DRUG ADDICTION PRESENTED BY HEIDEL MAY MAGDALES GELLE

DRUG ADDICTION PRESENTED BY: HEIDEL MAY MAGDALES GELLE DE LEON ANNE LORREINE REYES BSP-4 A

Pharmacology • Scientific study of drugs Psychoactive Drugs that influence subjective experience and behavior by acting on the nervous system.

Four ways of drug administration: 1. ) Oral ingestion – preferred route of administration for many drugs. Two main advantages: a. ) its ease b. ) relative safety Disadvantage: unpredictability

Four ways of drug administration: 2. ) Injection – is common in medical practice because the effects of injected drugs are strong, fast, and predictable a. ) subcutaneously (SC) – into the fatty tissue b. ) intramuscularly (IM) – into large muscles c. ) intravenously (IV) – directly into veins

Four ways of drug administration: 3. ) Inhalation – absorbed into the bloodstream through the rich network of capillaries in the lungs 4. ) Through Mucous Membranes - through mucous membranes of the nose, mouth, and rectum

blood-brain barrier • • Protective filter Makes it difficult for many potentially dangerous blood-borne chemicals to pass from the blood vessels of the CNS into its neurons

Mechanisms of Drug Action § § Act diffusely on neural membranes throughout the CNS Binds to particular synaptic receptors Influences the synthesis, transport, release, or deactivation of particular neurotransmitters Influences the chain of chemical reactions elicited in postsynaptic neurons by the activation of their receptors

Drug Metabolism/Elimination § § Conversion of active drugs to non-active forms Eliminates a drug’s ability to pass through lipid membranes of cells so that it can no longer penetrate the blood-brain barrier

Drug Tolerance § Is a state of decreased sensitivity to a drug that develops as a result of exposure to it. Demonstrated in two ways: 1. ) A given dose of drug has less effect. 2. ) It takes more of the drug to produce the same effect.

Drug Tolerance • • Cross tolerance – one drug can produce tolerance to other drugs that act on the same mechanism Drug sensitization – increase sensitivity to a drug Metabolic tolerance – drug tolerance that results from changes that reduce the amount of the drug getting to sites of action Functional tolerance – drug tolerance that results from changes that reduce the reactivity of the sites of action

Withdrawal Syndrome - adverse physiological reaction triggered by sudden elimination of a certain drug Physically dependent - individuals who suffer withdrawal reactions when they stop taking a drug

Addicts - Are those habitual drug users who continue to use drug despite its adverse effects on their health and social life, and despite their repeated efforts to stop using it

Role of Learning in Drug Tolerance a. ) Contingent Drug Tolerance – refers to demonstrations that tolerance develops only to drug effects that are actually experienced b. ) Conditioned Drug Tolerance – refers to demonstration that tolerance effects are maximally expressed only when a drug is administered in the same situation in which it has previously been administered

Role of Learning in Drug Tolerance b. 1) Conditioned Compensatory Responses – opposing conditional responses - as the stimuli that repeatedly predict the effects of a drug come to elicit greater and greater conditioned compensatory responses, they increasingly counteract the unconditional effects of the drug and produce situational specific tolerance Exteroceptive Stimuli – external, public stimuli Interoceptive Stimuli – internal, private stimuli

Five Commonly Abused Drugs

1. ) Tobacco Nicotine – major psychoactive ingredient of tobacco Tar – collective term for the other 4000 chemicals Compulsive Drug Craving – major defining feature of addiction � Nonsmokers often respond to a few puffs of a cigarette with various combinations of nausea, vomiting, coughing, sweating, abdominal cramps, dizziness, flushing, and diarrhea. In contrast, smokers report that they are more relaxed, more alert, and less hungry after a cigarette.

1. ) Tobacco � Smoking reduces tension. However, smokers are actually more tense than smokers. � Individuals who live or work with smokers are more likely to develop heart disease and cancer than those who don’t Smoking Risks: a. ) Smoking during pregnancy increases the likelihood of miscarriage, stillbirth, and early death of the child. b. ) Smoker’s syndrome – characterized by chest pain, labored breathing, wheezing, coughing, and a heightened susceptibility to infections of respiratory tract.

