Oxytocin signaling in the treatment of drug addiction: Therapeutic opportunities and challenges

Che, Xiaohang; Cai, Jialing; Liu, Yueyang; Xu, Tianyu; Yang, Jingyu; Wu, Chunfu

doi:10.1016/j.pharmthera.2021.107820

Cited by 15 publications

(19 citation statements)

References 256 publications

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“…Decreased alcohol intake following OXT administration has been observed in mice, rats, and prairie voles. These studies have been previously reviewed ( 8 , 9 , 14 , 15 , 25 , 39 – 41 ). The success of preclinical studies may offer clues and opportunities to potentiate the effect of OXT treatment in humans.…”

Section: Enhancing Exogenous Oxt's Ability To Decrease Alcohol Drinkingmentioning

confidence: 99%

“…OXT's lack of stability, low brain penetrance and non-specific effects on AVP receptors prompted researchers to consider developing OXTR agonists ( 14 , 60 ). The majority of developed and tested OXTR agonist are peptides, with presumably minimal penetrance of the blood-brain barrier.…”

Section: Development Of More Potent and Efficacious Oxtr Agonistsmentioning

confidence: 99%

“…Development of non-peptide OXTR agonists continues to progress. Three small-molecule agonists have been reported ( 14 , 60 , 71 , 72 ). TC-OT-39 has an EC 50 of ~100 nM at OXTR as an agonist, but also a moderate affinity at V1a AVP receptors as an antagonist.…”

Section: Development Of More Potent and Efficacious Oxtr Agonistsmentioning

confidence: 99%

“…In turn, alcohol can affect OXT levels and underlying neurocircuitry (11)(12)(13). These observations suggested that stimulating the OXT system could curb excessive alcohol use by targeting several phases of the addiction cycle: modulating alcohol's effects during the intoxication phase, decreasing alcohol's toxicity during the abstinence/withdrawal phase and/or decreasing craving during the anticipation/preoccupation phase (14)(15)(16)(17). Indeed, OXT administration decreased alcohol self-administration in numerous preclinical studies (16,(18)(19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

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Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder

Ryabinin

Zhang

2022

Front. Psychiatry

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Development of better treatments for alcohol use disorder (AUD) is urgently needed. One promising opportunity for this development is the potential of targeting the oxytocin peptide system. Preclinical studies showed that administration of exogenous oxytocin or, more recently, stimulation of neurons expressing endogenous oxytocin lead to a decreased alcohol consumption across several rodent models. Initial clinical studies also showed that administration of oxytocin decreased craving for alcohol and heavy alcohol drinking. However, several more recent clinical studies were not able to replicate these effects. Thus, although targeting the oxytocin system holds promise for the treatment of AUD, more nuanced approaches toward development and application of these treatments are needed. In this mini-review we discuss potential caveats resulting in differential success of attempts to use oxytocin for modulating alcohol use disorder-related behaviors in clinical studies and evaluate three directions in which targeting the oxytocin system could be improved: (1) increasing potency of exogenously administered oxytocin, (2) developing oxytocin receptor agonists, and (3) stimulating components of the endogenous oxytocin system. Both advances and potential pitfalls of these directions are discussed.

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Section: Enhancing Exogenous Oxt's Ability To Decrease Alcohol Drinkingmentioning

confidence: 99%

Section: Development Of More Potent and Efficacious Oxtr Agonistsmentioning

confidence: 99%

Section: Development Of More Potent and Efficacious Oxtr Agonistsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder

Ryabinin

Zhang

2022

Front. Psychiatry

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“…Methamphetamine is a common drug of abuse and contributes to many detrimental health outcomes [1]. Drug addiction is one of the leading causes of mortality worldwide, and despite advances in understanding the neurobiology of drug addiction, treatment options are severely limited [2]. Current therapies for stimulant use disorder include antidepressant, anxiolytic, and mild stimulatory pharmacologic agents, though none are FDA approved.…”

Section: Introductionmentioning

confidence: 99%

Oxytocin, a Novel Treatment for Methamphetamine Use Disorder

Edinoff

Thompson

Merriman

et al. 2022

Neurology International

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The treatment of substance abuse with oxytocin is a novel approach to a challenging public health issue that continues to contribute to a growing economic cost for societies worldwide. Methamphetamine addiction is one of the leading causes of mortality worldwide, and despite advances in understanding the neurobiology of methamphetamine addiction, treatment options are limited. There are no medications that the Food and Drug Administration currently approves for stimulant use disorder. Off-label use of therapies for stimulant misuse include antidepressants, anxiolytics, and milder stimulants as replacement agents. Due to the shortcomings of these attempts to treat a complicated psychiatric disorder, recent attention to oxytocin therapy (OT) has gained momentum in clinical studies as a possible therapy in the context of social stress, social anxiety, social cognition, and psychosis. Oxytocin produces enhanced connectivity between cortical regions. The results from studies in rodents with OT suggest that central neuromodulation of oxytocin may be beneficial across transition states of stimulant dependence and may alleviate intense withdrawal symptoms. Studies of oxytocin in the context of other drugs of abuse, including cocaine, cannabis, and alcohol, also support the potential of oxytocin to treat stimulant use disorder, methamphetamine type. Methamphetamine abuse continues to be a significant cause of distress and dysfunction throughout the world. The effects of oxytocin on methamphetamine use outlined in this review should act as a catalyst for further investigation into the efficacy of treating stimulant use disorder, methamphetamine type with oxytocin in humans. More human-based research should initiate studies involving the long-term efficacy, side effects, and patient selection.

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Oxytocin and cardiometabolic interoception: Knowing oneself affects ingestive and social behaviors

et al. 2022

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Oxytocin signaling in the treatment of drug addiction: Therapeutic opportunities and challenges

Cited by 15 publications

References 256 publications

Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder

Barriers and Breakthroughs in Targeting the Oxytocin System to Treat Alcohol Use Disorder

Oxytocin, a Novel Treatment for Methamphetamine Use Disorder

Oxytocin and cardiometabolic interoception: Knowing oneself affects ingestive and social behaviors

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