Contact
Biomedical Research Center251 Bayview Boulevard
Suite 200, Room 01B606
Baltimore, MD 21224
Email: mehdi.farokhnia@nih.gov
Research Interests
Mehdi received his medical degree from Tehran University of Medical Sciences and completed a postdoctoral fellowship, supported by an Intramural Research Training Award, in Dr. Leggio’s lab at the NIH Clinical Center. During his postdoctoral fellowship, Mehdi conducted several clinical and translational projects, including two major protocols (13-AA-0040 and 13-AA-0043) as the Lead Associate Investigator. His research has been focused on understanding the neurobiology of addictive behaviors and identifying/testing novel therapeutic targets for alcohol and other substance use disorders. He uses a combination of behavioral, pharmacological, genetic, and neuroimaging methods and is also interested in investigating innovative human laboratory approaches that may facilitate the crosstalk between preclinical and clinical research, with a particular focus on behavioral pharmacology and substance use. Another line of research that Mehdi is pursuing includes utilizing big data to characterize biobehavioral substrates of health disparity (e.g., racial differences) in risk/resilience to addiction and other mental health disorders.
Publications
Selected Publications
2020
Lee, Mary R; Tapocik, Jenica D; Ghareeb, Mwlod; Schwandt, Melanie L; Dias, Alexandra A; Le, April N; Cobbina, Enoch; Farinelli, Lisa A; Bouhlal, Sofia; Farokhnia, Mehdi; Heilig, Markus; Akhlaghi, Fatemeh; Leggio, Lorenzo
In: Mol Psychiatry, 2020, ISSN: 1476-5578 (Electronic); 1359-4184 (Linking).
@article{Lee:2018aa,
title = {The novel ghrelin receptor inverse agonist PF-5190457 administered with alcohol: preclinical safety experiments and a phase 1b human laboratory study.},
author = {Mary R Lee and Jenica D Tapocik and Mwlod Ghareeb and Melanie L Schwandt and Alexandra A Dias and April N Le and Enoch Cobbina and Lisa A Farinelli and Sofia Bouhlal and Mehdi Farokhnia and Markus Heilig and Fatemeh Akhlaghi and Lorenzo Leggio},
url = {https://www.ncbi.nlm.nih.gov/pubmed/29728704},
doi = {10.1038/s41380-018-0064-y},
issn = {1476-5578 (Electronic); 1359-4184 (Linking)},
year = {2020},
date = {2020-05-04},
journal = {Mol Psychiatry},
address = {Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.},
abstract = {Rodent studies indicate that ghrelin receptor blockade reduces alcohol consumption. However, no ghrelin receptor blockers have been administered to heavy alcohol drinking individuals. Therefore, we evaluated the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and behavioral effects of a novel ghrelin receptor inverse agonist, PF-5190457, when co-administered with alcohol. We tested the effects of PF-5190457 combined with alcohol on locomotor activity, loss-of-righting reflex (a measure of alcohol sedative actions), and on blood PF-5190457 concentrations in rats. Then, we performed a single-blind, placebo-controlled, within-subject human study with PF-5190457 (placebo/0 mg b.i.d., 50 mg b.i.d., 100 mg b.i.d.). Twelve heavy drinkers during three identical visits completed an alcohol administration session, subjective assessments, and an alcohol cue-reactivity procedure, and gave blood samples for PK/PD testing. In rats, PF-5190457 did not interact with the effects of alcohol on locomotor activity or loss-of-righting reflex. Alcohol did not affect blood PF-5190457 concentrations. In humans, all adverse events were mild or moderate and did not require discontinuation or dose reductions. Drug dose did not alter alcohol concentration or elimination, alcohol-induced stimulation or sedation, or mood during alcohol administration. Potential PD markers of PF-5190457 were acyl-to-total ghrelin ratio and insulin-like growth factor-1. PF-5190457 (100 mg b.i.d.) reduced alcohol craving during the cue-reactivity procedure. This study provides the first translational evidence of safety and tolerability of the ghrelin receptor inverse agonist PF-5190457 when co-administered with alcohol. PK/PD/behavioral findings support continued research of PF-5190457 as a potential pharmacological agent to treat alcohol use disorder.