scholarly journals Role of the 5-HT2A Receptor in Acute Effects of LSD on Empathy and Circulating Oxytocin

2021 ◽  
Vol 12 ◽  
Author(s):  
Friederike Holze ◽  
Isidora Avedisian ◽  
Nimmy Varghese ◽  
Anne Eckert ◽  
Matthias E. Liechti
Keyword(s):  
Random Order ◽  
Therapeutic Effects ◽  
Acute Effects ◽  
Emotional Empathy ◽  
Double Blind ◽  
Mediating Role ◽  
Oxytocin Release ◽  
Implicit And Explicit ◽  
Primary Action

The psychedelic lysergic acid diethylamide (LSD) has experienced a revival in research, including clinical trials that evaluate LSD-assisted psychotherapy. LSD induces perceptual alterations and influences emotion processing in ways that may support psychotherapy. Here, we investigated the effects of LSD on emotional empathy and mediating role of the serotonin 5-hydroxytryptamine-2A (5-HT2A) receptor by administering 25, 50, 100, and 200 µg LSD alone and 200 µg LSD combined with pretreatment with the 5-HT2A receptor antagonist ketanserin (40 mg) using a placebo-controlled, double-blind, random-order, crossover design in 16 healthy subjects. The Multifaceted Empathy Test (MET) was used to assess the effects of LSD on emotional empathy. Plasma oxytocin levels were also measured. LSD dose-dependently increased implicit and explicit emotional empathy, with the highest 200 µg LSD dose having a significant effect compared with placebo. The 200 µg dose of LSD also moderately increased plasma oxytocin levels compared with placebo. Ketanserin reduced the LSD-induced elevations of oxytocin but not the LSD-induced increases in emotional empathy. These findings confirm that LSD enhances empathy, and this effect may be partially independent of its primary action on 5-HT2A receptors to induce subjective psychedelic effects. In contrast, LSD-induced oxytocin release may depend on 5-HT2A receptor stimulation, which is consistent with the psychedelic effect of LSD. Further studies are needed to investigate whether LSD may also enhance empathy and potentially produce therapeutic effects in patients who have deficits in empathy and impairments in social functioning.

scholarly journals Brain dopamine response in human opioid addiction

2008 ◽  
Vol 193 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Mark R.C. Daglish ◽  
Tim M. Williams ◽  
Sue J. Wilson ◽  
Lindsay G. Taylor ◽  
Chin B. Eap ◽  
...  
Keyword(s):  
Dopamine Release ◽  
Subjective Experience ◽  
Methadone Maintenance ◽  
Random Order ◽  
Rat Striatum ◽  
Dopamine System ◽  
Double Blind ◽  
Brain Scans ◽  
Positron Emission

BackgroundDrugs of dependence cause dopamine release in the rat striatum. Human neuroimaging studies have shown an increase in dopamine in the equivalent region in response to stimulants and other drugsAimsWe tested whether opioids provoke dopamine release and its relationship to the subjective experienceMethodIn two combined studies 14 heroin addicts on methadone maintenance treatment underwent two positron emission tomography brain scans of the dopamine system using [11C]-raclopride following an injection of placebo and either 50 mg intravenous diamorphine or 10 mg subcutaneous hydromorphone in a double-blind, random order designResultsBoth opioids produced marked subjective and physiological effects, but no measurable change in [11C]-raclopride bindingConclusionsThe absence of a dopamine response to opioid agonists contrasts with that found with stimulant drugs and suggests dopamine may not play the same role in addiction to opioids. This questions the role of dopamine in the subjective experience of heroin in opioid addicts

scholarly journals Negative arousability and relationship satisfaction: The mediating role of empathy

2019 ◽  
Vol 22 (1) ◽  
pp. 73-90
Author(s):  
Ariadna B. Łada ◽  
Maria Kaźmierczak
Keyword(s):  
Relationship Satisfaction ◽  
Emotional Regulation ◽  
Short Form ◽  
Empathic Concern ◽  
Personal Distress ◽  
Emotional Empathy ◽  
Mediating Role ◽  
The Relationship

Temperamental traits and empathy are both associated with emotional regulation; they thus shape both the quality of an individual’s life and the functioning of his or her social relationships. However, the mediating effects of emotional empathy in the relationship between temperamental characteristics and relationship satisfaction have not been closely analyzed and therefore require further study. This study examined the effects of temperamental arousability – global negative arousability and its components (fear, sadness, discomfort, frustration) – on emotional empathy and, consequently, on relationship satisfaction. One hundred and fifty young adults (104 women, 46 men) aged 20 to 35 participated in the study. The participants had been in romantic relationships for at least six months. The study used a sociodemographic survey and a set of questionnaires which included the Adult Temperament Questionnaire – Short Form, the Empathic Sensitiveness Scale and the RELAT Questionnaire. The results showed that empathic concern fully mediated the relationship between global negative arousability and relationship satisfaction. Furthermore, the effects of fear and sadness on relationship satisfaction were fully mediated by empathic concern and personal distress. Additionally, personal distress fully mediated the relationship between discomfort and relationship satisfaction. Neither empathic concern nor personal distress were mediators in the relationship between frustration and relationship satisfaction. It can therefore be concluded that although partners who exhibit higher global negative arousability report lower relationship satisfaction, they might become more satisfied when being more compassionate and caring towards others.

