biggest increase in confidence and competence associated with their ED placement. F2 doctors had levels of job satisfaction and anxiety/depression that were comparable to or better than those of other NHS workers, and adequate quality and safety of care are being provided for head injury and COPD.ConclusionsThere are ongoing challenges in delivering high-quality FT at the local level, especially in time-pressured specialties such as EM. There are also challenges in how FT detects and manages doctors who are struggling with their work. The survey was the first to document the well-being of foundation doctors over the course of their second year, and average scores compared well with those of other doctors and health-care workers. F2 doctors are benefiting from the training provided as we found improvements in perceived confidence and competence over the year, with the ED placement being of most value to F2 doctors in this respect. Although adequate quality of care was demonstrated, we found no significant relationships between well-being of foundation doctors and the quality of care they provided to patients, suggesting the need for further work in this area.FundingThe National Institute for Health Research Health Services and Delivery Research programme.

scholarly journals Randomized, double-blind, placebo-controlled phase I dose escalation study of Dan Qi Tong Mai tablet in healthy volunteers

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhong-ping Gou ◽  
Wei Zhang ◽  
Xiu-fang Liang ◽  
Ying Wang ◽  
Ju-hong Mou ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Healthy Volunteers ◽  
Dose Escalation ◽  
Salvia Miltiorrhiza ◽  
Vital Signs ◽  
Active Ingredients ◽  
Dose Escalation Study ◽  
Double Blind ◽  
Dose Study

Abstract Background This study aims to assess the tolerability and safety of DQTM tablet, which contains a complex mixture of Salvia miltiorrhiza salvianolic acids and Panax notoginseng saponins. Methods A double-blind, randomized, placebo-controlled phase I dose escalation study was conducted in 84 healthy volunteers. In a single ascending dose study, active ingredients were administered in various doses (90, 270, 540, 1080, 1800, 2880, 4320 or 5760 mg) to 60 subjects in cohorts 1–8. In a multiple ascending dose study, active ingredients were administered at doses of 360, 720 or 2160 mg twice daily to 24 subjects in cohorts 9–11 for 14 consecutive days. Safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiography, laboratory tests and adverse events. Results No serious adverse events or clinically significant changes in vital signs or electrocardiography were observed. One subject experienced mildly elevated levels of alanine aminotransferase and aspartate transaminase but recovered spontaneously. Five subjects experienced a small increase in the number of daily stools. Conclusions DQTM tablet was well tolerated at single doses of up to 5760 mg and twice-daily doses of up to 2160 mg for 14 consecutive days. The most frequent adverse event was an increase in the number of daily stools.

scholarly journals Assessment of impact of the COVID-19 pandemic from the perspective of patients with rheumatic and musculoskeletal diseases in Europe: results from the REUMAVID study (phase 1)

RMD Open ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. e001546
Author(s):  
Marco Garrido-Cumbrera ◽  
Helena Marzo-Ortega ◽  
Laura Christen ◽  
Pedro Plazuelo-Ramos ◽  
Dale Webb ◽  
...  
Keyword(s):  
Disease Activity ◽  
Online Survey ◽  
Musculoskeletal Diseases ◽  
Phase 1 ◽  
Depression Scale ◽  
Well Being ◽  
Healthcare Services ◽  
Study Phase ◽  
Cross Sectional ◽  
The Impact

AimTo assess the impact of the COVID-19 pandemic on patients with rheumatic and musculoskeletal diseases (RMDs).MethodsREUMAVID is a cross-sectional study using an online survey developed by an international multidisciplinary patient-led collaboration across seven European countries targeting unselected patients with RMDs. Healthcare access, daily activities, disease activity and function, well-being (WHO Five Well-Being Index (WHO-5)), health status, anxiety/depression (Hospital Anxiety and Depression Scale (HADS)) and access to information were evaluated. Data were collected in April–July 2020 (first phase).ResultsData from the first phase included 1800 patients with 15 different RMDs (37.2% axial spondyloarthritis, 29.2% rheumatoid arthritis, 17.2% osteoarthritis and others). Mean age was 53, 80% female and 49% had undertaken university studies. During the beginning of the pandemic, 58.4% had their rheumatology appointment cancelled and 45.6% reported not having received any information relating to the possible impact of SARS-CoV-2 infection in their RMDs, with the main source being patient organisations (27.6%).Regarding habits, 24.6% increased smoking, 18.2% raised their alcohol consumption, and 45.6% were unable to continue exercising. Self-reported disease activity was high (5.3±2.7) and 75.6% reported elevated pain. Half the patients (49.0%) reported poor well-being (WHO-5) and 46.6% that their health had changed for the worse during lockdown. According to HADS, 57.3% were at risk of anxiety and 45.9% of depression.ConclusionThroughout the first wave of the COVID-19 pandemic, patients with RMDs have experienced disruption in access to healthcare services, poor lifestyle habits and negative effects on their overall health, well-being and mental health. Furthermore, information on COVID-19 has not reached patients appropriately.

scholarly journals Phase 1 Dose‐Escalation Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Tofacitinib in Japanese Healthy Volunteers

2019 ◽  
Vol 9 (1) ◽  
pp. 11-20 ◽  
Author(s):  
So Miyoshi ◽  
Sriram Krishnaswami ◽  
Shigeyuki Toyoizumi ◽  
Hiroyuki Nakamura ◽  
Samuel H. Zwillich
Keyword(s):  
Healthy Volunteers ◽  
Dose Escalation ◽  
Phase 1 ◽  
Dose Escalation Study

scholarly journals An open-label, exploratory documentation of proving-symptoms of CVN01 (Coronavirus nosode from the clinical sample) in healthy volunteers

2021 ◽  
Vol 20 (2-3) ◽  
pp. 44-50
Author(s):  
Rajesh Shah ◽  
Gitanjali Talele
Keyword(s):  
Healthy Volunteers ◽  
Clinical Sample ◽  
Phase 1 ◽  
Vital Signs ◽  
Liver Function Tests ◽  
Open Label ◽  
Phase 1 Study ◽  
Study Materials ◽  
Prophylactic Use ◽  
Fatal Adverse Events

INTRODUCTION Homeopathic Pathogenetic Trials (Proving) are human studies to examine the pathogenetic effects of investigational drugs in high dilution on healthy volunteers. As a part of the new coronavirus nosode development process for prophylactic use, the phase 1 study was conducted. The documentation of proving symptoms for a fast-track nosode development for a pandemic condition was the objectives of this study. MATERIALS AND METHODS An open-label trial to evaluate the safety and proving symptoms of Coronavirus nosode given orally to 10 volunteers (18-65 years age and of both the genders). Volunteers were administered 6 doses of nosode as 6 pills twice daily for 3 consecutive days. Pre and post examinations (physical), vital signs, and laboratory investigations, were done at day 0, 17, 34. Symptoms experienced by the volunteers were recorded. RESULTS Symptoms reported by volunteers were analyzed. The symptoms reported were mild to severe but reversible and matching with the symptoms produced by the viral infection. There were no serious/fatal adverse events during the study. The basic biochemistry and Liver Function tests were not affected by the Nosode. CONCLUSION New nosode developed during a pandemic condition produced certain symptoms in the homeopathic pathogenetic trial as a part of the Phase 1 study.

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