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Rodent studies indicate that ghrelin receptor blockade reduces alcohol consumption. However, no ghrelin receptor blockers have been administered to heavy alcohol drinking individuals. Therefore, we evaluated the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and behavioral effects of a novel ghrelin receptor inverse agonist, PF-5190457, when co-administered with alcohol. We tested the effects of PF-5190457 combined with alcohol on locomotor activity, loss-of-righting reflex (a measure of alcohol sedative actions), and on blood PF-5190457 concentrations in rats. Then, we performed a single-blind, placebo-controlled, within-subject human study with PF-5190457 (placebo/0 mg b.i.d., 50 mg b.i.d., 100 mg b.i.d.). Twelve heavy drinkers during three identical visits completed an alcohol administration session, subjective assessments, and an alcohol cue-reactivity procedure, and gave blood samples for PK/PD testing. In rats, PF-5190457 did not interact with the effects of alcohol on locomotor activity or loss-of-righting reflex. Alcohol did not affect blood PF-5190457 concentrations. In humans, all adverse events were mild or moderate and did not require discontinuation or dose reductions. Drug dose did not alter alcohol concentration or elimination, alcohol-induced stimulation or sedation, or mood during alcohol administration. Potential PD markers of PF-5190457 were acyl-to-total ghrelin ratio and insulin-like growth factor-1. PF-5190457 (100 mg b.i.d.) reduced alcohol craving during the cue-reactivity procedure. This study provides the first translational evidence of safety and tolerability of the ghrelin receptor inverse agonist PF-5190457 when co-administered with alcohol. PK/PD/behavioral findings support continued research of PF-5190457 as a potential pharmacological agent to treat alcohol use disorder.
Farokhnia, Mehdi; McDiarmid, Gray R; Newmeyer, Matthew N; Munjal, Vikas; Abulseoud, Osama A; Huestis, Marilyn A; Leggio, Lorenzo
In: Translational Psychiatry, 10 (1), pp. 71, 2020, ISBN: 2158-3188.
@article{Farokhnia:2020aa,
title = {Effects of oral, smoked, and vaporized cannabis on endocrine pathways related to appetite and metabolism: a randomized, double-blind, placebo-controlled, human laboratory study},
author = {Mehdi Farokhnia and Gray R McDiarmid and Matthew N Newmeyer and Vikas Munjal and Osama A Abulseoud and Marilyn A Huestis and Lorenzo Leggio},
url = {https://pubmed.ncbi.nlm.nih.gov/32075958/},
doi = {10.1038/s41398-020-0756-3},
isbn = {2158-3188},
year = {2020},
date = {2020-01-01},
journal = {Translational Psychiatry},
volume = {10},
number = {1},
pages = {71},
abstract = {As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 $pm$0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug ×time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug ×time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
As perspectives on cannabis continue to shift, understanding the physiological and behavioral effects of cannabis use is of paramount importance. Previous data suggest that cannabis use influences food intake, appetite, and metabolism, yet human research in this regard remains scant. The present study investigated the effects of cannabis administration, via different routes, on peripheral concentrations of appetitive and metabolic hormones in a sample of cannabis users. This was a randomized, crossover, double-blind, placebo-controlled study. Twenty participants underwent four experimental sessions during which oral cannabis, smoked cannabis, vaporized cannabis, or placebo was administered. Active compounds contained 6.9 $pm$0.95% (~50.6 mg) ∆9-tetrahydrocannabinol (THC). Repeated blood samples were obtained, and the following endocrine markers were measured: total ghrelin, acyl-ghrelin, leptin, glucagon-like peptide-1 (GLP-1), and insulin. Results showed a significant drug main effect (p = 0.001), as well as a significant drug ×time-point interaction effect (p = 0.01) on insulin. The spike in blood insulin concentrations observed under the placebo condition (probably due to the intake of brownie) was blunted by cannabis administration. A significant drug main effect (p = 0.001), as well as a trend-level drug ×time-point interaction effect (p = 0.08) was also detected for GLP-1, suggesting that GLP-1 concentrations were lower under cannabis, compared to the placebo condition. Finally, a significant drug main effect (p = 0.01) was found for total ghrelin, suggesting that total ghrelin concentrations during the oral cannabis session were higher than the smoked and vaporized cannabis sessions. In conclusion, cannabis administration in this study modulated blood concentrations of some appetitive and metabolic hormones, chiefly insulin, in cannabis users. Understanding the mechanisms underpinning these effects may provide additional information on the cross-talk between cannabinoids and physiological pathways related to appetite and metabolism.
