LSD, madness and healing: Mystical experiences as possible link between psychosis model and therapy model

Abstract Background For a century, psychedelics have been investigated as models of psychosis for demonstrating phenomenological similarities with psychotic experiences and as therapeutic models for treating depression, anxiety, and substance use disorders. This study sought to explore this paradoxical relationship connecting key parameters of the psychotic experience, psychotherapy, and psychedelic experience. Methods In a randomized, double-blind, placebo-controlled, crossover design, 24 healthy volunteers received 50 μg d-lysergic acid diethylamide (LSD) or inactive placebo. Psychotic experience was assessed by aberrant salience (Aberrant Salience Inventory, ASI), therapeutic potential by suggestibility (Creative Imagination Scale, CIS) and mindfulness (Five Facet Mindfulness Questionnaire, FFMQ; Mindful Attention Awareness Scale, MAAS; Experiences Questionnaire, EQ), and psychedelic experience by four questionnaires (Altered State of Consciousness Questionnaire, ASC; Mystical Experiences Questionnaire, MEQ; Challenging Experiences Questionnaire, CEQ; Ego-Dissolution Inventory, EDI). Relationships between LSD-induced effects were examined. Results LSD induced psychedelic experiences, including alteration of consciousness, mystical experiences, ego-dissolution, and mildly challenging experiences, increased aberrant salience and suggestibility, but not mindfulness. LSD-induced aberrant salience correlated highly with complex imagery, mystical experiences, and ego-dissolution. LSD-induced suggestibility correlated with no other effects. Individual mindfulness changes correlated with aspects of aberrant salience and psychedelic experience. Conclusions The LSD state resembles a psychotic experience and offers a tool for healing. The link between psychosis model and therapeutic model seems to lie in mystical experiences. The results point to the importance of meaning attribution for the LSD psychosis model and indicate that psychedelic-assisted therapy might benefit from therapeutic suggestions fostering mystical experiences.

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Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects

Clinical Science ◽

10.1042/cs0950719 ◽

1998 ◽

Vol 95 (6) ◽

pp. 719-724 ◽

Cited By ~ 34

Author(s):

C. Mark B. EDWARDS ◽

Jeannie F. TODD ◽

Mohammad A. GHATEI ◽

Stephen R. BLOOM

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Plasma Glucose ◽

Healthy Subjects ◽

Therapeutic Potential ◽

Double Blind ◽

Gut Hormone ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus. 2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined. 3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations. 4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.

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A phase 1 study of single and repeat oral doses of GSK3439171A, a highly selective H-PGDS inhibitor, in healthy adult participants

10.22541/au.162552379.93685989/v1 ◽

2021 ◽

Author(s):

Thomas Haws ◽

Nilay Thakkar ◽

Summer Goodson ◽

Caroline Sychterz ◽

Nisha George ◽

...

Keyword(s):

