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

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.

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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

Frontiers in Pharmacology ◽

10.3389/fphar.2021.760671 ◽

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.

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Are High-Dose Perioperative Steroids Necessary in Patients Undergoing Colorectal Surgery Treated with Steroid Therapy Within the Past 12 Months?

The American Surgeon ◽

10.1177/000313481107701004 ◽

2011 ◽

Vol 77 (10) ◽

pp. 1295-1299 ◽

Cited By ~ 6

Author(s):

Karen Zaghiyan ◽

Gil Melmed ◽

Zuri Murrell ◽

Phillip Fleshner

Keyword(s):

Colorectal Surgery ◽

Chart Review ◽

Vital Signs ◽

Hemodynamic Instability ◽

Beta Blockade ◽

High Dose ◽

The Past ◽

Significant Difference ◽

Inflammatory Bowel ◽

A Prospective Study

Patients previously on corticosteroids within 1 year before surgery are routinely treated with perioperative high-dose corticosteroids. However, there is little evidence to support this practice. We postulated that patients off steroids but treated with corticosteroids within 1 year before surgery may be safely managed without perioperative steroids. A chart review was performed on patients with inflammatory bowel disease (IBD) treated with corticosteroids within 1 year before surgery. Patients received either perioperative high-dose steroids (HDS) or no steroids (NS). Perioperative vital signs were assessed. Forty-nine operations were performed. Eleven patients received HDS and 38 patients received NS. Aside from a higher incidence of tachycardia (heart rate greater than 100 beats/min) in the HDS group (82%) compared with the NS group (42%), there was no significant difference in hemodynamic instability between the two groups. One patient in the NS group required a single dose of intraoperative vasopressor after aggressive beta-blockade. All other episodes of hemodynamic instability resolved with no intervention, fluid boluses, or blood transfusion. No patients required rescue high-dose steroids for adrenal insufficiency. In patients with IBD undergoing major colorectal surgery, treated with corticosteroids within the past year, management without perioperative steroids seems safe. A prospective study assessing perioperative corticosteroid dosing is in progress.

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Acute Pharmacological Effects of Oral and Intranasal Mephedrone: An Observational Study in Humans

Pharmaceuticals ◽

10.3390/ph14020100 ◽

2021 ◽

Vol 14 (2) ◽

pp. 100

Author(s):

Esther Papaseit ◽

Eulalia Olesti ◽

Clara Pérez-Mañá ◽

Marta Torrens ◽

Francina Fonseca ◽

...

Keyword(s):

Observational Study ◽

Oral Fluid ◽

Subjective Effects ◽

Vital Signs ◽

Cardiovascular Effects ◽

Well Being ◽

Research Centre ◽

New Psychoactive Substances ◽

Pharmacological Effects ◽

Self Administration

Mephedrone (4-methylmethcathinone) is a synthetic cathinone with psychostimulant properties which remains one of the most popular new psychoactive substances (NPS). It is frequently used orally and/or intranasally. To date, no studies have evaluated the acute effects and pharmacokinetics after self-administration of mephedrone orally (ingestion) and intranasally (insufflation) in naturalistic conditions. An observational study was conducted to assess and compare the acute pharmacological effects, as well as the oral fluid (saliva) concentrations of mephedrone self-administered orally and intranasally. Ten healthy experienced drug users (4 females and 6 males) self-administered a single dose of mephedrone, orally (n = 5, 100–200 mg; mean 150 mg) or intranasally (n = 5, 50–100 mg, mean 70 mg). Vital signs (blood pressure, heart rate, and cutaneous temperature) were measured at baseline (0), 1, 2, and 4 h after self-administration. Each participant completed subjective effects questionnaires: A set of Visual Analogue Scales (VAS), the 49-item Addiction Research Centre Inventory (ARCI), and Evaluation of the Subjective Effects of Substances with Abuse Potential (VESSPA-SSE) at baseline, 1, 2, and 4 h after self-administration. Oral fluid and urine were collected during 4 h. Both routes of mephedrone self-administration enhanced ratings of euphoria and well-being effects and increased cardiovascular effects in humans. Although it was at times assessed that the oral route produced greater and larger effects than the intranasal one, concentrations of mephedrone in oral fluid and also the total amount of mephedrone and metabolites in urine showed that concentrations of mephedrone are considerably higher when self-administered intranasally in comparison to orally. Controlled clinical trials are needed to confirm our observational results.