scholarly journals Diuretic effect of hypoxia, hypocapnia, and hyperpnea in humans: relation to hormones and O2 chemosensitivity

2000 ◽  
Vol 88 (2) ◽  
pp. 599-610 ◽  
Author(s):  
Wulf Hildebrandt ◽  
Andy Ottenbacher ◽  
Markus Schuster ◽  
Erik R. Swenson ◽  
Peter Bärtsch
Keyword(s):  
Random Order ◽  
Systemic Blood Pressure ◽  
Urine Flow ◽  
Hypoxic Ventilatory Response ◽  
Venous Compliance ◽  
Double Blind ◽  
Diuretic Response ◽  
Male Subjects ◽  
Sodium Clearance

We studied the contributions of hypoxemia, hypocapnia, and hyperpnea to the acute hypoxic diuretic response (HDR) in humans and evaluated the role of peripheral O2 chemosensitivity and renal hormones in HDR. Thirteen healthy male subjects (age 19–38 yr) were examined after sodium equilibration (intake: 120 mmol/day) during 90 min of normoxia (NO), poikilocapnic hypoxia (PH), and isocapnic hypoxia (IH) ( days 1–3, random order, double blind), as well as normoxic voluntary hyperpnea (HP; day 4), matching ventilation during IH. O2 saturation during PH and IH was kept equal to a mean level measured between 30 and 90 min of breathing 12% O2 in a pretest. Urine flow during PH and IH (1.81 ± 0.92 and 1.94 ± 1.03 ml/min, respectively) but not during HP (1.64 ± 0.96 ml/min) significantly exceeded that during NO (control, 1.38 ± 0.71 ml/min). Urine flow increases vs. each test day's baseline were significant with PH, IH, and HP. Differences in glomerular filtration rate, fractional sodium clearance, urodilatin, systemic blood pressure, or leg venous compliance were excluded as factors of HDR. However, slight increases in plasma and urinary endothelin-1 and epinephrine with PH and IH could play a role. In conclusion, the early HDR in humans is mainly due to hypoxia and hypocapnia. It occurs without natriuresis and is unrelated to O2 chemosensitivity (hypoxic ventilatory response).

scholarly journals Rapamycin, an Immunosuppressant and mTORC1 Inhibitor, Triples the antidepressant Response Rate of Ketamine at 2 Weeks Following Treatment: A double-blind, placebo-controlled, cross-over, randomized clinical trial

2018 ◽  
Author(s):  
Chadi Abdallah ◽  
Lynnette A Averill ◽  
Ralitza Gueorguieva ◽  
Selin Goktas ◽  
Prerana Purohit ◽  
...  
Keyword(s):  
Rating Scale ◽  
Response Rate ◽  
Acute Effects ◽  
Antidepressant Response ◽  
Double Blind ◽  
Significant Treatment ◽  
Time Interaction ◽  
Antidepressant Effects

BACKGROUND: Ketamine exerts rapid and robust antidepressant effects thought to be mediated by activation of the mechanistic target of rapamycin complex 1 (mTORC1). To test this hypothesis, depressed patients were pretreated with rapamycin, an mTORC1 inhibitor, prior to receiving ketamine. METHODS: Twenty-three patients suffering a major depressive episode were randomized to oral rapamycin (6 mg) or placebo, each was followed 2 hours later by ketamine 0.5 mg/kg in a double-blind cross-over design with treatment days separated by at least 2 weeks. Depression severity was assessed using Montgomery Asberg Depression Rating Scale (MADRS). Antidepressant response was defined as a MADRS improvement of 50% or more. RESULTS: Over the two-week follow-up, we found a significant treatment by time interaction (F(8,245) = 2.02, p = 0.04), reflecting prolonged antidepressant effects post rapamycin+ketamine treatment. At 2 weeks, we found a significantly higher response rate following rapamycin+ketamine (41%) compared to placebo+ketamine (13%, p = 0.04). However, rapamycin pretreatment did not alter the acute effects of ketamine. CONCLUSION: Unexpectedly, pretreatment with rapamycin prolonged rather than blocked the acute antidepressant effects of ketamine. This observation raises questions about the role of mTORC1 in the antidepressant effects of ketamine, raises the possibility that rapamycin may extend the benefits of ketamine, and thereby potentially sheds light on mechanisms that limit the duration of ketamine effects. The supplementing of ketamine with rapamycin may be a treatment strategy for reducing the frequency of ketamine infusions during maintenance treatment.

scholarly journals Oxytocin enhancement of emotional empathy: generalization across cultures and effects on amygdala activity

