Immune Influencers in Action: Metabolites and Enzymes of the Tryptophan-Kynurenine Metabolic Pathway

Biomedicines, Journal Year: 2021, Volume and Issue: 9(7), P. 734 - 734

Published: June 25, 2021

The tryptophan (TRP)-kynurenine (KYN) metabolic pathway is a main player of TRP metabolism through which more than 95% catabolized. activated by acute and chronic immune responses leading to wide range illnesses including cancer, diseases, neurodegenerative diseases psychiatric disorders. presence positive feedback loops facilitates amplifying the vice versa. TRP-KYN synthesizes multifarious metabolites oxidants, antioxidants, neurotoxins, neuroprotectants immunomodulators. immunomodulators are known facilitate system towards tolerogenic state, resulting in low-grade inflammation (LGI) that commonly present obesity, poor nutrition, exposer chemicals or allergens, prodromal stage various diseases. KYN, kynurenic acid, xanthurenic acid cinnabarinic aryl hydrocarbon receptor ligands serve as Furthermore, enzymes be stress hormone cortisol inflammatory cytokines, genotypic variants were observed contribute thus 2,3-dioxygenase, indoleamine 2,3-dioxygenases kynurenine-3-monooxygenase pathway. This review article discusses with special emphasis on its interaction shift LGI overviews major symptoms, pro- anti-inflammatory cytokines toxic protective KYNs explore linkage between LGI, KYNs, disorders, depressive disorder, bipolar substance use post-traumatic schizophrenia autism spectrum disorder.

Language: Английский

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Public health monitoring of cannabis use in Europe: prevalence of use, cannabis potency, and treatment rates

The Lancet Regional Health - Europe, Journal Year: 2021, Volume and Issue: 10, P. 100227 - 100227

Published: Sept. 24, 2021

Cannabis is one of the most widely used substances worldwide. Heavy use associated with an increased risk cannabis disorders, psychotic acute cognitive impairment, traffic injuries, respiratory problems, worse pregnancy outcomes, and there are indications for genotoxic epigenotoxic adverse effects. International regulation medical non-medical changing rapidly substantially, highlighting importance robust public health monitoring. This study aimed to describe trends key indicators in European Union (27 member states + UK, Norway Turkey) period 2010 2019, their implications, identify steps required improve current practice monitoring harm Europe.Data on four (prevalence use, prevalence disorder [CUD], treatment rates, potency products) Europe were extracted from United Nations Office Drugs Crime, Monitoring Centre Drug Addiction Global Burden Disease study. For CUD, first last available estimate each country compared. rates potency, linear regression models conducted.Between past-month by 27% adults (from 3·1 3·9%), pronounced relative increases observed among 35-64 year-olds. In 13 out 26 countries, over 20% all users reported high-risk patterns. The rate entry problems per 100,000 27·0 (95% CI: 17·2 36·8) 35·1 23·6 46·7) has mostly plateaued since 2015. Modest found herbal 6·9% 10·6% THC) while median THC values tripled resin 7·6% 24·1% THC).In past decade, levels have major concerns about impact use. Continued efforts data quality reporting, including cannabis-attributable harm, will be necessary evaluate international changes regulation.This received no specific funding.

Language: Английский

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Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies

BMJ, Journal Year: 2023, Volume and Issue: unknown, P. e072348 - e072348

Published: Aug. 30, 2023

Objective To systematically assess credibility and certainty of associations between cannabis, cannabinoids, cannabis based medicines human health, from observational studies randomised controlled trials (RCTs). Design Umbrella review. Data sources PubMed, PsychInfo, Embase, up to 9 February 2022. Eligibility criteria for selecting Systematic reviews with meta-analyses RCTs that have reported on the efficacy safety or were included. Credibility was graded according convincing, highly suggestive, weak, not significant (observational evidence), by GRADE (Grading Recommendations, Assessment, Development Evaluations) Quality assessed AMSTAR 2 (A Measurement Tool Assess Reviews 2). Sensitivity analyses conducted. Results 101 included (observational=50, RCTs=51) (AMSTAR high 33, moderate 31, low 32, critically 5). From supported certainty, increased adverse events related central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 3.73)), psychological effects (3.07 (1.79 5.26)), vision (3.00 5.03)) in people mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but psychiatric, gastrointestinal events, somnolence among others (GRADE=moderate). Cannabidiol 50% reduction seizures (0.59 (0.38 0.92)) seizure (0.36 0.96)) pneumonia, For chronic cannabinoids reduced pain 30% (0.37 0.93), GRADE=high), across different (n=7), distress. epilepsy, cannabidiol risk diarrhoea (2.25 (1.33 3.81)), had no effect sleep disruption populations measures global impression (n=2), quality life, In general population, worsened positive psychotic symptoms (5.21 (3.36 8.01)) total psychiatric (7.49 (5.31 10.42)) negative symptoms, cognition (n=11) healthy people, threshold (0.74 0.91)), unpleasantness (0.60 (0.41 0.88)) (GRADE=high). inflammatory bowel disease, life (0.34 (0.22 0.53) multiple sclerosis, dizziness, dry mouth, nausea, cancer, disruption, (n=2) Cannabis medicines, resulted poor tolerability various Evidence convincing (main sensitivity analyses) pregnant women, small gestational age (1.61 (1.41 1.83)), birth weight (1.43 (1.27 1.62)); drivers, car crash (1.21 1.34)); psychosis (1.71 (1.47 2.00)). Harmful noted additional neonatal outcomes, outcomes crash, population including suicide attempt, depression, mania, impaired users (all suggestive suggestive). Conclusions Convincing converging evidence supports avoidance during adolescence early adulthood, prone mental health disorders, pregnancy before while driving. is effective epilepsy. are palliative medicine without events. Study registration PROSPERO CRD42018093045. Funding None.

