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Lysergic acid diethylamide (LSD) is a classic psychedelic, 3,4-methylenedioxymethamphetamine (MDMA) is an empathogen, and d-amphetamine is a classic stimulant. All three substances are used recreationally. LSD and MDMA are being investigated as medications to assist psychotherapy, and d-amphetamine is used for the treatment of attention-deficit/hyperactivity disorder. All three substances induce distinct acute subjective effects. However, differences in acute responses to these prototypical psychoactive substances have not been characterized in a controlled study. We investigated the acute autonomic, subjective, and endocrine effects of single doses of LSD (0.1 mg), MDMA (125 mg), d-amphetamine (40 mg), and placebo in a randomized, double-blind, cross-over study in 28 healthy subjects. All of the substances produced comparable increases in hemodynamic effects, body temperature, and pupil size, indicating equivalent autonomic responses at the doses used. LSD and MDMA increased heart rate more than d-amphetamine, and d-amphetamine increased blood pressure more than LSD and MDMA. LSD induced significantly higher ratings on the 5 Dimensions of Altered States of Consciousness scale and Mystical Experience Questionnaire than MDMA and d-amphetamine. LSD also produced greater subjective drug effects, ego dissolution, introversion, emotional excitation, anxiety, and inactivity than MDMA and d-amphetamine. LSD also induced greater impairments in subjective ratings of concentration, sense of time, and speed of thinking compared with MDMA and d-amphetamine. MDMA produced greater ratings of good drug effects, liking, high, and ego dissolution compared with d-amphetamine. d-Amphetamine increased ratings of activity and concentration compared with LSD. MDMA but not LSD or d-amphetamine increased plasma concentrations of oxytocin. None of the substances altered plasma concentrations of brain-derived neurotrophic factor. These results indicate clearly distinct acute effects of LSD, MDMA, and d-amphetamine and may assist the dose-finding in substance-assisted psychotherapy research.

Rationale Lysergic acid diethylamide (LSD) and other serotonergic hallucinogens can induce profound alterations of consciousness and mystical-type experiences, with reportedly long-lasting effects on subjective well-being and personality. Methods We investigated the lasting effects of a single dose of LSD (200 μg) that was administered in a laboratory setting in 16 healthy participants. The following outcome measures were assessed before and 1 and 12 months after LSD administration: Persisting Effects Questionnaire (PEQ), Mysticism Scale (MS), Death Transcendence Scale (DTS), NEO-Five Factor Inventory (NEO-FFI), and State-Trait Anxiety Inventory (STAI). Results On the PEQ, positive attitudes about life and/or self, positive mood changes, altruistic/positive social effects, positive behavioral changes, and well-being/life satisfaction significantly increased at 1 and 12 months and were subjectively attributed by the subjects to the LSD experience. Five-Dimensions of Altered States of Consciousness (5D-ASC) total scores, reflecting acutely induced alterations in consciousness, and Mystical Experience Questionnaire (MEQ30) total scores correlated with changes in well-being/life satisfaction 12 months after LSD administration. No changes in negative attitudes, negative mood, antisocial/negative social effects, or negative behavior were attributed to the LSD experience. After 12 months, 10 of 14 participants rated their LSD experience as among the top 10 most meaningful experiences in their lives. Five participants rated the LSD experience among the five most spiritually meaningful experiences in their lives. On the MS and DTS, ratings of mystical experiences significantly increased 1 and 12 months after LSD administration compared with the pre-LSD screening. No relevant changes in personality measures were found. Conclusions In healthy research subjects, the administration of a single dose of LSD (200 μg) in a safe setting was subjectively considered a personally meaningful experience that had long-lasting subjective positive effects. Trial registration Registration identification number: NCT01878942.

