Article
Biochemistry & Molecular Biology
Agnieszka Sulima, Fatemeh Akhlaghi, Lorenzo Leggio, Kenner C. Rice
Summary: Preclinical and human studies have suggested the involvement of the ghrelin system in alcohol-related behaviors, opening up the possibility of using ghrelin receptor blockers as a pharmacological intervention for alcohol use disorder (AUD). A recent phase 1b human study with a ghrelin receptor inverse agonist, PF-5190457, demonstrated the safety and tolerability of this compound when co-administered with alcohol, as well as providing insights into biotransformation pathways and the discovery of a newly identified major metabolite, PF-6870961. The synthesis of this metabolite allows for further evaluation of its properties in vitro and in vivo.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Pharmacology & Pharmacy
Francisca Villavicencio-Tejo, Osvaldo Flores-Bastias, Lucas Marambio-Ruiz, Diliana Perez-Reytor, Eduardo Karahanian
Summary: High ethanol intake induces neuroinflammation and decreases GLT-1 expression, leading to long-term drinking behavior. Fibrates can inhibit neuroinflammation, reduce ethanol consumption, and normalize glutamatergic tone by reverting astrogliosis and NF-kappa B activation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Kamel Chettab, Chantel Fitzsimmons, Alexey Novikov, Morgane Denis, Capucine Phelip, Doriane Mathe, Pierre Antoine Choffour, Sabine Beaumel, Eric Fourmaux, Patrick Norca, David Kryza, Anne Evesque, Lars Petter Jordheim, Emeline Perrial, Eva-Laure Matera, Martine Caroff, Jerome Kerzerho, Charles Dumontet
Summary: Bacterial lipopolysaccharides (LPS) have potent anti-tumor activity but their toxicity prevents effective systemic administration in humans. This study demonstrates that liposomal encapsulation of LPS preserves its anti-tumor activity and enhances the efficacy of rituximab, an anti-CD20 antibody, in lymphoma models. Liposomal encapsulation also reduces cytokine induction and toxicity while maintaining immunoadjuvant effects, making it a promising systemically active anticancer agent.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Clinical Neurology
Mehdi Farokhnia, Kelly M. Abshire, Aaron Hammer, Sara L. Deschaine, Anitha Saravanakumar, Enoch Cobbina, Zhi-Bing You, Carolina L. Haass-Koffler, Mary R. Lee, Fatemeh Akhlaghi, Lorenzo Leggio
Summary: This study examined the neuroendocrine response to exogenous ghrelin administration combined with alcohol in heavy-drinking individuals. Results showed that ghrelin increased blood concentrations of certain hormones acutely and throughout the session, providing insights into its role in the context of alcohol use disorder. This suggests that the ghrelin system may be a potential pharmacotherapeutic target for alcohol use disorder.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2021)
Article
Endocrinology & Metabolism
Glenn D. Crater, Karine Lalonde, Francois Ravenelle, Michael Harvey, Jean-Pierre Despres
Summary: This study evaluated the clinical safety and pharmacodynamic profile of a novel CB1R inverse agonist, INV-202, in adults with features of metabolic syndrome. The results showed that INV-202 was well tolerated and produced significant weight loss, reductions in waist circumference and BMI. These findings suggest that INV-202 has potential in improving metabolic syndrome.
DIABETES OBESITY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Sara L. Deschaine, Mehdi Farokhnia, Adriana Gregory-Flores, Lia J. Zallar, Zhi-Bing You, Hui Sun, Deon M. Harvey, Renata C. N. Marchette, Brendan J. Tunstall, Bharath K. Mani, Jacob E. Moose, Mary R. Lee, Eliot Gardner, Fatemeh Akhlaghi, Marisa Roberto, James L. Hougland, Jeffrey M. Zigman, George F. Koob, Leandro F. Vendruscolo, Lorenzo Leggio
Summary: Alcohol decreases ghrelin levels in both rats and humans, but this decrease is not in proportion to alcohol's caloric value or through direct interaction with the ghrelin system.
Article
Behavioral Sciences
Thomas Gough, Paul Christiansen, Abigail K. Rose, Charlotte A. Hardman
Summary: Alcohol consumption can affect meal-related memories but does not contribute towards alcohol-induced overeating. Certain types of meal memory recall may be impaired by alcohol intoxication, likely due to disruption of memory formation during the encoding phase.
Article
Biochemistry & Molecular Biology
Melissa A. Cyders, Martin H. Plawecki, Zachary T. Whitt, Ann E. K. Kosobud, David A. Kareken, Ulrich S. Zimmermann, Sean J. O'Connor
Summary: The study examined how intravenous alcohol self-administration paradigms in humans can model liking and wanting behaviors, providing a potential translational link between preclinical and clinical trials. The results showed that individual differences in alcohol seeking behavior were related to both enjoying and craving alcohol, suggesting promising applications in modeling alcohol use disorder behaviors.
