Current Psychopharmacology - Volume 10, Issue 2, 2021

Introduction: Polymorphic gene variants, particularly the genetic determinants of low dopamine function (hypodopaminergia), are known to associate with Substance Use Disorder (SUD) and a predisposition to PTSD. Addiction research and molecular genetic applied technologies supported by the National Institutes of Health (NIH) have revealed the complex functions of brain reward circuitry and its crucial role in addiction and PTSD symptomatology. Discussion: It is noteworthy that Israeli researchers compared mice with a normal immune system with mice lacking adaptive immunity and found that the incidence of PTSD increased several-fold. It is well established that raising endorphinergic function increases immune response significantly. Along these lines, Blum’s work has shown that D-Phenylalanine (DPA), an enkephalinase inhibitor, increases brain endorphins in animal models and reduces stress in humans. Enkephalinase inhibition with DPA treats Post Traumatic Stress Disorder (PTSD) by restoring endorphin function. The Genetic Addiction Risk Severity (GARS) can characterize relevant phenotypes, genetic risk for stress vulnerability vs. resilience. GARS could be used to pre-test military enlistees for adaptive immunity or as part of PTSD management with customized neuronutrient supplementation upon return from deployment. Conclusion: Based on GARS values, with particular emphasis on enhancing immunological function, pro-dopamine regulation may restore dopamine homeostasis. Recognition of the immune system as a “sixth sense” and assisting adaptive immunity with Precision Behavioral Management (PBM), accompanied by other supportive interventions and therapies, may shift the paradigm in treating stress disorders.

Autism spectrum disorder is the term used in the most recent edition of the diagnostic and statistical manual of neurodevelopmental disorders, which includes conditions such as autism. Etiological factors such as environmental toxins, food, genes, bacterial infections, and viruses are the reasons behind autism. In the lack of diagnostic criteria, early studies of the disorder reported differences in motor and cognitive abilities in persons with autism. Autism neuropathological features are correlated with different brain areas, such as the cerebral cortex, amygdala, and hippocampus. Autism is associated with mitochondrial dysfunction, oxidative stress, neuroinflammatory reactions, neuroexcitation, and abnormal synapse formation. Pre-clinically, the administration of propionic acid in the brains of rats by stereotaxic technique exacerbates autistic behavioral and neurochemical alterations. Prescription drugs to alleviate neurological disorders for autism are risperidone (Blocks D2 and 5HT2A receptors) and aripiprazole (D2 and 5HT1A partial agonist) approved by the US-FDA, which comes with limited therapeutic intervention. Findings suggest that malfunctions of propionic acid-disrupted neuronal mitochondrial coenzyme Q10 (CoQ10) and etc-complexes are the most pathogenic events for autism. As a result, the current review focused on the history of disease, clinical and pre-clinical drugs under investigation and suggested mediating neuroprotective intervention in autism with mitochondrial CoQ10 activation. Additionally, a greater understanding of the mitochondrial signaling pathway is an effort to improve successful treatment not only for Autism but also for other neurological disorders.

Background: There is a relationship between the etiology and management of clinical depression and vitamin deficiencies. Aim: To review the effect of dietary folic acid supplementation on cause, severity and treatment of depression. Methods: A narrative review of empirical and theoretical literature on the effect of folic acid supplementation on the severity and treatment outcomes of depression. Results: Many enzymes and neurotransmitters depend on folic acid for optimal functions. The monoamine hypothesis of depression confirms the depletion of serotonin, dopamine, and norepinephrine. The systemic level of methyl folate is dependent upon the enzyme methylenetetrahydrofolate reductase [MTHFR], which is encoded by a polymorphic gene [C677T-MTHFR], as well as being dependent on dietary folic acid intake. However, folate has procarcinogenic properties because its coenzymes are involved in de novo purine and thymine nucleotide biosynthesis. Besides, folate deficiency in normal tissues may also predispose to neoplastic transformation, while folate supplementation may suppress the development of tumors in normal tissues. Epidemiological studies revealed that low folate status is associated with depression; especially in terms of severity and the outcome of antidepressant use. Conclusion: The role of folic acid in the etiology and the management of depression cannot be overemphasized. Folate supplementation has been yielding positive results in the management of depression.

