Lindsay E Johnson, Lilian Balyan, Amy Magdalany, Fizza Saeed, Robert Salinas, Starla Wallace, Charles A Veltri, Marc T Swogger, Zach Walsh, Oliver Grundmann
Mitragyna speciosa , otherwise known as kratom, is a plant in the coffee family (Rubiaceae) native to Southeast Asia and Thailand whose leaves have been shown to cause opioid-like and stimulant responses upon ingestion. The major pharmacologically active compounds present in kratom, mitragynine and 7-hydroxymitragynine (7-HMG), are both indole alkaloids and are responsible for its opioid-like activity. While kratom is most commonly known for its affinity for mu-opioid receptors, research has shown one of its active components has effects on the same receptors to which some antipsychotics bind, such as D2 dopamine, serotonin (5-HT2C and 5-HT7 ), and alpha-2 adrenergic receptors displaying possible indications of kratom to be used as both antipsychotics and antidepressants...
June 2020: Yale Journal of Biology and Medicine
Kathryn Eron, Lindsey Kohnert, Ashlie Watters, Christina Logan, Melissa Weisner-Rose, Philip S Mehler
IMPORTANCE: Sensory integration modalities, such as weighted blankets, are used in occupational therapy practice to assist with emotional and physical regulation. However, the research related to the use and effectiveness of weighted blankets is sparse. OBJECTIVE: To identify, evaluate, and synthesize the current literature to help develop the impetus needed to launch a research study into the effectiveness of using weighted blankets to decrease anxiety and insomnia...
March 2020: American Journal of Occupational Therapy: Official Publication of the American Occupational Therapy Association
Deanna Montgomery, Jessica P Anand, Mason A Baber, Jack J Twarozynski, Joshua G Hartman, Lennon J Delong, John R Traynor, Henry I Mosberg
The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring...
November 26, 2019: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Melissa Rizk, Lama Mattar, Laurence Kern, Sylvie Berthoz, Jeanne Duclos, Odile Viltart, Nathalie Godart
Abnormally high levels of physical activity have been documented throughout the literature in patients with eating disorders (ED), especially those diagnosed with anorexia nervosa (AN). Yet no clear definition, conceptualization, or treatment of the problematic use of physical activity (PPA) in ED patients exists. The aim of this review is to propose a new classification of PPA, report the prevalence, triggers, predictors, maintainers and other related factors of PPA in ED patients, in addition to proposing a comprehensive model of the development of PPA in AN...
January 9, 2020: Nutrients
Jeffrey M Witkin, Anna E Martin, Lalit K Golani, Nina Z Xu, Jodi L Smith
Conventional antidepressants (biogenic amine mechanisms) are not fully efficacious (e.g., symptoms remain after treatment, not all patients respond), produce effects only after weeks of daily dosing, and do not impact all disease symptoms. In contrast, a new class of antidepressants has been emerging since 2006 that has demonstrated rapid onset, large effect size, activity after only a single or few dose applications, and positive impact in treatment refractory patients and against some treatment-resistant symptoms (e...
2019: Advances in Pharmacology
Yedy Israel, María Elena Quintanilla, Fernando Ezquer, Paola Morales, Daniela Santapau, Pablo Berríos-Cárcamo, Marcelo Ezquer, Belen Olivares, Mario Herrera-Marschitz
Chronic alcohol intake leads to neuroinflammation and cell injury, proposed to result in alterations that perpetuate alcohol intake and cued relapse. Studies show that brain oxidative stress is consistently associated with alcohol-induced neuroinflammation, and literature implies that oxidative stress and neuroinflammation perpetuate each other. In line with a self-perpetuating mechanism, it is hypothesized that inhibition of either oxidative stress or neuroinflammation could reduce chronic alcohol intake and relapse...