Therapeutic Potential ◽

Drug Hypersensitivity ◽

Phase 1 ◽

Geometric Mean ◽

Human Study ◽

Study Drug ◽

Prostaglandin D2 ◽

Dose Escalation Study ◽

Double Blind ◽

Oral Doses

Aim: Prostaglandin D2 (PGD2) is implicated in the pathophysiology of inflammatory diseases. GSK3439171A is a potent, reversible, and highly selective azetidine urea inhibitor of haematopoietic prostaglandin D synthase (H-PGDS, a key promoter of PGD2 production in several inflammatory cell types). Based on favourable preclinical data, we performed a first-time-in-human study to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK3439171A, and the effect of food on these parameters. Methods: This was a phase 1, randomized, double-blind, placebo-controlled, dose-escalation study. Single and repeat oral doses of GSK3439171A were administered to healthy males aged 18–65 years. Levels of inflammatory markers including tetranor-prostaglandin D metabolite (tPGDM) were measured in urine samples. Results: Sixty-six participants were enrolled, with 57 receiving GSK3439171A. Single doses (5–180 mg) and repeat once-daily doses (5 and 11 mg for 14 days; 40 mg for 7 days) were administered. Seven participants (12%) had adverse events (AEs) related to study drug, mainly drug hypersensitivity (n=4 [7%]; non-serious, transient skin rash). There were no serious AEs (SAEs) or clinically significant changes in vital signs, electrocardiogram, or laboratory parameters. Dose-proportional increases in Cmax and AUC(0–inf) were observed, and the geometric mean half-life of GSK3439171A was up to 12 hours. Results were similar when GSK3439171A was taken with or without food. No consistent suppression of tPGDM levels was observed. Conclusion: GSK3439171A was well tolerated in healthy participants and there were no SAEs. Selective inhibition of H-PGDS offers therapeutic potential for muscle-related disorders (e.g. Duchenne Muscular Dystrophy) and muscular recovery following injury.

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Overcoming epistemic injustices in the biomedical study of ayahuasca: Towards ethical and sustainable regulation

Transcultural Psychiatry ◽

10.1177/13634615211062962 ◽

2022 ◽

pp. 136346152110629

Author(s):

Eduardo Ekman Schenberg ◽

Konstantin Gerber

Keyword(s):

Traditional Medicine ◽

Traditional Knowledge ◽

Indigenous Peoples ◽

Biological Diversity ◽

Therapeutic Potential ◽

Indigenous Rights ◽

Benefit Sharing ◽

Convention On Biological Diversity ◽

Epistemic Authority ◽

Double Blind

After decades of biomedical research on ayahuasca's molecular compounds and their physiological effects, recent clinical trials show evidence of therapeutic potential for depression. However, indigenous peoples have been using ayahuasca therapeutically for a very long time, and thus we question the epistemic authority attributed to scientific studies, proposing that epistemic injustices were committed with practical, cultural, social, and legal consequences. We question epistemic authority based on the double-blind design, the molecularization discourse, and contextual issues about safety. We propose a new approach to foster epistemically fair research, outlining how to enforce indigenous rights, considering the Brazilian, Peruvian, and Colombian cases. Indigenous peoples have the right to maintain, control, protect, and develop their biocultural heritage, traditional knowledge, and cultural expressions, including traditional medicine practices. New regulations about ayahuasca must respect the free, prior, and informed consent of indigenous peoples according to the International Labor Organization Indigenous and Tribal Peoples Convention no. 169. The declaration of the ayahuasca complex as a national cultural heritage may prevent patenting from third parties, fostering the development of traditional medicine. When involving isolated compounds derived from traditional knowledge, benefit-sharing agreements are mandatory according to the United Nations’ Convention on Biological Diversity. Considering the extremely high demand to treat millions of depressed patients, the medicalization of ayahuasca without adequate regulation respectful of indigenous rights can be detrimental to indigenous peoples and their management of local environments, potentially harming the sustainability of the plants and of the Amazon itself, which is approaching its dieback tipping point.

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Therapeutic Potential of Choline Magnesium Trisalicylate as an Alternative to Aspirin for Patients with Bleeding Tendencies

Scottish Medical Journal ◽

10.1177/003693308703200603 ◽

1987 ◽

Vol 32 (6) ◽

pp. 167-168 ◽

Cited By ~ 11

Author(s):

B.J.Z. Danesh ◽

A.R. Saniabadi ◽

R.I. Russell ◽

G.D.O. Lowe

Keyword(s):

Salicylic Acid ◽

Platelet Aggregation ◽

Whole Blood ◽

Therapeutic Potential ◽

Ex Vivo ◽

Random Order ◽

Bleeding Complications ◽

Double Blind ◽

Inhibition Of Platelet Aggregation ◽

Spontaneous Aggregation

We have compared the effects of acetyl salicylic acid (ASA, aspirin) and choline magnesium trisalicylate (CMT), a non-acetylated salicylate product, on platelet aggregation in human whole blood ex-vivo. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen, arachidonic acid (AA), as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received, on two separate occasions 10 days apart, a single oral dose of 652 mg ASA or 655 mg CMT. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen (p<0.005), AA (p<0.01) and spontaneous aggregation (p<0.01), whereas such effects were not observed after CMT ingestion. We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