Article
Neurosciences
Carolina L. Haass-Koffler, Roberta Perciballi, Molly Magill, Antonella Loche, Roberto Cacciaglia, Lorenzo Leggio, Robert M. Swift
Summary: This study demonstrates that GET 73 has good safety and tolerability when co-administered with alcohol, and does not affect the pharmacokinetics of GET 73 or alcohol. GET 73 increases the subjective sedative effects of alcohol, but has no effect on alcohol cue-induced craving and self-administration.
PSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Mehdi Farokhnia, Brittney D. Browning, Madeline E. Crozier, Hui Sun, Fatemeh Akhlaghi, Lorenzo Leggio
Summary: Growing evidence suggests that the GLP-1 system plays a role in alcohol seeking and consumption, and GLP-1 analogues may be a potential treatment for AUD. This study found that alcohol administration significantly reduced GLP-1 levels in heavy-drinking individuals with AUD. Additionally, individuals with AUD showed higher expression of GLP-1 receptors in the hippocampus. These findings provide novel insights into the interaction between alcohol and GLP-1.
Article
Biochemistry & Molecular Biology
Sara L. Deschaine, Mehdi Farokhnia, Adriana Gregory-Flores, Lia J. Zallar, Zhi-Bing You, Hui Sun, Deon M. Harvey, Renata C. N. Marchette, Brendan J. Tunstall, Bharath K. Mani, Jacob E. Moose, Mary R. Lee, Eliot Gardner, Fatemeh Akhlaghi, Marisa Roberto, James L. Hougland, Jeffrey M. Zigman, George F. Koob, Leandro F. Vendruscolo, Lorenzo Leggio
Summary: Alcohol decreases ghrelin levels in both rats and humans, but this decrease is not in proportion to alcohol's caloric value or through direct interaction with the ghrelin system.
Review
Pharmacology & Pharmacy
Celine Nicolas, Natalie E. Zlebnik, Mehdi Farokhnia, Lorenzo Leggio, Satoshi Ikemoto, Yavin Shaham
Summary: This review suggests that there may not necessarily be a gender difference in vulnerability to psychostimulant and opioid craving and relapse, although imaging studies indicate potential sex differences in brain responses to drug cues and stress. Preclinical studies show evidence for sex differences in cocaine seeking reinstatement and incubation, but not in methamphetamine or opioid seeking reinstatement or incubation.
PHARMACOLOGICAL REVIEWS
(2022)
Article
Biochemistry & Molecular Biology
Andras H. Leko, M. Adrienne McGinn, Mehdi Farokhnia
Summary: This study discusses the role of the mineralocorticoid receptor (MR) as a potential pharmacotherapeutic target for alcohol use disorder (AUD), including its associations with the aldosterone/MR system, the effects of MR antagonism on alcohol consumption, and the underlying neurobiology of these effects.
ACS CHEMICAL NEUROSCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Mehdi Farokhnia, Brittney D. Browning, Madeline E. Crozier, Hui Sun, Fatemeh Akhlaghi, Lorenzo Leggio
Summary: Growing evidence suggests that the GLP-1 system plays a role in alcohol seeking and consumption, and GLP-1 analogues may be a potential treatment for AUD. This study found that alcohol administration significantly reduced GLP-1 levels in heavy-drinking individuals with AUD. Additionally, individuals with AUD showed higher expression of GLP-1 receptors in the hippocampus. These findings provide novel insights into the interaction between alcohol and GLP-1.
Article
Multidisciplinary Sciences
Mehdi Farokhnia, Samantha J. Fede, Erica N. Grodin, Brittney D. Browning, Madeline E. Crozier, Melanie L. Schwandt, Colin A. Hodgkinson, Reza Momenan, Lorenzo Leggio
Summary: Growing evidence suggests that genetic variation at the GLP-1R is associated with differences in brain functional connectivity based on the severity of alcohol use. Significant findings in the salience and default mode networks are particularly relevant, given their role in the neurobiology of AUD and addictive behaviors.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Sara L. Deschaine, Morten A. Hedegaard, Claire L. Pince, Mehdi Farokhnia, Jacob E. Moose, Ingrid A. Stock, Sravani Adusumalli, Fatemeh Akhlaghi, James L. Hougland, Agnieszka Sulima, Kenner C. Rice, George F. Koob, Leandro F. Vendruscolo, Birgitte Holst, Lorenzo Leggio
Summary: The metabolite PF-6870961 of PF-5190457 has been identified as a potential treatment for alcohol use disorder. It shows binding affinity and inverse agonist activity at GHSR1a, and can suppress food intake in rats through GHSR receptor-mediated pathways.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2023)
Article
Biochemistry & Molecular Biology
Jillian T. Battista, Daria Piacentino, Melanie L. Schwandt, Mary R. Lee, Monica L. Faulkner, Mehdi Farokhnia, Lorenzo Leggio
Summary: Early life adversity (ELA) has lasting effects on adult mental and physical health, including higher risk of psychiatric conditions such as depression, anxiety, and alcohol misuse. Inflammation, assessed through hsCRP, may mediate the relationship between ELA and alcohol use. Study findings indicate that early life stress and alcohol consumption are associated with increased hsCRP levels, suggesting that elevated inflammation may contribute to unhealthy alcohol use in adulthood.
