scholarly journals No evidence that LSD microdosing affects recall or the balance between distracter resistance and updating

2021 ◽  
Author(s):  
Sean James Fallon

AbstractThe effect of low doses (<=20 μg) of LSD on working memory, in the absence of altered states of consciousness, remain largely unexplored. Given its possible effects on serotonin 5-HT2A receptors and dopaminergic signalling, it could be hypothesised that LSD microdoses modulate working memory recall. Moreover, in line with computational models, LSD microdoses could exert antagonistic effects on distracter resistance and updating. Here, we tested this hypothesis in a randomised double-blind, placebo-controlled study comparing three different LSD microdoses (5 μg, 10μg and 20μg) with placebo. After capsule administration, participants performed a modified delay-match-to-sample (DMTS) dopamine-sensitive task. The standard DMTS task was modified to include novel items in the delay period between encoding and probe. These novel items either had to be ignored or updated into working memory. There was no evidence that LSD microdoses affected the accuracy or efficiency of working memory recall and there was no evidence for differential effects on ignoring or updating. Due to the small sample of participants, these results are preliminary and larger studies are required to establish whether LSD microdoses affect short-term recall.

2017 ◽  
Vol 2 (20;2) ◽  
pp. 27-35
Author(s):  
PyungBok Lee

Background: Topical capsaicin therapy may be of benefit in providing pain relief in patients with peripheral neuropathy. Objectives: To investigate the efficacy and safety of 0.625% (50 µg/cm2 ) and 1.25% (100 µg/cm2 ) capsaicin patches (CPs) compared to conventional 0.075% capsaicin cream or placebo patches in patients suffering from peripheral neuropathy. Study Design: Early Phase II, multi-center, randomized, semi-double-blind, and placebocontrolled clinical trial. Setting: Two medical college teaching hospitals. Methods: Sixty patients were randomized to the 0.625% CP, 1.25% CP, placebo-controlled patch, or 0.075% capsaicin cream. The primary efficacy endpoint was the mean difference in the change of daily numerical rating scale (NRS) pain score. Secondary endpoints included values for the Daily Sleep Interference Scale, the percentage of patients achieving a ≥ 30% or ≥ 50% reduction in pain, and data for Global Impression Change (GIC) and EQ-5D. Results: Patients treated with the 0.625% CP and 0.075% capsaicin cream showed statistically significant improvements in pain after 6-weeks of test drug application. Daily sleep disorder scores were improved only for those patients applying the 0.075% capsaicin cream. For patient-derived GIC scores, the majority (11 of 12) of patients in the 0.625% CP group reported that their pain was improved. For the safety evaluation, 2 severe adverse events were reported for the 0.075% capsaicin cream group only. Repetitive patch application was related to minor skin problems such as a burning sensation, erythema, pruritus, and vesicles in 28 patients (46.67%). Limitations: The small sample size and relatively high dropout rates. Conclusion: Our data indicate that the 0.625% CP may prove to be an effective and safe alternative with which to treat patients with peripheral neuropathy and could replace the high concentration (8%) CP. Further studies are now needed to definitively establish efficacy. Key words: Capsaicin, patch, CP, topical capsaicin, neuropathic pain, peripheral neuropathic pain, PNP, high concentration CP


1997 ◽  
Vol 15 (1) ◽  
pp. 6-9 ◽  
Author(s):  
RAC Chate

Acupressure effectively reduces the amount of nausea experienced, both in the first trimester of pregnancy, and after either opiates or cytotoxic agents. The aim of this randomised, controlled study was to establish whether it could also reduce any sensation of nausea related to the taking of maxillary dental impressions. The sample comprised 8 males and 14 females, with a mean age of 14.64 years and whose self-registration of nausea following an impression was greater than 33% of a 100mm visual analogue. The test involved a second impression with prior application of pressure on either PC.6, the sixth point on the Chinese pericardial meridian, or a placebo point on the forearm of the patient's dominant limb. A random mental choice as to which point to press was made by each patient, and double blind conditions prevailed. After the withdrawal of the impression, another visual analogue was marked. Of the 9 patients who had used the placebo point during the test impression, there had been a mean reduction of 29% in the scale of nausea experienced. Of the 13 who had used the PC.6 acupressure point, the mean reduction was 30%. The difference was not significant. Three and a half minutes of acupressure on PC.6 did not reduce the sensation of nausea induced by tactile stimulation of the soft palate in this small sample of susceptible patients.


