Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study

Background: Microdoses of psychedelics (i.e. a sub-hallucinogenic dose taken every third day) can reduce symptoms of depression, anxiety and stress according to anecdotal reports and observational studies. Research with medium to high doses of psilocybin points towards potential underlying mechanisms, including the modulation of emotion and interoceptive processing. Aims: In this preregistered study, we investigated whether psilocybin microdoses alter self-reported interoceptive awareness and whether repeated microdosing over 3 weeks modulates emotion processing and reduces symptoms of anxiety and depression. Methods: We used a double-blind, placebo-controlled, within-subject crossover design. Participants completed the Multidimensional Assessment of Interoceptive Awareness Questionnaire 1½ h after self-administering their second dose (or placebo), and the emotional go/no-go task and the shortened Depression Anxiety Stress Scale 1½ h after self-administering their seventh dose. Results: Our confirmatory analyses revealed that psilocybin microdosing did not affect emotion processing or symptoms of anxiety and depression compared with placebo. Our exploratory analyses revealed that psilocybin microdosing did not affect self-reported interoceptive awareness, that symptoms of depression and stress were significantly reduced in the first block compared with baseline, that participants broke blind in the second block and that there was no effect of expectations. Further research in a substance-naïve population with clinical range anxiety and depressive symptoms is needed to substantiate the potential beneficial effects of microdosing.

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The benefit of a supplement with the antioxidant melatonin on redox status and muscle damage in resistance-trained athletes

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0677 ◽

2017 ◽

Vol 42 (7) ◽

pp. 700-707 ◽

Cited By ~ 16

Author(s):

Roberto C. Leonardo-Mendonça ◽

Javier Ocaña-Wilhelmi ◽

Tomás de Haro ◽

Carlos de Teresa-Galván ◽

Eduardo Guerra-Hernández ◽

...

Keyword(s):

Oxidative Stress ◽

Muscle Damage ◽

Antioxidant Properties ◽

Redox Status ◽

Absorption Capacity ◽

Double Blind ◽

Beneficial Effects ◽

Before And After ◽

High Doses ◽

Exercise Induced

Previous data showed that the administration of high doses of melatonin improved the circadian system in athletes. Here, we investigated in the same experimental paradigm whether the antioxidant properties of melatonin has also beneficial effects against exercise-induced oxidative stress and muscle damage in athletes. Twenty-four athletes were treated with 100 mg·day−1 of melatonin or placebo 30 min before bedtime during 4 weeks in a randomized double-blind scheme. Exercise intensity was higher during the study that before starting it. Blood samples were collected before and after treatment, and plasma was used for oxygen radical absorption capacity (ORAC), lipid peroxidation (LPO), nitrite plus nitrate (NOx), and advanced oxidation protein products (AOPP) determinations. Glutathione (GSH), glutathione disulphide (GSSG) levels, and glutathione peroxidase (GPx) and reductase (GRd) activities, were measured in erythrocytes. Melatonin intake increased ORAC, reduced LPO and NOx levels, and prevented the increase of AOPP, compared to placebo group. Melatonin was also more efficient than placebo in reducing GSSG·GSH−1 and GPx·GRd−1 ratios. Melatonin, but not placebo, reduced creatine kinase, lactate dehydrogenase, creatinine, and total cholesterol levels. Overall, the data reflect a beneficial effect of melatonin treatment in resistance-training athletes, preventing extra- and intracellular oxidative stress induced by exercise, and yielding further skeletal muscle protection against exercise-induced oxidative damage.

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The combination of fluoxetine and environmental enrichment reduces postpartum stress-related behaviors through the oxytocinergic system and HPA axis in mice

Scientific Reports ◽

10.1038/s41598-021-87800-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hamideh Bashiri ◽

Danielle J. Houwing ◽

Judith R. Homberg ◽

Ali-Akbar Salari

Keyword(s):

Postpartum Depression ◽

Hpa Axis ◽

Environmental Enrichment ◽

Anxiety And Depression ◽

Central Administration ◽

Postpartum Stress ◽

High Doses ◽

Underlying Mechanisms ◽

Gestational Stress ◽

The Impact

AbstractGestational stress can increase postpartum depression in women. To treat maternal depression, fluoxetine (FLX) is most commonly prescribed. While FLX may be effective for the mother, at high doses it may have adverse effects on the fetus. As environmental enrichment (EE) can reduce maternal stress effects, we hypothesized that a subthreshold dose of FLX increases the impact of EE to reduce anxiety and depression-like behavior in postpartum dams exposed to gestational stress. We evaluated this hypothesis in mice and to assess underlying mechanisms we additionally measured hypothalamic–pituitary–adrenal (HPA) axis function and brain levels of the hormone oxytocin, which are thought to be implicated in postpartum depression. Gestational stress increased anxiety- and depression-like behavior in postpartum dams. This was accompanied by an increase in HPA axis function and a decrease in whole-brain oxytocin levels in dams. A combination of FLX and EE remediated the behavioral, HPA axis and oxytocin changes induced by gestational stress. Central administration of an oxytocin receptor antagonist prevented the remediating effect of FLX + EE, indicating that brain oxytocin contributes to the effect of FLX + EE. These findings suggest that oxytocin is causally involved in FLX + EE mediated remediation of postpartum stress-related behaviors, and HPA axis function in postpartum dams.