Background: Conventional medical therapies for neurodegenerative diseases primarily target anti-inflammatory interventions, immune suppression of autoimmune pathologies, and, depending on the diagnosed pathological mechanisms, neurotransmitter reuptake inhibition, among other tactics. However, the incidence of neuroinflammatory pathologies appears to be progressively increasing. The National Institutes of Health, National Institute of Environmental Health Sciences in 2016, estimated that 5.4 million Americans were living with Alzheimer's. If no effective solutions are found and implemented, within 30 years of this publication, according to data from Harvard, more than 12 million Americans will suffer from neurodegenerative diseases. Methods: Rather than investigating greater etiological depth, modern medicine seems to have been designed to addressing obvious symptomologies to relieve suffering for as long as possible until neuropathological progress inevitably wins in achieving complete functional disability and death. Researchers are reporting herein evidence-based effective treatment therapies that are outside conventional medical standard of care therapies. Conclusion: These therapies are the result of a deeper exploration into etiological factors, including an expanded understanding of the role of anaerobic pathologies in the etiology of neuroinflammatory disorders and methods of reverting to a competent aerobic metabolism. Such therapies include a liquid VMP35 MNC; a greater focus on viral mechanistic pathologies and their remission; and understanding of the genetic basis for a loss of neurological interconnectivity and consequential reward deficiencies in combination with neuronutrient deficiencies, enabling neuronutrient repletion with nutrigenomic therapies such as the KB220Z.

Background: Globally, an alarming number of pharmaceutically active compounds are now routinely added to the street drugs of abuse, cocaine and heroin. In some cases, seventeen (17) or more potentially toxic compounds are found in a single street purchased bag or block of cocaine or heroin. Pharmacologically active compounds, impurities, or breakdown products from drug manufacturing and industrial chemicals (collectively referred to as toxic adulterants) are now found in street drugs. They include, but are not limited to: antipsychotics, antidepressants, anxiolytics, antihistamines, anthelmintics, anesthetics, antiinflammatorys, antipyretics, analgesics, antispasmodics, antiarrhythmics, antimalarials, veterinary medications, bronchodilators, expectorants, sedatives, muscle relaxers, natural/synthetic hallucinogens, decongestants, new psychoactive substances (NPS), industrial compounds, fungicides, and impurities in the manufacturing process. All can be found within a single street purchase of heroin or cocaine. Routine clinical or workplace drug testing will not detect all these toxic adulterants. Only specialty forensic tests, specifically ordered, will detect them. The synergistic effect on the human body of such an unprecedented combination of pharmacologically active compounds is unknown and potentially deadly. This is especially seen in daily substance users who are exposed to these combinations multiple times a day over an extended period of time. Individuals with substance use disorders (SUDs) have several co-occurring health problems that make them more susceptible to COVID-19, including compromised immune, pulmonary, cardiovascular, and respiratory systems. These problems are high-risk factors for the acquisition of COVID-19 infection and more serious complications from the virus, including hospitalization and death. Objective: The study aims to bring to the attention of public health officials, addiction medicine specialists, treatment officials, therapists, and the general public the alarming increase of dangerous toxic adulterants being added to street drugs and their potentially lethal synergistic effects. Also, it aims to provide insights into how these new formulations can have serious pathophysiological effects on individuals with Substance Abuse Disorders (SUDs) during the COVID-19 pandemic. Methods: The literature on street drug cutting agents, toxic adulterants, NPS, manufacturing byproducts, and other industrial compounds will be reviewed. Also, a review of the literature of pathophysiological effects, especially on SUD patients, in light of the COVID-19 pandemic will be presented. This is combined with international and USA studies that were carried out by the Colombo Plan that identified these new combinations of toxic adulterants in street drugs, using state-of-the-art field and forensic laboratory detection technologies. Results: The majority of street drugs, in some cases more than ninety-five percent, now have multiple toxic adulterants. It is rare that a street purchase of cocaine or heroin does not contain multiple toxic adulterants, cutting agents, NPS, manufacturing byproducts, or industrial chemicals. Conclusion: This dangerous new composition in world street drug supply is unprecedented and may be the undetected cause of many psychostimulant and opioid overdose deaths, as many toxic adulterants are not routinely tested in post-mortem or street drug seizure cases. In addition, several of these toxic adulterants create a catastrophic drop in white blood cells, causing neutropenia and making the substance users susceptible to a wide range of opportunistic infections, including COVID-19. This profound change in the world street drug supply has catastrophic implications for individuals with SUDs and our health care system, especially in the era of the COVID-19 pandemic.

