Behavioral Tolerance: Research and Treatment Implications
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Tolerance and Dependence
Tolerance and Dependence Drug Tolerance is a decrease in the effect of a drug as a consequence of repeated exposure. • Change over repeated exposures. • Different effects may show different tolerance. • Tolerance is reversible. Mechanisms of Tolerance • Pharmacokinetic Tolerance • Enzyme Induction Effects. • Pharmacodynamic Tolerance • NT depletion • Receptor Plasticity 1 Receptor Plasticity and Tolerance • Drugs that are NT agonists can cause receptor downregulation. • Drugs that are NT antagonists can cause receptor upregulation. Pharmacodynamic drug tolerance can also affect “normal” synaptic transmission. • Serious side-effect of drug use. Mechanisms of tolerance continued… Learned Tolerance - Learned behaviors compensate for drug effects. • Practice effects. • Reward and punishment . Context-Specific Tolerance • Stimuli in the environment (context) become able to counteract the effects of a drug. Pavlovian Conditioning • A neutral stimulus paired with a biologically relevant stimulus becomes able to elicit a response. Siegel et al. (1982) - Demonstrated that drug tolerance can be conditioned. 2 Group Control 15 injections of saline in distinctive room. High dose of heroin in distinctive room on Day 16. • Results: 96% died of overdose. Group Same 15 injections of heroin in distinctive room. Hig h dose o f hero in in dis tincti ve room on D ay 16 . • Results: 32% died of overdose. Group Different 15 injections of heroin in distinctive room. High dose of heroin in new room on Day 16. • Results: 64% died of overdose. Siegel’s Theory: • When an environment consistently predicts drug administration... • … the environment begins to elicit a “compensatory” response that is opposite to the drug’s effect. • The compensatory response counteracts the drug’s effect. -
AND DRUG' ABUSE' ( , \ I ., : for VOLUNTEER .AFTERCARE OFFICERS
=£q, G& ~. ~I o II g ~ L>- ".,-~..- ". 'PR'OBATIQN AND AFTERCA'RE SERVICE " rI ! ,~ i I!' 0 i! ,1 u I', :( ~ II' 1 r :.:" I I) 'tbLLECTED ,READINGS ,~ ~ - '., ,\ ON It, DR!J.GS ·AND DRUG' ABUSE' ( , \ i ., : FOR VOLUNTEER .AFTERCARE OFFICERS. ri ll, "' , 'I: o '.> .. , 4 . , . I:o..-__________:i-.._---... __ ~~ ___~;L __~ ______ fF PROBATION AND AFTERCARE SERVICE COLLECTED READUNGS ON DRUGS AND DRUG ABUSE FOR VOLUNTEER AFTERCARE OFFICERS 1977 a If' t «(, CONTENTS ARTICLE PAGE PART I - THE DRUG SCENE Speech by Dr Goh Keng Swee, Deputy Prime Minister and Minister of Defence, at the Launching of the NADAC Month at the National Theatre Or! Wedr!e~dev, 4th August 1976. 1 II Speech by Mr Chua Sian Chin, Minister for Home Affairs and Education at the Opening Ceremony of the First Meeting of ASEAN Drug Experts at the Crystal Ballroom, Hyatt Hotel, on Tuesday, 26th October 1976. 6 PART II - PREVENTIVE EDUCATION III The Objectives of Anti-Drug Abuse Education by Dr Tow Siang Hwa, Past President, Singapore Anti-Narcotics Association 8 .. PART III - DRUGS AND THEIR EFFECTS IV CommonlY Abused Drugs by Dr Yeow Teow Seng, Associate Profassor oi Pharmacology, University of Singapore 12 V The Non-Medical Uses of Dependence-Producing Drugs by Dr Leong Hon Koon 18 VI Psychiatric Aspects of Drug Abuse by Dr Paul W Ngui, Consultant Psychlatrist 23 VII Sad End to All Drug Trips by Dr Chao Tzu Cheng, Senior Forensic Pathologist, Ministry of Health 27 PART IV - SOCIAL CONSIDERATIONS OF DRUG ABUSE VIII Patterns & Social Consequences of Drug Abuse & the Rehabilitation of Drug Addict by K V Veloo, Chief Probation & Aftercare Officer 29 IX Social Factors of Drug Abuse by K V Veloo, Chief Probation & Aftercare Officer 34 f X Some Causes of Adolescent Problems , by S Vasoo, Deputy Director, Singapore Council of Social Service 39 " ,. -
How Psychoactive Drugs Affect Us