2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 390-390 ◽  
Author(s):  
Andrew N de la Torre ◽  
Ismael Castaneda ◽  
Aram F. Hezel ◽  
Newell F. Bascomb ◽  
Gouri Shankar Bhattacharyya ◽  
...  

390 Background: Propranolol and etodolac (designated VT-122) target the adrenergic and prostaglandin stress systems activated in HCC. These stress-induced systems are proposed to induce changes in the tumor microenvironment and immune system leading to tumor promotion and immune tolerance. In a separate study, administration of VT-122 prior to sorafenib showed an increase in median overall survival (OS) of 21 months when VT-122 is administered before sorafenib compared to 10 months OS for sorafenib alone. The aim of the current study was to evaluate the effect of administering VT-122 at least 30 days after starting sorafenib. Methods: Patients with HCC receiving sorafenib for at least 30 days were eligible for this double-blind, placebo-controlled study. Patients were randomized to receive sorafenib with either VT-122 or placebo. Patients received therapy for up to 12 months or until treatment failure. VT-122 was administered twice daily. The primary endpoint was duration of therapy (DoT) and the secondary endpoint was OS. Results: Twenty patients were randomized, 11 and 9 patients to the VT122 and placebo arm, respectively. Each arm was balanced with regards to age (mean of 60.4 years), Child Pugh status (9 Child Pugh A, 11 Child Pugh B7), hepatitis virus status (6 HBV and 1 HCV positive) and C-reactive protein (CRP) (20.4 mg/L). VT122 with sorafenib was well tolerated with no unexpected serious adverse events reported. Mean OS was 13.9 months and 9.6 months in the VT-122 and placebo arms, respectively. Mean DoT (unvalidated) was 10.1 months and 7.5 months in the VT-122 and placebo arms, respectively. Conclusions: Co-administration of VT-122 with sorafenib was well tolerated and showed an increase in duration of therapy and OS versus sorafenib alone. The small sample size and number of events precludes the ability to make any significant efficacy conclusions. The increase in survival was not as great as that seen in a separate study in which VT122 was started prior to sorafenib. A further Phase 3 study of VT122 administered prior to sorafenib in patients with HCC is warranted. Clinical trial information: NCT01265576.


2014 ◽  
Vol 26 (11) ◽  
pp. 2594-2651 ◽  
Author(s):  
Beatrice A. Golomb ◽  
Matthew Allison ◽  
Sabrina Koperski ◽  
Hayley J. Koslik ◽  
Sridevi Devaraj ◽  
...  

We sought to assess whether coenzyme Q10 (CoQ10) benefits the chronic multisymptom problems that affect one-quarter to one-third of 1990–1 Gulf War veterans, using a randomized, double-blind, placebo-controlled study. Participants were 46 veterans meeting Kansas and Centers for Disease Control criteria for Gulf War illness. Intervention was PharmaNord (Denmark) CoQ10 100 mg per day (Q100), 300 mg per day (Q300), or an identical-appearing placebo for 3.5 [Formula: see text] 0.5 months. General self-rated health (GSRH), the primary outcome, differed across randomization arms at baseline, and sex significantly predicted GSRH change, compelling adjustment for baseline GSRH and prompting sex-stratified analysis. GSRH showed no significant benefit in the combined-sex sample. Among males (85% of participants), Q100 significantly benefited GSRH versus placebo and versus Q300, providing emphasis on Q100. Physical function (summary performance score, SPS) improved on Q100 versus placebo. A rise in CoQ10 approached significance as a predictor of improvement in GSRH and significantly predicted SPS improvement. Among 20 symptoms each present in half or more of the enrolled veterans, direction-of-difference on Q100 versus placebo was favorable for all except sleep problems; sign test 19:1, [Formula: see text]) with several symptoms individually significant. Significance for these symptoms despite the small sample underscores large effect sizes, and an apparent relation of key outcomes to CoQ10 change increases prospects for causality. In conclusion, Q100 conferred benefit to physical function and symptoms in veterans with Gulf War illness. Examination in a larger sample is warranted, and findings from this study can inform the conduct of a larger trial.


2019 ◽  
Vol 33 (10) ◽  
pp. 1254-1263 ◽  
Author(s):  
Sean James Fallon ◽  
Annika Kienast ◽  
Kinan Muhammed ◽  
Yuen-siang Ang ◽  
Sanjay G Manohar ◽  
...  

