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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
Ibudilast attenuates subjective effects of methamphetamine in a placebo-controlled inpatient study
Matthew J Worley1, Aimee-Noelle Swanson, Keith G Heinzerling1
1Department of Family Medicine, University of California, Los Angeles, 10880 Wilshire Blvd., Suite 1800, Los Angeles, CA 90024, United States.
Background:
Despite numerous clinical trials no efficacious medications for methamphetamine (MA) have been identified. Neuroinflammation, which has a role in MA-related reward and neurodegeneration, is a novel MA pharmacotherapy target. Ibudilast inhibits activation of microglia and pro-inflammatory cytokines and has reduced MA self-administration in preclinical research. This study examined whether ibudilast would reduce subjective effects of MA in humans.
Methods:
Adult, non-treatment seeking, MA-dependent volunteers (N=11) received oral placebo, moderate ibudilast (40 mg), and high-dose ibudilast (100mg) via twice-daily dosing for 7 days each in an inpatient setting. Following infusions of saline, MA 15 mg, and MA 30 mg participants rated 12 subjective drug effects on a visual analog scale (VAS).
Results:
As demonstrated by statistically-significant ibudilast × MA condition interactions (p<.05), ibudilast reduced several MA-related subjective effects including High, Effect (i.e., any drug effect), Good, Stimulated and Like. The ibudilast-related reductions were most pronounced in the MA 30 mg infusions, with ibudilast 100mg significantly reducing Effect (97.5% CI [-12.54, -2.27]), High (97.5% CI [-12.01, -1.65]), and Good (97.5% CI [-11.20, -0.21]), compared to placebo.
Conclusions:
Ibudilast appeared to reduce reward-related subjective effects of MA in this early-stage study, possibly due to altering the processes of neuroinflammation involved in MA reward. Given this novel mechanism of action and the absence of an efficacious medication for MA dependence, ibudilast warrants further study to evaluate its clinical efficacy.
Insights
Ibudilast may reduce the subjective effects of methamphetamine (MA) by targeting neuroinflammation. This early study suggests ibudilast could be a potential treatment for MA dependence, warranting further investigation.
Area of Science:
- Neuroscience
- Pharmacology
- Clinical Trials
Background:
- No effective medications currently exist for methamphetamine (MA) dependence.
- Neuroinflammation plays a role in MA-related reward and neurodegeneration, presenting a novel therapeutic target.
- Ibudilast, an inhibitor of microglial activation and pro-inflammatory cytokines, has shown promise in preclinical MA research.
Purpose of the Study:
- To investigate the efficacy of ibudilast in reducing the subjective effects of methamphetamine in humans.
- To explore the potential of ibudilast as a pharmacotherapy for MA dependence.
Main Methods:
- Eleven adult, non-treatment seeking, MA-dependent volunteers participated in an inpatient study.
- Participants received oral placebo, moderate (40 mg), and high-dose (100 mg) ibudilast twice daily for seven days.
- Subjective drug effects were assessed using visual analog scales (VAS) following saline, 15 mg MA, and 30 mg MA infusions.
Main Results:
- Ibudilast significantly reduced several MA-related subjective effects, including 'High,' 'Effect,' 'Good,' 'Stimulated,' and 'Like' (p<.05).
- Reductions were most pronounced with the 100 mg ibudilast dose during 30 mg MA infusions.
- Specifically, 100 mg ibudilast significantly decreased 'Effect,' 'High,' and 'Good' compared to placebo.
Conclusions:
- Ibudilast demonstrated a potential to reduce the reward-related subjective effects of MA.
- The findings suggest ibudilast may modulate neuroinflammation processes involved in MA reward.
- Further research is warranted to evaluate the clinical efficacy of ibudilast for MA dependence due to its novel mechanism and the lack of current treatments.
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