Consequences of adolescent drug use

Translational Psychiatry, Journal Year: 2023, Volume and Issue: 13(1)

Published: Oct. 6, 2023

Abstract Substance use in adolescence is a known risk factor for the development of neuropsychiatric and substance disorders adulthood. This part due to fact that critical aspects brain occur during adolescence, which can be altered by drug use. Despite concerted efforts educate youth about potential negative consequences use, initiation remains common amongst adolescents world-wide. Additionally, though there has been substantial research on topic, many questions remain predictors adolescent In following review, we will highlight some most recent literature neurobiological behavioral effects rodents, non-human primates, humans, with specific focus alcohol, cannabis, nicotine, interactions between these substances. Overall, consumption substances produce long-lasting changes across variety structures networks have enduring behavior, emotion, cognition.

Language: Английский

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Cannabis and synaptic reprogramming of the developing brain

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(7), P. 423 - 438

Published: May 21, 2021

Language: Английский

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The Polypharmacological Effects of Cannabidiol

Molecules, Journal Year: 2023, Volume and Issue: 28(7), P. 3271 - 3271

Published: April 6, 2023

Cannabidiol (CBD) is a major phytocannabinoid present in Cannabis sativa (Linneo, 1753). This naturally occurring secondary metabolite does not induce intoxication or exhibit the characteristic profile of drugs abuse from cannabis like Δ9-tetrahydrocannabinol (∆9-THC) does. In contrast to ∆9-THC, our knowledge neuro-molecular mechanisms CBD limited, and its pharmacology, which appears be complex, has yet been fully elucidated. The study pharmacological effects grown exponentially recent years, making it necessary generate frequently updated reports on this important metabolite. article, rationalized integration action molecular targets implications animal models human diseases, such as epilepsy, pain, neuropsychiatric disorders, Alzheimer’s disease, inflammatory are presented. We identify around 56 different for CBD, including enzymes ion channels/metabotropic receptors involved neurologic conditions. Herein, we compiled found scientific literature multiple actions CBD. vitro vivo findings essential understanding polypharmacological nature natural product.

Language: Английский

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THC and CBD: Similarities and differences between siblings

Neuron, Journal Year: 2023, Volume and Issue: 111(3), P. 302 - 327

Published: Jan. 12, 2023

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Phytocannabinoids: Exploring Pharmacological Profiles and Their Impact on Therapeutical Use

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4204 - 4204

Published: April 10, 2024

Phytocannabinoids, a diverse group of naturally occurring compounds extracted from the Cannabis plant, have attracted interest due to their potential pharmacological effects and medicinal uses. This comprehensive review presents intricate profiles phytocannabinoids while exploring impacts these substances on biological systems. From more than one hundred cannabinoids which were identified in plant so far, cannabidiol (CBD) tetrahydrocannabinol (THC) are two most extensively studied phytocannabinoids. CBD is non-psychoactive compound, exhibits anti-inflammatory, neuroprotective, anxiolytic properties, making it promising candidate for wide array medical conditions. THC, known its psychoactive effects, possesses analgesic antiemetic contributing therapeutic potential. In addition THC CBD, range additional shown intriguing including cannabichromene (CBC), cannabigerol (CBG), cannabinol (CBN). The endocannabinoid system, made up enzymes involved production breakdown endocannabinoids, cannabinoid receptors (CB1 CB2), endogenous ligands (endocannabinoids), essential preserving homeostasis several physiological processes. Beyond ability modify ion channels, neurotransmitter receptors, anti-oxidative pathways. complex interaction between systems offers hope novel treatment approaches lays groundwork further developments field cannabinoid-based medicine. summarizes state field, points out information gaps, emphasizes need studies fully realize

Language: Английский

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Local modulation by presynaptic receptors controls neuronal communication and behaviour

Nature reviews. Neuroscience, Journal Year: 2022, Volume and Issue: 23(4), P. 191 - 203

Published: Feb. 28, 2022

Language: Английский

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Role of the Endocannabinoid System in the Regulation of Intestinal Homeostasis

Cellular and Molecular Gastroenterology and Hepatology, Journal Year: 2022, Volume and Issue: 14(4), P. 947 - 963