Background: Working memory (WM) deficits in neuropsychiatric disorders have often been attributed to altered dopaminergic signalling. Specifically, D2 receptor stimulation is thought to affect the ease with which items can be gated into and out of WM. In addition, this effect has been hypothesised to vary according to baseline WM ability, a putative index of dopamine synthesis levels. Moreover, whether D2 stimulation affects WM vicariously through modulating relatively WM-free cognitive control processes has not been explored. Aims: We examined the effect of administering a dopamine agonist on the ability to ignore or update information in WM. Method: A single dose of cabergoline (1 mg) was administered to healthy older adult humans in a within-subject, double-blind, placebo-controlled study. In addition, we obtained measures of baseline WM ability and relatively WM-free cognitive control (overcoming response conflict). Results: Consistent with predictions, baseline WM ability significantly modulated the effect that drug administration had on the proficiency of ignoring and updating. High-WM individuals were relatively better at ignoring compared to updating after drug administration. Whereas the opposite occurred in low-WM individuals. Although the ability to overcome response conflict was not affected by cabergoline, a negative relationship between the effect the drug had on response conflict performance and ignoring was observed. Thus, both response conflict and ignoring are coupled to dopaminergic stimulation levels. Conclusions: Cumulatively, these results provide evidence that dopamine affects subcomponents of cognitive control in a diverse, antagonistic fashion and that the direction of these effects is dependent upon baseline WM.


Nutrients ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 218
Author(s):  
Emma L. Wightman ◽  
Philippa A. Jackson ◽  
Bethany Spittlehouse ◽  
Thomas Heffernan ◽  
Damien Guillemet ◽  
...  

The sage (Salvia) plant contains a host of terpenes and phenolics which interact with mechanisms pertinent to brain function and improve aspects of cognitive performance. However, previous studies in humans have looked at these phytochemicals in isolation and following acute consumption only. A preclinical in vivo study in rodents, however, has demonstrated improved cognitive outcomes following 2-week consumption of CogniviaTM, a proprietary extract of both Salvia officinalis polyphenols and Salvia lavandulaefolia terpenoids, suggesting that a combination of phytochemicals from sage might be more efficacious over a longer period of time. The current study investigated the impact of this sage combination on cognitive functions in humans with acute and chronic outcomes. Participants (n = 94, 25 M, 69 F, 30–60 years old) took part in this randomised, double-blind, placebo-controlled, parallel groups design where a comprehensive array of cognitions were assessed 120- and 240-min post-dose acutely and following 29-day supplementation with either 600 mg of the sage combination or placebo. A consistent, significant benefit of the sage combination was observed throughout working memory and accuracy task outcome measures (specifically on the Corsi Blocks, Numeric Working Memory, and Name to Face Recall tasks) both acutely (i.e., changes within day 1 and day 29) and chronically (i.e., changes between day 1 to day 29). These results fall slightly outside of those reported previously with single Salvia administration, and therefore, a follow-up study with the single and combined extracts is required to confirm how these effects differ within the same cohort.


2020 ◽  
Vol 48 (7) ◽  
pp. 030006052093983
Author(s):  
Ramzi A. Tabbalat ◽  
Imad Alhaddad ◽  
Ayman Hammoudeh ◽  
Yousef S. Khader ◽  
Hassan Abu Khalaf ◽  
...  

Background Studies using 1 mg of colchicine to prevent postoperative atrial fibrillation (POAF) reported conflicting results. Moreover, colchicine was associated with significant gastrointestinal (GI) side effects. This study examined whether low-dose colchicine effectively prevents POAF and whether low-dose therapy is associated with lower rates of colchicine-induced GI side effects. Methods In this prospective, randomized, double-blind, placebo-controlled study, consecutive adult patients admitted for elective cardiac surgeries randomly received a 1-mg dose of colchicine (n = 81) or placebo (n = 71) orally 12 to 24 hours before surgery followed by a daily dose of 0.5 mg until hospital discharge. The primary efficacy endpoint was the development of at least one episode of POAF of ≥5 minutes. The primary safety endpoint was the development of adverse events, especially diarrhea. Results The in-hospital mortality rate was 3.9%. POAF occurred in 13 patients (16.1%) in the colchicine group and 13 patients (18.3%) in the placebo group (odds ratio 0.85 [95% Confidence Interval = 0.37−1.99]). Diarrhea occurred in two patients in each group and necessitated treatment discontinuation in one patient in each group. Conclusion Low-dose colchicine did not prevent POAF in patients undergoing cardiac surgery. These results should be interpreted cautiously because of the small sample size and early study termination. ClinicalTrials.gov Unique Identifier number: NCT03015831


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