January 2021: Addiction Biology
Yoko Hirata, Yuki Ito, Madoka Takashima, Kazuya Yagyu, Kentaro Oh-Hashi, Hiromi Suzuki, Kenji Ono, Kyoji Furuta, Makoto Sawada
Oxidative stress plays an important role in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. The oxindole compound GIF-2165X-G1 is a hybrid molecule composed of the oxindole skeleton of the neuroprotective compound GIF-0726-r and the polyphenolic skeleton of the antioxidant curcumin. We previously reported that novel oxindole derivatives such as GIF-0726-r and GIF-2165X-G1 prevent endogenous oxidative stress-induced cell death in mouse hippocampal HT22 cells. In this study, we present a detailed investigation of the effect of GIF-2165X-G1 on endogenous oxidative stress in HT22 cells in comparison with GIF-0726-r and curcumin...
January 2, 2020: ACS Chemical Neuroscience
Ting Lei, Zhenxin Hu, Ruolin Ding, Jianfang Chen, Shiqi Li, Fuhui Zhang, Xuemei Pu, Nanrong Zhao
Metabotropic glutamate receptors of class C GPCRs exist as constitutive dimers, which play important roles in activating excitatory synapses of the central nervous system. However, the activation mechanism induced by agonists has not been clarified in experiments. To address the problem, we used microsecond all-atom molecular dynamics (MD) simulation couple with protein structure network (PSN) to explore the glutamate-induced activation for the mGluR1 homodimer. The results indicate that glutamate binding stabilizes not only the closure of Venus flytrap domains but also the polar interaction of LB2-LB2, in turn keeping the extracelluar domain in the active state...
January 15, 2020: ACS Chemical Neuroscience
Bruce Parsons, Rainer Freynhagen, Stephan Schug, Ed Whalen, Marie Ortiz, Pritha Bhadra Brown, Lloyd Knapp
Background: Euphoria is a complex, multifactorial problem that is reported as an adverse event in clinical trials of analgesics including pregabalin. The relationship between the reporting of euphoria events and pregabalin early treatment responses was examined in this exploratory post-hoc analysis. Methods: Data were from patients with neuropathic or non-neuropathic chronic pain enrolled in 40 randomized clinical trials, who received pregabalin (75-600 mg/day) or placebo...
2019: Journal of Pain Research
Ceren Sahin Ozkartal, Erdem Tuzun, Cem Ismail Kucukali, Canan Ulusoy, Murat Giris, Feyza Aricioglu
Innate immunity activation in the central nervous system (CNS) is known to contribute to the development of depression through NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasome assembly. Furthermore, administration of agmatine (AGM), a nitric oxide synthase (NOS) inhibitor, reverses stress-induced NLRP3 inflammasome activation in rats. We examined the effects of chronically-administered nitric oxide (NO) pathway modulating drugs on NLRP1/3-mediated neuroinflammatory responses and depressive-like behaviors in chronic unpredictable mild stress (CUMS) depression model of rats...
December 15, 2019: Brain Research
Bernard J Crespi
The first treatments showing effectiveness for some psychiatric disorders, such as lithium for bipolar disorder and chlorpromazine for schizophrenia, were discovered by accident. Currently, psychiatric drug design is seen as a scientific enterprise, limited though it remains by the complexity of brain development and function. Relatively few novel and effective drugs have, however, been developed for many years. The purpose of this article is to demonstrate how evolutionary biology can provide a useful framework for psychiatric drug development...
2019: Evolution, Medicine, and Public Health
Elena L Paley
Alzheimer's disease (AD)-associated sequence (ADAS) of cultured fecal bacteria was discovered in human gut targeted screening. This study provides important information to expand our current understanding of the structure/activity relationship of ADAS and putative inhibitors/activators that are potentially involved in ADAS appearance/disappearance. The NCBI database analysis revealed that ADAS presents at a large proportion in American Indian Oklahoman (C&A) with a high prevalence of obesity/diabetes and in colorectal cancer (CRC) patients from the US and China...
2019: Journal of Alzheimer's Disease: JAD
Arisoy Ozden, Halaris Angelos, Aricioglu Feyza, Wild Elizabeth, Piletz John
L-Arginine pathway metabolites appear to play differential roles in the pathogenesis of major depressive disorder (MDD). Studies have revealed an antidepressant and anxiolytic effect of agmatine and putrescine. Possible mechanisms of these effects include inhibition of nitric oxide synthase and N-methyl-D-aspartate receptors. The present study sought to determine whether MDD is associated with altered levels of arginine metabolites and whether these metabolites are associated with depression, anxiety and stress severity...