HOW PSYCHOACTIVE DRUGS AFFECT US Part II 7th February 2014 Ms. Cathy Ngarachu Physiological Responses to Drugs • Determines how drugs affect people and why it is difficult to control their levels of use. • They include: • Tolerance to Drug • Tissue Dependence • Psychological Dependence & Reward-reinforcing action of drugs • Withdrawal Tolerance • Results from the body’s attempt to eliminate a drug that it treats as a toxin • With continued drug use the body tries to neutralize the toxic effects by: • Requiring larger amounts of the drugs to achieve the original effects • Degree of effects depend on the : • Amount used • Duration of use • Frequency of use • Individual’s chemistry • State of mind Kinds of Tolerance • Dispositional Tolerance • Speeds up the metabolism to handle the drug in order to eliminate it • Example: Increases the amount of cytocells and mitochondria in the liver to neutralize the drug….. So it will take more of the drug to achieve the same level of intoxication Kinds of Tolerance • Pharmacodynamic Tolerance • Results from the desensitization of nerve cells to the action of the drug • Ex. The nerve cells become less sensitive and begin producing an antidote or antagonist to the drug, ie. The brain will generate more opiod receptor sites. Kinds of Tolerance • Behavioral Tolerance: • Brain adjustments that affect behavior • Someone who is high may make himself appear sober when threatened, then revert back to the high state • Reverse Tolerance • Person has greater sensitivity to the drug, after prolong use, and the body’s ability to metabolize the drug decreases. • Ex. A person who has drunk a 12-pack of beer daily for ten years, may find themselves drinking 3-4 beers to achieve the effect due to tissue damage of the liver and kidneys. -
Neurobiological and Neurobehavioral Mechanisms of Chronic Alcohol Drinking
Neurobiological and Neurobehavioral Mechanisms of Chronic Alcohol Drinking Neurobiological and Neurobehavioral Mechanisms of Chronic Alcohol Drinking Alcoholism comprises a set of complex behaviors seeking behaviors, have been developed. These in which an individual becomes increasingly models, which remain an integral part of the preoccupied with obtaining alcohol. These study of alcoholism, include animals that pref- behaviors ultimately lead to a loss of control over erentially drink solutions containing alcohol, consumption of the drug and to the development animals that self-administer alcohol during of tolerance, dependence, and impaired social and withdrawal, animals with a history of dependence occupational functioning. that self-administer alcohol, and animals that self- administer alcohol after a period of abstinence Although valuable information regarding toler- from the drug. Genetic models for alcoholism ance and dependence has been, and continues to also exist and include animals that have been bred be, gathered through human studies, much of the selectively for high alcohol consumption. Studies detailed understanding of the impact of exposure using such models are uncovering the systemic, to alcohol on behavior and on the biological cellular, and molecular neurobiological mech- mechanisms underlying those behaviors has been anisms that appear to contribute to chronic obtained through the use of animal models for alcohol consumption. The challenge of current alcoholism and a variety of in vitro, or cellular, and future studies is to understand which specific systems. Through the use of cellular systems and cellular and subcellular systems undergo mole- animal models, researchers can control the genetic cular changes to influence tolerance and depen- background and experimental conditions under dence in motivational systems that lead to which a specific alcohol-related behavior or chronic drinking. -
Principles of Drug Addiction Treatment: a Research-Based Guide (Third Edition)
Publications Revised January 2018 Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition) Table of Contents Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition) Preface Principles of Effective Treatment Frequently Asked Questions Drug Addiction Treatment in the United States Evidence-Based Approaches to Drug Addiction Treatment Acknowledgments Resources Page 1 Principles of Drug Addiction Treatment: A Research-Based Guide (Third Edition) The U.S. Government does not endorse or favor any specific commercial product or company. Trade, proprietary, or company names appearing in this publication are used only because they are considered essential in the context of the studies described. Preface Drug addiction is a complex illness. It is characterized by intense and, at times, uncontrollable drug craving, along with compulsive drug seeking and use that persist even in the face of devastating consequences. This update of the National