2019
Assari, Shervin; Smith, James; Mistry, Ritesh; Farokhnia, Mehdi; Bazargan, Mohsen
Substance Use among Economically Disadvantaged African American Older Adults; Objective and Subjective Socioeconomic Status. Journal Article
In: Int J Environ Res Public Health, 16 (10), 2019.
@article{Assari:2019aa,
title = {Substance Use among Economically Disadvantaged African American Older Adults; Objective and Subjective Socioeconomic Status.},
author = {Shervin Assari and James Smith and Ritesh Mistry and Mehdi Farokhnia and Mohsen Bazargan},
url = {https://pubmed.ncbi.nlm.nih.gov/31126049/},
doi = {10.3390/ijerph16101826},
year = {2019},
date = {2019-05-23},
journal = {Int J Environ Res Public Health},
volume = {16},
number = {10},
abstract = {Purpose. This study investigated the effects of objective and subjective socioeconomic status (SES) indicators on two health behaviors, cigarette smoking and alcohol drinking, among African American older adults. Methods. This community-based study recruited 619 economically disadvantaged African American older adults (age ≥ 65 years) residing in South Los Angeles. Structured face-to-face interviews were conducted to collect data. Data on demographic factors (age and gender), subjective SES (financial difficulties), objective SES (educational attainment), living arrangement, marital status, healthcare access (insurance), and health (number of chronic medical conditions, self-rated health, sick days, depression, and chronic pain) and health behaviors (cigarette smoking and alcohol drinking) were collected from participants. Logistic regressions were used to analyze the data. Results. High financial difficulties were associated with higher odds of smoking cigarettes and drinking alcohol, independent of covariates. Educational attainment did not correlate with our outcomes. Similar patterns emerged for cigarette smoking and alcohol drinking. Conclusion. Subjective SES indicators such as financial difficulties may be more relevant than objective SES indicators such as educational attainment to health risk behaviors such as cigarette smoking and alcohol drinking among African American older adults in economically constrain urban environments. Smoking and drinking may serve as coping mechanisms with financial difficulty, especially among African American older adults. In line with the minorities' diminished returns (MDR) theory, and probably due to discrimination against racial minorities, educational attainment has a smaller protective effect among economically disadvantaged African American individuals against health risk behaviors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Purpose. This study investigated the effects of objective and subjective socioeconomic status (SES) indicators on two health behaviors, cigarette smoking and alcohol drinking, among African American older adults. Methods. This community-based study recruited 619 economically disadvantaged African American older adults (age ≥ 65 years) residing in South Los Angeles. Structured face-to-face interviews were conducted to collect data. Data on demographic factors (age and gender), subjective SES (financial difficulties), objective SES (educational attainment), living arrangement, marital status, healthcare access (insurance), and health (number of chronic medical conditions, self-rated health, sick days, depression, and chronic pain) and health behaviors (cigarette smoking and alcohol drinking) were collected from participants. Logistic regressions were used to analyze the data. Results. High financial difficulties were associated with higher odds of smoking cigarettes and drinking alcohol, independent of covariates. Educational attainment did not correlate with our outcomes. Similar patterns emerged for cigarette smoking and alcohol drinking. Conclusion. Subjective SES indicators such as financial difficulties may be more relevant than objective SES indicators such as educational attainment to health risk behaviors such as cigarette smoking and alcohol drinking among African American older adults in economically constrain urban environments. Smoking and drinking may serve as coping mechanisms with financial difficulty, especially among African American older adults. In line with the minorities' diminished returns (MDR) theory, and probably due to discrimination against racial minorities, educational attainment has a smaller protective effect among economically disadvantaged African American individuals against health risk behaviors.
Farokhnia, Mehdi; Faulkner, Monica L; Piacentino, Daria; Lee, Mary R; Leggio, Lorenzo
Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder Journal Article
In: Physiology & Behavior, 204 , pp. 49 - 57, 2019, ISSN: 0031-9384.
