Neuroendocrinology of Stress and Addiction

2021 ◽  
Author(s):  
Steven Kinsey ◽  
Olivia Vanegas ◽  
Kristen Trexler ◽  
Floyd Steele ◽  
Matthew Eckard
Keyword(s):  
Stress Response ◽  
Psychotropic Drugs ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
Drug Withdrawal ◽  
Host Organism ◽  
Repeated Use ◽  
Drug Abstinence ◽  
Withdrawal Syndromes ◽  
Development Of Tolerance

The stress response evolved as a series of neural and endocrine mechanisms that protect the host organism from threats to homeostasis. Repeated use of psychotropic drugs can lead to the development of tolerance (i.e., decreased drug activity at a given dose) and drug dependence, as indicated by withdrawal syndromes following drug abstinence. Drug withdrawal is often overtly stressful, although acute drug exposure may also represent a threat to homeostasis. This article explores the neuroendocrine effects of drugs of abuse and some of the ways in which stress and appetitive mechanisms interact.

scholarly journals What I have learnt from helping thousands of people taper off antidepressants and other psychotropic medications

2021 ◽  
Vol 11 ◽  
pp. 204512532199127
Author(s):  
Adele Framer
Keyword(s):  
Withdrawal Syndrome ◽  
Online Community ◽  
Medical Information ◽  
Scientific Literature ◽  
Drug Withdrawal ◽  
Psychotropic Medications ◽  
Lessons Learned ◽  
Medical Providers ◽  
Drug Reactions ◽  
Withdrawal Syndromes

Although psychiatric drug withdrawal syndromes have been recognized since the 1950s – recent studies confirm antidepressant withdrawal syndrome incidence upwards of 40% – medical information about how to safely go off the drugs has been lacking. To fill this gap, over the last 25 years, patients have developed a robust Internet-based subculture of peer support for tapering off psychiatric drugs and recovering from withdrawal syndrome. This account from the founder of such an online community covers lessons learned from thousands of patients regarding common experiences with medical providers, identification of adverse drug reactions, risk factors for withdrawal, tapering techniques, withdrawal symptoms, protracted withdrawal syndrome, and strategies to cope with symptoms, in the context of the existing scientific literature.

Psychotropic Drugs in Pregnancy and Lactation

PEDIATRICS ◽  
1982 ◽  
Vol 69 (2) ◽  
pp. 241-244
Author(s):  
Sydney Segal ◽  
Albert W. Pruitt ◽  
Walter R. Anyan ◽  
Reba M. Hill ◽  
Ralph E. Kauffman ◽  
...  
Keyword(s):  
Psychotropic Drugs ◽  
Structural Changes ◽  
Drug Exposure ◽  
Final Decision ◽  
Behavioral Alterations ◽  
Drug Dosing ◽  
Behavioral Studies ◽  
Increased Risk ◽  
Pregnancy And Lactation

Accurate prediction of fetal/neonatal risks following maternal psychotropic drug consumption by the human will require much additional study. Based upon our present understanding of fetal exposure to psychotropic drugs, there would appear to be an increased risk for spontaneous malformations in the case of lithium. There have been inconsistent reports of structural abnormalities following exposure to phenothiazines and benzodiazepines. In animal models that demonstrate structural changes due to neuroleptic exposure, in general, extremely large dosages of medication had been given. Thus, their correlative value is limited. Behavioral alterations in animals following drug exposure during pregnancy tend to support increased concerns about the safety of psychotropic drugs for the fetus but cannot be used alone in making a final decision. Behavioral studies evaluating drugs in breast milk have been restricted to experimental animals; hence, the associated risks from this form of drug dosing in man remain unknown. At present, neither gross anatomic nor motor side effects have been apparent in the infant. The question of the development of subtle behavioral changes as a long-term consequence will remain undetermined until careful assessments have been completed.

Drug Withdrawal

2020 ◽  
pp. 97-116
Author(s):  
George F. Koob
Keyword(s):  
Substance Use ◽  
Stress Response ◽  
Substance Use Disorders ◽  
Negative Reinforcement ◽  
Drug Withdrawal ◽  
Primary Factor ◽  
Motivational Factor ◽  
Drug Seeking ◽  
Molecular Changes ◽  
Negative Emotional State