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Emotional breakthrough and psychedelics: Validation of the Emotional Breakthrough Inventory

Journal of Psychopharmacology ◽

10.1177/0269881119855974 ◽

2019 ◽

Vol 33 (9) ◽

pp. 1076-1087 ◽

Cited By ~ 16

Author(s):

Leor Roseman ◽

Eline Haijen ◽

Kelvin Idialu-Ikato ◽

Mendel Kaelen ◽

Rosalind Watts ◽

...

Keyword(s):

Mystical Experience ◽

Well Being ◽

Mental Wellbeing ◽

Distinct Component ◽

Psychological Changes ◽

Before And After ◽

High Internal Consistency ◽

Prior Hypothesis ◽

Experience Questionnaire

Background: Psychedelic therapy is gaining recognition and the nature of the psychedelic experience itself has been found to mediate subsequent long-term psychological changes. Much emphasis has been placed on the occurrence of mystical-type experiences in determining long-term responses to psychedelics yet here we demonstrate the importance of another component, namely: emotional breakthrough. Methods: Three hundred and seventy-nine participants completed online surveys before and after a planned psychedelic experience. Items pertaining to emotional breakthrough were completed one day after the psychedelic experience, as were items comprising the already validated Mystical Experience Questionnaire and the Challenging Experience Questionnaire. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores were used to predict changes in well-being (Warwick-Edinburgh Mental Wellbeing Scale) in a subsample of 75 participants with low well-being baseline scores (⩽45). Results: Factor analyses revealed six emotional breakthrough items with high internal consistency (Cronbach’s alpha=0.932) and supported our prior hypothesis that emotional breakthrough is a distinct component of the psychedelic experience. Emotional breakthrough scores behaved dose-dependently, and were higher if the psychedelic was taken with therapeutic planning and intent. Emotional breakthrough, Mystical Experience Questionnaire and Challenging Experience Questionnaire scores combined, significantly predicted subsequent changes in well-being ( r=0.45, p=0.0005, n=75), with each scale contributing significant predictive value. Emotional breakthrough and Mystical Experience Questionnaire scores predicted increases in well-being and Challenging Experience Questionnaire scores predicted less increases. Conclusions: Here we validate a six-item ‘Emotional Breakthrough Inventory’. Emotional breakthrough is an important and distinct component of the acute psychedelic experience that appears to be a key mediator of subsequent longer-term psychological changes. Implications for psychedelic therapy are discussed.

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Inhaled 5-methoxy-N,N-dimethyltryptamine: Supportive context associated with positive acute and enduring effects

Journal of Psychedelic Studies ◽

10.1556/2054.2019.033 ◽

2019 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Nathan D. Sepeda ◽

John M. Clifton ◽

Laura Y. Doyle ◽

Rafael Lancelotta ◽

Roland R. Griffiths ◽

...

Keyword(s):

Mystical Experience ◽

Experimental Studies ◽

Secondary Data ◽

Well Being ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Short Acting ◽

Positive Effects ◽

Interactive Relationship ◽

Experience Questionnaire

Background and aims 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) is a potent, short-acting psychedelic that produces strong hallucinogenic effects. The association between the context (i.e., set and setting) of 5-MeO-DMT use and the acute and enduring effects of the substance is unknown. Therefore, this study examined these associations using secondary data from two cross-sectional survey studies. Methods The acute and enduring effects of inhaled synthetic 5-MeO-DMT were compared between individuals who used 5-MeO-DMT in a non-structured context (NSC; n = 216, female = 10%, Mage = 35.5, SD = 11.8) and those who used in a structured context (SC; n = 362, female = 45%, Mage = 47.7, SD = 13.3). Questionnaires were administered online and responses were anonymized for privacy purposes. Respondents were asked to retrospectively rate their first experience with synthesized 5-MeO-DMT on measures of mystical experience, challenging experience, and enduring effects. Results Both groups endorsed high ratings on the Mystical Experience Questionnaire; however, mean scores were significantly higher in the SC group compared to the NSC group. Similarly, the proportion of respondents who had a complete mystical experience was significantly larger in the SC group (83%) compared to the NSC group (54%). Ratings of enduring effects (i.e., meaningfulness, spirituality, and well-being) were also significantly higher, and the intensity of challenging experiences was significantly lower, in the SC group compared to the NSC group. Conclusions 5-MeO-DMT appears to occasion mystical-type experiences with enduring positive effects, which are more intense when 5-MeO-DMT is administered in a safe and supportive context. Future prospective experimental studies should examine the effects of 5-MeO-DMT and its interactive relationship with supportive contextual factors.

