Addiction and Drug Addiction and Drug AbuseAbuse

ByBy

S.Bohlooli, PhDS.Bohlooli, PhD

Cultural ConsiderationCultural Consideration

Licit or Illicit ?!Licit or Illicit ?! Resultant criminal activity leads to make an Resultant criminal activity leads to make an

agent considered as illicit.agent considered as illicit. Activity like: robbery, prostitution and other Activity like: robbery, prostitution and other

antisocial activity.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) Agent (drug) AvailabilityAvailability CostCost Purity/potencyPurity/potency Mode of administration:Mode of administration:

Chewing (absorption Chewing (absorption viavia oral mucous membranes) oral mucous membranes) GastrointestinalGastrointestinal IntranasalIntranasal Subcutaneous and intramuscularSubcutaneous and intramuscular Intravenous Intravenous Inhalation Inhalation

Speed of onset and termination of effectsSpeed of onset and termination of effects Pharmacokinetics: combination of agent and hostPharmacokinetics: combination of agent and host

Host (user)Host (user) HeredityHeredity

Innate toleranceInnate tolerance Speed of developing acquired toleranceSpeed of developing acquired tolerance Likelihood of experiencing intoxication as Likelihood of experiencing intoxication as

pleasurepleasure Psychiatric symptomsPsychiatric symptoms Prior experiences/expectationsPrior experiences/expectations Propensity for risk-taking behaviorPropensity for risk-taking behavior

EnvironmentEnvironment

Social settingSocial setting Community attitudesCommunity attitudes

Peer influence, role modelsPeer influence, role models Availability of other reinforcers (sources of Availability of other reinforcers (sources of

pleasure or recreation)pleasure or recreation) Employment or educational opportunitiesEmployment 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-VII. Co-administration/Co-abuseabuse

Many of these drugs are used in combination with Many of these drugs are used in combination with other drugs from one or more categories.other drugs from one or more categories. Alcohol is used, for example, with almost Alcohol is used, for example, with almost

everything else.everything else. Smoking (nicotine intake) is prevalent in patients Smoking (nicotine intake) is prevalent in patients

using other drugs.using other drugs.

Be aware of the possibility of combination of drugs Be aware of the possibility of combination of drugs when treating intoxication, withdrawal or overdose, when treating intoxication, withdrawal or overdose, each drug will require a specific treatment. each drug will require a specific treatment.

Neurobiology of Abused DrugsNeurobiology of Abused Drugs

Many drugs acts through G protein coupled Many drugs acts through G protein coupled receptor (dopamine, opioid and cannabinoid)receptor (dopamine, opioid and cannabinoid)

Chloride Ion channel associated with GABA Chloride Ion channel associated with GABA (benzodiazepines)(benzodiazepines)

Excitatory amino acid receptors Excitatory amino acid receptors (phencyclidine)(phencyclidine)

I. Animal StudiesI. Animal Studies

A)A) Drug-self administrationDrug-self administration Drugs as reinforcers in Drugs as reinforcers in

animals.animals. High correlation withHigh correlation with

human dependencehuman dependence

liability.liability.

Morphine/HeroinMorphine/Heroin

Self-AdministrationSelf-Administration

II. Brain Reward SystemII. Brain Reward SystemChanges in brain function => Reward=> CravingChanges in brain function => Reward=> Craving

Involve the Dopaminergic SystemInvolve the Dopaminergic System Mesolimbic pathway:Ventral tegmental area Mesolimbic pathway:Ventral tegmental area

(VTA), medial forebrain bundle, nucleus (VTA), medial forebrain bundle, nucleus accumbens and the prefrontal cortex.accumbens and the prefrontal cortex.

Nigrostriatal pathway: Sustantia nigra, Nigrostriatal pathway: Sustantia nigra, striatum.striatum.

Mesocortical pathway: VTA, cingulate and Mesocortical pathway: VTA, cingulate and frontal CTX.frontal CTX.

Tubero-Infundibular: Arcuate N. in Tubero-Infundibular: Arcuate N. in hypothalamus.hypothalamus.

THE DOPAMINERGIC SYSTEMTHE DOPAMINERGIC SYSTEM

THE MESOLIMBIC DOPAMINERGIC REWARD PATHWAY

Dopamine Synapse

DA

L-DOPA

Tyrosine

Tyrosine

Dopamine Reuptake System

Alcohol consumption Alcohol consumption

SedationSedation Relief of anxietyRelief of anxiety Slurred speechSlurred speech AtaxiaAtaxia Impaired judgmentImpaired judgment Disinhebited behaviorDisinhebited behavior

Alcohol Withdrawal Syndrome

Alcohol craving Confusion

Tremor, irritability Visual hallucinations

Nausea Fever, profuse sweating

Sleep disturbance Tachycardia

Tachycardia Nausea, diarrhea

Hypertension Dilated pupils

Sweating Severe agitation

Perceptual distortion

Seizures (12 to 48 hours after last drink)

Delirium tremens (rare in uncomplicated withdrawal)

Benzodiazepine Withdrawal SymptomsFollowing 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 useClinical aspect of opioid use

Rush: an orgasm like reactionRush: an orgasm like reaction EuphoriaEuphoria Feeling of tranquility and sleepinessFeeling of tranquility and sleepiness

Opioid WithdrawalSYMPTOMS SIGNS  

Regular Withdrawal  

Craving for opioids Pupillary dilation  

Restlessness, irritability Sweating  

Increased sensitivity to pain Piloerection ("gooseflesh")  

Nausea, cramps Tachycardia  

Muscle aches Vomiting, diarrhea  

Dysphoric mood Increased blood pressure  

Insomnia, anxiety Yawning  

Fever  

Protracted Withdrawal  

AnxietyInsomniaDrug craving

Cyclic changes in weight, pupil size, respiratory center sensitivity  

CNS stimulantsCNS stimulants

Clinical aspects of stimulantsClinical aspects of stimulants

RushRush Mental alertnessMental alertness Marked euphoriaMarked 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 foodLack of food Lack of sleepLack of sleep

Cocaine Withdrawal Symptoms and Signs

Dysphoria, depression

Sleepiness, fatigue

Cocaine craving

Bradycardia

Clinical effect of marijuanaClinical effect of marijuana

Being highBeing high EuphoriaEuphoria Uncontrollable laughterUncontrollable laughter Alteration of time senseAlteration of time sense DepersonalizationDepersonalization Sharpened visionSharpened vision Late: becoming relaxed, experience of introspective and Late: becoming relaxed, experience of introspective and

dream-like effectdream-like effect Difficulty in concentration and thinkingDifficulty in concentration and thinking

Marijuana Withdrawal Syndrome

Restlessness

Irritability

Mild agitation

Insomnia

Sleep EEG disturbance

Nausea, cramping

Drugs Kill the Brain