@article{FAROKHNIA201949,
title = {Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder},
author = {Mehdi Farokhnia and Monica L Faulkner and Daria Piacentino and Mary R Lee and Lorenzo Leggio},
url = {https://pubmed.ncbi.nlm.nih.gov/30738971/},
doi = {https://doi.org/10.1016/j.physbeh.2019.02.008},
issn = {0031-9384},
year = {2019},
date = {2019-01-01},
journal = {Physiology & Behavior},
volume = {204},
pages = {49 - 57},
abstract = {Alcohol use disorder (AUD) is a leading cause of morbidity and mortality worldwide. However, treatment options, including pharmacotherapies, are limited in number and efficacy. Accumulating evidence suggests that elements of the gut-brain axis, such as neuroendocrine pathways and gut microbiome, are involved in the pathophysiology of AUD and, therefore, may be investigated as potential therapeutic targets. One pathway that has begun to be examined in this regard is the ghrelin system. Here, we review preclinical and clinical data on the relationship between ghrelin and alcohol-related outcomes, with a special focus on the role of the ghrelin system as a treatment target for AUD. Observational studies indicate that endogenous ghrelin levels are positively associated with craving for alcohol, subjective responses to alcohol, and brain activity in response to alcohol cues. Knockout rodent models suggest that deletion of the ghrelin peptide or receptor gene leads to reduction of alcohol intake and other alcohol-related outcomes. Different research groups have found that ghrelin administration increases, while ghrelin receptor (GHS-R1a) blockade reduces alcohol intake and other alcohol-related outcomes in rodents. Ghrelin administration in heavy-drinking individuals increases alcohol craving and self-administration and modulates brain activity in response to alcohol reward anticipation. PF-5190457, a GHS-R1a blocker, has been shown to be safe and tolerable when co-administered with alcohol. Furthermore, preliminary results suggest that this compound may reduce cue-elicited craving for alcohol in heavy-drinking individuals – a finding in need of replication. Collectively, the existing literature supports further examination of the ghrelin system as a therapeutic target for AUD. More research is also needed to understand the biobehavioral and molecular mechanisms underlying ghrelin's functions and to examine different interventional approaches to target the ghrelin system for AUD treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alcohol use disorder (AUD) is a leading cause of morbidity and mortality worldwide. However, treatment options, including pharmacotherapies, are limited in number and efficacy. Accumulating evidence suggests that elements of the gut-brain axis, such as neuroendocrine pathways and gut microbiome, are involved in the pathophysiology of AUD and, therefore, may be investigated as potential therapeutic targets. One pathway that has begun to be examined in this regard is the ghrelin system. Here, we review preclinical and clinical data on the relationship between ghrelin and alcohol-related outcomes, with a special focus on the role of the ghrelin system as a treatment target for AUD. Observational studies indicate that endogenous ghrelin levels are positively associated with craving for alcohol, subjective responses to alcohol, and brain activity in response to alcohol cues. Knockout rodent models suggest that deletion of the ghrelin peptide or receptor gene leads to reduction of alcohol intake and other alcohol-related outcomes. Different research groups have found that ghrelin administration increases, while ghrelin receptor (GHS-R1a) blockade reduces alcohol intake and other alcohol-related outcomes in rodents. Ghrelin administration in heavy-drinking individuals increases alcohol craving and self-administration and modulates brain activity in response to alcohol reward anticipation. PF-5190457, a GHS-R1a blocker, has been shown to be safe and tolerable when co-administered with alcohol. Furthermore, preliminary results suggest that this compound may reduce cue-elicited craving for alcohol in heavy-drinking individuals – a finding in need of replication. Collectively, the existing literature supports further examination of the ghrelin system as a therapeutic target for AUD. More research is also needed to understand the biobehavioral and molecular mechanisms underlying ghrelin's functions and to examine different interventional approaches to target the ghrelin system for AUD treatment.
Farokhnia, Mehdi; Browning, Brittney D; Leggio, Lorenzo
Prospects for pharmacotherapies to treat alcohol use disorder: an update on recent human studies Journal Article
In: Current Opinion in Psychiatry, 32 (4), 2019, ISBN: 0951-7367.