Language: Английский

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Therapeutic effect of psilocybin in addiction: A systematic review

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Feb. 9, 2023

Background Psychedelic-assisted therapy [e.g., with lysergic acid diethylamide (LSD)] has shown promising results as treatment for substance use disorders (SUDs). Previous systematic reviews assessing the efficacy of psilocybin in SUDs only included clinical trials conducted last 25 years, but they may have missed that were before 1980s, given much research been done psychedelics mid-20th century. In this review, we specifically assessed patients a SUD or non-substance-related disorder no publication date restrictions our search strategy. Methods A literature was performed according to Preferred Reporting Items Systematic and Meta-Analysis (PRISMA) guidelines from earliest published manuscript up September 2, 2022, seven electronic databases, including evaluating psilocybin. Results total four studies (six articles, which two articles long-term follow-up same trial) review. Psilocybin-assisted administered n = 151 dose ranging 6 40 mg. Three focused on alcohol disorder, one study tobacco disorder. pilot ( 10), percentage heavy drinking days decreased significantly between baseline weeks 5–12 (mean difference 26.0, 95% CI 8.7–43.2, p 0.008). another single-arm 31), 32% (10/31) became completely abstinent duration years). double-blind, placebo-controlled randomized controlled trial (RCT, 95), during 32-week double-blind period lower compared placebo 13.9, 3.0–24.7, 0.01). 15), 7-day point prevalence smoking abstinence at 26 80% (12/15), 52 67% (10/15). Conclusion Only RCT three small identified combined some form psychotherapy All indicated beneficial effect psilocybin-assisted symptoms. Larger RCTs need evaluate whether is effective SUD.

Language: Английский

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Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(12), P. 2094 - 2103

Published: Nov. 20, 2023

Abstract As recreational use of cannabis is being decriminalized in many places and medical widely sanctioned, there are growing concerns about increases disorder (CanUD), which associated with numerous comorbidities. Here we performed a genome-wide association study CanUD the Million Veteran Program (MVP), followed by meta-analysis 1,054,365 individuals ( n cases = 64,314) from four broad ancestries designated reference panel used for assignment (European 886,025, African 123,208, admixed American 38,289 East Asian 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant was observed all but smallest population (East Asian). We discovered loci unique ancestry: 22 European, 2 Asian, 1 ancestries. A genetically informed causal relationship analysis indicated possible effect genetic liability on lung cancer risk, suggesting potential unanticipated future psychiatric public health consequences that require further disentangle other known risk factors such as cigarette smoking.

Language: Английский

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Signaling-specific inhibition of the CB1 receptor for cannabis use disorder: phase 1 and phase 2a randomized trials

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(6), P. 1487 - 1499

Published: June 1, 2023

Cannabis use disorder (CUD) is widespread, and there no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, signaling-specific inhibitor cannabinoid receptor 1 (CB1-SSi). AEF0117 selectively inhibits subset intracellular effects resulting from Δ9-tetrahydrocannabinol (THC) binding without modifying behavior per se. In mice non-human primates, decreased self-administration THC-related behavioral impairment producing significant adverse effects. single-ascending-dose (0.2 mg, 0.6 2 mg 6 mg; n = 40) multiple-ascending-dose (0.6 24) phase trials, healthy volunteers were randomized ascending-dose cohorts (n 8 cohort; 6:2 placebo randomization). both studies, was safe well tolerated (primary outcome measurements). double-blind, placebo-controlled, crossover 2a trial, with CUD two (0.06 14; 15). significantly reduced cannabis' positive subjective measurement, assessed by visual analog scales) 19% mg) 38% (1 compared (P < 0.04). also cannabis 0.05). CUD, did not precipitate withdrawal. These data suggest that potentially efficacious treatment for CUD.ClinicalTrials.gov identifiers: NCT03325595 , NCT03443895 NCT03717272 .