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Psychedelic experience dose-dependently modulated by cannabis: results of a prospective online survey

Psychopharmacology ◽

10.1007/s00213-021-05999-1 ◽

2021 ◽

Author(s):

Joanna Kuc ◽

Hannes Kettner ◽

Fernando Rosas ◽

David Erritzoe ◽

Eline Haijen ◽

...

Keyword(s):

Online Survey ◽

Mystical Experience ◽

Subjective Effects ◽

Analysis Of Covariance ◽

Altered States ◽

Subjective Experiences ◽

Novel Treatments ◽

States Of Consciousness ◽

Contextual Setting ◽

Experience Questionnaire

Abstract Rationale. Classic psychedelics are currently being studied as novel treatments for a range of psychiatric disorders. However, research on how psychedelics interact with other psychoactive substances remains scarce. Objectives The current study aimed to explore the subjective effects of psychedelics when used alongside cannabis. Methods Participants (n = 321) completed a set of online surveys at 2 time points: 7 days before, and 1 day after a planned experience with a serotonergic psychedelic. The collected data included demographics, environmental factors (so-called setting) and five validated questionnaires: Mystical Experience Questionnaire (MEQ), visual subscales of Altered States of Consciousness Questionnaire (ASC-Vis), Challenging Experience Questionnaire (CEQ), Ego Dissolution Inventory (EDI) and Emotional Breakthrough Inventory (EBI). Participants were grouped according to whether they had reported using no cannabis (n = 195) or low (n = 53), medium (n = 45) or high (n = 28) dose, directly concomitant with the psychedelic. Multivariate analysis of covariance (MANCOVA) and contrasts was used to analyse differences in subjective effects between groups while controlling for potential confounding contextual ‘setting’ variables. Results The simultaneous use of cannabis together with classic serotonergic psychedelics was associated with more intense psychedelic experience across a range of measures: a linear relationship was found between dose and MEQ, ASC-Vis and EDI scores, while a quadratic relationship was found for CEQ scores. No relationship was found between the dose of cannabis and the EBI. Conclusions Results imply a possible interaction between the cannabis and psychedelic on acute subjective experiences; however, design limitations hamper our ability to draw firm inferences on directions of causality and the clinical implications of any such interactions.

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Interactions between mephedrone and alcohol in humans: Cardiovascular and subjective effects

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.122 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S115-S115 ◽

Cited By ~ 3

Author(s):

M. Farré ◽

C. Perez-Maña ◽

E. de Souza ◽

J. Mateus ◽

E. Theunisen ◽

...

Keyword(s):

Short Form ◽

Subjective Effects ◽

Vital Signs ◽

Cardiovascular Effects ◽

Well Being ◽

Abuse Liability ◽

Double Blind ◽

New Novel ◽

Synthetic Cathinone ◽

Competing Interest

IntroductionMephedrone is a synthetic cathinone derivative included in the class of “New-Novel Psychoactive Substances”. Synthetic cathinones are marketed as “bath salts” or “plant food” and gained notable popularity for similar effects to 4-methylenedioxymethamphetamine (MDMA, ecstasy), or amphetamines. Mephedrone is commonly consumed simultaneously with alcohol.Objectives and aimsThe aim of the present study was to evaluate the interactions between mephedrone and ethanol in humans.MethodsTwelve healthy male, recreational users of psychostimulants participated as outpatients in four experimental sessions. They received a single oral dose of mephedrone (200 mg) and alcohol (0.8 g/kg), mephedrone placebo and alcohol (0.8 g/kg), mephedrone (200 mg) and placebo alcohol, and both placebos. Design was double-blind, double-dummy, randomized, cross-over and controlled with placebo. Study variables included: vital signs (blood pressure, heart rate, temperature, and pupil diameter), subjective effects (visual analogue scales-VAS, ARCI-49 item short form, and VESSPA questionnaire).ResultsThe combination produced an increase in the cardiovascular effects of mephedrone and induced more intense feeling of euphoria and well-being in comparison to mephedrone and alcohol. Mephedrone reduced the drunkenness and sedation produced by alcohol.ConclusionsThese results are similar to those obtained with the combination of other psychostimulants as amphetamines and MDMA. Abuse liability of the combination is greater that induced by mephedrone.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Measuring Impact of Stress in Sandwich Generation Caring for Demented Parents