@article{cite-keyb,
title = {Prospects for pharmacotherapies to treat alcohol use disorder: an update on recent human studies},
author = {Mehdi Farokhnia and Brittney D Browning and Lorenzo Leggio},
url = {https://pubmed.ncbi.nlm.nih.gov/31107292/},
doi = {10.1097/YCO.0000000000000519},
isbn = {0951-7367},
year = {2019},
date = {2019-01-01},
journal = {Current Opinion in Psychiatry},
volume = {32},
number = {4},
keywords = {},
pubstate = {published},
tppubtype = {article}
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2018
Farokhnia, Mehdi; Deschaine, Sara L; Sadighi, Armin; Farinelli, Lisa A; Lee, Mary R; Akhlaghi, Fatemeh; Leggio, Lorenzo
In: Mol Psychiatry, 2018, ISSN: 1476-5578 (Electronic); 1359-4184 (Linking).
@article{Farokhnia:2018aab,
title = {A deeper insight into how GABA-B receptor agonism via baclofen may affect alcohol seeking and consumption: lessons learned from a human laboratory investigation.},
author = {Mehdi Farokhnia and Sara L Deschaine and Armin Sadighi and Lisa A Farinelli and Mary R Lee and Fatemeh Akhlaghi and Lorenzo Leggio},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30382188},
doi = {10.1038/s41380-018-0287-y},
issn = {1476-5578 (Electronic); 1359-4184 (Linking)},
year = {2018},
date = {2018-10-31},
journal = {Mol Psychiatry},
address = {Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.},
abstract = {Previous studies suggest that GABA-B receptor agonism may represent an effective pharmacological approach to treat addictive disorders. Baclofen is a selective GABA-B receptor agonist which has been investigated as a potential treatment for alcohol use disorder. However, research is needed to understand the biobehavioral mechanisms underlying baclofen's effect on alcohol use. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals were randomized to receive baclofen (30 mg/d) or placebo for a week, and then participated in a laboratory experiment consisting of three procedures: alcohol cue-reactivity, priming, and self-administration. During the experiment, craving and other subjective responses to alcohol were assessed, and blood samples were collected for pharmacokinetic measurements. The effects of baclofen on the relationships between different alcohol-related laboratory parameters were investigated. Baclofen pharmacokinetic parameters and their correlations with behavioral measures were also examined. Results showed that baclofen disrupted the link between alcohol priming and self-administration, as indicated by significant interaction effects between drug condition (baclofen vs. placebo) and some of the priming variables (alcohol craving: F3},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Previous studies suggest that GABA-B receptor agonism may represent an effective pharmacological approach to treat addictive disorders. Baclofen is a selective GABA-B receptor agonist which has been investigated as a potential treatment for alcohol use disorder. However, research is needed to understand the biobehavioral mechanisms underlying baclofen's effect on alcohol use. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals were randomized to receive baclofen (30 mg/d) or placebo for a week, and then participated in a laboratory experiment consisting of three procedures: alcohol cue-reactivity, priming, and self-administration. During the experiment, craving and other subjective responses to alcohol were assessed, and blood samples were collected for pharmacokinetic measurements. The effects of baclofen on the relationships between different alcohol-related laboratory parameters were investigated. Baclofen pharmacokinetic parameters and their correlations with behavioral measures were also examined. Results showed that baclofen disrupted the link between alcohol priming and self-administration, as indicated by significant interaction effects between drug condition (baclofen vs. placebo) and some of the priming variables (alcohol craving: F3
Farokhnia, Mehdi; Sheskier, Mikela B; Lee, Mary R; Le, April N; Singley, Erick; Bouhlal, Sofia; Ton, Timmy; Zhao, Zhen; Leggio, Lorenzo
In: Neuropharmacology, 137 , pp. 230 - 239, 2018, ISSN: 0028-3908.