Published: Jan. 1, 2022

The maintenance of intestinal homeostasis is fundamentally important to health. Intestinal barrier function and immune regulation are key determinants therefore tightly regulated by a variety signaling mechanisms. endocannabinoid system lipid mediator widely expressed in the gastrointestinal tract. Accumulating evidence suggests critical nexus involved physiological processes that underlie control homeostasis. In this review we will illustrate how permeability, fluid secretion, regulation. We also demonstrate reciprocal between gut microbiome. role complex multifaceted, responding both internal external factors while serving as an effector for SummaryThe distributed throughout plays pivotal integrity, environmental homeostatic system. fundamental importance requires integration digestive defensive functions protect against insults arise from digestion, harmful pathogens toxins, commensal microbiota live gut, simultaneously promoting efficient utilization food. A central determinant function.1Zuo L. Kuo W.T. Turner J.R. Tight junctions targets effectors mucosal homeostasis.Cell Mol Gastroenterol Hepatol. 2020; 10: 327-340Abstract Full Text PDF PubMed Scopus (0) Google Scholar, 2Odenwald M.A. epithelial barrier: therapeutic target?.Nat Rev 2017; 14: 9Crossref (434) 3Allaire J.M. Crowley S.M. Law H.T. Chang S.Y. Ko H.J. Vallance B.A. epithelium: coordinator immunity.Trends Immunol. 2018; 39: 677-696Abstract (277) Scholar dynamic arrangement composed physical (tight junctions) cells secretory together preserve integrity epithelium, being sufficiently permeable allow antigen sampling passage nutrients, electrolytes, water. poised trigger effective mechanisms rapidly rid itself unwanted luminal contents through enteric neuroimmune has enormous capacity mount responses microbial potentially food antigens.4Sharkey K.A. Beck P.L. McKay D.M. 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Verne G.N. health disease.Neurogastroenterol Motil. 2012; 24: 503-512Crossref (402) Because preserving (GI) tract, it not surprising there numerous, highly sophisticated systems controlling various aspects These include intrinsic cellular mechanisms, autocrine paracrine factors, mediators, intercellular molecules, well extrinsic nervous mechanisms.2Odenwald 4Sharkey Scholar,10Peterson L.W. cells: regulators homeostasis.Nat 2014; 141-153Crossref (1445) 11Honda Littman D.R. adaptive disease.Nature. 535: 75-84Crossref (847) 12Wells Brummer R.J. Derrien MacDonald T.T. Troost Cani P.D. Theodorou Dekker J. Méheust A. De Vos W.M. Mercenier Nauta Garcia-Rodenas C.L. Homeostasis potential biomarkers.Am J Physiol Gastrointest Liver Physiol. 312: G171-G193Crossref (242) indicates (ECS) vital brain-gut-microbiota axis, regulator homeostasis.13Cani Plovier Hul Geurts Delzenne N.M. 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Trang chronic pain: microglia modulation.Front Neural Circuits. 2022; 15816747Crossref was discovered after isolation Δ9-tetrahydrocannabinol (THC) major psychoactive constituent cannabis.26Mechoulam Hanuš L.O. Pertwee Howlett A.C. Early phytocannabinoid chemistry beyond.Nat 757-764Crossref (200) This finding led development ligands were used identify cannabis. There now 3 classes cannabinoids recognized: phytocannabinoids derived cannabis plant, THC cannabidiol (CBD); synthetic cannabinoids, chemical agonists HU210, CP55,940, WIN55,212-2 antagonists rimonabant, AM250, AM630; endocannabinoids, anandamide (AEA) 2-arachidonoylglycerol (2-AG), discuss further review.27Pertwee Abood M.E. Alexander S.P.H. Elphick Greasley P.J. Hansen H.S. Kunos Mechoulam Ross R.A. International union basic clinical pharmacology: LXXIX—cannabinoid ligands: beyond CB1 CB2.Pharmacol Rev. 62: 588-631Crossref Interested readers directed excellent reviews cannabinoids.15Lu Scholar,27Pertwee 28Pacher P. Kogan Beyond endocannabinoids.Annu Pharmacol Toxicol. 