The Neurobiology of Methamphetamine Addiction and the Potential to Reduce Misuse Through Conjugate Vaccines Targeting Toll-Like Receptor 4

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.