Drug withdrawal has long been considered a key symptom in the diagnosis of alcohol and substance use disorders. In this chapter, it is also conceptualized as a major motivational factor that drives compulsive drug taking. Drawing from the negative emotional components of withdrawal, termed hyperkatifeia (i.e., the negative emotional and motivational signs of withdrawal), the hypothesis here is that withdrawal sets up another major source of reinforcement—namely, negative reinforcement—for drug seeking in substance use disorders. From the perspective of the hyperkatifeia phenotype, withdrawal then returns to being a key part of moderate to severe alcohol and substance use disorders to become the primary factor that motivates sustained drug seeking. Such hyperkatifeia is mediated by a multidetermined neurocircuitry that compromises within-system neurochemical systems that are involved in the rewarding effects of drugs and promotes the activation of pro-stress neuromodulators that combine with a weakening or inadequate anti-stress response. Altogether, these neurocircuitry, neurochemical, and molecular changes lead to a negative emotional state (hyperkatifeia) that sets up an allostatic hedonic load that drives negative reinforcement. Under this framework, strong multidetermined buffers, if activated and sufficient to allow the reward and pro-stress systems to recover, may help return the organism to homeostasis.

scholarly journals Dependence, withdrawal and rebound of CNS drugs: an update and regulatory considerations for new drugs development

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Alicja Lerner ◽  
Michael Klein
Keyword(s):  
Drug Withdrawal ◽  
Multiple Scales ◽  
New Drugs ◽  
Systematic Evaluation ◽  
Dsm 5 ◽  
Drug Classes ◽  
Abrupt Discontinuation ◽  
Cns Drugs ◽  
Withdrawal Syndromes ◽  
Clinical Drug

Abstract The purpose of this article is to describe dependence and withdrawal phenomena related to CNS drugs discontinuation and to clarify issues related to the evaluation of clinical drug withdrawal and rebound as they relate to safety in new drug development. The article presents current understanding and definitions of drug dependence and withdrawal which are also relevant and important features of addiction, though not the same. Addiction, called substance use disorder in DSM-5, affects an individual’s brain and behaviour, represents uncontrollable drug abuse and inability to stop taking a drug regardless of the harm it causes. Characteristic withdrawal syndromes following abrupt discontinuation of CNS-active drugs from numerous drug classes are described. These include drugs both scheduled and non-scheduled in the Controlled Substances Act, which categorizes drugs in five schedules based on their relative abuse potentials and dependence liabilities and for regulatory purposes. Schedules 1 and 2 contain drugs identified as those with the highest abuse potential and strictest regulations. Less recognized aspects of drug withdrawal, such as rebound and protracted withdrawal syndromes for several drug classes are also addressed. Part I presents relevant definitions and describes clinical withdrawal and dependence phenomena. Part II reviews known withdrawal syndromes for the different drug classes, Part III describes rebound and Part IV describes protracted withdrawal syndromes. To our knowledge, this is the first compilation of withdrawal syndromes for CNS drugs. Part V provides details of evaluation of dependence and withdrawal in the clinical trials for CNS drugs, which includes general design recommendations, and several tools, such as withdrawal questionnaires and multiple scales that are helpful in the systematic evaluation of withdrawal. The limitations of different aspects of this method of dependence and withdrawal evaluation are also discussed.

scholarly journals Possible Immunosuppressive Effects of Drug Exposure and Environmental and Nutritional Effects on Infection and Vaccination

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
H. P. Huemer
Keyword(s):  
Immune Response ◽  
Side Effects ◽  
Cellular Immune Response ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
Synergistic Effects ◽  
Immunosuppressive Agents ◽  
Wide Distribution ◽  
Cellular Immune ◽  
Study Designs

A variety of drugs which are not primarily considered to be immunosuppressive agents have been described to modulate the humoral and cellular immune response in humans or animals. Thereby they may have an influence on the effectiveness and possible side effects of vaccines. This mini review lists some of the different substance classes and also some of endogeneous, infectious, nutritional, and environmental influences with suspected capability to interfere with immunizations. Studies in most cases focused on substances with known immunosuppressive functions, but there is growing evidence for immunomodulatory effects also of commonly used drugs with wide distribution. In particular combinations of those antiproliferative and antiphlogistic side effects of different substance classes have not been studied in detail but may substantially interfere with the development of a functional humoral and cellular immune response. The drugs of importance include antipyretics, anticoagulants, tranquilizers, and substances influencing lipid metabolism but also commonly used drugs of abuse like alcohol or cannabinoids. Additional substances of environmental, nutritional, or microbiological origin may also play a role but their combinatory/synergistic effects have been disregarded so far due to the lack of systematic data and the complex study designs necessary to elucidate those complex epidemiologic questions.

