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Brain Research Jun 2020The neuropeptide oxytocin (OXT) plays a key role in adaptive processes associated with reward, tolerance, memory and stress responses. Through interactions with brain... (Review)
Review
The neuropeptide oxytocin (OXT) plays a key role in adaptive processes associated with reward, tolerance, memory and stress responses. Through interactions with brain reward and stress systems, OXT is known to play a role in several neuropsychiatric disorders, particularly those that involve altered social integration, such as alcohol and drug addiction (Heilig et al., 2016). As such, there is growing interest in the oxytocin system as a potential therapeutic target for the treatment of alcohol and substance use disorders. Accumulating preclinical evidence suggests that administration of OXT influences the development of tolerance, sensitization and withdrawal symptoms, and modulates numerous alcohol/drug-seeking and alcohol/drug-taking behaviors. Further, there is some evidence to suggest that OXT may help to reverse neuroadaptations that occur as a result of chronic alcohol or drug exposure. To date, there have been only a handful of clinical studies conducted in alcohol and drug dependent populations. This review summarizes the preclinical and clinical literature on the effects of OXT administration on alcohol- and drug-related behaviors. In addition, we discuss OXT interactions with the hypothalamic-pituitaryadrenal axis and multiple neurotransmitter systems within addiction circuitry.
Topics: Alcoholism; Animals; Behavior, Addictive; Drug Tolerance; Drug-Seeking Behavior; Humans; Oxytocin; Recurrence; Substance Withdrawal Syndrome; Substance-Related Disorders
PubMed: 32142721
DOI: 10.1016/j.brainres.2020.146761 -
Neurobehavioral effects of environmental enrichment and drug abuse vulnerability: An updated review.Pharmacology, Biochemistry, and Behavior Nov 2022Environmental enrichment consisting of social peers and novel objects is known to alter neurobiological functioning and have an influence on the behavioral effects of... (Review)
Review
Environmental enrichment consisting of social peers and novel objects is known to alter neurobiological functioning and have an influence on the behavioral effects of drugs of abuse in preclinical rodent models. An earlier review from our laboratory (Stairs and Bardo, 2009) provided an overview of enrichment-specific changes in addiction-like behaviors and neurobiology. The current review updates the literature in this extensive field. Key findings from this updated review indicate that enrichment produces positive outcomes in drug abuse vulnerability beyond just psychostimulants. Additionally, recent studies indicate that enrichment activates key genes involved in cell proliferation and protein synthesis in nucleus accumbens and enhances growth factors in hippocampus and neurotransmitter signaling pathways in prefrontal cortex, amygdala, and hypothalamus. Remaining gaps in the literature and future directions for environmental enrichment and drug abuse research are identified.
Topics: Humans; Substance-Related Disorders; Behavior, Addictive; Nucleus Accumbens; Prefrontal Cortex; Amygdala
PubMed: 36228739
DOI: 10.1016/j.pbb.2022.173471 -
Viruses Dec 2022Chronic low-grade inflammation remains an essential feature of HIV-1 infection under combined antiretroviral therapy (cART) and contributes to the accelerated cognitive... (Review)
Review
Chronic low-grade inflammation remains an essential feature of HIV-1 infection under combined antiretroviral therapy (cART) and contributes to the accelerated cognitive defects and aging in HIV-1 infected populations, indicating cART limitations in suppressing viremia. Interestingly, ~50% of the HIV-1 infected population on cART that develops cognitive defects is complicated by drug abuse, involving the activation of cells in the central nervous system (CNS) and neurotoxin release, altogether leading to neuroinflammation. Neuroinflammation is the hallmark feature of many neurodegenerative disorders, including HIV-1-associated neurocognitive disorders (HAND). Impaired autophagy has been identified as one of the underlying mechanisms of HAND in treated HIV-1-infected people that also abuse drugs. Several lines of evidence suggest that autophagy regulates CNS cells' responses and maintains cellular hemostasis. The impairment of autophagy is associated with low-grade chronic inflammation and immune senescence, a known characteristic of pathological aging. Therefore, autophagy impairment due to CNS cells, such as neurons, microglia, astrocytes, and pericytes exposure to HIV-1/HIV-1 proteins, cART, and drug abuse could have combined toxicity, resulting in increased neuroinflammation, which ultimately leads to accelerated aging, referred to as neuroinflammaging. In this review, we focus on the potential role of autophagy in the mechanism of neuroinflammaging in the context of HIV-1 and drug abuse.
