Methamphetamine: Effects on the brain, gut and immune system

Abstract

Methamphetamine (METH) is a powerful central nervous system stimulant which elevates mood, alertness, energy levels and concentration in the short-term. However, chronic use and/or at higher doses METH use often results in psychosis, depression, delusions and violent behavior. METH was formerly used to treat conditions such as obesity and attention deficit hyperactivity disorder, but now is primarily used recreationally. Its addictive nature has led to METH abuse becoming a global problem. At a cellular level, METH exerts a myriad of effects on the central and peripheral nervous systems, immune system and the gastrointestinal system. Here we present how these effects might be linked and their potential contribution to the pathogenesis of neuropsychiatric disorders. In the long term, this pathway could be targeted therapeutically to protect people from the ill effects of METH use. This model of METH use may also provide insight into how gut, nervous and immune systems might break down in other conditions that may also benefit from therapeutic intervention.

Glial cell diversity and methamphetamine-induced neuroinflammation in human cerebral organoids

“…We observed that astroglial cell types exhibited a robust transcriptional response when exposed to METH treatment. Astrocytes provide trophic support for neurons and surrounding cells and are involved in the regulation of transmission and synaptic activity, thus they represent a crucial component of the central nervous system when studying METH-related neurotoxicity and particularly cytokine and immune dysregulation, yet they are often overlooked [1,27,41].…”

“…Methamphetamine (METH) is a stimulant which induces a temporary state of intense euphoria; however, studies have shown that METH also commonly leads to psychosis, depression, and attenuated immune systems [1,2]. In 2005, the economic impact of METH use in the United States alone was $23.4 billion [3] and as many as 1.3 million people over the age of 12 have reported having used METH [1]. Clinical studies have shown that acute and chronic METH abuse induces system-wide alterations to the brain on both the structural and biochemical level [4].…”

“…Because METH affects a wide range of biological processes including oxidative stress, apoptotic cell death, metabolism, dopamine and serotonin dysfunction, and cytokine regulation [1,[9][10][11], studying the mechanisms by These authors contributed equally: Jason Dang, Shashi Kant Tiwari which METH works in 2D homogenous neuronal cultures may be insufficient. Thus, we propose the use of cerebral organoid models, which are composed of neural progenitor cells, glial and neuronal cell types grown in a 3D selforganizing manner, to study the effect of METH on the human brain.…”

Increases in methamphetamine use among heroin treatment admissions in the United States, 2008–17

“…The phenomenon of increasing methamphetamine use among people using opioids is of great concern. Methamphetamine use carries its own risks, including a range of physical and mental health consequences such as psychosis and other mental disorders, cognitive and neurological deficits, cardiovascular and renal dysfunction, transmission of HIV, viral hepatitis and sexually transmitted infections and increased mortality . Individuals who use both opioids and methamphetamine are more likely to be homeless, inject drugs daily or more than once a day, reuse or share syringes and report a non‐fatal overdose in the past year compared to people who inject either drug alone .…”

Inflammasome Activation by Methamphetamine Potentiates Lipopolysaccharide Stimulation of IL-1β Production in Microglia

“…On the one hand, alarming signals such as HMGB1 are suggested to play a priming role in neuronal stress-induced neuroinflammatory responses (Frank et al, 2015). On the other hand, chronic Meth abuser is more susceptible to various infections (Salamanca et al, 2014) and the potential disruptive effects of Meth on intestinal permeability are receiving more and more attention (Prakash et al, 2017). With the concurrent damage of BBB after Meth abuse, increased systematic level of endotoxins might get access to the brain (Northrop and Yamamoto, 2015).…”