January 2020: Journal of Psychiatric Research
Kan Hong Zheng, Afra Khan, Eduardo D Espiridion
Phenibut, a γ-aminobutyric acid (GABA) analog, is a synthetic, nootropic GABAB receptor agonist used to treat anxiety, insomnia, alcohol withdrawal, and other conditions. The drug is licensed and widely used in Russia however, phenibut can be purchased through online vendors in other countries. The current literature on the effects of phenibut intoxication and withdrawal in humans is limited. In this case report, a 23-year-old male with a history of heavy phenibut and alcohol use presented to the emergency department with suicidal thoughts, somatic complaints, and seeking help with detoxification...
July 24, 2019: Curēus
Harrison J VanDolah, Brent A Bauer, Karen F Mauck
Cannabidiol (CBD) oils are low tetrahydrocannabinol products derived from Cannabis sativa that have become very popular over the past few years. Patients report relief for a variety of conditions, particularly pain, without the intoxicating adverse effects of medical marijuana. In June 2018, the first CBD-based drug, Epidiolex, was approved by the US Food and Drug Administration for treatment of rare, severe epilepsy, further putting the spotlight on CBD and hemp oils. There is a growing body of preclinical and clinical evidence to support use of CBD oils for many conditions, suggesting its potential role as another option for treating challenging chronic pain or opioid addiction...
June 12, 2019: Mayo Clinic Proceedings
Lael Reinstatler, Nagy A Youssef
OBJECTIVE: To review the published literature on the efficacy of ketamine for the treatment of suicidal ideation (SI). METHODS: The PubMed and Cochrane databases were searched up to January 2015 for clinical trials and case reports describing therapeutic ketamine administration to patients presenting with SI/suicidality. Searches were also conducted for relevant background material regarding the pharmacological function of ketamine. RESULTS: Nine publications (six studies and three case reports) met the search criteria for assessing SI after administration of subanesthetic ketamine...
March 2015: Drugs in R&D
Katherine T Martucci, Kelly H MacNiven, Nicholas Borg, Brian Knutson, Sean C Mackey
Neural responses to incentives are altered in chronic pain and by opioid use. To understand how opioid use modulates the neural response to reward/value in chronic pain, we compared brain functional magnetic resonance imaging (fMRI) responses to a monetary incentive delay (MID) task in patients with fibromyalgia taking opioids (N = 17), patients with fibromyalgia not taking opioids (N = 17), and healthy controls (N = 15). Both groups of patients with fibromyalgia taking and not taking opioids had similar levels of pain, psychological measures, and clinical symptoms...
July 3, 2019: Scientific Reports
Brian M Cox, Thomas E Cote, Irwin Lucki
The marked increase in deaths related to opioid drugs after 1999 was associated with an increase in the number of prescriptions for opioid drugs. This was accompanied by increasing demand for improved management of chronically painful conditions. These factors suggest that improvements are needed in the education of physicians with regard to the management of chronic pain, the optimal therapeutic application of opioid drugs, and the avoidance of substance use disorders. In this article, we address the evidence that physician education can influence prescribing practices and we discuss approaches to enhance the preclinical and clinical education of medical students in pain management and substance use disorders...
November 2019: Journal of Pharmacology and Experimental Therapeutics
Jay N Giedd
No abstract text is available yet for this article.
July 1, 2019: American Journal of Psychiatry
Thomas Larrieu, Sophie Layé
The central nervous system (CNS) has the highest concentration of lipids in the organism after adipose tissue. Among these lipids, the brain is particularly enriched with polyunsaturated fatty acids (PUFAs) represented by the omega-6 (ω6) and omega-3 (ω3) series. These PUFAs include arachidonic acid (AA) and docosahexaenoic acid (DHA), respectively. PUFAs have received substantial attention as being relevant to many brain diseases, including anxiety and depression. This review addresses an important question in the area of nutritional neuroscience regarding the importance of ω3 PUFAs in the prevention and/or treatment of neuropsychiatric diseases, mainly depression and anxiety...
2018: Frontiers in Physiology
2019-07-11 23:08:52
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