The central nervous system (CNS) is one of the most complex physiological systems, and treatment of CNS disorders represents an area of major medical need. One critical aspect of the CNS is its lack of regeneration, such that damage is often permanent. The damage often leads to neurodegeneration, and so strategies for neuroprotection could lead to major medical advances. The G protein-coupled receptor (GPCR) family is one of the major receptor classes, and they have been successfully targeted clinically. One class of GPCRs is those activated by bioactive lysophospholipids as ligands, especially sphingosine-1-phosphate (S1P) and lysophosphatidic acid (LPA). Research has been increasingly demonstrating the important roles that S1P and LPA, and their receptors, play in physiology and disease. In this review, I describe the role of S1P and LPA receptors in neurodegeneration and potential roles in neuroprotection. Much of our understanding of the role of S1P receptors has been through pharmacological tools. One such tool, fingolimod (also known as FTY720), which is a S1P receptor agonist but a functional antagonist in the immune system, is clinically efficacious in multiple sclerosis by producing a lymphopenia to reduce autoimmune attacks; however, there is evidence that fingolimod is also neuroprotective. Furthermore, fingolimod is neuroprotective in many other neuropathologies, including stroke, Parkinson’s disease, Huntington’s disease, Rett syndrome, Alzheimer’s disease, and others that are discussed here. LPA receptors also appear to be involved, being upregulated in a variety of neuropathologies. Antagonists or mutations of LPA receptors, especially LPA₁, are neuroprotective in a variety of conditions, including cortical development, traumatic brain injury, spinal cord injury, stroke and others discussed here. Finally, LPA receptors may interact with other receptors, including a functional interaction with plasticity related genes.

Neuroinflammation can be caused by disease, aging, infection, brain injury, toxicity, or stress. It is a contributory factor in the neuropathology of serious conditions that include multiple sclerosis (MS), Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), and autoimmune encephalomyelitis (EAE). The neuroinflammatory response involves the activation of microglia, astrocytes, the endothelial cells of the blood-brain barrier, and peripherally-derived immune cells. The endocannabinoid system is composed of the natural cannabinoids, anandamide and 2-arachidonoyl glycerol (2-AG), enzymes regulating their synthesis/catabolism, and the cannabinoid CB₁ and CB₂ receptors. It regulates multiple systems in the body including inflammation and endocannabinoid system dysregulation is involved in numerous inflammatory conditions. The Cannabis sativa plant produces over 100 phytocannabinoids, some of which interact with the endocannabinoid system. The major phytocannabinoids are delta-9-tetrahydrocannabinol (delta-9-THC), cannabidiol (CBD), and cannabigerol (CBG). Compelling evidence is emerging that many phytocannabinoids have anti-inflammatory and antioxidant properties. Phytocannabinoids including delta-9-THC, CBD, and CBG bind to a wide variety of targets in the endocannabinoid and/or other systems, which probably accounts for their diversity of effects in non-clinical and clinical studies. The benefits of certain phytocannabinoids have been proven by regulatory approval for medical use of CBD (Epidiolex^®), chemically synthesized delta-9-THC (Marinol^® and Syndros^®) and 1:1 delta-9-THC/CBD (Sativex^®). Furthermore, the widely recognized therapeutic properties of Cannabis have been a key driver in legalizing the medical use of Cannabis in 38 USA states. In this review, the potential of phytocannabinoids as effective treatments in neuroinflammatory disorders is discussed based on a critical evaluation of the non-clinical and clinical evidence. We focused on delta-9-THC, CBD, and CBG because they are the most abundant phytocannabinoids in Cannabis sativa and a substantial body of scientific data exists to describe their respective pharmacological mechanisms.

To quantitatively analyze the effects of acoustic neurostimulation on the symptoms of depression, anxiety, stress, and sleep quality in healthy workers. Eleven physiological and psychological variables (V1–V11) representing stress levels, sleep quality, and cortisol levels were acquired from a recent article (https://doi.org/10.37349/ent.2023.00064) that analyzed the effects of brainwave entrainment (BWE) techniques—binaural beats (BB), isochronic tones (IT), or a combination of the two (BB + IT). Principal component analysis (PCA) was used to create principal components to analyze the contribution of each variable to the efficacy. A thermodynamic cycle and equations based on a Venn diagram were used to understand the differences in treatment effectiveness in individual and combined auditory stimulations. PCA reduced the dimensionality of variables from eleven to three. PC1 represented auditory treatment efficacy, while neither PC2 nor PC3 did. All eleven variables had a negative correlation to PC1, with stress (V3) showing the most negative correlation and salivary cortisol level (V11) showing the least. Treatments using BB were more effective than treatments with IT or BB + IT. PCA successfully aided in the analysis of auditory treatment efficacies. All examined variables, especially the stress scale (V3), had a negative correlation in treatment efficacy, aligning with the results of the original paper. Analysis using the thermodynamic cycle and Venn diagram based on PCA provided an explanation why a combined treatment (BB + IT) was less effective than BB alone in the collective consideration of all eleven variables. This study demonstrates that the thermodynamic cycle and Venn diagram in conjunction with PCA are useful analytical tools for the quantitative analysis of multi-factor systems.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by both non-motor and motor symptoms, due to the loss of dopamine-producing neurons in the brain. Monoamine oxidase-B (MAO-B) inhibitors are essential in the treatment of PD, as they increase dopamine levels and could potentially slow down the progression of the disease. MAO-B inhibitors block the ability of the enzyme to degrade dopamine in the brain. MAO-B inhibitors work by inhibiting this enzyme, which raises dopamine levels and helps reduce motor symptoms, such as akinesia and stiffness in the muscles. In addition to their impact on dopamine levels, MAO-B inhibitors may possess neuroprotective properties. Research indicates that these inhibitors can shield neurons from the harmful byproducts of dopamine breakdown, such as dihydroxy acetaldehyde and hydrogen peroxide. This neuroprotective effect could potentially slow the progression of PD and protect against neuronal damage. MAO-B inhibitors are effective in treating both advanced and early stages of PD. They are recommended as initial treatments for individuals with early PD and can also be used as supplementary therapy in advanced PD to assist in managing motor complications. Additionally, MAO-B inhibitors have shown promise for the treatment of non-motor symptoms of PD, such as fatigue and sleep disturbances. MAO-B inhibitors are an important class of drugs for the treatment of PD, offering both symptomatic relief and potential disease-modifying effects. The goal of ongoing research and development of MAO-B inhibitors is to enhance their safety and selectivity profiles, which could lead to improved treatment approaches for PD and other neurodegenerative disorders.