Article
Substance Abuse
Mehdi Farokhnia, Tammy Wang, Tony Jourdan, Grzegorz Godlewski, Lisa A. Farinelli, George Kunos, Lorenzo Leggio
Summary: Growing evidence suggests that the interaction between the central nervous system and the periphery, particularly through fibroblast growth factor 21 (FGF21), plays a crucial role in the development of neuropsychiatric conditions and addictive disorders. This study examined the relationship between alcohol use disorder (AUD) and FGF21 levels in non-treatment seeking individuals using both outpatient and laboratory settings. The findings showed that while FGF21 levels remained stable during the outpatient phase, there was a significant increase in serum FGF21 concentrations following alcohol self-administration in a controlled laboratory experiment. These results highlight the potential of targeting the FGF21 system as a pharmacotherapy for AUD.
DRUG AND ALCOHOL DEPENDENCE
(2023)
Article
Medicine, Research & Experimental
Vicky Chuong, Mehdi Farokhnia, Sophia Khom, Claire L. Pince, Sophie K. Elvig, Roman Vlkolinsky, Renata C. N. Marchette, George F. Koob, Marisa Roberto, Leandro F. Vendruscolo, Lorenzo Leggio
Summary: Growing evidence suggests the involvement of the GLP-1 system in addictive behaviors, and GLP-1 analogues like semaglutide may be a potential treatment for AUD. This study found that semaglutide dose-dependently reduced binge-like drinking in mice and also decreased alcohol intake in rats with binge-like and dependence-induced drinking. Additionally, semaglutide modulated GABA neurotransmission in the central amygdala and infralimbic cortex, indicating its potential as a novel pharmacotherapy for AUD.
Meeting Abstract
Substance Abuse
Mehdi Farokhnia, Christopher T. Rentsch, Vicky Chuong, M. Adrienne McGinn, Sophie K. Elvig, Eliza A. Douglass, Luis A. Gonzalez, Jenna E. Sanfilippo, Renata C. N. Marchette, Brendan J. Tunstall, David A. Fiellin, George F. Koob, Amy C. Justice, Lorenzo Leggio, Leandro F. Vendruscolo
Article
Psychiatry
Madeline E. Crozier, Mehdi Farokhnia, Susan Persky, Lorenzo Leggio, Brenda Curtis
Summary: Self-stigma is associated with the severity of alcohol use disorder and craving. Higher levels of self-stigma are related to more severe AUD, greater alcohol consumption, and more obsessive thoughts and compulsive behaviors related to alcohol.
Meeting Abstract
Neurosciences
Mehdi Farokhnia, Lorenzo Leggio, Renee Johnson
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Neurosciences
Andras Leko, Mehdi Farokhnia, Lindsay Kryszak, Shelley N. Jackson, Lisa Farinelli, Lorenzo Leggio
NEUROPSYCHOPHARMACOLOGY
(2022)
Meeting Abstract
Public, Environmental & Occupational Health
Mehdi Farokhnia, Christopher Rentsch, Vicky Chuong, Adrienne McGinn, Sophie Elvig, Eliza Douglass, Jenna Sanfilippo, Renata Marchette, Brendan Tunstall, David Fiellin, George Koob, Amy C. Justice, Lorenzo Leggio, Leandro Vendruscolo
PHARMACOEPIDEMIOLOGY AND DRUG SAFETY
(2022)
Article
Substance Abuse
Julia C. Harris, Ethan H. Mereish, Monica L. Faulkner, Shervin Assari, Kelvin Choi, Lorenzo Leggio, Mehdi Farokhnia
Summary: The study investigated differences in the association between alcohol drinking and cigarette smoking among non-Hispanic Black and White individuals. Results showed a decoupling in the drinking-smoking link among Black compared to White individuals, emphasizing the importance of considering racial/ethnic background in substance use research and treatment.
ALCOHOL AND ALCOHOLISM
(2022)