The 5‐HT<sub>2C</sub> receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment‐seeking individuals

Campbell, Erin J.; Bonomo, Yvonne; Pastor, Adam; Collins, Lisa; Norman, Amanda; Galettis, Peter; Johnstone, Janice; Lawrence, Andrew J

doi:10.1002/prp2.767

Cited by 16 publications

(5 citation statements)

References 58 publications

(100 reference statements)

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“…Next, we wanted to ask: how does an insult that disrupts social and arousal behaviors impact the BNST 5HT2c and LHb 5HT2c systems? Studies in humans and animal models suggest that a history of alcohol consumption reduces social behaviors and increases anxiety-like behaviors, which may involve alcohol-induced adaptations in LHb and/or BNST 5HT 2c receptor expression and signaling 22 , 24 , 25 , 27 .To investigate this possibility, we subjected mice to three weeks of DiD, and then after one week of abstinence assessed their behavior in the 3-chamber sociability task, the open field test, and the acoustic startle test (Fig. 5A ).…”

Section: Resultsmentioning

confidence: 99%

Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice

et al. 2023

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Binge alcohol consumption induces discrete social and arousal disturbances in human populations that promote increased drinking and accelerate the progression of Alcohol Use Disorder. Here, we show in a mouse model that binge alcohol consumption disrupts social recognition in females and potentiates sensorimotor arousal in males. These negative behavioral outcomes were associated with sex-specific adaptations in serotonergic signaling systems within the lateral habenula (LHb) and the bed nucleus of the stria terminalis (BNST), particularly those related to the receptor 5HT2c. While both BNST and LHb neurons expressing this receptor display potentiated activation following binge alcohol consumption, the primary causal mechanism underlying the effects of alcohol on social and arousal behaviors appears to be excessive activation of LHb5HT2c neurons. These findings may have valuable implications for the development of sex-specific treatments for mood and alcohol use disorders targeting the brain’s serotonin system.

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Section: Resultsmentioning

confidence: 99%

Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice

et al. 2023

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“…Furthermore, METH has been reported to interact with the re-uptake of 5-HT, resulting in an acute increase in extracellular level of 5-HT, which, in addition to dopamine, is a key mechanism underlying the drug addiction ( 37 ). Moreover, a recent study reported that the withdrawal syndrome following the termination of drug addiction is also associated with profound changes in 5-HT activity ( 38 ). Leucyl-isoleucine is involved in leucine biosynthesis, and mutations in leucine-rich kinases are the common causes of Parkinson’s disease, leading to dopamine neuron loss and motor dysfunction through abnormal increases in neuronal protein synthesis ( 39 ).…”

Section: Discussionmentioning

confidence: 99%

Variations in the oral microbiome and metabolome of methamphetamine users

Wang,

Feng,

Yang

et al. 2024

mSystems

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Drug addiction can seriously damage human physical and mental health, while detoxification is a long and difficult process. Although studies have reported changes in the oral microbiome of methamphetamine (METH) users, the role that the microbiome plays in the process of drug addiction is still unknown. This study aims to explore the function of the microbiome based on analysis of the variations in the oral microbiome and metabolome of METH users. We performed the 16S rRNA sequencing analysis based on the oral saliva samples collected from 278 METH users and 105 healthy controls (CTL). In addition, the untargeted metabolomic profiling was conducted based on 220 samples. Compared to the CTL group, alpha diversity was reduced in the group of METH users and the relative abundances of Peptostreptococcus and Gemella were significantly increased, while the relative abundances of Campylobacter and Aggregatibacter were significantly decreased. Variations were also detected in oral metabolic pathways, including enhanced tryptophan metabolism, lysine biosynthesis, purine metabolism, and steroid biosynthesis. Conversely, the metabolic pathways of porphyrin metabolism, glutathione metabolism, and pentose phosphate were significantly reduced. It was speculated that four key microbial taxa, i.e., Peptostreptococcus , Gemella , Campylobacter , and Aggregatibacter , could be involved in the toxicity and addiction mechanisms of METH by affecting the above metabolic pathways. It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders was gradually increased. Our study provides novel insights into exploring the toxic damage and addiction mechanisms underlying the METH addiction. IMPORTANCE It was found that with the increase of drug use years, the content of tryptamine associated with neuropsychiatric disorders gradually increased. The prediction models based on oral microbiome and metabolome could effectively predict the methamphetamine (METH) smoking. Our study provides novel insights into the exploration of the molecular mechanisms regulating the toxic damage and addiction of METH as well as new ideas for early prevention and treatment strategies of METH addiction.

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“…However, there has been progress in developing several selective 5-HT2C agonists, which have been investigated as potential therapeutics for the treatment of multiple psychiatric disorders, particularly impulse-related disorders such as SUDs (Higgins et al, 2013;Campbell et al, 2021).…”

Section: The 5-ht2c Receptor As a Therapeutic Target For Substance Us...mentioning

confidence: 99%

Beyond the 5-HT_2AReceptor: Classic and Nonclassic Targets in Psychedelic Drug Action

Cameron,

Benetatos,

Lewis

et al. 2023

J. Neurosci.

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Serotonergic psychedelics, such as psilocybin and LSD, have garnered significant attention in recent years for their potential therapeutic effects and unique mechanisms of action. These compounds exert their primary effects through activating serotonin 5-HT2Areceptors, found predominantly in cortical regions. By interacting with these receptors, serotonergic psychedelics induce alterations in perception, cognition, and emotions, leading to the characteristic psychedelic experience. One of the most crucial aspects of serotonergic psychedelics is their ability to promote neuroplasticity, the formation of new neural connections, and rewire neuronal networks. This neuroplasticity is believed to underlie their therapeutic potential for various mental health conditions, including depression, anxiety, and substance use disorders. In this mini-review, we will discuss how the 5-HT2Areceptor activation is just one facet of the complex mechanisms of action of serotonergic psychedelics. They also interact with other serotonin receptor subtypes, such as 5-HT1Aand 5-HT2Creceptors, and with neurotrophin receptors (e.g., tropomyosin receptor kinase B). These interactions contribute to the complexity of their effects on perception, mood, and cognition. Moreover, as psychedelic research advances, there is an increasing interest in developing nonhallucinogenic derivatives of these drugs to create safer and more targeted medications for psychiatric disorders by removing the hallucinogenic properties while retaining the potential therapeutic benefits. These nonhallucinogenic derivatives would offer patients therapeutic advantages without the intense psychedelic experience, potentially reducing the risks of adverse reactions. Finally, we discuss the potential of psychedelics as substrates for post-translational modification of proteins as part of their mechanism of action.

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The 5‐HT_2C receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment‐seeking individuals

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 16 publications

References 58 publications

Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice

Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice

Variations in the oral microbiome and metabolome of methamphetamine users

Beyond the 5-HT_2AReceptor: Classic and Nonclassic Targets in Psychedelic Drug Action

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The 5‐HT2C receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment‐seeking individuals

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 16 publications

References 58 publications

Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice

Subcortical serotonin 5HT2c receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice

Variations in the oral microbiome and metabolome of methamphetamine users

Beyond the 5-HT2AReceptor: Classic and Nonclassic Targets in Psychedelic Drug Action

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Product

Resources

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The 5‐HT_2C receptor as a therapeutic target for alcohol and methamphetamine use disorders: A pilot study in treatment‐seeking individuals

Beyond the 5-HT_2AReceptor: Classic and Nonclassic Targets in Psychedelic Drug Action