New Addictive Substances

Sinomenine is a natural compound extracted from the medicinal plant Sinomenium acutum. Its supplementation has been shown to present benefits in a variety of animal models of central nervous system (CNS) disorders, such as cerebral ischemia, intracerebral hemorrhage, traumatic brain injury (TBI), Alzheimer's disease (AD), Parkinson's disease (PD), epilepsy, depression, multiple sclerosis, morphine tolerance, and glioma. Therefore, sinomenine is now considered a potential agent for the prevention and/or treatment of CNS disorders...

Psychedelics are hallucinogenic drugs that alter the state of consciousness substantially. They bring about psychological, auditory, and visual changes. The psychedelics act on the brain, implying that they have a powerful psychological impact. One of the main factors contributing to disability worldwide is pain. The majority of people deal with pain on a daily basis. Living with chronic pain affects daily life and has social implications. Chronic pain can be associated with any disease that may be genetic, idiopathic, or traumatic...

Δ9-tetrahydrocannabinol (Δ9-THC) isomers, especially Δ8-tetrahydrocannabinol (Δ8-THC), are increasing in foods, beverages, and e-cigarettes liquids. A major factor is passage of the Agriculture Improvement Act (AIA) that removed hemp containing less than 0.3 % Δ9-THC from the definition of "marijuana" or cannabis. CBD-rich hemp flooded the market resulting in excess product that could be subjected to CBD cyclization to produce Δ8-THC. This process utilizes strong acid and yields toxic byproducts that frequently are not removed prior to sale and are currently inadequately studied...

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4 H -[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals...

OBJECTIVE: To identify the presence of unapproved pharmaceutical drugs in over-the-counter dietary supplements marketed to improve memory and cognitive function. METHODS: Supplements were identified by searching 2 supplement databases for products labeled as containing omberacetam, aniracetam, phenylpiracetam, or oxiracetam, 4 drugs not approved for human use in the United States. Products were purchased online and analyzed using nontargeted liquid chromatography-quadrupole time-of-flight mass spectrometry methods...

PURPOSE: Since the appearance of fentanyl followed by its many kinds of analogues around 1988, North America has been exposed to fierce synthetic opioid pandemic resulting in more than 130,000 deaths due to their overdoses until May 2019, when China declared to prohibit the licit fentanyl analog production. However, the Chinese announcement did not go into force in USA due to the adroit strategies of tough traffickers. Thus, contrary to the expectation, the number of synthetic opioid products and their poisoning cases in USA has increased by about 30%; especially, various benzimidazole synthetic opioids have revived on the illicit drug market during a recent few years...

To the Editor, The ongoing rise of New Psychoactive Substances (NPS), i.e. psychotropic molecules devised and synthesized to replicate the effects of traditional drugs of abuse in order to circumvent banned substances schedules, has been posing a challenge of enormous magnitude to substance detection systems and law enforcement worldwide. Still, it would be remiss to ignore the role played by the unprecedented public health emergency relating to the COVID-19 pandemic in the exacerbation of the NPS crisis. The diversion of resources has in fact hindered conventional approaches to drug monitoring, surveillance, control, and public health responses...

A high-fat, high-fructose diet (HFFD) impairs cognitive functions and increases susceptibility to neurodegenerative disorders. Irisin and heat shock protein 70 (HSP70) are well known for their role in neuroprotection. The possible neuroprotective effects of fenofibrate on HFFD-induced cognitive dysfunction and the involvement of irisin and HSP70 in these effects were investigated in this study. Rats were divided into normal control, HFFD, dimethylsulfoxide+HFFD, and fenofibrate+HFFD groups. At the end of the experiment, fenofibrate treatment restored hippocampus histological characteristics to almost normal and improved HFFD-induced cognitive deficit...

Dopamine regulates normal functions such as movement, reinforcement learning, and cognition, and its dysfunction has been implicated in multiple psychiatric and neurological disorders. Dopamine acts through D1- (D1R and D5R) and D2-class (D2R, D3R, and D4R) receptors and activates both G protein- and β-arrestin-dependent signaling pathways. Current dopamine receptor-based therapies are used to ameliorate motor deficits in Parkinson's disease or as antipsychotic medications for schizophrenia. These drugs show efficacy for ameliorating only some symptoms caused by dopamine dysfunction and are plagued by debilitating side effects...