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COMPARISON OF THE EFFECT OF ASPIRIN (ASA) AND CHOLINE MAGNESIUM TRISALICYLATE (CMT) ON PLATELET AGGREGATION IN WHOLE BLOOD EX-VIVO

10.1055/s-0038-1644866 ◽

1987 ◽

Author(s):

B J Z Danesh ◽

A R Saniabadi ◽

R I Russell ◽

G D O Lowe ◽

C D Forbes

Keyword(s):

Platelet Aggregation ◽

Whole Blood ◽

Therapeutic Potential ◽

Ex Vivo ◽

Random Order ◽

Blood Platelet ◽

Bleeding Complications ◽

Double Blind ◽

Inhibition Of Platelet Aggregation ◽

Spontaneous Aggregation

Suppression of platelet aggregation by ASA limits the therapeutic use of this drug as an analgesic in patients with bleeding tendencies. CMT is a non-acetylated salicylate derivative with analgesic and anti-inflammatory effect similar to that of ASA. We compared platelet aggregation in human whole blood ex-vivo, three hours after ingestion of ASA and. CMT. Using a whole blood platelet counter, platelet aggregation was quantified by measuring the fall in the number of single platelets at peak aggregation in response to collagen (lμg/ml) arachidonic acid (AA, 0.5 mM) as well as spontaneous aggregation. In double blind and random order, 12 healthy volunteers received a single oral dose of ASA and CMT containing 500 mg equivalent salicylate, on two separate occasions, 10 days apart. Despite a comparable absorption of salicylic acid from the two drugs, ingestion of ASA resulted in a marked inhibition of platelet aggregation induced by collagen, AA and spontaneous aggregation, whereas such effects were not observed after CMT ingestion.We suggest that CMT may have therapeutic potential as an alternative to aspirin when inhibition of platelet aggregation can induce bleeding complications.

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F2695: A New Therapeutic Potential for Major Depression. A Phase II Double-blind Randomised Trial Results

European Psychiatry ◽

10.1016/s0924-9338(09)70603-0 ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

L. Mansuy

Keyword(s):

Major Depression ◽

Depressive Disorders ◽

Therapeutic Potential ◽

Randomised Trial ◽

Major Depressive ◽

Double Blind ◽

Efficacy Analysis ◽

Significant Difference ◽

Major Depressive Disorders ◽

The Difference

F2695 is a novel antidepressant exerts simultaneous noradrenergic and serotoninergic neurotransmitter effects.F2695 SR was administered in patients with Major Depression in a randomized, multinational, double-blind, placebo-controlled 10-week study, assessing the efficacy and safety of F2695 SR progressive titration safety adapted doses from 75 mg to 100 mg od, in out-patients with Major Depressive Disorders. The 563 randomized patients fulfilled the diagnostic criteria for Major Depressive Disorders and presented moderate or severe Major Depressive Disorders. Efficacy analysis found a significant difference between F2695 and placebo in favour of the active treatment in term of a significantly greater improvement in MADRS total score with F2695 compared with placebo (p< 0.0001). In addition, significantly more patients achieved MADRS response (a decrease in total score equal or superior to 50%) and MADRS remission (defined as a total score inferiorior to10) in the F2695 group than in the placebo group such an effect being usually not seen on this measure in the relatively short time span of a ten-week study. At the doses tested, F2695 was effective from early in the treatment (week 2) and the difference in efficacy compared with placebo increased steadily throughout the study.The severity to entry in this study was relatively high and the mean MADRS entry score was 31, about 40% of patients were in the severe category of depression.This study: provided evidence of the efficacy of F2695 in major depression population. Therapeutic effect was sustained in term of effect-size, responders and remissions rate, in front of placebo.