Night shift work can associate with an increased risk for depression. As night workers experience a ‘misalignment’ between their circadian system and daily sleep–wake behaviors, with negative health consequences, we investigated whether exposure to circadian misalignment underpins mood vulnerability in simulated shift work. We performed randomized within-subject crossover laboratory studies in non-shift workers and shift workers. Simulated night shifts were used to induce a misalignment between the endogenous circadian pacemaker and sleep/wake cycles (circadian misalignment), while environmental conditions and food intake were controlled. Circadian misalignment adversely impacted emotional state, such that mood and well-being levels were significantly decreased throughout 4 days of continuous exposure to circadian misalignment in non-shift workers, as compared to when they were under circadian alignment (interaction of “circadian alignment condition” vs. “day”, mood: p  < 0.001; well-being: p  < 0.001; adjusted p -values). Similarly, in shift workers, mood and well-being levels were significantly reduced throughout days of misalignment, as compared to circadian alignment (interaction of “circadian alignment condition” vs. “day”, mood: p  = 0.002; well-being: p  = 0.002; adjusted p -values). Our findings indicate that circadian misalignment is an important biological component for mood vulnerability, and that individuals who engage in shift work are susceptible to its deleterious mood effects.

While theorists have speculated that different affective traits are linked to reliable brain activity during anticipation of gains and losses, few have directly tested this prediction. We examined these associations in a community sample of healthy human adults (n=52) as they played a Monetary Incentive Delay task while undergoing functional magnetic resonance imaging (FMRI). Factor analysis of personality measures revealed that subjects independently varied in trait Positive Arousal and trait Negative Arousal. In a subsample (n=14) retested over 2.5years later, left nucleus accumbens (NAcc) activity during anticipation of large gains (+$5.00) and right anterior insula activity during anticipation of large losses (−$5.00) showed significant test–retest reliability (intraclass correlations>0.50, p's<0.01). In the full sample (n=52), trait Positive Arousal correlated with individual differences in left NAcc activity during anticipation of large gains, while trait Negative Arousal correlated with individual differences in right anterior insula activity during anticipation of large losses. Associations of affective traits with neural activity were not attributable to the influence of other potential confounds (including sex, age, wealth, and motion). Together, these results demonstrate selective links between distinct affective traits and reliably-elicited activity in neural circuits associated with anticipation of gain versus loss. The findings thus reveal neural markers for affective dimensions of healthy personality, and potentially for related psychiatric symptoms. •Left NAcc activity during gain anticipation is stable over 2.5years.•Right anterior insula activity during loss anticipation is stable over 2.5years.•Trait positive arousal correlates with NAcc activity during gain anticipation.•Trait negative arousal correlates with insula activity during loss anticipation.•Findings highlight neural markers for affective traits and psychiatric symptoms.

Background Research suggests that the positive affect system may be an important yet underexplored treatment target in anxiety and depression. Existing interventions primarily target the negative affect system, yielding modest effects on measures of positive emotions and associated outcomes (e.g., psychological well‐being). The objective of the present pilot study was to evaluate the efficacy of a new transdiagnostic positive activity intervention (PAI) for anxiety and depression. Method Twenty‐nine treatment‐seeking individuals presenting with clinically impairing symptoms of anxiety and/or depression were randomly allocated to a 10‐session protocol comprised of PAIs previously shown in nonclinical samples to improve positive thinking, emotions, and behaviors (e.g., gratitude, acts of kindness, optimism; n = 16) or a waitlist (WL) condition (n = 13). Participants were assessed at pre‐ and posttreatment, as well as 3‐ and 6‐month follow‐up, on measures of positive and negative affect, symptoms, and psychological well‐being. ClinicalTrials.gov Identifier: NCT02330627 Results The PAI group displayed significantly larger improvements in positive affect and psychological well‐being from pre‐ to posttreatment compared to WL. Posttreatment and follow‐up scores in the PAI group were comparable to general population norms. The PAI regimen also resulted in significantly larger reductions in negative affect, as well as anxiety and depression symptoms, compared to WL. Improvements across all outcomes were large in magnitude and maintained over a 6‐month follow‐up period. Conclusions Targeting the positive affect system through a multicomponent PAI regimen may be beneficial for generating improvements in positive emotions and well‐being, as well as reducing negative affect and symptoms, in individuals with clinically impairing anxiety or depression.