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Tolerance and the effect of high doses of wheat bran extract, containing arabinoxylan–oligosaccharides, and oligofructose on faecal output: a double-blind, randomised, placebo-controlled, cross-over trial

Journal of Nutritional Science ◽

10.1017/jns.2014.52 ◽

2014 ◽

Vol 3 ◽

Cited By ~ 10

Author(s):

Isabelle E. J. A. François ◽

Olivier Lescroart ◽

Wim S. Veraverbeke ◽

Karen Windey ◽

Kristin Verbeke ◽

...

Keyword(s):

Wheat Bran ◽

Random Order ◽

Double Blind ◽

Moisture Concentration ◽

Faecal Output ◽

Soluble Fibre ◽

Beneficial Effects ◽

Gi Symptoms ◽

High Doses ◽

Wheat Bran Extract

AbstractWheat bran extract (WBE) is a food-grade soluble fibre preparation that is highly enriched in arabinoxylan–oligosaccharides. In this placebo-controlled cross-over human intervention trial, tolerance to WBE as well as the effects of WBE on faecal parameters, including faecal output and bowel habits, were studied. After a 2-week run-in period, twenty healthy volunteers consumed WBE (15 g/d in the first week, 30 g/d in the second week), oligofructose (15 g/d in the first week, 30 g/d in the second week) and placebo (for 2 weeks) in a random order, with 2-week washout periods between each treatment period. Subjects collected a 72 h stool sample for analysis of faecal output, stool pH and stool moisture concentration. Additionally, the volunteers completed questionnaires scoring occurrence frequency and distress severity of eighteen gastrointestinal (GI) symptoms. An overall GI symptom measure was calculated to analyse the overall effect of WBE and oligofructose on GI symptoms. Intake of both 30 g/d WBE and 30 g/d oligofructose lowered stool pH, indicative of increased colonic fermentation, and increased stool moisture concentration as compared with placebo intake. Intake of 30 g/d oligofructose increased the overall GI symptom measure by 1·9-fold as compared with placebo intake. Intake of WBE at doses up to 30 g/d did not affect the overall GI symptom measure. WBE exerts beneficial effects on stool characteristics and is well tolerated at up to 30 g/d. Oligofructose exerts comparable beneficial effects on stool characteristics. However, intake of 30 g/d oligofructose appears to cause GI discomfort to some extent.

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Beneficial effects of dark chocolate on exercise capacity in sedentary subjects: underlying mechanisms. A double blind, randomized, placebo controlled trial

Food & Function ◽

10.1039/c6fo00611f ◽

2016 ◽

Vol 7 (9) ◽

pp. 3686-3693 ◽

Cited By ~ 23

Author(s):

Pam R. Taub ◽

Israel Ramirez-Sanchez ◽

Minal Patel ◽

Erin Higginbotham ◽

Aldo Moreno-Ulloa ◽

...

Keyword(s):

Exercise Capacity ◽

Controlled Trial ◽

Dark Chocolate ◽

Double Blind ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Sedentary Subjects

We wished to examine the effects of dark chocolate on sedentary individuals' exercise capacity and underlying mechanisms.

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Moderating Role of Stress, Anxiety, and Depression in the Relationship Between Tinnitus and Hearing Loss Among Patients

Pakistan Journal of Psychological Research ◽

10.33824/pjpr.2019.34.4.41 ◽

2020 ◽

Vol 34 (4) ◽

pp. 753-772

Author(s):

Ammar Ahmed ◽

Muhammad Aqeel ◽

Tanvir Akhtar ◽

Sammeen Salim ◽

Bashir Ahmed

Keyword(s):