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Nα -Methyl Histamine Safety and Efficacy in Migraine Prophylaxis: Phase III Study

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100004960 ◽

2006 ◽

Vol 33 (2) ◽

pp. 195-199 ◽

Cited By ~ 22

Author(s):

Rebeca O. Millán-Guerrero ◽

Rebeca Isais-Millán ◽

Trujillo-Hernández Benjamín ◽

Carlos E. Tene

Keyword(s):

Therapeutic Potential ◽

International Headache Society ◽

Pharmacological Study ◽

Subcutaneous Administration ◽

Migraine Prophylaxis ◽

Phase Iii ◽

Controlled Clinical Trial ◽

Double Blind ◽

Adverse Experiences ◽

Phase Iii Study

ABSTRACT:Background:The histamine catabolite, Nα-methylhistamine, possesses a selective affinity for H3 receptors. For this reason, we considered evaluating the efficacy of this histaminergic H3 agonist in migraine prophylactic treatment.Objective:To study the therapeutic potential of the subcutaneous administration of Nα-methylhistamine in migraine prophylaxis, in a Phase III clinical pharmacological study.Methods:Using a controlled double-blind, placebo controlled clinical trial for 12 weeks, 60 patients with migraine, who fit the criteria established by the International Headache Society, were selected. The efficacy of subcutaneous administration of Nα-methylhistamine 1 to 3 ng twice a week against placebo was studied, evaluating the outcome of headache intensity, frequency, duration, and analgesic intake.Results:Comparison between the groups treated with placebo (n=30) and Nα-methylhistamine (n=30), on data collected for the 4th, 8th and 12th weeks of treatment, revealed that Nα-methylhistamine exerted a significant (p<0.0001) reduction (compared to placebo) in intensity, frequency, and duration of migraine attacks, as well as on the use of analgesic intake. No significant (p>0.05) adverse experiences or side effects developed in either group.Conclusions:The present study provides evidence of the efficacy of Nα-methylhistamine, given subcutaneously at doses of 1 to 3 ng twice a week, offering a new therapeutic alternative and laying the clinical and pharmacological groundwork for the use of histaminergic H3-agonists in migraine prophylaxis, which may specifically inhibit the neurogenic edema response involved in migraine pathophysiology.

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Locus coeruleus integrity and the effect of atomoxetine on response inhibition in Parkinson's disease

10.1101/2020.09.03.20176800 ◽

2020 ◽

Author(s):

Claire O'Callaghan ◽

Frank Hubert Hezemans ◽

Rong Ye ◽

Catarina Rua ◽

P Simon Jones ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Locus Coeruleus ◽

Response Inhibition ◽

Therapeutic Potential ◽

Reaction Times ◽

Stop Signal ◽

Stop Signal Task ◽

Double Blind ◽

Caudal Portion

Cognitive decline is a common feature of Parkinson's disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson's disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomised crossover design, 19 people with Parkinson's disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7T imaging of the locus coeruleus using a neuromelanin-sensitive magnetisation transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in Parkinson's disease patients. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalised treatment approaches.

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The Effects of Probiotic Supplementation on Anthropometric Growth and Gut Microbiota Composition in Patients With Prader-Willi Syndrome: A Randomized Double-Blinded Placebo-Controlled Trial

Frontiers in Nutrition ◽

10.3389/fnut.2021.587974 ◽

2021 ◽

Vol 8 ◽

Author(s):

Xue-Jun Kong ◽

Guobin Wan ◽

Ruiyi Tian ◽

Siyu Liu ◽

Kevin Liu ◽

...