Mental fatigue (MF) can impair cognitive and physical performance in sport. We tested the hypothesis that a shorter adaptive Time Load Dual Back (TLDB) task induces MF faster than a longer Stroop; and subsequently impairs cognitive and intermittent running performance. This study employed a randomized within-participant design. 25 trained individuals performed a Yo-Yo test after one of four experimental conditions (30-min Stroop, 20-min and 10-min TLDB tasks, and active control). Cognitive performance was assessed using the Psychomotor Vigilance Task (PVT) before and after the experimental conditions. Measures of mood, workload, MF, RPE, heart rate (HR), heart rate variability (HRV) and blood lactate were collected. ANOVAs determined the effect of the 4 conditions. Stroop and 20-min TLDB conditions impaired running performance similarly (p = .015), while no differences are reported for 10-min TLDB and Control. No significant differences in physiological parameters were reported during the Yo-Yo test although RPE was significantly higher in the Stroop and 20-min TLDB conditions (p = .014). Stroop and both TLDBs conditions impaired PVT's cognitive performance (p = .029), MF (p = .012), mental demand (p < .001), HR (p = .021) and HRV (p = .033); with 20-min TLDB task having the higher significant impact. Mood alterations were similar between Stroop and TLDB conditions. Intermittent running (Yo-Yo) and cognitive (PVT) performances, and subjective ratings were impaired by 30-min Stroop and 20-min TLDB tasks; while 10-min TLDB did not to impair performance. Shorter adaptive modes seem to be more effective in inducing MF and could have relevant clinical applications to assess conditions such as traumatic brain injury and concussion.

Abstract Study Objectives To examine the effects of cognitive behavioral treatments for insomnia (CBT-I) and pain (CBT-P) in patients with comorbid fibromyalgia and insomnia. Methods One hundred thirteen patients (Mage = 53, SD = 10.9) were randomized to eight sessions of CBT-I (n = 39), CBT-P (n = 37), or a waitlist control (WLC, n = 37). Primary (self-reported sleep onset latency [SOL], wake after sleep onset [WASO], sleep efficiency [SE], sleep quality [SQ], and pain ratings) and secondary outcomes (dysfunctional beliefs and attitudes about sleep [DBAS]; actigraphy and polysomnography SOL, WASO, and SE; McGill Pain Questionnaire; Pain Disability Index; depression; and anxiety) were examined at posttreatment and 6 months. Results Mixed effects analyses revealed that both treatments improved self-reported WASO, SE, and SQ relative to control at posttreatment and follow-up, with generally larger effect sizes for CBT-I. DBAS improved in CBT-I only. Pain and mood improvements did not differ by group. Clinical significance analyses revealed the proportion of participants no longer reporting difficulties initiating and maintaining sleep was higher for CBT-I posttreatment and for both treatments at 6 months relative to control. Few participants achieved >50% pain reductions. Proportion achieving pain reductions of >30% (~1/3) was higher for both treatments posttreatment and for CBT-I at 6 months relative to control. Conclusions CBT-I and CBT-P improved self-reported insomnia symptoms. CBT-I prompted improvements of larger magnitude that were maintained. Neither treatment improved pain or mood. However, both prompted clinically meaningful, immediate pain reductions in one third of patients. Improvements persisted for CBT-I, suggesting that CBT-I may provide better long-term pain reduction than CBT-P. Research identifying which patients benefit and mechanisms driving intervention effects is needed. Clinical Trial Sleep and Pain Interventions in Fibromyalgia (SPIN), clinicaltrials.gov, NCT02001077.

Drug treatments for pain often do not outperform placebo, and a better understanding of placebo mechanisms is needed to improve treatment development and clinical practice. In a large-scale fMRI study ( N  = 392) with pre-registered analyses, we tested whether placebo analgesic treatment modulates nociceptive processes, and whether its effects generalize from conditioned to unconditioned pain modalities. Placebo treatment caused robust analgesia in conditioned thermal pain that generalized to unconditioned mechanical pain. However, placebo did not decrease pain-related fMRI activity in brain measures linked to nociceptive pain, including the Neurologic Pain Signature (NPS) and spinothalamic pathway regions, with strong support for null effects in Bayes Factor analyses. In addition, surprisingly, placebo increased activity in some spinothalamic regions for unconditioned mechanical pain. In contrast, placebo reduced activity in a neuromarker associated with higher-level contributions to pain, the Stimulus Intensity Independent Pain Signature (SIIPS), and affected activity in brain regions related to motivation and value, in both pain modalities. Individual differences in behavioral analgesia were correlated with neural changes in both modalities. Our results indicate that cognitive and affective processes primarily drive placebo analgesia, and show the potential of neuromarkers for separating treatment influences on nociception from influences on evaluative processes. The mechanisms underlying placebo analgesia are not fully understood. Here the authors show that a placebo treatment inducing analgesia in healthy participants reduced fMRI activity in systems related to evaluative and affective processes, but not systems related to nociceptive pain processing.

