Addiction and Drug Abuse By S.Bohlooli, PhD

Cultural Consideration Licit or Illicit ?! Licit or Illicit ?! Resultant criminal activity leads to make an agent considered as illicit. Resultant criminal activity leads to make an agent considered as illicit. Activity like: robbery, prostitution and other antisocial activity. Activity like: robbery, prostitution and other antisocial activity.

Drug Misuse A drug might be used for a wrong indication, or wrong dosage, and or too long period Drug Abuse abuse might be construed as any use of drug for non medical purpose

substance dependence (addiction) cluster of symptoms indicating that the individual continues use of the substance despite significant substance-related problems.

PHYSICAL AND PSYCHOLOGICAL DEPENDENCE Physical dependence is a state that develops as a result of the adaptation (tolerance) produced by a resetting of homeostatic mechanisms in response to repeated drug use. Psychological dependence is manifested by compulsive drug seeking behavior in which the individual uses the drug repetitively for personal satisfaction often in the face of known risks to health

Tolerance is the most common response to repetitive use of the same drug and can be defined as the reduction in response to the drug after repeated administrations

Types of Tolerance Innate (preexisting sensitivity or insensitivity) Acquired Pharmacokinetic (dispositional or metabolic) Pharmacodynamic Learned tolerance  Behavioral Conditioned Acute tolerance Reverse tolerance (sensitization) Cross-tolerance

Origins of Substance Dependence Agent (drug) Host (user) Environment

Agent (drug) Availability Availability Cost Cost Purity/potency Purity/potency Mode of administration: Mode of administration: Chewing (absorption via oral mucous membranes) Chewing (absorption via oral mucous membranes) Gastrointestinal Gastrointestinal Intranasal Intranasal Subcutaneous and intramuscular Subcutaneous and intramuscular Intravenous Intravenous Inhalation Inhalation Speed of onset and termination of effects Speed of onset and termination of effects Pharmacokinetics: combination of agent and host Pharmacokinetics: combination of agent and host

Host (user) Heredity Heredity Innate tolerance Innate tolerance Speed of developing acquired tolerance Speed of developing acquired tolerance Likelihood of experiencing intoxication as pleasure Likelihood of experiencing intoxication as pleasure Psychiatric symptoms Psychiatric symptoms Prior experiences/expectations Prior experiences/expectations Propensity for risk-taking behavior Propensity for risk-taking behavior

Environment Social setting Social setting Community attitudes Community attitudes Peer influence, role models Peer influence, role models Availability of other reinforcers (sources of pleasure or recreation) Availability of other reinforcers (sources of pleasure or recreation) Employment or educational opportunities Employment or educational opportunities

Withdrawal Syndrome Withdrawal signs and symptoms occur when drug administration in a physically dependent person is abruptly terminated. Withdrawal symptoms have at least two origins: (1) removal of the drug of dependence, (2) central nervous system hyperarousal due to readaptation to the absence of the drug of dependence.

VII. Co-administration/Co- abuse Many of these drugs are used in combination with other drugs from one or more categories. Many of these drugs are used in combination with other drugs from one or more categories. Alcohol is used, for example, with almost everything else. Alcohol is used, for example, with almost everything else. Smoking (nicotine intake) is prevalent in patients using other drugs. Smoking (nicotine intake) is prevalent in patients using other drugs. Be aware of the possibility of combination of drugs when treating intoxication, withdrawal or overdose, each drug will require a specific treatment. Be aware of the possibility of combination of drugs when treating intoxication, withdrawal or overdose, each drug will require a specific treatment.

Neurobiology of Abused Drugs Many drugs acts through G protein coupled receptor (dopamine, opioid and cannabinoid) Many drugs acts through G protein coupled receptor (dopamine, opioid and cannabinoid) Chloride Ion channel associated with GABA (benzodiazepines) Chloride Ion channel associated with GABA (benzodiazepines) Excitatory amino acid receptors (phencyclidine) Excitatory amino acid receptors (phencyclidine)

I. Animal Studies A) Drug-self administration Drugs as reinforcers in animals. Drugs as reinforcers in animals. High correlation with High correlation with human dependence liability.