2018 ◽  
Author(s):  
YaYuan Geng ◽  
Weihua Zhao ◽  
Feng Zhou ◽  
Xiaole Ma ◽  
Shuxia Yao ◽  
...  
Keyword(s):  
Skin Conductance ◽  
Posterior Cingulate Cortex ◽  
Independent Experiment ◽  
Functional Coupling ◽  
Emotional Empathy ◽  
Double Blind ◽  
Amygdala Activity ◽  
Positive Valence ◽  
The Right

AbstractAccumulating evidence suggests that the neuropeptide oxytocin can enhance empathy although it is unclear which specific behavioral and neural aspects are influenced, and whether the effects are modulated by culture, sex and trait autism. Based on previous findings in Caucasian men, we hypothesized that a single intranasal dose of oxytocin would specifically enhance emotional empathy via modulatory effects on the amygdala in an Asian (Chinese) population and explored the modulatory role of sex and trait autism on the effects. We first conducted a double-blind, randomized between-subject design experiment using a modified version of the multifaceted empathy task (MET) to determine whether oxytocin’s facilitation of emotional empathy can be replicated in Chinese men (n = 60). To further explore neural mechanisms behind and potential sex differences, functional MRI and skin conductance measures were acquired in an independent experiment incorporating men and women (n = 72). Oxytocin enhanced emotional empathy across experiments and sex, an effect that was accompanied by reduced amygdala activity and increased skin conductance responses. On the network level oxytocin enhanced functional coupling of the right amygdala with the insula and posterior cingulate cortex for positive valence stimuli but attenuated coupling for negative valence stimuli. The effect of oxytocin on amygdala functional connectivity with the insula was modulated by trait autism. Overall, our findings provide further support for the role of oxytocin in facilitating emotional empathy and demonstrate that effects are independent of culture and sex and involve modulatory effects on the amygdala and its interactions with other key empathy regions.

scholarly journals ACTH Infusion Impairs Baroreflex Sensitivity—Implications for Cardiovascular Hypoglycemia-Associated Autonomic Failure

2020 ◽  
Vol 105 (7) ◽  
pp. 2345-2353
Author(s):  
Janet H Leung ◽  
Omar F Bayomy ◽  
Istvan Bonyhay ◽  
Johanna Celli ◽  
Jeffrey White ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Baroreflex Sensitivity ◽  
Autonomic Failure ◽  
Random Order ◽  
Double Blind ◽  
Clinical Research Center ◽  
Early Afternoon ◽  
Treatment Analysis ◽  
Placebo Infusion

Abstract Context Hypoglycemia attenuates cardiovascular homeostatic autonomic control. This attenuation, known as the cardiovascular component of hypoglycemia-associated autonomic failure (HAAF), is characterized most notably by decreased baroreflex sensitivity (BRS) that begins during hypoglycemia and persists until at least the next day, despite return to euglycemia. Understanding the mechanisms underlying this reduction in BRS is important because BRS attenuation is associated with increased morbidity and mortality. Objective The objective of this work is to investigate the role of the adrenocorticotropin (ACTH)-adrenal axis in decreasing BRS. We tested the hypothesis that infusion of ACTH 1–24 (cosyntropin), as compared to placebo, would acutely suppress BRS, and that this decrease in BRS would be present the next day. Design A double-blind, placebo-controlled, random-order, cross-over study was conducted. Setting This study took place in a clinical research center. Participants Participants included healthy men and women. Interventions Interventions included an intravenous infusion of cosyntropin (70 μg/hour for 2.5 hours in the morning and again in the early afternoon) vs normal saline placebo. Main Outcome Measures Outcome measures included BRS during and 16 hours after cosyntropin vs placebo infusions. Results Cosyntropin infusion attenuated BRS (mm Hg/ms) as compared to placebo (baseline 17.8 ± 1.38 vs 17.0 ± 2.07; during 14.4 ± 1.43 vs 17.3 ± 1.65; and next day 14.8 ± 1.42 vs 18.9 ± 2.04; P < .05, time by treatment, analysis of variance). BRS was decreased during the final 30 minutes of the morning cosyntropin infusion as compared to baseline (P < .01) and remained suppressed the next day (16 hours after afternoon infusion) (P < .025). Placebo infusion did not significantly change BRS. Corrected QT interval was not affected. Conclusions ACTH attenuates BRS, raising the possibility that hypoglycemia-induced increases in ACTH may contribute to the cardiovascular component of HAAF.

scholarly journals Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin

2020 ◽  
Vol 45 (12) ◽  
pp. 2003-2011 ◽  
Author(s):  
N. L. Mason ◽  
K. P. C. Kuypers ◽  
F. Müller ◽  
J. Reckweg ◽  
D. H. Y. Tse ◽  
...  
Keyword(s):  
Subjective Experience ◽  
Therapeutic Effects ◽  
Double Blind ◽  
Prefrontal Cortical ◽  
Parallel Group Design ◽  
Parallel Group ◽  
Brain And Behavior ◽  
And Behavior ◽  
Glutamate System

Abstract There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one’s self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.

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