@article{FAROKHNIA2018230,
title = {Neuroendocrine response to GABA-B receptor agonism in alcohol-dependent individuals: Results from a combined outpatient and human laboratory experiment},
author = {Mehdi Farokhnia and Mikela B Sheskier and Mary R Lee and April N Le and Erick Singley and Sofia Bouhlal and Timmy Ton and Zhen Zhao and Lorenzo Leggio},
url = {https://pubmed.ncbi.nlm.nih.gov/29665351/},
doi = {https://doi.org/10.1016/j.neuropharm.2018.04.011},
issn = {0028-3908},
year = {2018},
date = {2018-01-01},
journal = {Neuropharmacology},
volume = {137},
pages = {230 - 239},
abstract = {Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the nervous system, plays an important role in biobehavioral processes that regulate alcohol seeking, food intake, and stress response. The metabotropic GABA-B receptor has been investigated as a potential therapeutic target for alcohol use disorder, by using orthosteric agonists (e.g., baclofen) and positive allosteric modulators. Whether and how pharmacological manipulation of the GABA-B receptor, in combination with alcohol intake, may affect feeding- and stress-related neuroendocrine pathways remains unknown. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals received baclofen (30 mg/day) or placebo in a naturalistic outpatient setting for one week, and then performed a controlled laboratory experiment which included alcohol cue-reactivity, fixed-dose priming, and self-administration procedures. Blood samples were collected, and the following neuroendocrine markers were measured: ghrelin, leptin, amylin, glucagon-like peptide-1 (GLP-1), insulin, prolactin, thyroid-stimulating hormone, growth hormone, cortisol, and adrenocorticotropic hormone (ACTH). During the outpatient phase, baclofen significantly increased blood concentrations of acyl-ghrelin (p = 0.01), leptin (p = 0.01), amylin (p = 0.004), and GLP-1 (p = 0.02). Significant drug × time-point interaction effects for amylin (p = 0.001) and insulin (p = 0.03), and trend-level interaction effects for GLP-1 (p = 0.06) and ACTH (p = 0.10) were found during the laboratory experiment. Baclofen, compared to placebo, had no effect on alcohol drinking in this study (p's ≥ 0.05). Together with previous studies, these findings shed light on the role of the GABAergic system and GABA-B receptors in the shared neurobiology of alcohol-, feeding-, and stress-related behaviors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the nervous system, plays an important role in biobehavioral processes that regulate alcohol seeking, food intake, and stress response. The metabotropic GABA-B receptor has been investigated as a potential therapeutic target for alcohol use disorder, by using orthosteric agonists (e.g., baclofen) and positive allosteric modulators. Whether and how pharmacological manipulation of the GABA-B receptor, in combination with alcohol intake, may affect feeding- and stress-related neuroendocrine pathways remains unknown. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals received baclofen (30 mg/day) or placebo in a naturalistic outpatient setting for one week, and then performed a controlled laboratory experiment which included alcohol cue-reactivity, fixed-dose priming, and self-administration procedures. Blood samples were collected, and the following neuroendocrine markers were measured: ghrelin, leptin, amylin, glucagon-like peptide-1 (GLP-1), insulin, prolactin, thyroid-stimulating hormone, growth hormone, cortisol, and adrenocorticotropic hormone (ACTH). During the outpatient phase, baclofen significantly increased blood concentrations of acyl-ghrelin (p = 0.01), leptin (p = 0.01), amylin (p = 0.004), and GLP-1 (p = 0.02). Significant drug × time-point interaction effects for amylin (p = 0.001) and insulin (p = 0.03), and trend-level interaction effects for GLP-1 (p = 0.06) and ACTH (p = 0.10) were found during the laboratory experiment. Baclofen, compared to placebo, had no effect on alcohol drinking in this study (p's ≥ 0.05). Together with previous studies, these findings shed light on the role of the GABAergic system and GABA-B receptors in the shared neurobiology of alcohol-, feeding-, and stress-related behaviors.
Farokhnia, M; Grodin, E N; Lee, M R; Oot, E N; Blackburn, A N; Stangl, B L; Schwandt, M L; Farinelli, L A; Momenan, R; Ramchandani, V A; Leggio, L
In: Molecular Psychiatry, 23 (10), pp. 2029–2038, 2018, ISBN: 1476-5578.