GeroPsych ◽

10.1024/1662-9647/a000114 ◽

2014 ◽

Vol 27 (4) ◽

pp. 171-179 ◽

Cited By ~ 6

Author(s):

Laurence M. Solberg ◽

Lauren B. Solberg ◽

Emily N. Peterson

Keyword(s):

Factor Analysis ◽

Exploratory Factor Analysis ◽

Social Worker ◽

Resource Availability ◽

Well Being ◽

Sandwich Generation ◽

Item Questionnaire ◽

Significant Difference ◽

Adult Caregivers ◽

The Impact

Stress in caregivers may affect the healthcare recipients receive. We examined the impact of stress experienced by 45 adult caregivers of their elderly demented parents. The participants completed a 32-item questionnaire about the impact of experienced stress. The questionnaire also asked about interventions that might help to reduce the impact of stress. After exploratory factor analysis, we reduced the 32-item questionnaire to 13 items. Results indicated that caregivers experienced stress, anxiety, and sadness. Also, emotional, but not financial or professional, well-being was significantly impacted. There was no significant difference between the impact of caregiver stress on members from the sandwich generation and those from the nonsandwich generation. Meeting with a social worker for resource availability was identified most frequently as a potentially helpful intervention for coping with the impact of stress.

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Finnish refugee children’s experiences of Swedish refugee camps during the Second World War

MIGRATION LETTERS ◽

10.33182/ml.v12i1.254 ◽

2015 ◽

Vol 12 (1) ◽

pp. 28-37

Author(s):

Merja Paksuniemi

Keyword(s):

Well Being ◽

Second World War ◽

Refugee Children ◽

Refugee Camps ◽

World War ◽

Daily Routines ◽

Decisive Importance ◽

Significant Difference ◽

Camp Life ◽

Second World

This article seeks to demonstrate how Finnish refugee children experienced living in Swedish refugee camps during the Second World War (1939–1945). The study focuses on children’s opinions and experiences reflected through adulthood. The data were collected through retrospective interviews with six adults who experienced wartime as children in Finland and were evacuated to Sweden as refugees. Five of the interviewees were female and one of them was male. The study shows, it was of decisive importance to the refugee children’s well-being to have reliable adults around them during the evacuation and at the camps. The findings demonstrate that careful planning made a significant difference to the children´s adaptations to refugee camp life. The daily routines at the camp, such as regular meals, play time and camp school, reflected life at home and helped the children to continue their lives, even under challenging circumstances.

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Isolation of an Anti-fatigue Preparation from Cellulase-treated Maca by Hydroalcoholic Extraction

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.17:93-98 ◽

2017 ◽

Vol 17 (1) ◽

pp. 93-98

Author(s):

Zheng Yue ◽

Zhang Wen-Cheng ◽

Wu Ze-Yu ◽

Fu Chuan-Xiang ◽

Gao Han ◽

...

Keyword(s):

Positive Control ◽

Glycogen Storage ◽

Hepatic Glycogen ◽

Time To Exhaustion ◽

High Dose ◽

Hydroalcoholic Extract ◽

Swimming Time ◽

Significant Difference ◽

Pre Treatment ◽

Better Than

The purpose of this study was to evaluate the anti-fatigue activity of maca hydroalcoholic extract (ME), which mainly contains macamides and polysaccharides. ME was prepared by circumfluence extraction with enzymatic pre-treatment. Anti-fatigue activity of ME was investigated in weight-loaded forced swimming mice, with pure macamides and commercially available maca tablet as positive control. Compared with normal group, pure macamides treatment group could prolong the swimming time to exhaustion, but there was no statistically significant difference (P > 0.05); while ME (middle-dose and high-dose groups) could effectively prolong the swimming durations (P < 0.05). Supplementation with pure macamides significantly decreased blood lactic acid (BLA), whereas ME significantly increased hepatic glycogen (HG), decreased BLA, and blood urea nitrogen (BUN) compared with those in normal control (P < 0.05). The results suggested that the anti-fatigue effect of ME was better than that of pure macamides, which can be explained by the increase of glycogen storage and the reduction of metabolites accumulation.

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