60: 637-659Crossref 29Di Piscitelli its modulation phytocannabinoids.Neurotherapeutics. 692-698Crossref (159) 30Ligresti Petrocellis From cannabinoid endocannabinoids: pleiotropic pathological pharmacology.Physiol 96: 1593-1659Crossref (213) original description, consists two G protein-coupled (GPCRs), (CB) receptor 1 (CB1) 2 (CB2), endogenous biosynthetic degradative enzymes availability these ligands.15Lu Scholar,31Piomelli molecular logic signalling.Nat 2003; 4: 873-884Crossref (1567) Since many other considered part ECS,19Cristino outline below. membrane-derived molecules. primary N-arachidonoyl ethanolamine 2-AG. Unlike classical neurotransmitters stored vesicles, synthesized "on demand" response stimulus.32Lutz B. Neurobiology signaling.Dialogues 207-222Crossref Primary stimuli synthesis elevation intracellular calcium activation number GPCRs.32Lutz degradation pathways main shown Figure 1. Anandamide begins with conversion phosphatidylethanolamine into (NAPE) calcium-dependent enzyme N-acyltransferase. then produced hydrolysis NAPE N-acylphosphatidylethanolamine-hydrolyzing phospholipase D (NAPE-PLD). Three additional AEA described.33Liu Wang Harvey-White Osei-Hyiaman Razdan Gong Q. Chan Zhou Z. Huang B.X. Kim H.-Y. pathway anandamide.Proc Natl Acad Sci U S 2006; 103: 13345-13350Crossref (350) 34Hussain Uyama Tsuboi Ueda N. Mammalian responsible biosynthesis N-acylethanolamines.Biochim Biophys Acta - Cell Biol Lipids. 1862: 1546-1561Crossref 35Simon G.M. Cravatt B.F. proceeding glycerophospho-N-acyl α/β-hydrolase 4 pathway.J Chem. 281: 26465-26472Abstract (285) (1) Phospholipase C (PLC) converts phosphoanandamide, which dephosphorylated form AEA. (2) produces glycerophosphoanandamide NAPE, converted glycerophosphodiesterase-1, (3) soluble A2 acts 2-lyso-NAPE, lyso-PLD. fatty acid amide hydrolase (FAAH). FAAH hydrolyzes arachidonic ethanolamine.36Fowler C.J. Jonsson K.O. Tiger Fatty hydrolase: biochemistry, pharmacology, possibilities hydrolyzing anandamide, 2-arachidonoylglycerol, palmitoylethanolamide, oleamide.Biochem 2001; 517-526Crossref (114) Scholar,37Van Egmond Straub V.M. Der Stelt Targeting signaling: MAG lipase inhibitors.Annu 61: 441-463Crossref (11) 2-AG dependent PLC activity diacylglycerol (DAGL). acid-containing membrane lipids produce diacylglycerol, DAGL.38Fowler Doherty turnover.Adv 80: 31-66Crossref addition, may be made 2-arachidonoyl-phosphoinositol 2-arachidonoyl-lyso-phosphoinositol A1, subsequently lyso-phosphoinositol-PLC.38Fowler Scholar,39Labar Wouters Lambert monoacylglycerol lipase: interface fat signalling.Curr Med 17: 2588-2607Crossref primarily metabolized (MAGL) glycerol acid.39Labar Scholar,40Fowler Monoacylglycerol target drug development?.Br 166: 1568-1585Crossref However, studies mice revealed via domain-containing protein (ABHD)-6 ABHD-12.41Cao J.K. Kaplan Stella ABHD6: place beyond.Trends Sci. 40: 267-277Abstract (21) 42Navia-Paldanius Savinainen Laitinen J.T. Biochemical characterization human domain containing 6 (ABHD6) 12 (ABHD12).J Lipid Res. 53: 2413-2424Abstract (123) 43Ogasawara Ichu T.A. Jing Hulce J.J. Reed Ulanovskaya O.A. Discovery optimization selective vivo active inhibitors lysophosphatidylserine 1643-1656Crossref (16) sources identified expression genes relevant synthesizing neurons glia projections dorsal root ganglion.44Hockley J.R.F. Taylor T.S. Callejo Wilbrey A.L. Gutteridge Bach Winchester W.J. Bulmer D.C. McMurray Smith E.S.J. Single-cell RNAseq reveals seven colonic sensory neuron.Gut. 68: 633-644Crossref (98) 45Zeisel Hochgerner Lönnerberg Johnsson Memic van der Zwan Häring Braun Borm L.E. La Manno Codeluppi S. Furlan Lee Skene Harris K.D. Hjerling-Leffler