Keyword(s):

Gut Microbiome ◽

Therapeutic Potential ◽

Controlled Trial ◽

Genetic Disorder ◽

Prader Willi Syndrome ◽

Gut Health ◽

Double Blind ◽

Microbiome Composition ◽

Bifidobacterium Animalis ◽

Probiotic Treatment

Background: Prader-Willi Syndrome (PWS) is a rare genetic disorder associated with developmental delay, obesity, and neuropsychiatric comorbidities. Bifidobacterium animalis subsp. lactis has demonstrated anti-obesity and anti-inflammatory effects in previous studies.Aim: To evaluate the effects of Bifidobacterium animalis subsp. lactis probiotics supplementation on anthropometric growth, behavioral symptoms, and gut microbiome composition in patients with PWS.Methods: Ethical Approval was issued by the Internal Review Board (IRB) of the Second Affiliated Hospital of Kunming Medical University (Review-YJ-2016-06). We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 68 patients with Prader-Willi syndrome aged 11 months−16 years (mean = 4.2 years old) who were randomly assigned to receive daily B. lactis-11 probiotics (6 × 1010 CFUs) or a placebo sachet. Weight, height, ASQ-3, ABC, SRS-2, and CGI-I were compared between the two groups at baseline and at 6 and 12 weeks into treatment. Gut microbiome data were analyzed with the QIIME 2 software package, and functional gene analysis was conducted with PICRUSt-2.Results: We found a significant increase in height (mean difference = 2.68 cm, P < 0.05) and improvement in CGI-I (P < 0.05) in the probiotics group compared to the placebo group. No significant change in weight or psychological measures were observed. Probiotic treatment altered the microbiome composition to favor weight loss and gut health and increased the abundance of antioxidant production-related genes.Conclusions: The findings suggest a novel therapeutic potential for Bifidobacterium animalis subsp. lactis probiotics in Prader-Willi syndrome patients, although further investigation is warranted.

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Efficacy of probiotics in irritable bowel syndrome: A randomized, double blind placebo-controlled study

Bangabandhu Sheikh Mujib Medical University Journal ◽

10.3329/bsmmuj.v6i1.29020 ◽

2016 ◽

Vol 6 (1) ◽

pp. 21 ◽

Cited By ~ 1

Author(s):

Md. Zahidur Rahman ◽

Mohammad Shoaib Chowdhury ◽

Mohammad Asadur Rahman ◽

Shohely Parveen ◽

Rajib Barua ◽

...

Keyword(s):

Irritable Bowel Syndrome ◽

Placebo Group ◽

Intestinal Microbiota ◽

Therapeutic Potential ◽

Intestinal Barrier ◽

Controlled Study ◽

Double Blind ◽

Before And After ◽

Irritable Bowel

Background: Gut flora have important trophic effects on intestinal epithelia and on immune structure and fonction.They also protect colonized host against invasion by alien microbes.Recent research suggests that an imbalance of the intestinal microbiota and a dysfunctional intestinal barrier might trigger irritable bowel syndrome (lBS). As probiotics have been reported to restore the intestinal microbiota and the gut barrier, the therapeutic potential of probiotics within IBS became of strong interest. Objectives: To assess the efficacy of probiotics in lBS. Methods: Patients of 15 to 60 years old and both sexes were included f om the out patient department (OPD) of gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU). A validated lBS-QOL instmment consisted of 34 questions used to assess improvement of quality of Iife before and after treatment. A total of 65 diarrhoea predominant LBS patients were randomised to receive either probiotics(n-33) or placebo(n-32) twice daily frir 6 weeks.Results: At the end of 6 weeks therapy, improvement in various symptoms(abclominal pain, stool frequency, consistency and 11atulence) in probiotics group was statistically significant. Mean QOL score before treatment was 103 in probiotics group and I 06 in placebo group. After 6 weeks of treatment mean QOL score was 82 in probiotics group and I 02.58 in placebo group. No side effects of the therapeutic agents were observed in any patient during the trial. Conclusions: Probiotics effectively alleviates global IBS and improves TBS symptoms simultaneously with an improvement of quality of life.

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