Previous studies investigating the diurnal variation of physiological and psychological variables during exercise have yielded conflicting results. The present investigation was designed to assess the impact of time-of-day on short-term repetitive maximal performance [ i.e., single and two consecutive bouts of 5m shuttle run test (5mSRT), long jump test] as well as cognitive ability and psychological variables [ i.e., mood states (POMS) and Hooper questionnaire] in male and female adolescents. In a randomized study design, 21 healthy adolescents (12 females and 9 males; age: 15.9±1.04 years) performed at 08h00 and 16h00 two consecutive 5mSRT (with 20 min of rest interval in-between), to assess the greatest distance (GD), the total distance (TD), the average distance (AD) and the fatigue index (FI), and the long jump test (LJT). Perceived exertion (RPE) was recorded immediately after each 5mSRT. The POMS and Hooper questionnaires and the digit-cancellation test ( i.e., attention) were realized during each session. The results showed that TD and AD were greater in the morning than in the afternoon during the 1 st (p = 0.048 and 0.048, respectively) and the 2 nd (p = 0.0016 and 0.0017, respectively) 5mSRT; while GD was time-of-day independent (p = 0.16). For the FI, results demonstrated a significant time-of-day effect with highest values recorded in the afternoon compared to the morning during the 2 nd 5mSRT (p = 0.017). In contrast, attention scores and the long jump test performance recorded before and after each 5mSRT were time-of-day independent for all measures (p > 0.05). Likewise, POMS parameters [anxiety (p = 0.15), depression (p = 0.71), anger (p = 0.23), fatigue (p = 0.07), confusion (p = 0.58), vigor (p = 0.16), TMD (p = 0.06) and interpersonal relationships (p = 0.19)], RPE [1 st (p = 0.22) and 2 nd (p = 0.43) 5mSRT] and delayed onset muscle soreness (p = 0.34) were time-of-day independent; while, fatigue (p = 0.03), sleep (p = 0.01) and stress (p = 0.027) estimated by the Hooper questionnaire were higher in the afternoon compared to the morning. In conclusion, morning is more effective than afternoon session for improving short-term repetitive maximal performance and reducing fatigue during the 5mSRT for adolescents. However, regarding psychological parameters and cognitive function and contrarily to previous researches, there is no time-of-day effects.

Sensory rooms are those equipped with various visual, auditory, and other sensory items that can be adjusted according to user preferences. Although several studies have reported the effectiveness of sensory rooms, their physiological effects remain unclear. This pilot study aims to investigate the effect of sensory rooms on vagal function, mood states, and attentional functions. Thirty-nine healthy young adults were randomly divided into the sensory room intervention (SRI) and sedentary activity (SA) groups, and given a 30-minute intervention. The SRI group spent time in a dimly lit room with beaded cushions and aroma oils. The SA group engaged in activities such as handicrafts and puzzles. We compared changes in respiratory sinus arrhythmia (RSA) at rest, RSA variability during discomfort sensory stimulation, mood states, and attentional functions between the groups, both before and after the intervention. As a result, 1) SRI significantly increased RSA compared with SA. 2) It also reduced the variability of RSA in response to specific sensory stimuli compared with SA. 3) However, no significant differences existed in negative mood or attentional function between the groups. The results suggest that sensory rooms might contribute to the sensory modulation, including that of the autonomic nervous system. Further investigation with larger samples in clinical settings, particularly among individuals with sensory modulation issues and mental illness, is necessary to confirm and generalize these findings.