1. ) Tobacco c. ) Chronic smokers are highly susceptible to a variety of potentially lethal lung disorders: pneumonia, bronchitis (inflammation of bronchioles of the lungs), emphysema (loss of elasticity of the lung from chronic irritation), lung cancer d. ) Increases the risk of cancer in the larynx (voice box), mouth, esophagus, kidneys, pancreas, bladder, and stomach. e. ) Greater risk of developing a variety of cardiovascular diseases, which may culminate heart attack or stroke

2. ) Alcohol molecules are small and soluble in both fat and water, they invade all parts of the body. Classified as a depressant because at moderates-tohigh doses it depresses neural firing, however at low doses it can stimulate neural firing and facilitate social interaction Moderate dose – alcohol drinker experiences various degrees of cognitive, perceptual, verbal and motor impairment, as well as a loss of control that can lead to variety of socially unacceptable actions

2. ) Alcohol High Dose – result in unconsciousness, and if blood vessels reach 0. 5%, there is a risk of death from respiratory depression. The telltale red facial flush of alcohol intoxication is produced by the dilation of blood vessels in the skins, this dilation increases the amount of heat that is lost from the blood to the air and leads to a decrease in body temperature (hypothermia) Alcohol is diuretic because it increases the production of urine in the kidneys.

2. ) Alcohol Withdrawal – hangover – mild headache, nausea, vomiting, and tremulousness Three phase: 1. ) First phase - begins at 5 -6 hours after the cessation of a long bout of heavy drinking 2. ) Second phase – typically occurs between 15 and 30 hours after cessation of drinking, convulsive activity 3. ) Third Phase – begins a day or two after the cessation of drinking and lasts for 3 -4 days – Delirium Tremens: characterized by disturbing hallucinations, bizarre delusions, agitation, confusion, hyperthermia (high body temperature), & tachycardia (rapid heartbeat)

2. ) Alcohol Risks: a. ) Chronic alcohol consumption produces extensive brain damage. b. ) Korsakoff’s Syndrome – neuropsychological disorder characterized by memory loss, sensory and motor dysfunction, and in its advanced stages, severe dementia c. ) Cirrhosis - extensive scarring of the liver, which is the major cause o death among heavy alcohol users d. ) Fetal Alcohol Syndrome – cause of pregnant woman who consume substantial quantities of alcohol - brain damage, mental retardation, poor coordination, poor muscle tone, low birth weight, retarded growth, physical deformity

3. ) Marijuana Name commonly given to the dried leaves and flowers of Cannabis Sativa-the common hemp plant THC (delta-9 -tetrahydrocannabinol) – attributes to the psychoactive effects of marijuana Hashish- extracted from resin and dried down to form a dark corklike material Hash Oil – processed hashish Marijuana was legally classified as a narcotic – legal term generally used to refer to opiates

3. ) Marijuana At high doses, short-term memory is impaired, and the ability to carry out tasks involving multiple steps to reach a specific goal declines. Minority of marijuana smokers who smoke it regularly tend to develop respiratory problems: cough, bronchitis, and asthma. Long-term heavy use of marijuana has effects that are far less severe than those of its legal cousins: nicotine and alcohol. Marijuana use causes permanent memory loss.

3. ) Marijuana Causes schizophrenia Block seizures, to dilate the bronchioles of asthmatics, to decrease the severity of glaucoma (a disorder characterized by an increase in te pressure of the fluid inside the body), and to reduce anxiety and some kinds of pain. Anandamide – first endocannabinoid neurotransmitter to be isolated and characterized

4. Cocaine and Other Stimulants – are dugs whose primary effect is to produce general increases in neural and behavioral activity Cocaine – prepared from the leaves of the coca bush Coca Paste – a crude extract from the coca bush Cocaine Hydrochloride – nefarious white powder that is simply referred as cocaine Crack – potent, cheap, smokable form of cocaine

4. Cocaine and Other Stimulants Cocaine Sprees – binges in which extremely high levels of intake are maintained for periods of a day or two Cocaine Psychosis – syndrome of psychotic behavior observed during cocaine sprees § Amphetamine is usually consumed orally in the potent form called d-amphetamine (dextroamphetamine) § Amphetamine Psychosis – syndrome produced