Topics: Humans; HIV-1; Neuroinflammatory Diseases; HIV Infections; Autophagy; HIV Seropositivity; Inflammation; Substance-Related Disorders
PubMed: 36680084
DOI: 10.3390/v15010044 -
Journal of Occupational and... Jul 2022Investigate the associations between drug abuse and the prevalence of the engagement and burnout dichotomy in law professionals.
OBJECTIVE
Investigate the associations between drug abuse and the prevalence of the engagement and burnout dichotomy in law professionals.
METHODS
Eligible participants completed a questionnaire where odds ratios of drug abuse and other confounding variables and their association to engagement or burnout were calculated using multiple logistic regression.
RESULTS
When looking at all law professionals, burnout is a statistically significant predictor for drug abuse ( P = 0.04, not shown). Law professionals whose burnout scores fell in the highest bin have 4.71 (95% CI [1.38-16.08]) times higher odds of having a problem with drug abuse than those whose burnout scores fell in the second bin.
CONCLUSION
Study findings showed a possible way to affect the prevalence of drug abuse in law professionals by affecting the engagement and burnout dichotomy.
Topics: Burnout, Professional; Burnout, Psychological; Humans; Lawyers; Substance-Related Disorders; Surveys and Questionnaires
PubMed: 35732047
DOI: 10.1097/JOM.0000000000002550 -
Current Opinion in Psychology Dec 2019Substances of abuse are characterized by their rewarding effects and engagement of reward pathways in the brain. However, these substances also provide rapid relief of... (Review)
Review
Substances of abuse are characterized by their rewarding effects and engagement of reward pathways in the brain. However, these substances also provide rapid relief of negative affect, and thus are highly negatively reinforcing. Accordingly, negative affectivity and other affective vulnerabilities (factors related to the experience of affect) are strongly linked to problematic substance use and substance use disorders. In this review, we provide a critical overview of the literature on affective vulnerabilities in substance use disorders. We discuss how both the experience of affect (e.g. negative affectivity, stress reactivity) and the interpretation of affect (e.g. distress intolerance, anxiety sensitivity) are pertinent to the development, maintenance, and treatment of substance use disorders.
Topics: Affect; Anxiety; Humans; Substance-Related Disorders
PubMed: 30851660
DOI: 10.1016/j.copsyc.2019.01.011 -
Clinical Neuropharmacology 2020Among opioid-dependent patients on maintenance therapy, concomitant drug abuse is a serious problem. Dextromethorphan, an over-the-counter antitussive agent that can be...
BACKGROUND
Among opioid-dependent patients on maintenance therapy, concomitant drug abuse is a serious problem. Dextromethorphan, an over-the-counter antitussive agent that can be purchased without prescription, is a drug with a high potential for misuse, especially when consumed in high doses.The objective of this study was to investigate possible abuse of dextromethorphan among substituted opioid-dependent patients and comparison of subjective and objective findings.Due to its ability to increase serotonin levels, opioid-dependent patients may be particularly susceptible to dextromethorphan misuse. Dextromethorphan misuse may have side effects, including psychiatric symptoms and serotonin syndrome, and may induce assault, suicide, or homicide.
METHODS
A total of 104 opioid-dependent patients in maintenance treatment were included in this cross-sectional study conducted in the outpatient department of the Psychiatric Hospital, University of Zurich. Study participants were divided into 2 groups based on laboratory results: dextromethorphan abusers (n = 12) and nonabusers (n = 92). The objective use and concentrations of dextromethorphan was detected using 3-month hair toxicology analysis.Statistical analysis was performed by using χ test, Student t test, Mann-Whitney U test, and Barnard exact test.