Institute on Drug Abuse’s Principles of Drug Addiction Treatment is intended to address addiction to a wide variety of drugs, including nicotine, alcohol, and illicit and prescription drugs. It is designed to serve as a resource for healthcare providers, family members, and other stakeholders trying to address the myriad problems faced by patients in need of treatment for drug abuse or addiction. Addiction affects multiple brain circuits, including those involved in reward and motivation, learning and memory, and inhibitory control over behavior. That is why addiction is a brain disease. Some individuals are more vulnerable than others to becoming addicted, depending on the interplay between genetic makeup, age of exposure to drugs, and other environmental influences. -
Neuroplasticity in the Mesolimbic System Induced by Sexual Experience and Subsequent Reward Abstinence
Western University Scholarship@Western Electronic Thesis and Dissertation Repository 6-21-2012 12:00 AM Neuroplasticity in the Mesolimbic System Induced by Sexual Experience and Subsequent Reward Abstinence Kyle Pitchers The University of Western Ontario Supervisor Lique M. Coolen The University of Western Ontario Graduate Program in Anatomy and Cell Biology A thesis submitted in partial fulfillment of the equirr ements for the degree in Doctor of Philosophy © Kyle Pitchers 2012 Follow this and additional works at: https://ir.lib.uwo.ca/etd Recommended Citation Pitchers, Kyle, "Neuroplasticity in the Mesolimbic System Induced by Sexual Experience and Subsequent Reward Abstinence" (2012). Electronic Thesis and Dissertation Repository. 592. https://ir.lib.uwo.ca/etd/592 This Dissertation/Thesis is brought to you for free and open access by Scholarship@Western. It has been accepted for inclusion in Electronic Thesis and Dissertation Repository by an authorized administrator of Scholarship@Western. For more information, please contact [email protected]. NEUROPLASTICITY IN THE MESOLIMBIC SYSTEM INDUCED BY SEXUAL EXPERIENCE AND SUBSEQUENT REWARD ABSTINENCE (Spine Title: Sex, Drugs and Neuroplasticity) (Thesis Format: Integrated Article) By Kyle Kevin Pitchers Graduate Program in Anatomy and Cell Biology A thesis submitted in partial fulfillment of the requirements for degree of Doctor of Philosophy The School of Graduate and Postdoctoral Studies The University of Western Ontario London, Ontario, Canada © Kyle K. Pitchers, 2012 THE UNIVERSITY -
Selective Serotonin Reuptake Inhibitors, Fluoxetine and Paroxetine, Attenuate the Expression of the Established Behavioral Sensitization Induced by Methamphetamine
Neuropsychopharmacology (2007) 32, 658–664 & 2007 Nature Publishing Group All rights reserved 0893-133X/07 $30.00 www.neuropsychopharmacology.org Selective Serotonin Reuptake Inhibitors, Fluoxetine and Paroxetine, Attenuate the Expression of the Established Behavioral Sensitization Induced by Methamphetamine 1 1 1 1 1 ,1 Yujiro Kaneko , Atsushi Kashiwa , Takashi Ito , Sumikazu Ishii , Asami Umino and Toru Nishikawa* 1 Section of Psychiatry and Behavioral Sciences, Tokyo Medical and Dental University Graduate School, Yushima, Bunkyo-ku, Tokyo, Japan To obtain an insight into the development of a new pharmacotherapy that prevents the treatment-resistant relapse of psychostimulant- induced psychosis and schizophrenia, we have investigated in the mouse the effects of selective serotonin reuptake inhibitors (SSRI), fluoxetine (FLX) and paroxetine (PRX), on the established sensitization induced by methamphetamine (MAP), a model of the relapse of these psychoses, because the modifications of the brain serotonergic transmission have been reported to antagonize the sensitization phenomenon. In agreement with previous reports, repeated MAP treatment (1.0 mg/kg a day, subcutaneously (s.c.)) for 10 days induced a long-lasting enhancement of the increasing effects of a challenge dose of MAP (0.24 mg/kg, s.c.) on motor activity on day 12 or 29 of withdrawal. The daily injection of FLX (10 mg/kg, s.c.) or PRX (8 mg/kg, s.c.) from 12 to 16 days of withdrawal of repeated MAP administration markedly attenuated the ability of the MAP pretreatment to augment the motor responses to the challenge dose of the stimulant 13 days after the SSRI injection. The repeated treatment with FLX or PRX alone failed to affect the motor stimulation following the challenge of saline and MAP 13 days later. -
ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update
The ASAM NATIONAL The ASAM National Practice Guideline 2020 Focused Update Guideline 2020 Focused National Practice The ASAM PRACTICE GUIDELINE For the Treatment of Opioid Use Disorder 2020 Focused Update Adopted by the ASAM Board of Directors December 18, 2019. © Copyright 2020. American Society of Addiction Medicine, Inc. All rights reserved. Permission to make digital or hard copies of this work for personal or classroom use is granted without fee provided that copies are not made or distributed for commercial, advertising or promotional purposes, and that copies bear this notice and the full citation on the fi rst page. Republication, systematic reproduction, posting in electronic form on servers, redistribution to lists, or other uses of this material, require prior specifi c written permission or license from the Society. American Society of Addiction Medicine 11400 Rockville Pike, Suite 200 Rockville, MD 20852 Phone: (301) 656-3920 Fax (301) 656-3815 E-mail: [email protected] www.asam.org CLINICAL PRACTICE GUIDELINE The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update 2020 Focused Update Guideline Committee members Kyle Kampman, MD, Chair (alpha order): Daniel Langleben, MD Chinazo Cunningham, MD, MS, FASAM Ben Nordstrom, MD, PhD Mark J. Edlund, MD, PhD David Oslin, MD Marc Fishman, MD, DFASAM George Woody, MD Adam J. Gordon, MD, MPH, FACP, DFASAM Tricia Wright, MD, MS Hendre´e E. Jones, PhD Stephen Wyatt, DO Kyle M. Kampman, MD, FASAM, Chair 2015 ASAM Quality Improvement Council (alpha order): Daniel Langleben, MD John Femino, MD, FASAM Marjorie Meyer, MD Margaret Jarvis, MD, FASAM, Chair Sandra Springer, MD, FASAM Margaret Kotz, DO, FASAM George Woody, MD Sandrine Pirard, MD, MPH, PhD Tricia E. -
MRO Manual Before 2004
Note: This manual is essentially the same as the 1997 HHS Medical Review Officer (MRO) Manual except for changes related to the new Federal Custody and Control Form (CCF). The appendix has also been deleted since the new Federal Custody and Control Form is available as a separate file on the website. Medical Review Officer Manual for Federal Agency Workplace Drug Testing Programs for use with the new Federal Drug Testing Custody and Control Form (OMB Number 0930-0158, Exp Date: June 30, 2003) This manual applies to federal agency drug testing programs that come under Executive Order 12564 and the Department of Health and Human Services (HHS) Mandatory Guidelines. Table of Contents Chapter 1. The Medical Review Officer (MRO) ............................................................... 1 Chapter 2. Federal Drug Testing Custody and Control Form .......................................... 3 Chapter 3. The MRO Review Process ............................................................................ 3 A. Administrative Review of the CCF ........................................................................... 3 I. State Initiatives and Laws ....................................................................................... 15 Chapter 4. Specific Drug Class Issues .......................................................................... 15 A. Amphetamines ....................................................................................................... 15 B. Cocaine ................................................................................................................ -
Pharmacology - Neuroadaptation
Pharmacology - Neuroadaptation All drugs of dependence are associated with increased dopamine activity in the so-called reward pathway of the brain-- this pathway that gives us pleasure and tells us what's good for our survival. The overstimulation of the reward system when we use drugs of abuse, or develop an addiction, sets in motion a reinforcing pattern that teaches us to repeat the behaviour. Over time, as drug use and addiction continues and develops, the brain adapts to the overwhelming surges in dopamine. And it adapts by producing less dopamine, by reducing the number and activity of the dopamine receptors, and by essentially turning down the volume on the dopamine system. Our brain strives for balance. In some respects, we can conceptualise it as constantly adapting and changing to function