Inflammation in the brain, driven by microglia and pattern recognition receptors like Toll-like receptors, is linked to neuropsychiatric illnesses such as schizophrenia, depression, and Alzheimer's disease. The orphan receptor sigma-1 (Sig-1R) and serotonin receptors (5-HTRs), both G protein-coupled receptors, modulate immune responses by controlling NF-κB and MAPK pathways, influencing cytokine release. The endogenous tryptamine N,N-dimethyltryptamine (DMT) acts on both Sig-1R and 5-HTRs, suppressing inflammation by blocking cytokine release from dendritic cells and inhibiting Th1 and Th17 T cell activation. DMT's regulation of NF-κB and MAPKs via G proteins suggests potential as a therapeutic for chronic inflammatory and autoimmune diseases, though its hallucinogenic properties remain a challenge. Selective Sig-1R agonists promote neuroprotection and regeneration.
Recreational and therapeutic use of psychostimulants such as amphetamine, cocaine, methamphetamine, MDMA, methylphenidate, caffeine, and nicotine can cause brain dysfunction and neurotoxic effects. This review of research from 2018 to 2023 examines evidence from both experimental models and humans, highlighting that central toxicity from these substances poses serious health risks, especially as their use rises among young people and adults. Understanding the factors and mechanisms behind these noxious brain effects is crucial for grasping the acute and lasting harm that may occur in users.
Synthetic psychoactive substances, including amphetamine derivatives, hallucinogens, dissociatives, and synthetic cannabinoids, can cause toxic effects in both the peripheral and central nervous systems. Preclinical and clinical studies show that these substances, besides their abuse potential, elicit varying degrees of harm. Recreational use is increasing among young and adult people, posing a serious health risk. This review summarizes recent findings on toxicity from both older and newer synthetic drugs in humans and experimental animals.