The methamphetamine epidemic continues to worsen each year and has contributed to more overdose deaths than opioids. Methamphetamine was listed in the top ten lethal drugs in 2021 in the United States. The drug has been shown to cause health problems such as addiction and neurological and behavioral changes. One possible solution to address this crisis is through vaccinations. Vaccinations consist of injecting a controlled substance with the goal of creating compound-specific antibodies. Although still early in development, vaccinations have been found to improve withdrawal symptoms and decrease drug-seeking behavior with minimal health side effects in rodent studies. This paper provides an overview of the clinical presentation and neurobiology of methamphetamine addiction and drug-seeking behaviors. The responses and adverse effects of conjugate vaccines IXTv-100 with adjuvant glucopyranosyl lipid A administered in oil-water stable emulsion and tetanus-toxoid conjugated to succinyl-methamphetamine adsorbed on aluminum hydroxide combined with adjuvant E6020 are examined.

2020-03-01·Psychopharmacology3区 · 医学

Effects of a methamphetamine vaccine, IXT-v100, on methamphetamine-related behaviors

3区 · 医学

Article

作者: Guerin, Glenn F ; Keller, Courtney M ; Goeders, Nicholas E ; Owens, S Michael ; Spence, Allyson L ; Stevens, Misty W

RATIONALEVaccines have been developed as a potential treatment for methamphetamine (meth) use disorder (MUD). Immunization with the meth vaccine IXT-v100 has previously been shown to elicit antibodies with high affinity for meth and thus may be an effective treatment for MUD.OBJECTIVESThese studies were designed to determine the efficacy of IXT-v100 on meth-taking and meth-seeking behaviors in rats.METHODSIn the acquisition and maintenance study, male and female rats were trained to self-administer meth (0.06 mg/kg/infusion) over an 8-week period following vaccination. In the last 4 weeks, the dose of meth was increased or decreased each week. To assess meth-seeking behavior, the meth-primed reactivity model was used. Rats were trained to self-administer meth for 5 weeks, followed by a 5-week or 11-week forced abstinence period during which the animals were vaccinated. Rats were then placed back into the self-administration chamber immediately after being injected with meth (1 mg/kg, i.p.) but did not receive meth during the session. Responses were recorded and used as a measure of meth seeking.RESULTSResults from the acquisition and maintenance study in Wistar rats show that vaccination with IXT-v100 adjuvanted with glucopyranosyl lipid A stable emulsion decreases the percentage of animals that will self-administer a moderate level of meth. In the meth-primed reactivity studies, results from males showed that vaccination significantly attenuates meth-seeking behavior.CONCLUSIONTogether, these results suggest vaccination with IXT-v100 may be effective at decreasing meth-taking and meth-seeking behaviors in humans suffering with MUD.

2019-11-01·Drug and Alcohol Dependence2区 · 医学

Antibody production and pharmacokinetics of METH in rats following vaccination with the METH vaccine, IXT-v100, adjuvanted with GLA-SE

2区 · 医学

Article

作者: West, C Michael ; Gunnell, Melinda G ; Rüedi-Bettschen, Daniela ; Owens, S Michael ; Stevens, Misty W ; Tawney, Rachel

BACKGROUNDMethamphetamine use disorder continues to be inadequately treated, but improvements are being made in the field of immunotherapeutics, including vaccines, which could provide new options for treatment. Cocaine and nicotine vaccines have been tested clinically, but have yet to elicit the necessary antibody concentrations required to be effective. Methamphetamine vaccines have been tested in multiple nonclinical models and appear promising. Improved adjuvants have the potential to further stimulate the immune system to reach effective levels of antibodies. Previously, the methamphetamine vaccine IXT-v100 was administered with GLA-SE, a toll-like receptor 4 agonist, in mice to produce higher levels of antibodies than when it was administered with two other widely used adjuvants, Alhydrogel and Sigma Adjuvant System.METHODSThe purpose of this research was to evaluate IXT-v100, given in combination with the adjuvant GLA-SE, to determine its efficacy in antagonizing methamphetamine disposition in a rat pharmacokinetic study. Additional rat studies were conducted to compare the ability of IXT-v100 manufactured with greater hapten densities to elicit higher antibody levels.RESULTSAs expected based on prior studies with anti-methamphetamine monoclonal antibodies, the antibodies resulting from vaccination with IXT-v100 altered methamphetamine pharmacokinetics by increasing serum concentrations and extending the half-life. Furthermore, intentional variations in the ratio of components during manufacturing led to production of vaccines with higher hapten densities. The higher hapten densities resulted in production of antibodies that maintained the ability to bind methamphetamine with high affinity.CONCLUSIONSThe results support continued development of IXT-v100 for the treatment of methamphetamine use disorder.

100 项与 IXT-v100 相关的药物交易

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