Hearing Loss ◽

Psychological Problems ◽

Anxiety And Depression ◽

Adaptation Level ◽

Depression Anxiety Stress Scale ◽

Neuropsychological Theory ◽

Anxiety Depression ◽

The Relationship ◽

Moderating Role

Adaptation level theory of tinnitus and neuropsychological theory of tinnitus are extensively used frameworks for understanding emotional and psychological distress among tinnitus sufferers. Objective of the present study was to investigate potential associations between hearing loss, tinnitus, anxiety, depression, and stress. The Tinnitus Handicap Inventory (Newman, Jacobson, & Spitzer, 1996) and the Depression, Anxiety, Stress Scale (Lovibond & Lovibond, 1995)scales were administered to a sample of 110 tinnitus outpatients recruited from Audiology departments of Lahore and Rawalpindi hospitals. Results revealed tinnitus was positively linked with psychological problems. Additionally, it was established that tinnitus is a positive significant predictor for anxiety, stress and depression. The moderation models related to the interactions between psychological problems and hearing loss were negative significant predictors for tinnitus symptoms. Moreover, the comparative analysis between gender differences revealed a significant diversity in the levels of stress, anxiety, and depression. Results also elucidated that patients at initial stages of hearing loss were more prone towards reporting tinnitus symptoms along with emerging psychological problems.

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Augmentation Strategies for Clozapine-Resistant Patients with Schizophrenia

Current Pharmaceutical Design ◽

10.2174/1381612826666200110102254 ◽

2020 ◽

Vol 26 (2) ◽

pp. 218-227

Author(s):

Yi-Hang Chiu ◽

Chia-Yueh Hsu ◽

Mong-Liang Lu ◽

Chun-Hsin Chen

Keyword(s):

Sample Size ◽

Repetitive Transcranial Magnetic Stimulation ◽

Mood Stabilizers ◽

Treatment Resistant ◽

Double Blind ◽

Beneficial Effects ◽

Augmentation Strategies ◽

Pubmed Database ◽

Augmentation Strategy ◽

Larger Sample

Background: Clozapine has been used in treatment-resistant patients with schizophrenia. However, only 40% of patients with treatment-resistant schizophrenia have response to clozapine. Many augmentation strategies have been proposed to treat those clozapine-resistant patients, but the results are inconclusive. In this review, we intended to review papers dealing with the augmentation strategies in the treatment of clozapineresistant patients with schizophrenia. Method: We reviewed randomized, double-blind, placebo- or sham-controlled trials (RCT) for clozapine-resistant patients with schizophrenia in Embase, PsycINFO, Cochrane, and PubMed database from January 1990 to June 2019. Results: Antipsychotics, antidepressants, mood stabilizers, brain stimulation, such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation, and other strategies, were used as an augmentation in clozapine-resistant patients with schizophrenia. Except for better evidence in memantine with 2 RCTs and cognitive behavior therapy in 2 studies to support its effectiveness, we found that all the other effective augmentations, including sulpiride, ziprasidone, duloxetine, mirtazapine, ECT, sodium benzoate, ginkgo biloba, and minocycline, had only one RCT with limited sample size. Conclusion: In this review, no definite effective augmentation strategy was found for clozapine-resistant patients. Some potential strategies with beneficial effects on psychopathology need further studies with a larger sample size to support their efficacy.

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Dehulled Adlay Consumption Modulates Blood Pressure in Spontaneously Hypertensive Rats and Overweight and Obese Young Adults

Nutrients ◽

10.3390/nu13072305 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2305

Author(s):

Wan-Ju Yeh ◽

Jung Ko ◽

Wei-Yi Cheng ◽

Hsin-Yi Yang

Keyword(s):

Blood Pressure ◽

Daily Intake ◽

Experimental Period ◽

Overweight And Obesity ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Grain Foods

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group’s systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.

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Beneficial effects of natural compounds on experimental liver ischemia-reperfusion injury

Food & Function ◽

10.1039/d1fo00289a ◽

2021 ◽

Author(s):

Camila Dossi ◽

Romina Vargas ◽

Rodrigo Valenzuela ◽

Luis Videla

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Natural Compounds ◽

Liver Ischemia ◽

Hepatic Surgery ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Experimental Liver

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development...

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Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

Scientific Reports ◽

10.1038/s41598-021-94849-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Patricia Soriano Roque ◽

Mehdi Hooshmandi ◽

Laura Neagu-Lund ◽

Shelly Yin ◽

Noosha Yousefpour ◽

...

Keyword(s):

Cognitive Impairment ◽

Synaptic Plasticity ◽

General Anesthesia ◽

Preventive Treatment ◽

Intranasal Insulin ◽

Translational Repressor ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Induced Apoptosis ◽

Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

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In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

Scientific Reports ◽

10.1038/s41598-021-94228-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rosangela Montanaro ◽

Alessio D’Addona ◽

Andrea Izzo ◽

Carlo Ruosi ◽

Vincenzo Brancaleone

Keyword(s):

Inflammatory Markers ◽

In Vitro Study ◽

Inos Expression ◽

Beneficial Effects ◽

Tnf Α ◽

Inflammatory State ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

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