Arenas Ernfors Marklund Linnarsson Molecular architecture mouse system.Cell. 174: 999-1014.e22Abstract (875) 46Drokhlyansky Smillie C.S. Wittenberghe Ericsson Griffin G.K. Eraslan Dionne Cuoco M.S. Goder-Reiser M.N. Sharova Kuksenko Aguirre A.J. Boland Graham Rozenblatt-Rosen Xavier Regev single-cell resolution.Cell. 182: 1606-1622.e23Abstract (91) Recent single cell RNA suggested interesting, albeit minor, Paneth goblet cells.47Haber Biton Rogel Herbst R.H. Shekhar Burgin Delorey T.M. Howitt Katz Y. Tirosh Beyaz Zhang Raychowdhury Garrett W.S. Shi H.N. Yilmaz survey small epithelium.Nature. 551: 333-339Crossref (611) although gaining understanding ECS-related genes, functional entirely clear, do complete change during conditions. CB GPCRs coupled Gi/o proteins leading inhibition adenylyl cyclase decreased production cyclic adenosine monophosphate (cAMP).48Howlett CB2 pharmacology.Adv 169-206Crossref (124) release βγ dimers causes N- P/Q-type Ca2+ channels inwardly rectifying A-type potassium channels.32Lutz Scholar,48Howlett initiate Src-mediated cascades mitogen-activated kinases focal adhesion kinases. Activation generally inhibitory, "molecular brake", limit excitation across synapse, reduce cells, cells. Interaction ligand-bound β-arrestin required internalization termination extracellular signaling, but β-arrestins themselves signal transducers pathways, signal-regulated kinase c-Jun terminal kinase, mediate some actions cannabinoids.32Lutz receptor-interacting 1a, interacts GPCR β-arrestin.49Oliver E.E. Hughes Puckett M.K. Chen Lowther interacting 1a (CRIP1a) disease.Biomolecules. 1-22Crossref (8) Some biased toward over cAMP cell-specific actions, can exploited therapeutically.50Al-Zoubi Morales Reggio P.H. Structural insights signaling.Int 20: 1837Crossref (36) Scholar,51Ibsen Connor Glass bias.Cannabis 2: 48-60Crossref illustrated 2. exist multiple forms heterodimers homodimers, very essentially every organ tissue body, subject dysregulation conditions.15Lu Scholar,52Trautmann neural circuitry tract.Int Neurobiol. 125: 85-126Crossref Of particular relevance, (ENS) autonomic (CNS) one most abundant brain.53Duncan Davison J.S. article: system.Aliment 2005; 667-683Crossref presynaptically all neurons, except nitric oxide synthase-expressing inhibitory motor neurons.52Trautmann Scholar,53Duncan found terminals afferent nerves innervating glucose-dependent insulinotropic polypeptide producing (K cells) cholecystokinin (I enteroendocrine upper intestine.54Glass L.L. Calero-Nieto F.J. Jawaid W. Larraufie Kay Göttgens Reimann Gribble F.M. RNA-sequencing distinct population proglucagon-expressing specific intestine.Mol Metab. 1296-1303Crossref (49) Scholar,55Argueta D.A. Perez P.A. Makriyannis Patrizio N.V. inhibit satiation diet-induced obesity.Front 704Crossref leads decrease neurotransmitter synapse depression excitatory neurotransmission ENS. predominantly B neutrophils, mast macrophages; however, limited regions CNS, ENS, nerves.56Atwood B.K. CB2: identity crisis.Br 160: 467-479Crossref (422) 57Duncan Mouihate Keenan C.M. Buckley N.E. Patel Pittman Q.J. modulate contractility lipopolysaccharide-treated rats.Am 2008; 295: G78-G87Crossref 58Wright Rooney Feeney Tate Robertson Welham Ward Differential colon: promote wound healing.Gastroenterology. 129: 437-453Abstract (206) 59Galiègue Mary Marchand Dussossoy Carrière Carayon Bouaboula Shire Le Fur Casellas Expression peripheral tissues leukocyte subpopulations.Eur Biochem. 1995; 232: 54-61Crossref (1314) 60Beltramo Bernardini Bertorelli Campanella Nicolussi Fredduzzi Reggiani receptor-mediated antihyperalgesia: possible direct involvement mechanisms.Eur 23: 1530-1538Crossref (238) 61Cabral G.A. 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Language: Английский