scholarly journals Alterations in excitatory and inhibitory synaptic development within the mesolimbic dopamine pathway in a mouse model of prenatal drug exposure

2020 ◽  
Author(s):  
Taylor Boggess ◽  
Hannah Sexton ◽  
Anna Mazur ◽  
Richard D. Egleton ◽  
Lawrence M. Grover ◽  
...  
Keyword(s):  
Mouse Model ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
Prenatal Drug Exposure ◽  
Opioid Abuse ◽  
Mesolimbic Dopamine ◽  
Synaptic Development ◽  
Microscopy Imaging ◽  
The Mean ◽  
Mesolimbic Dopamine Pathway

AbstractThe rise in rates of opioid abuse in recent years has led to an increase in the incidence of neonatal abstinence syndrome (NAS). Despite having a greater understanding of NAS and its symptoms, there still remains a lack of information surrounding the long-term effects of prenatal exposure to drugs of abuse on neurological development. One potential outcome of prenatal drug exposure that has been increasingly explored is disruption in normal synaptogenesis within the central nervous system. Both opioids and gabapentin, an antiepileptic drug commonly co-abused by opioid abuse disorder patients, have been shown to interfere with the normal functioning of astrocytes, non-neuronal glial cells known to serve many functions, including regulation of synaptic development. The goal of this study was to investigate the effects of prenatal drug exposure on synaptogenesis within brain regions associated with the mesolimbic dopamine pathway, the primary reward pathway within the brain associated with drug abuse and addiction, in a pregnant mouse model. Immunohistochemistry (IHC) and confocal fluorescence microscopy imaging studies on the brains of postnatal day 21 (P21) mouse pups revealed a significant increase in the mean number of excitatory synapses within the anterior cingulate cortex (ACC), nucleus accumbens (NAc), and prefrontal cortex (PFC) in mice that were prenatally exposed to either the opioid drug buprenorphine or gabapentin. These studies also revealed a significant decrease in the mean number of inhibitory synapses within the NAc and PFC of mice treated with buprenorphine. This observed net increase in excitatory signaling capability within the developing mesolimbic dopamine pathway suggests that exposure to drugs of abuse in utero can trigger maladaptive neuronal connectivity that persists beyond the earliest stages of life.

scholarly journals Schizophrenia and drug addiction comorbidity: recent advances in our understanding of behavioural susceptibility and neural mechanisms

2020 ◽  
Vol 2 ◽  
pp. e10
Author(s):  
Victoria Menne ◽  
Rose Chesworth
Keyword(s):  
Substance Abuse ◽  
Drug Addiction ◽  
Drug Exposure ◽  
Drugs Of Abuse ◽  
The Self ◽  
Self Medication ◽  
Receptor System ◽  
Drug Classes ◽  
Abused Drugs ◽  
Schizophrenia Susceptibility

Schizophrenia is a severe psychiatric disorder which is worsened substantially by substance abuse/addiction. Substance abuse affects nearly 50% of individuals with schizophrenia, extends across several drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants) and worsens overall functioning of patients. Prominent theories explaining schizophrenia and addiction comorbidity include the primary addiction hypothesis (i.e. schizophrenia susceptibility primes drug reward circuits, increasing drug addiction risk following drug exposure), the two-hit hypothesis (i.e. drug abuse and other genetic and/or environmental risk factors contribute to schizophrenia development) and the self-medication hypothesis (i.e. drug use alleviates schizophrenia symptoms). Animal models can be used to evaluate the utility and validity of these theories. Since this literature was last reviewed by Ng and colleagues in 2013 [Neurosci Biobehav Rev, 37(5)], significant advances have been made to our understanding of schizophrenia and substance abuse comorbidity. Here we review advances in the field since 2013, focussing on two key questions: 1) Does schizophrenia susceptibility increase susceptibility to drug addiction (assessing the primary addiction hypothesis), and 2) Do abused drugs exacerbate or ameliorate schizophrenia symptoms (assessing the two-hit hypothesis and the self-medication hypothesis). We addressed these questions using data from several schizophrenia preclinical models (e.g. genetic, lesion, neurodevelopmental, pharmacological) across drug classes (e.g. nicotine, cannabinoids, ethanol, psychostimulants). We conclude that addiction-like behaviour is present in several preclinical schizophrenia models, and drugs of abuse can exacerbate but also ameliorate schizophrenia-relevant behaviours. These behavioural changes are associated with altered receptor system function (e.g. dopaminergic, glutamatergic, GABAergic) critically implicated in schizophrenia and addiction pathology.

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