Language: Английский

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Cannabis: a multifaceted plant with endless potentials

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: June 15, 2023

Cannabis sativa , also known as “hemp” or “weed,” is a versatile plant with various uses in medicine, agriculture, food, and cosmetics. This review attempts to evaluate the available literature on ecology, chemical composition, phytochemistry, pharmacology, traditional uses, industrial toxicology of . So far, 566 compounds have been isolated from including 125 cannabinoids 198 non-cannabinoids. The psychoactive physiologically active part cannabinoid, mostly found flowers, but present smaller amounts leaves, stems, seeds. Of all phytochemicals, terpenes form largest composition plant. Pharmacological evidence reveals that plants contain which exhibit potential antioxidants, antibacterial agents, anticancer anti-inflammatory agents. Furthermore, reported applications food cosmetic industries. Significantly, cultivation has minimal negative impact environment terms cultivation. Most studies focused make-up, pharmacological effects, not much about toxic effects. Overall, enormous for biological well other medicinal uses. However, further research necessary fully understand explore beneficial properties

Language: Английский

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Cannabis and Cannabinoids in Adults With Cancer: ASCO Guideline

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: 42(13), P. 1575 - 1593

Published: March 13, 2024

To guide clinicians, adults with cancer, caregivers, researchers, and oncology institutions on the medical use of cannabis cannabinoids, including synthetic cannabinoids herbal derivatives; single, purified cannabinoids; combinations ingredients; full-spectrum cannabis.

Language: Английский

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Clinical management of cannabis withdrawal

Addiction, Journal Year: 2021, Volume and Issue: 117(7), P. 2075 - 2095

Published: Nov. 18, 2021

Abstract Background and Aims Cannabis withdrawal is a well‐characterized phenomenon that occurs in approximately half of regular dependent cannabis users after abrupt cessation or significant reductions products contain Δ 9 ‐tetrahydrocannabinol (THC). This review describes the diagnosis, prevalence, course management highlights opportunities for future clinical research. Methods Narrative literature. Results Symptom onset typically 24–48 hours most symptoms generally peak at days 2–6, with some lasting up to 3 weeks more heavy users. The common features are anxiety, irritability, anger aggression, disturbed sleep/dreaming, depressed mood loss appetite. Less physical include chills, headaches, tension, sweating stomach pain. Despite limited empirical evidence, supportive counselling psychoeducation first‐line approaches withdrawal. There no medications currently approved specifically medically assisted (MAW). Medications have been used manage short‐term (e.g. sleep, nausea). A number promising pharmacological agents examined controlled trials, but these underpowered positive findings not reliably replicated. Some agonists) ‘off‐label’ practice. Inpatient admission MAW may be clinically indicated patients who comorbid mental health disorders polysubstance use avoid severe complications. Conclusions significance its precipitate relapse use. Complicated occur people concurrent

Language: Английский

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Neuromodulation of Hippocampal-Prefrontal Cortical Synaptic Plasticity and Functional Connectivity: Implications for Neuropsychiatric Disorders

Frontiers in Cellular Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: Oct. 11, 2021

The hippocampus-prefrontal cortex (HPC-PFC) pathway plays a fundamental role in executive and emotional functions. Neurophysiological studies have begun to unveil the dynamics of HPC-PFC interaction both immediate demands long-term adaptations. Disruptions functional connectivity can contribute neuropsychiatric symptoms observed mental illnesses neurological conditions, such as schizophrenia, depression, anxiety disorders, Alzheimer’s disease. Given dysfunctional physiology, it is crucial understand mechanisms that modulate communication. Two main regulate interactions are synaptic plasticity modulatory neurotransmission. Synaptic be investigated inducing potentiation or while spontaneous inferred by statistical dependencies between local field potentials regions. In turn, several neurotransmitters, acetylcholine, dopamine, serotonin, noradrenaline, endocannabinoids, fine-tuning connectivity. Despite experimental evidence, effects neuromodulation on neuronal from cellular behavioral levels not fully understood. current literature lacks review focuses neurotransmitter with activity. Here we reviewed showing systems long- short-term plasticity. We also looked for neuromodulatory oscillatory coordination. Finally, implications disruption cognition disorders. comprehensive overview these impairments could help better communication generate insights into etiology physiopathology clinical conditions.

Language: Английский

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