in a way that we can act and feel normal, a process called homeostasis. And when we talk about homeostasis occurring in the brain, we use the term neuroadaptation. When we consume a drug, we alter the functioning of our brain. We upset the balance, and as a result, our brain tries to adapt. It tries to minimise the effect of the drug and get back to normal. If we use a drug frequently, then the brain will adapt to try and be in balance when the drug is present. But if we then stop taking the drug, our brain is no longer in balance, and it can take a really long time for the brain to re-adapt. In psychopharmacology, we refer to these processes as drug tolerance and physical drug dependence. -
Rapid and Persistent Sensitization to the Reinforcing Effects of Cocaine
Neuropsychopharmacology (2006) 31, 121–128 & 2006 Nature Publishing Group All rights reserved 0893-133X/06 $30.00 www.neuropsychopharmacology.org Rapid and Persistent Sensitization to the Reinforcing Effects of Cocaine ,1,2 2 1,2 Drake Morgan* , Yu Liu and David CS Roberts 1 2 Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA; Neuroscience Program, Wake Forest University School of Medicine, Winston-Salem, NC, USA The development of drug addiction involves a transition from recreational use to compulsive drug seeking and taking, and this progression can occur rapidly with cocaine use. These data highlight the importance of early drug exposure and the development of drug dependence; however, little experimental attention has been paid to this phenomenon in animal models of drug abuse. The present experiments demonstrate a progressive and rapid sensitization to the reinforcing strength of cocaine assessed using a progressive ratio (PR) schedule in rats. The first experiment found that rats show increased breakpoints over a 2-week period following acquisition. Subsequent experiments examined the role of total cocaine intake during the initial exposure period and found that low intakes (20 mg/ kg/day  5 days) resulted in sensitization, whereas relatively higher intake (60 or 100 mg/kg/day  5 days) suppressed the development of sensitization. In contrast, this higher level of intake (60 mg/kg/day  5 days) only transiently suppressed the expression of sensitization. Examination of breakpoints maintained by various doses of cocaine revealed an upward and leftward displacement of the cocaine dose– effect curve, relative to nonsensitized animals. -
Biological Components of Substance Abuse and Addiction
Biological Components of Substance Abuse and Addiction September 1993 OTA-BP-BBS-117 NTIS order #PB94-134624 GPO stock #052-003-01350-9 Recommended Citation: U.S. Congress, Mice of Technology Assessment, BioZogicaZ Components of Substance Abuse and Addiction, OTA-BP-BBS-1 17 (Washington, DC: U.S. Government printing Offke, September 1993). II 10[ \cllc h> 111( I Is ( l(l\ c1 Illllclll 1’1 Illllllp ( )Illcc $L1pCrlfl[L’llL! L’11[ of [)(). UIIIC’111.. \lJl[ $[t~[~ \\( )1’ \\ J.hlllg({lll. [)( ?( l~()? ‘~ ~?h ISBN 0-16 -042096-2 Foreword ubstance abuse and addiction are complex phenomena that defy simple explanation or description. A tangled interaction of factors contributes to an individual’s experimentation with, use, and perhaps subsequent abuse of drugs. Regardless of the mix of contributing factors, the actions and effectss exerted by drugs of abuse underlie all substance abuse and addiction. In order to understand substance abuse and addiction it is first necessary to understand how drugs work in the brain, why certain drugs have the potential for being abused, and what, if any, biological differences exist among individuals in their susceptibility to abuse drugs. This background paper is the first of two documents being produced by OTA as part of an assessment of Technologies for Understanding the Root Causes of Substance Abuse and Addiction. The assessment was requested by the House Committee on Government Operations, the Senate Committee on Governmental Affairs, and the Senate Committee on Labor and Human Resources. This background paper describes biological contributing factors to substance abuse and addiction. The second document being produced by this study will discuss the complex interactions of biochemical, physiological, psychological, and sociological factors leading to substance abuse and addiction.