4. Cocaine and Other Stimulants § § Metamphetamine – commonly used in its even more potent, smokable, crystalline form 3, 4 -methylenedioxy-metamphetamine – ecstasy Crack Cocaine Psste

5. ) The Opiates: Heroin and Morphine Opium – the sap that exudes from the seeds of the opium poppy Opiates – common term for morphine, codeine, and other drugs that have similar structures or effects - exert their effects by binding to receptors whose normal function is to bind to endogenous opiates - two classes of receptors: endorphins & enkephalins

5. ) The Opiates: Heroin and Morphine Dr. Jekyll side, the opiates are unmatched as analgesics (painkillers), and they are extremely effective in the treatment of cough and diarrhea. Morphine addiction was known as Soldier’s addiction. Opium was an ingredient in cakes, candies, and wines, as well as in a variety of over-the-counter medical offerings. The Harrison Narcotics Act, passed in 1914, made it illegal to sell or use opium, morphine, or cocaine in the US—although morphine and its analogues are still legally prescribed for their medical properties.

5. ) The Opiates: Heroin and Morphine Heroin – semisynthetic opiate – synthesized by the addiction of two acetyl groups to the morphine molecule, which greatly increased its ability to penetrate the blood-brain barrier. Heroin Rush – is a wave of intense abdominal, orgasmic pleasure that evolves into a state of serene, drowsy euphoria. Methadone – primary treatment for heroin addiction

5. ) The Opiates: Heroin and Morphine Buprenorphine – approved for the treatment of heroin addiction – has a high and long-lasting affinity for opiate receptors and thus blocks the effects on the brain of other opiates, without producing powerful euphoria.

Physical-Dependence Theories of Addiction Physical dependence traps addicts in a vicious circle of drug taking and withdrawal symptoms Drug users whose intake has reached a level sufficient to induce physical dependence are driven by their withdrawal symptoms to self-administer the drug each time they attempt to curtail their intake. Detoxified Addicts – are addicts who have no drugs in their bodies and who are no longer experiencing withdrawal symptoms

Two reasons why detoxification fail as treatment for addiction: 1. ) Some highly addictive drugs, such as cocaine and amphetamines, do not produce severe withdrawal distress. 2. ) The pattern of drug taking routinely displayed by many addicts involves an alternating cycle of binges and detoxification.

Positive-Incentive theories of addiction Was based on the assumption that most addicts take drugs not to escape or to avoid the unpleasant consequences of withdrawal, but rather to obtain the drug’s positive effects. Hold that the primary factor in most cases of addiction is the craving for the positive-incentive (expected pleasure-producing) properties of the drug.

Incentive-Sensitization Theory Robinson and Berridge (2003) – it isn’t the pleasure (liking) of drug taking per se that it is the basis of addiction; it is the anticipated pleasure (wanting) of drug taking They must explain why there is often such a big difference between the hedonic value of drug taking and the positiveincentive value of drug taking. They must explain the process that transforms a drug user into a drug addict. Positive-Incentive Value – refers specifically to the anticipated pleasure associated with an action Hedonic Value – refers to the amount of pleasure that is actually produced.

Relapse To return to one’s drug taking habit after a period of voluntary abstinence 3 different causes of relapse: 1. ) stress is a major factor in relapse. 2. ) Drug priming – a single exposure to the formerly abused drug 3. ) exposure to environmental cues (people, times, places, or objects that have been associated with drug taking)

Intracranial Self Stimulation Rats, humans, and many other species will administer brief bursts of weak electrical stimulation to specific sites in their own brains. Olds & Milner (1954) – argued that the specific brain sites that mediate self-stimulation are those that normally mediate the pleasurable effects of natural rewards (food, water, sex) Pleasure Centers – brains sites capable of mediating the phenomenon

Intracranial Self Stimulation Unitary phenomenon – its fundamental properties were the same regardless of the site of stimulation. The circuits mediating intracranial self-stimulation are natural reward circuits. � � � Brain stimulation through electrodes that mediate self-stimulation often elicits a natural motivated behaviors such as eating, drinking, or copulation in the presence of the appropriate goal object. Producing increases in natural motivation often increases selfstimulation. It became clear that differences between the situations in which the rewarding effects of brain stimulation an those of natural rewards were usually studied contribute to the impression that these effects are qualitatively different.