@article{Farokhnia:2018aab,
title = {Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals},
author = {M Farokhnia and E N Grodin and M R Lee and E N Oot and A N Blackburn and B L Stangl and M L Schwandt and L A Farinelli and R Momenan and V A Ramchandani and L Leggio},
url = {https://pubmed.ncbi.nlm.nih.gov/29133954/},
doi = {10.1038/mp.2017.226},
isbn = {1476-5578},
year = {2018},
date = {2018-01-01},
journal = {Molecular Psychiatry},
volume = {23},
number = {10},
pages = {2029--2038},
abstract = {Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut--brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg−1) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97$pm$10.65},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut--brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg−1) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97$pm$10.65
2017
Farokhnia, M; Schwandt, M L; Lee, M R; Bollinger, J W; Farinelli, L A; Amodio, J P; Sewell, L; Lionetti, T A; Spero, D E; Leggio, L
Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study Journal Article
In: Translational Psychiatry, 7 (4), pp. e1108–e1108, 2017, ISBN: 2158-3188.
@article{Farokhnia:2017aab,
title = {Biobehavioral effects of baclofen in anxious alcohol-dependent individuals: a randomized, double-blind, placebo-controlled, laboratory study},
author = {M Farokhnia and M L Schwandt and M R Lee and J W Bollinger and L A Farinelli and J P Amodio and L Sewell and T A Lionetti and D E Spero and L Leggio},
url = {https://www.nature.com/articles/tp201771},
doi = {10.1038/tp.2017.71},
isbn = {2158-3188},
year = {2017},
date = {2017-01-01},
journal = {Translational Psychiatry},
volume = {7},
number = {4},
pages = {e1108--e1108},
abstract = {Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Baclofen has been suggested as a potential pharmacotherapy for alcohol use disorder, but the clinical data are conflicting. Here we investigated the biobehavioral effects of baclofen in a sample of anxious alcohol-dependent individuals. This was a randomized, double-blind, placebo-controlled, human laboratory study in non-treatment seeking alcohol-dependent individuals with high trait anxiety (N=34). Participants received baclofen (30 mg per day) or placebo for at least 8 days, then performed an experimental session consisting of alcohol cue-reactivity followed by alcohol administration procedure (alcohol priming, then alcohol self-administration). Total amount of alcohol self-administered was the primary outcome; alcohol craving, subjective/physiological responses and mood/anxiety symptoms were also evaluated. There was no significant medication effect on the total amount of alcohol consumed during the alcohol self-administration (P=0.76). Baclofen blunted the positive association between maximum breath alcohol concentration during priming and the amount of alcohol consumption (significant interaction
2014
Farokhnia, Mehdi; Sabzabadi, Maryam; Pourmahmoud, Hossein; Khodaie-Ardakani, Mohammad-Reza; Hosseini, Seyed-Mohammad-Reza; Yekehtaz, Habibeh; Tabrizi, Mina; Rezaei, Farzin; Salehi, Bahman; Akhondzadeh, Shahin
In: Psychopharmacology, 231 (3), pp. 533–542, 2014, ISBN: 1432-2072.
@article{Farokhnia:2014aa,
title = {A double-blind, placebo controlled, randomized trial of riluzole as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia},
author = {Mehdi Farokhnia and Maryam Sabzabadi and Hossein Pourmahmoud and Mohammad-Reza Khodaie-Ardakani and Seyed-Mohammad-Reza Hosseini and Habibeh Yekehtaz and Mina Tabrizi and Farzin Rezaei and Bahman Salehi and Shahin Akhondzadeh},
url = {https://pubmed.ncbi.nlm.nih.gov/24013610/},
doi = {10.1007/s00213-013-3261-z},
isbn = {1432-2072},
year = {2014},
date = {2014-01-01},
journal = {Psychopharmacology},
volume = {231},
number = {3},
pages = {533--542},
abstract = {Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies.
2013
Farokhnia, Mehdi; Azarkolah, Anita; Adinehfar, Forod; Khodaie-Ardakani, Mohammad-Reza; Hosseini, Seyed-Mohammad-Reza; Yekehtaz, Habibeh; Tabrizi, Mina; Rezaei, Farzin; Salehi, Bahman; Sadeghi, Seyed-Mohammad-Hossein; Moghadam, Marzieh; Gharibi, Fardin; Mirshafiee, Omid; Akhondzadeh, Shahin
In: Clinical Neuropharmacology, 36 (6), 2013, ISBN: 0362-5664.