Background: Recently, numerous large clinical trials have been performed to evaluate the effectiveness and tolerability of extended-release formulations of carbamazepine in bipolar disorder. Objective: In the current study, we compared lithium with a prolonged-release form of carbamazepine (Tegretol CR) to evaluate its efficiency and safety in a group of patients with a diagnosis of acute mania. Methods: Fifty patients with the diagnosis of acute mania were selected for a three-week, doubleblind study, and were randomly administered lithium carbonate or tegretol CR. The main outcome measured in the present evaluation was the Manic State Rating Scale (MSRS), which was scored at baseline and weekly intervals up to the third week. Moreover, insight and overall illness severity and improvement were assessed using the Schedule for Assessment of Insight (SAI), the Clinical Global Impressions-Global Improvement scale (CGI-I), and the Clinical Global Impressions Severity Scale (CGI-S), respectively. The statistical significance was defined with a p-value ≤0.05, and the treatment efficacy was analyzed by independent samples t-test and repeated measures analysis of variance (ANOVA). Results: Despite the fact that the mean total score of MSRS improved significantly with respect to both lithium carbonate and tegretol CR at the end of the third week, the between-group analysis showed a significant advantage of lithium, regarding both frequency and intensity of symptoms, at the end of the study. The mean total score of SAI, as well, showed significant improvement caused by both of them. Nevertheless, while the CGI-I demonstrated significant improvement in participants taking lithium and tegretol CR, the CGI-S showed significant progress only with lithium. Besides, Cohen’s effect size analysis showed a large improvement of MSRS by lithium and medium improvement by tegretol CR. Post-hoc power analysis showed an intermediate power of 0.42 on behalf of the current evaluation. Conclusion: While both lithium carbonate and tegretol CR were found to be valuable for the improvement of manic symptoms, management with lithium appears to be more helpful.

Background: Essential oils are among the preferred alternative remedies for treating sleep disturbance, but empirical evidence for their effectiveness is varied. According to a new line of research, an inhaler designed to deliver high concentrations of essential oil molecules directly into the nose effectively influences the hypothalamic-pituitary-adrenal axis and the autonomous nervous system. Objective: This study was run to investigate whether insomnia complaints were reduced upon the use of the inhaler AromaStick® ‘Relax’. Methods: A documentation field study involving thirty individuals with a recorded history of nonspecific insomnia complaints was conducted to determine the inhaler’s specific effects. Results: Upon nightly use for one week, the odor inhaler strongly improved sleep quality and reduced symptoms associated with poor sleep. Depending on the dimensions tested, effect sizes ranged between 0.8 < d < 2.6. The strongest effects were found for ‘difficulty maintaining sleep’, ‘difficulty initiating sleep’ and ‘feeling recovered after sleeping’. Conclusion: The inhaler proved to be useful in mitigating sleep impairment. The effects were strongest in individuals reporting low sleep quality.