RESULTS
Dextromethorphan was abused by 12 (11.5%) patients, 11 (91.7%) of whom did not report concomitant abuse of dextromethorphan but were identified through hair analysis. In general, there were significant differences among patients abusing dextromethorphan compared with nondextromethorphan consumers in terms of trauma due to sexual maltreatment/violence, multiple traumas, or harmful use of hallucinogenic drugs.
CONCLUSIONS
Further studies are necessary to examine dextromethorphan and its impact on patients with psychiatric comorbidities and psychiatric medication. According to literature, there is a significant drug interaction risk due to the impact of dextromethorphan misuse on serotonin syndrome and psychiatric symptoms.1-3 We recommend active inquiry into and testing for concomitant drug abuse among substituted opioid-dependent patients to reduce the risk of drug interactions and side effects in this especially vulnerable group of patients.
Topics: Adult; Cross-Sectional Studies; Dextromethorphan; Female; Hair; Hallucinogens; Humans; Male; Mental Disorders; Middle Aged; Opiate Substitution Treatment; Opioid-Related Disorders; Outpatients; Sexual Behavior; Substance Abuse Detection; Substance-Related Disorders; Violence; Wounds and Injuries
PubMed: 32947422
DOI: 10.1097/WNF.0000000000000403 -
Neuropharmacology Apr 2022Cannabidiol (CBD) is one of the major constituents of Cannabis sativa L. that lacks psychotomimetic and rewarding properties and inhibits the rewarding and reinforcing... (Review)
Review
BACKGROUND
Cannabidiol (CBD) is one of the major constituents of Cannabis sativa L. that lacks psychotomimetic and rewarding properties and inhibits the rewarding and reinforcing effects of addictive drugs such as cocaine, methamphetamine (METH), and morphine. Additionally, CBD's safety profile and therapeutic potential are currently evaluated in several medical conditions, including pain, depression, movement disorders, epilepsy, multiple sclerosis, Alzheimer's disease, ischemia, and substance use disorder. There is no effective treatment for substance use disorders such as addiction, and this review aims to describe preclinical and clinical investigations into the effects of CBD in various models of opioid, psychostimulant, cannabis, alcohol, and nicotine abuse. Furthermore, the possible mechanisms underlying the therapeutic potential of CBD on drug abuse disorders are reviewed.
METHODS
The current review considers and summarizes the preclinical and clinical investigations into CBD's effects in various models of drug abuse include opioids, psychostimulants, cannabis, alcohol, and nicotine.
RESULTS
Several preclinical and clinical studies have proposed that CBD may be a reliable agent to inhibit the reinforcing and rewarding impact of drugs.
CONCLUSIONS
While the currently available evidence converges to suggest that CBD could effectively reduce the rewarding and reinforcing effects of addictive drugs, more preclinical and clinical studies are needed before CBD can be added to the therapeutic arsenal for treating addiction.
Topics: Animals; Cannabidiol; Cannabinoid Receptor Modulators; Humans; Substance-Related Disorders
PubMed: 35032495
DOI: 10.1016/j.neuropharm.2022.108948 -
Genes Nov 2023Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them,... (Review)
Review
Trauma in childhood and adolescence has long-term negative consequences in brain development and behavior and increases the risk for psychiatric disorders. Among them, post-traumatic stress disorder (PTSD) during adolescence illustrates the connection between trauma and substance misuse, as adolescents may utilize substances to cope with PTSD. Drug misuse may in turn lead to neuroadaptations in learning processes that facilitate the consolidation of traumatic memories that perpetuate PTSD. This reflects, apart from common genetic and epigenetic modifications, overlapping neurocircuitry engagement triggered by stress and drug misuse that includes structural and functional changes in limbic brain regions and the salience, default-mode, and frontoparietal networks. Effective strategies to prevent PTSD are needed to limit the negative consequences associated with the later development of a substance use disorder (SUD). In this review, we will examine the link between PTSD and SUDs, along with the resulting effects on memory, focusing on the connection between the development of an SUD in individuals who struggled with PTSD in adolescence. Neuroimaging has emerged as a powerful tool to provide insight into the brain mechanisms underlying the connection of PTSD in adolescence and the development of SUDs.