Mesencephalic Dopamine System Plays an important role in intra-cranial self-stimulation Is a system of dopaminergic neurons that projects from the mesencephalon into various regions of the telencephalon Have their cell bodies in two midbrain nuclei – substantia nigra and ventral tegmental area Nigrostriatal Pathway - most of the axons of dopaminergic neurons have their cell bodies in the substantia nigra and project to the dorsal striatum

Mesocortioclimbic pathway – axons of the dopaminergic neurons that have their cell bodies in the ventral tegmented area project to various cortical and limbic sites - plays an important role in mediating intracranial self-stimulation It is the particular neurons that project from the ventral tegmented area to the nucleus accumbens that have been most frequently implicated in the rewarding effects of brain stimulation. Natural rewards, and addictive drugs.

Drug self-administration Paradigm laboratory rats or primates press a lever to inject drugs into themselves through implanted cannulas (thin tubes). Conditioned place-preference paradigm • rats repeatedly receive drug in one compartment (the drug compartment) of a two-compartment box • Subjects are tested while they are drug-free, which means that the measure of the incentive value of a drug is not confounded by the other effects the drug might have on behavior

Dopamine transporters Are molecules in the presynaptic membrane of dopaminergic neurons that attract dopamine molecules in the synaptic cleft and deposit them back inside the neuron. * Cocaine has its agonistic effects on dopamine by binding to these transporters, blocking reuptake, and thus increasing extracellular dopamine levels. * As dopamine levels in the nucleus accumbens increased in response to the amphetamine injection, the subjects reported a parallel increases in their experience of euphoria.

Dopamine release in the Nucleus Accumbens: Reward or Expectation of Reward? Originally, dopamine release in the nucleus accumbens was assumed to be related to the experience of reward. Neural stimuli that signal the impending delivery of a reward (food or an addictive drug) can themselves trigger dopamine release in the nucleus accumbens Dopamine release in the nucleus accumbens is related to the expectation of a reward, rather than its experience. Stimuli that signal rewards can develop rewarding properties of their own Dopamine levels in the nucleus accumbens do reflect reward value, but not in a straightforward fashion.

Brain Mechanisms of Drug Addiction : Recent Development 1. ) Addiction is Psychologically Complex Drug addicts differ psychologically from healthy controls in a variety of ways. Drug Addicts have been found to make poor decisions, to engage in excessive risk taking, and to have deficits in self-control 2. ) Addiction Involves Many Parts of the Brain §Prefrontal cortex is of great interest because addicts display a pattern of behaviors typical of those who have sustained damage to that area §Prefrontal cortex receives input from the ventral tegmented area

3. ) Addiction Involves Many Neurotransmitters § § Glutamate has a role in addiction (Kailvas, 2004) – of particular interest are prefrontal glutaminergic neurons that project into the nucleus accumbens. Endogenous opiods, norepinephrine, GABA, and endocannabinoids 4. ) Addiction is Not Limited to Drugs § the inability to refrain from a behavior despite its adverse effects

Three stages of Drug Addiction 1. ) Initial Drug Taking Thought to be mediated in much the same was as any pleasurable activity, with the mesocorticolimbic pathway— in particular, he nucleus accumbens—playing a key role Prefrontal lobes play a major role in the decision to take a drug; hippocampus and related structures are assumed to provide information about previous relevant experiences, and the amygdala is thought to coordinate the positive or negative emotional reactions to the drug taking

2. ) Change to Craving and Compulsive Drug taking develops into a habit and then to a compulsion; that is, despite its numerous adverse effects, drug taking starts to dominate the addict’s life. Striatum reacts to drugs and drug associated cues Dorsal striatum- an area that is known to play a role in habit formation and retention Prefrontal cortex in controlling drug-related behaviors apparently declines, and stress circuits in the hypothalamus begin to interact with the dorsal striatum

3. ) Relapse Priming doses of the drug, drug associated cues, and stress Prefrontal cortex mediates priming-induced relapse Amygdala mediates conditional cue-induced relapse Hypothalamus mediates stress-induced relapse