Morphine/Heroin Self-Administration

II. Brain Reward System Changes in brain function => Reward=> Craving Involve the Dopaminergic System Mesolimbic pathway:Ventral tegmental area (VTA), medial forebrain bundle, nucleus accumbens and the prefrontal cortex. Mesolimbic pathway:Ventral tegmental area (VTA), medial forebrain bundle, nucleus accumbens and the prefrontal cortex. Nigrostriatal pathway: Sustantia nigra, striatum. Nigrostriatal pathway: Sustantia nigra, striatum. Mesocortical pathway: VTA, cingulate and frontal CTX. Mesocortical pathway: VTA, cingulate and frontal CTX. Tubero-Infundibular: Arcuate N. in hypothalamus. Tubero-Infundibular: Arcuate N. in hypothalamus.

THE DOPAMINERGIC SYSTEM

THE MESOLIMBIC DOPAMINERGIC REWARD PATHWAY

Dopamine Synapse DA L-DOPA Tyrosine

Dopamine Reuptake System

Alcohol consumption Sedation Sedation Relief of anxiety Relief of anxiety Slurred speech Slurred speech Ataxia Ataxia Impaired judgment Impaired judgment Disinhebited behavior Disinhebited behavior

Alcohol Withdrawal Syndrome Alcohol cravingConfusion Tremor, irritabilityVisual hallucinations NauseaFever, profuse sweating Sleep disturbanceTachycardia Nausea, diarrhea HypertensionDilated pupils SweatingSevere agitation Perceptual distortion Seizures (12 to 48 hours after last drink) Delirium tremens (rare in uncomplicated withdrawal)

Benzodiazepine Withdrawal Symptoms Following moderate dose usage Anxiety, agitation Increased sensitivity to light and sound Paresthesias, strange sensations Muscle cramps Myoclonic jerks Sleep disturbance Dizziness Following high-dose usage Seizures Delirium

Nicotine Withdrawal Syndrome Irritability, impatience, hostility Anxiety Dysphoric or depressed mood Difficulty concentrating Restlessness Decreased heart rate Increased appetite or weight gain

Clinical aspect of opioid use Rush: an orgasm like reaction Rush: an orgasm like reaction Euphoria Euphoria Feeling of tranquility and sleepiness Feeling of tranquility and sleepiness

Opioid Withdrawal SYMPTOMSSIGNS Regular Withdrawal Craving for opioidsPupillary dilation Restlessness, irritabilitySweating Increased sensitivity to painPiloerection ("gooseflesh") Nausea, crampsTachycardia Muscle achesVomiting, diarrhea Dysphoric moodIncreased blood pressure Insomnia, anxietyYawning Fever Protracted Withdrawal Anxiety Insomnia Drug craving Cyclic changes in weight, pupil size, respiratory center sensitivity

CNS stimulants

Clinical aspects of stimulants Rush Rush Mental alertness Mental alertness Marked euphoria Marked euphoria Delusion (bugs are crawling under skin!) Delusion (bugs are crawling under skin!) Spree use ( up to 4000 mg /day amphetamine) Spree use ( up to 4000 mg /day amphetamine) Lack of food Lack of food Lack of sleep Lack of sleep

Cocaine Withdrawal Symptoms and Signs Dysphoria, depression Sleepiness, fatigue Cocaine craving Bradycardia

Clinical effect of marijuana Being high Being high Euphoria Euphoria Uncontrollable laughter Uncontrollable laughter Alteration of time sense Alteration of time sense Depersonalization Depersonalization Sharpened vision Sharpened vision Late: becoming relaxed, experience of introspective and dream-like effect Late: becoming relaxed, experience of introspective and dream-like effect Difficulty in concentration and thinking Difficulty in concentration and thinking

Marijuana Withdrawal Syndrome Restlessness Irritability Mild agitation Insomnia Sleep EEG disturbance Nausea, cramping

Drugs Kill the Brain