Topics: Humans; Adolescent; Stress Disorders, Post-Traumatic; Substance-Related Disorders; Brain; Neuroimaging; Drug Misuse
PubMed: 38136935
DOI: 10.3390/genes14122113 -
Cells Aug 2020Despite the effectiveness of combined antiretroviral therapy (cART) in suppressing virus replication, chronic inflammation remains one of the cardinal features... (Review)
Review
Despite the effectiveness of combined antiretroviral therapy (cART) in suppressing virus replication, chronic inflammation remains one of the cardinal features intersecting HIV-1, cART, drug abuse, and likely contributes to the accelerated neurocognitive decline and aging in people living with HIV-1 (PLWH) that abuse drugs. It is also estimated that ~30-60% of PLWH on cART develop cognitive deficits associated with HIV-1-associated neurocognitive disorders (HAND), with symptomatology ranging from asymptomatic to mild, neurocognitive impairments. Adding further complexity to HAND is the comorbidity of drug abuse in PLWH involving activated immune responses and the release of neurotoxins, which, in turn, mediate neuroinflammation. Premature or accelerated aging is another feature of drug abusing PLWH on cART regimes. Emerging studies implicate the role of HIV-1/HIV-1 proteins, cART, and abused drugs in altering the inflammasome signaling in the central nervous system (CNS) cells. It is thus likely that exposure of these cells to HIV-1/HIV-1 proteins, cART, and/or abused drugs could have synergistic/additive effects on the activation of inflammasomes, in turn, leading to exacerbated neuroinflammation, ultimately resulting in premature aging referred to as "inflammaging" In this review, we summarize the current knowledge of inflammasome activation, neuroinflammation, and aging in central nervous system (CNS) cells such as microglia, astrocytes, and neurons in the context of HIV-1 and drug abuse.
Topics: Aging; Animals; Anti-HIV Agents; Comorbidity; Cytokines; Drug Interactions; HIV Infections; HIV-1; Humans; Inflammasomes; Inflammation; Neurocognitive Disorders; Substance-Related Disorders
PubMed: 32784383
DOI: 10.3390/cells9081857 -
Neuropharmacology Nov 2022New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of... (Review)
Review
New medicines containing classic hallucinogenic and entactogenic psychedelic substance are under development for various psychiatric and neurological disorders. Many of these, including psilocybin, lysergic acid diethylamide (LSD), and 3,4-methylenedioxymethamphetamine (MDMA) are Schedule I controlled substances of the United States Controlled Substances Act (US CSA), and similarly controlled globally. The implications of the CSA for research and medicines development, the path to approval of medicines, and their subsequent removal from Schedule I in the US are discussed. This entire process occurs within the framework of the CSA in the US and its counterparts internationally in accordance with international drug control treaties. Abuse potential related research in the US informs the eight factors of the CSA which provide the basis for rescheduling actions that must occur upon approval of a drug that contains a Schedule I substance. Abuse-related research also informs drug product labeling and the risk evaluation and mitigation strategies (REMS) will likely be required for approved medicines. Human abuse potential studies typically employed in CNS drug development may be problematic for substances with strong hallucinogenic effects such as psilocybin, and alternative strategies are discussed. Implications for research, medicinal development, and controlled substance scheduling are presented in the context of the US CSA and FDA requirements with implications for global regulation. We also discuss how abuse-related research can contribute to understanding mechanisms of action and therapeutic effects as well as the totality of the effects of the drugs on the brain, behavior, mood, and the constructs of spirituality and consciousness.
Topics: Controlled Substances; Hallucinogens; Humans; Lysergic Acid Diethylamide; Psilocybin; Substance-Related Disorders; United States
PubMed: 35987353
DOI: 10.1016/j.neuropharm.2022.109220