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Therapeutic Potential of Cannabis: A Comprehensive Review of Current and Future Applications

Biomedicines, Journal Year: 2023, Volume and Issue: 11(10), P. 2630 - 2630

Published: Sept. 25, 2023

Historically, cannabis has been valued for its pain-relieving, anti-inflammatory, and calming properties. Ancient civilizations like the Egyptians, Greeks, Chinese medicines recognized their therapeutic potential. The discovery of endocannabinoid system, which interacts with phytoconstituents, scientifically explained how affects human immune including central nervous system (CNS). This review explores evolving world cannabis-based treatments, spotlighting diverse applications. By researching current research clinical studies, we probe into cannabinoids Δ9-tetrahydrocannabinol (THC) cannabidiol (CBD) help to manage conditions ranging from chronic pain, persistent inflammation, cancer, inflammatory bowel disease, neurological disorders even viral diseases such as Human Immunodeficiency virus (HIV), SARS-CoV-2. emerging monkeypox. long-term recreational use can develop disorder (CUD), therefore, understanding factors contributing development maintenance addiction, genetic predisposition, neurobiological mechanisms, environmental influences, will be timely. Shedding light on adverse impacts CUD underscores importance early intervention, effective treatment approaches, public health initiatives address this complex issue in an landscape policies perceptions.

Language: Английский

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THC and CBD: Villain versus Hero? Insights into Adolescent Exposure

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5251 - 5251

Published: March 9, 2023

Cannabis is the most used drug of abuse worldwide. It well established that abundant phytocannabinoids in this plant are Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These two compounds have remarkably similar chemical structures yet vastly different effects brain. By binding to same receptors, THC psychoactive, while CBD has anxiolytic antipsychotic properties. Lately, a variety hemp-based products, including THC, become widely available food health industry, medical recreational use cannabis been legalized many states/countries. As result, people, youths, consuming because it considered “safe”. An extensive literature exists evaluating harmful both adults adolescents, but little known about long-term exposure, especially adolescence. The aim review collect preclinical clinical evidence cannabidiol.

Language: Английский

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Inhibiting degradation of 2-arachidonoylglycerol as a therapeutic strategy for neurodegenerative diseases

Pharmacology & Therapeutics, Journal Year: 2023, Volume and Issue: 244, P. 108394 - 108394

Published: March 24, 2023

Endocannabinoids are endogenous lipid signaling mediators that participate in a variety of physiological and pathological processes. 2-Arachidonoylglycerol (2-AG) is the most abundant endocannabinoid full agonist G-protein-coupled cannabinoid receptors (CB1R CB2R), which targets Δ9-tetrahydrocannabinol (Δ9-THC), main psychoactive ingredient cannabis. While 2-AG has been well recognized as retrograde messenger modulating synaptic transmission plasticity at both inhibitory GABAergic excitatory glutamatergic synapses brain, growing evidence suggests also functions an terminator neuroinflammation response to harmful insults, thus maintaining brain homeostasis. Monoacylglycerol lipase (MAGL) key enzyme degrades brain. The immediate metabolite arachidonic acid (AA), precursor prostaglandins (PGs) leukotrienes. Several lines indicate pharmacological or genetic inactivation MAGL, boosts levels reduces its hydrolytic metabolites, resolves neuroinflammation, mitigates neuropathology, improves cognitive animal models neurodegenerative diseases, including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's (PD), traumatic injury (TBI)-induced disease. Thus, it proposed MAGL potential therapeutic target for treatment diseases. As hydrolyzing 2-AG, several inhibitors have identified developed. However, our understanding mechanisms by produces neuroprotective effects diseases remains limited. A recent finding inhibition metabolism astrocytes, but not neurons, protects from TBI-induced neuropathology might shed some light on this unsolved issue. This review provides overview discusses possible underlying restraining degradation

Language: Английский

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