Hallucinogenic drugs potently affect brain and behavior and have also recently emerged as potentially promising agents in pharmacotherapy. Complementing laboratory rodents, the zebrafish ( Danio rerio ) is a powerful animal model organism for screening neuroactive drugs, including hallucinogens. Here, we test a battery of ten novel N -benzyl-2-phenylethylamine (NBPEA) derivatives with the 2,4- and 3,4-dimethoxy substitutions in the phenethylamine moiety and the -OCH3 , -OCF3 , -F, -Cl, and -Br substitutions in the ortho position of the phenyl ring of the N -benzyl moiety, assessing their acute behavioral and neurochemical effects in the adult zebrafish...

This case report presents a 40-year-old man presenting with mixed mental health symptoms including depression, anxiety, euphoria, sleep cycle disturbances, and alcohol use over several years. Multiple providers see the patient in varying specialties, initially focusing on depression, anxiety, and, later, substance use. Alcohol misuse can shadow underlying mental disorders. Therefore, early recognition and collaborative management are imperative to unveil the possibility of comorbid mental health disorders.

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Beyond their rapid rewarding effects, drugs of abuse can durably alter an individual's response to their environment as illustrated by the compulsive drug seeking and risk of relapse triggered by drug-associated stimuli. The persistence of these associations even long after cessation of drug use demonstrates the enduring mark left by drugs on brain reward circuits. However, within these circuits, neuronal populations are differently affected by drug exposure and growing evidence indicates that relatively small subsets of neurons might be involved in the encoding and expression of drug-mediated associations...

Depression is one of the leading causes of disability worldwide and a major contributor to the global burden of disease, yet the cellular and molecular etiology of depression remain largely unknown. Major Depressive Disorder (MDD) is associated with a variety of chronic physical inflammatory and autoimmune disorders, and mood disorders may act synergistically with other medical disorders to worsen patient outcomes. Here, we outline the neuroimmune complement, explore the evidence for altered immune system function in MDD, and present some of the potential mechanisms by which immune cells and molecules may drive the onset and course of MDD...

The past decade has witnessed a rapid growth of research on the basic science and clinical understanding of psychedelics. This chapter provides an overview of the human behavioral pharmacology of psychedelics focusing on three prototypic classic psychedelics-psilocybin, lysergic acid diethylamide (LSD), and dimethyltryptamine (DMT). A brief historical overview of the classic psychedelics and naming and drug classification is first specified. Next, special considerations in the conduct of human behavioral pharmacology work with psychedelics is described including the role of set and setting, mystical experience measurement, the use of effective blinding and placebos, and the abuse liability of psychedelics...

Substance use disorders (SUD) develop as a result of complex interactions between the environment, the subject, and the drug of abuse. Preclinical basic research investigating each of these tripartite components of SUD individually has resulted in advancements in our fundamental knowledge regarding the progression from drug abuse to SUD and severe drug addiction and the underlying behavioral and neurobiological mechanisms. How these complex interactions between the environment, the subject, and the drug of abuse impact the effectiveness of candidate or clinically used medications for SUD has not been as extensively investigated...

Behavioral pharmacology has been aided significantly by the development of innovative cognitive tasks designed to examine complex behavioral processes in laboratory animals. Performance outcomes under these conditions have provided key metrics of drug action which serve to supplement traditional in vivo assays of physiologic and behavioral effects of psychoactive drugs. This chapter provides a primer of cognitive tasks designed to assay different aspects of complex behavior, including learning, cognitive flexibility, memory, attention, motivation, and impulsivity...

Although μ-opioid peptide (MOP) receptor agonists are effective analgesics available in clinical settings, their serious adverse effects put limits on their use. The marked increase in abuse and misuse of prescription opioids for pain relief and opioid overdose mortality in the past decade has seriously impacted society. Therefore, safe analgesics that produce potent analgesic effects without causing MOP receptor-related adverse effects are needed. This review highlights the potential therapeutic targets for the treatment of opioid abuse and pain based on available evidence generated through preclinical studies and clinical trials...

Kratom products have been historically and anecdotally used in south Asian countries for centuries to manage pain and opioid withdrawal. The use of kratom products has dramatically increased in the United States. More than 45 kratom alkaloids have been isolated, yet the overall pharmacology of the individual alkaloids is still not well characterized. The purpose of this chapter is to summarize in vitro and in vivo opioid activities of the primary kratom alkaloid mitragynine and its more potent metabolite 7-hydroxymitragynine...

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