@article{Farokhnia:2013aa,
title = {N-Acetylcysteine as an Adjunct to Risperidone for Treatment of Negative Symptoms in Patients With Chronic Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study},
author = {Mehdi Farokhnia and Anita Azarkolah and Forod Adinehfar and Mohammad-Reza Khodaie-Ardakani and Seyed-Mohammad-Reza Hosseini and Habibeh Yekehtaz and Mina Tabrizi and Farzin Rezaei and Bahman Salehi and Seyed-Mohammad-Hossein Sadeghi and Marzieh Moghadam and Fardin Gharibi and Omid Mirshafiee and Shahin Akhondzadeh},
url = {https://journals.lww.com/clinicalneuropharm/Fulltext/2013/11000/N_Acetylcysteine_as_an_Adjunct_to_Risperidone_for.2.aspx},
isbn = {0362-5664},
year = {2013},
date = {2013-01-01},
journal = {Clinical Neuropharmacology},
volume = {36},
number = {6},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2012
Khajavi, Danial; Farokhnia, Mehdi; Modabbernia, Amirhossein; Ashrafi, Mandana; Abbasi, Seyed-Hesammedin; Tabrizi, Mina; Akhondzadeh, Shahin
Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study. Journal Article
In: J Clin Psychiatry, 73 (11), pp. 1428–1433, 2012, ISSN: 1555-2101 (Electronic); 0160-6689 (Linking).
@article{Khajavi:2012aa,
title = {Oral scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled study.},
author = {Danial Khajavi and Mehdi Farokhnia and Amirhossein Modabbernia and Mandana Ashrafi and Seyed-Hesammedin Abbasi and Mina Tabrizi and Shahin Akhondzadeh},
url = {https://pubmed.ncbi.nlm.nih.gov/23146150/
https://pubmed.ncbi.nlm.nih.gov/24201233/},
doi = {10.4088/JCP.12m07706},
issn = {1555-2101 (Electronic); 0160-6689 (Linking)},
year = {2012},
date = {2012-11-01},
journal = {J Clin Psychiatry},
volume = {73},
number = {11},
pages = {1428--1433},
abstract = {OBJECTIVE: To evaluate the antidepressant effect of oral scopolamine as an adjunct to citalopram. METHOD: In this randomized double-blind placebo-controlled study, patients were assessed in the outpatient clinics of 2 large hospitals from November 2011 to January 2012. Forty patients (18-55 years) with major depressive disorder (DSM-IV-TR criteria) and 17-Item Hamilton Depression Rating Scale (HDRS) score ≥ 22 were randomly assigned to scopolamine hydrobromide (1 mg/d) (n = 20) or placebo (n = 20) in addition to citalopram for 6 weeks. HDRS score was measured at baseline and days 4, 7, 14, 28, and 42. The primary outcome measure was HDRS score change from baseline to week 6 in the scopolamine group versus the placebo group. Response was defined as ≥ 50% decrease in HDRS score; remission, as HDRS score ≤ 7. RESULTS: Augmentation with scopolamine was significantly more effective than placebo (F(1,38) = 5.831},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To evaluate the antidepressant effect of oral scopolamine as an adjunct to citalopram. METHOD: In this randomized double-blind placebo-controlled study, patients were assessed in the outpatient clinics of 2 large hospitals from November 2011 to January 2012. Forty patients (18-55 years) with major depressive disorder (DSM-IV-TR criteria) and 17-Item Hamilton Depression Rating Scale (HDRS) score ≥ 22 were randomly assigned to scopolamine hydrobromide (1 mg/d) (n = 20) or placebo (n = 20) in addition to citalopram for 6 weeks. HDRS score was measured at baseline and days 4, 7, 14, 28, and 42. The primary outcome measure was HDRS score change from baseline to week 6 in the scopolamine group versus the placebo group. Response was defined as ≥ 50% decrease in HDRS score; remission, as HDRS score ≤ 7. RESULTS: Augmentation with scopolamine was significantly more effective than placebo (F(1,38) = 5.831
