Past and current drug repurposing clinical trials to treat cognition in methamphetamine use: a scoping review of pharmacotherapy candidates

Peters, Megan M. St.; Park, Chun Hui J.; Turner, Alyna; Guerin, Alexandre A.; Kim, Jee Hyun

doi:10.1016/j.addicn.2023.100064

Cited by 3 publications

(3 citation statements)

References 249 publications

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“…This present study contributes to research appreciating the importance of cognitive function in recovery from substance use disorders (107)(108)(109)(110). Methamphetamine-induced cognitive deficits reflect changes in the underlying cortical, subcortical, and neuro-modulatory mechanisms that underpin cognition and can interfere with treatment outcomes (111,112).…”

Section: Discussionmentioning

confidence: 83%

Immunotherapeutic treatment of inflammation in mice exposed to methamphetamine

Loftis,

Ramani,

Firsick

et al. 2023

Front. Psychiatry

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IntroductionCurrently, there are no FDA-approved medications to treat methamphetamine addiction, including the inflammatory, neurotoxic, and adverse neuropsychiatric effects. We have shown that partial (p)MHC class II constructs (i.e., Recombinant T-cell receptor Ligand – RTL1000), comprised of the extracellular α1 and β1 domains of MHC class II molecules linked covalently to myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide, can address the neuroimmune effects of methamphetamine addiction through its ability to bind to and down-regulate CD74 expression, block macrophage migration inhibitory factor (MIF) signaling, and reduce levels of pro-inflammatory chemokine ligand 2 (CCL2). The present study evaluated the effects of our third-generation pMHC II construct, DRmQ, on cognitive function and concentration of inflammatory cytokines in the frontal cortex, a region critical for cognitive functions such as memory, impulse control, and problem solving.MethodsFemale and male C57BL/6J mice were exposed to methamphetamine (or saline) via subcutaneous (s.c.) injections administered four times per day every other day for 14 days. Following methamphetamine exposure, mice received immunotherapy (DRmQ or ibudilast) or vehicle s.c. injections daily for five days. Cognitive function was assessed using the novel object recognition test (NORT). To evaluate the effects of immunotherapy on inflammation in the frontal cortex, multiplex immunoassays were conducted. ANOVA was used to compare exploration times on the NORT and immune factor concentrations.ResultsPost hoc analysis revealed increased novel object exploration time in MA-DRmQ treated mice, as compared to MA-VEH treated mice (non-significant trend). One-way ANOVA detected a significant difference across the groups in the concentration of macrophage inflammatory protein-2 (MIP-2) (p = 0.03). Post hoc tests indicated that mice treated with methamphetamine and DRmQ or ibudilast had significantly lower levels of MIP-2 in frontal cortex, as compared to mice treated with methamphetamine and vehicle (p > 0.05).DiscussionBy specifically targeting CD74, our DRQ constructs can block the signaling of MIF, inhibiting the downstream signaling and pro-inflammatory effects that contribute to and perpetuate methamphetamine addiction.

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Section: Discussionmentioning

confidence: 83%

Immunotherapeutic treatment of inflammation in mice exposed to methamphetamine

Loftis,

Ramani,

Firsick

et al. 2023

Front. Psychiatry

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“…In their commentary, Lasne et al highlight the relevance of the current findings to a growing understanding of the role of noradrenaline in cocaine-induced behavior and general reward-based learning. These findings are also translationally relevant; prazosin has been clinically trialed to determine if it reduces methamphetamine use, although the results are yet unpublished (St. Peters et al, 2023 ).…”

Section: The Contributionsmentioning

confidence: 99%

“…These findings are also translationally relevant; prazosin has been clinically trialed to determine if it reduces methamphetamine use, although the results are yet unpublished (St. Peters et al, 2023).…”

Section: The Contributionsmentioning

confidence: 99%

Editorial: Molecular underpinnings of relapse-like behavior: drug context and development

Orsini,

Kim,

Arguello

2024

Front. Behav. Neurosci.

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Associations between methamphetamine use disorder and SLC18A1 , SLC18A2 , BDNF , and FAAH gene sequence variants and expression levels

Guerin,

Spolding,

Bozaoglu

et al. 2024

Dialogues in Clinical Neuroscience

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Introduction Assessing candidate gene sequence variations and expression helps to understand methamphetamine use disorder and inform potential treatments. We investigated single nucleotide polymorphisms (SNPs) and gene expression in four candidate genes: SLC18A1, SLC18A2, BDNF, and FAAH, between controls and people with methamphetamine use disorder. Methods Fifty-nine participants (29 people with methamphetamine use disorder and 30 controls) completed a clinical interview, cognitive tasks, and provided a blood sample. SLC18A1, SLC18A2, BDNF , and FAAH SNPs were genotyped, and gene expression was assessed with real-time quantitative PCR. Results SLC18A1 Pro4Thr was associated with methamphetamine use disorder (OR = 6.22; p = .007). SLC18A2 variants, rs363227 and rs363387, were negatively associated with methamphetamine use severity ( p = .003) and positively associated with inhibitory control performance ( p = .006), respectively. BDNF Val66Met was associated with the severity of use ( p = .008). SLC18A2 and FAAH mRNA levels were lower in people who use methamphetamine relative to controls ( p = .021 and .010, respectively). Conclusions SLC18A1 is identified for the first time to play a potential role in methamphetamine use disorder. Lower levels of blood SLC18A2 and FAAH mRNA in people with methamphetamine use disorder suggest reduced monoamine reuptake, recycling, or release, and higher anandamide levels in this clinical group, which may be potential therapeutic targets.

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Past and current drug repurposing clinical trials to treat cognition in methamphetamine use: a scoping review of pharmacotherapy candidates

Cited by 3 publications

References 249 publications

Immunotherapeutic treatment of inflammation in mice exposed to methamphetamine

Immunotherapeutic treatment of inflammation in mice exposed to methamphetamine

Editorial: Molecular underpinnings of relapse-like behavior: drug context and development

Associations between methamphetamine use disorder and SLC18A1 , SLC18A2 , BDNF , and FAAH gene sequence variants and expression levels

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