A novel concept has been recently put forward in the mind/body interface (https://doi.org/10.37349/ent.2024.00074). The new concept has led to a new word: vitaction. Vitactions offer benefits to the brain and mind comparable to the advantages vitamins provide for the body’s overall health. The field of vitactions is as it was the vitamin field one century ago, i.e., without tools to make a complete classification. I propose to classify vitactions into five categories according to the behaviours necessary to maintain balanced brain functionality. A deficit of vitactions would contribute to the enormous prevalence in developed countries of diseases ranging from type 2 diabetes to neuropsychiatric diseases. The concept should help to identify which vitactions are deficient and to outline how they can be progressively implemented to improve the quality of life. The parallelism vitactions/vitamins also extends to overdosing; both hypervitaminosis and hypervitactinosis may be detrimental. This perspective article argues that vitactions should be considered at the practical and the scientific research levels, and that a balanced vitamin and vitaction supply is essential for a better life. In addition, reasons for proposing a synonym, “vitactin”, are given.

Peripheral nerve injuries (PNIs) constitute a significant concern as they predominantly affect young and productive age groups of the population, causing social and economic pressure on patients. PNIs are a global problem that can result in disability because of the disruption of nerve function. PNI leads to a reduction in nerve conduction velocity, which worsens or impairs the mobility of the innervated area. Managing PNI remains a major clinical challenge. Coenzyme Q10 (CoQ10) is a lipid-soluble antioxidant first identified in 1957. It is an important antioxidant necessary for the organs to maintain their normal function and the body’s chemical processes. It scavenges free radicals and reduces oxidative stress. Studies showed that antioxidants such as CoQ10 a potent antioxidant, help the regeneration of PNIs. It has been observed to increase the myelination process in nerve fibres and promote nerve regeneration in rats after injury. Therefore, this review handles the current positive effects of CoQ10 on peripheral nerve regeneration following injury.

Epilepsy, a complex neurological disorder, is influenced by intricate interactions within cortical, hippocampal, or thalamocortical neuronal networks, presenting a genetically complex condition with non-Mendelian inheritance patterns. This complexity is underscored by the involvement of numerous “susceptibilities” or “modifier” genes, complicating the assessment of risk and therapy outcomes. A critical inquiry in epilepsy treatment involves understanding how genetic diversity impacts treatment strategies and efficacy. Pharmacogenomic advancements have elaborated the connection between genetic variants and antiseizure medication (ASM) safety and response, marking a shift towards precision medicine in epilepsy care. Notably, genetic screening for variants such as HLA-B*1502 and HLA-A*3101 has demonstrated significant efficacy in preventing severe hypersensitivity reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), particularly among specific ethnic populations. However, putting pharmacogenomic discoveries into clinical practice faces numerous challenges, including educational, legal, and economic barriers, emphasizing the need for broader acceptance and integration of pharmacogenomic data. This review synthesizes recent studies on pharmacogenomics in epilepsy, highlighting the current advances and prospects for personalizing epilepsy treatment through genetic insights, aiming to enhance ASM safety, reduce adverse effects, and improve treatment outcomes. Through a comprehensive examination of the genetic basis of epilepsy and its influence on pharmacotherapy, this review endeavors to contribute to the evolving landscape of precision medicine in epilepsy care, advocating for a more individualized and effective treatment approach.

Transmethylation in the context of psychiatry has historically referred to the enzymatic transfer of a methyl group from one biochemical to another, whose resulting function can change so dramatically that a biochemical like tryptamine, for example, is converted into the hallucinogen dimethyltryptamine. Central to endogenous methylation activity is the folate cycle, which generates the primary transferable methyl groups in mammalian biochemistry. The relevance of this cycle to mental health becomes clear when the cycle is dysregulated, often leading to a buildup of both homocysteine and S-adenosylhomocysteine (SAH), while accompanied by a transient reduction in the intended physiologic target, S-adenosylmethionine (SAM). This paper includes an in-depth review of the causes of folate cycle perturbations associated with psychotic symptoms, expounding on alternative downstream pathways which are activated and pointing toward potential etiologic agents of the associated psychosis, the methylated tertiary amines N-methyl-salsolinol, N-methyl-norsalsolinol, and adrenochrome, which appear in scientific reports concerning their association with hallucinogenic and/or neurotoxic outcomes. Electrotopological state (E-state) data has been generated for these compounds, illustrating a strong similarity with hallucinogens, particularly in terms of the E-state of the nitrogen in their tertiary amine moieties. In light of the role the folate cycle plays in transmethylation, neuroprotective strategies to prevent the transition to psychosis are suggested, including the advisory that folate supplementation can be harmful depending on the status of other relevant biochemicals.