Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder

Heinzerling, Keith G.; Briones, Marisa; Thames, April D.; Hinkin, Charles H.; Zhu, Tianle; Wu, Ying; Shoptaw, Steven

doi:10.1007/s11481-019-09883-w

Cited by 18 publications

(12 citation statements)

References 46 publications

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“…Studies show positive correlations between exposure to abused drugs and other diseases/conditions [61][62][63]. These conditions are associated with dysregulated metabolomics pathways.…”

Section: Discussionmentioning

confidence: 99%

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

et al. 2022

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Studies have demonstrated that chronic consumption of abused drugs induces alterations in several proteins that regulate metabolism. For instance, methamphetamine exposure reduces glucose levels. Fatty and amino acid levels were altered in groups exposed to abused drugs. Therefore, in our study, we investigated the serum metabolomic profile of patients diagnosed with cannabis and/or amphetamine use disorders. Blood was obtained from subjects (control, amphetamine, and cannabis). Detection of serum metabolites was performed using gas chromatography. The ratio peak areas for metabolites were analyzed across the three groups. Both cannabis and amphetamine groups showed higher d-erythrotetrafuranose, octadecanoic acid, hexadecenoic acid, trans-9-octadecanoic acid, lactic acid and methyl thio hydantoin metabolites compared with the control group. Moreover, cannabis patients were found to possess higher glycine, 9,12 octadecanoic acid malonic acid, phosphoric acid and prostaglandin F1a than controls. Our analysis showed that the identified metabolic profile of cannabis or amphetamine use disorder patients was different than control group. Our data indicated that chronic exposure to cannabis or amphetamine dysregulated metabolites in the serum. Future studies are warranted to explore the effects of these abused drugs on the metabolic proteins.

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“…Studies show positive correlations between exposure to abused drugs and other diseases/conditions [61][62][63]. These conditions are associated with dysregulated metabolomics pathways.…”

Section: Discussionmentioning

confidence: 99%

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

et al. 2022

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“… 49 , 50 , 56 , 57 This has generated interest in its application in a number of neurological conditions. These include early-stage clinical trials in progressive Multiple Sclerosis, 58 , 59 ALS, 60 alcoholism, 61 , 62 drug addiction 63 , 64 and pain. 65 , 66 The combination of anti-inflammatory, neuroprotective and neuro-regenerative properties has led to interest for its use in DCM and is the basis for RECEDE-Myelopathy (NCT04631471), a phase 3, double-blind, randomized controlled trial assessing the efficacy of Ibudilast as an adjuvant treatment to decompressive surgery for DCM on mJOA score and neck pain.…”

Section: Regenerative Medicinementioning

confidence: 99%

Developing Novel Therapies for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 7]: Opportunities From Restorative Neurobiology

Gharooni

Fehlings

Boerger

et al. 2022

Global Spine Journal

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Study design Narrative review. Objectives To provide an overview of contemporary therapies for the James Lind Alliance priority setting partnership for degenerative cervical myelopathy (DCM) question: ‘Can novel therapies, including stem-cell, gene, pharmacological and neuroprotective therapies, be identified to improve the health and wellbeing of people living with DCM and slow down disease progression?’ Methods A review of the literature was conducted to outline the pathophysiology of DCM and present contemporary therapies that may hold therapeutic value in 3 broad categories of neuroprotection, neuroregeneration, and neuromodulation. Results Chronic spinal cord compression leads to ischaemia, neuroinflammation, demyelination, and neuronal loss. Surgical intervention may halt progression and improve symptoms, though the majority do not make a full recovery leading to lifelong disability. Neuroprotective agents disrupt deleterious secondary injury pathways, and one agent, Riluzole, has undergone Phase-III investigation in DCM. Although it did not show efficacy on the primary outcome modified Japanese Orthopaedic Association scale, it showed promising results in pain reduction. Regenerative approaches are in the early stage, with one agent, Ibudilast, currently in a phase-III investigation. Neuromodulation approaches aim to therapeutically alter the state of spinal cord excitation by electrical stimulation with a variety of approaches. Case studies using electrical neuromuscular and spinal cord stimulation have shown positive therapeutic utility. Conclusion There is limited research into interventions in the 3 broad areas of neuroprotection, neuroregeneration, and neuromodulation for DCM. Contemporary and novel therapies for DCM are now a top 10 priority, and whilst research in these areas is limited in DCM, it is hoped that this review will encourage research into this priority.

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“…Despite the limitations of these early-stage studies, they provide first evidence that ibudilast might serve as a potential pharmacotherapy for methamphetamine use disorders. However, a most recent study showed that ibudilast did not affect methamphetamine abstinence (Heinzerling et al, 2020). This randomize trials included 64 participants for ibudilast group and 61 for placebo.…”

Section: Clinical Implications For Toll-like Receptor 4-related Innatmentioning

confidence: 99%

Toll-Like Receptor 4 Signaling and Drug Addiction

Wü

2020

Front. Pharmacol.

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The emphasis of neuronal alterations and adaptations have long been the main focus of the studies of the mechanistic underpinnings of drug addiction. Recent studies have begun to appreciate the role of innate immune system, especially toll-like receptor 4 (TLR4) signaling in drug reward-associated behaviors and physiology. Drugs like opioids, alcohol and psychostimulants activate TLR4 signaling and subsequently induce proinflammatory responses, which in turn contributes to the development of drug addiction. Inhibition of TLR4 or its downstream effectors attenuated the reinforcing effects of opioids, alcohol and psychostimulants, and this effect is also involved in the withdrawal and relapse-like behaviors of different drug classes. However, conflicting results also argue that TLR4-related immune response may play a minimal part in drug addiction. This review discussed the preclinical evidence that whether TLR4 signaling is involved in multiple drug classes action and the possible mechanisms underlying this effect. Moreover, clinical studies which examined the potential efficacy of immune-base pharmacotherapies in treating drug addiction are also discussed.

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Randomized, Placebo-Controlled Trial of Targeting Neuroinflammation with Ibudilast to Treat Methamphetamine Use Disorder

Cited by 18 publications

References 46 publications

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

Serum Metabolomic Analysis of Male Patients with Cannabis or Amphetamine Use Disorder

Developing Novel Therapies for Degenerative Cervical Myelopathy [AO Spine RECODE-DCM Research Priority Number 7]: Opportunities From Restorative Neurobiology

Toll-Like Receptor 4 Signaling and Drug Addiction

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