Drug Abuse Notes

Drug Abuse

Consequences of Drug Abuse

• Homelessness
• Crime
• Violence
• Neurotoxicity
• AIDS, Cancer
• Mental Illness
• Strain on Health Care
• Loss of Productivity
• Accidents

Psychoactive Substances

• Psychoactive (psychotropic) substance: Any substance which, after absorption, influences mental processes, both cognitive and affective (emotion).
  • Stimulants: Psychoactive.
  • Suppressants: Psycho-depressants.
  • Hallucinogens: Psychotropic.

Definitions

• Substance abuse: Compulsive and recurring maladaptive behavior characterized by drug taking despite adverse socio-medical-legal consequences.
• Recreational use/negative coping.
• Substance abuse.
• Addiction.
• Dependence.
• Withdrawal.

Addiction

• Addiction: Compulsive substance use despite negative consequences.
• Medication: Some individuals abuse medication to treat illness.
• Social: Some people engage in drug use for social aspects.
• Stress: Limited coping skills to stressors.
• Economics: People who have disposable resources often abuse drugs.

Dependence Syndrome

• A strong desire or sense of compulsion to take the substance “craving”.
• Difficulties in controlling substance-taking.
• Evidence of tolerance.
• Progressive neglect of pleasures and interests.
• Persisting with substance use despite clear evidence of overtly harmful consequences.

Withdrawal State

• Symptoms occurring on absolute or relative withdrawal of a substance after repeated and prolonged use of the substance.

First Marijuana Use

• Ages:
  • <12: 1.5%
  • 12-17: 67%
  • 18-25: 5.5%
  • >25: 26%
• Addiction is a Developmental Disease: It Starts Early

Why Do People Take Drugs?

• To Feel Good
  • To have novel feelings, sensations, experiences
  • To share them
• To Feel Better
  • To lessen anxiety, worries, fears, depression, hopelessness

Four Dopamine Pathways & Schizophrenia

• Mesolimbic (SCZ - increase in DA causes positive symptoms)
• Mesocortical (SCZ - DA hypoactivity: negative & cognitive & affective symptoms)
• Nigrostriatal (Drugs - EPS & TD drug side effects)
• Tuberohypophyseal (Drugs - hyperprolactinemia side effects)

Effects of Drugs on Dopamine Release

• Graphs showing dopamine (DA), DOPAC, and HVA release in the accumbens following administration of amphetamine, cocaine, and nicotine.
• Dose-response curve for nicotine.

Psychotic Disorder-Drug Induced

• Psychotic phenomena occurring during or immediately after psychoactive substance use.
• Schizophrenia-like.
• Predominantly delusional, hallucinatory, depressive, manic.
• Persistence for more than 48 hours.

Mental Disorders Due to Use of Alcohol

• Other psychotic disorders:
  • Alcoholic hallucinations
  • Korsakov's psychosis - dementia observed during the last stages of severe chronic alcoholism; involves loss of memory
• Treatment of alcoholism
  • Withdrawal from alcohol, benzodiazepines, clomethiazol
  • Aversion therapy; Antabuse
  • Psychotherapy

Comorbidity: Drug Users and Mental Disorders

*Drug users have a higher risk of developing mental disorders

• Examples:
  • Normal population: Alcoholism (23%)
  • Alcoholism: 90%+
  • Other addictions: 90%+
  • Schizophrenia: 85%
  • Depression: 80%

Why Mental Illnesses and Substance Abuse Co-occur?

• Self-medication hypothesis:
  • Substance abuse begins as a means to alleviate symptoms of mental illness.
• Causal effects of substance abuse:
  • Substance abuse may increase vulnerability to mental illness.
• Common or correlated causes:
  • The life processes and risk factors that give rise to mental illness and substance abuse may be related or overlap.

Drug Abuse and AIDS Deaths

• 4 out of 10 U.S. AIDS deaths are related to drug abuse.

What is Addiction?

• Addiction is a Brain Disease
  • Characterized by:
    • Compulsive Behavior
    • Continued abuse of drugs despite negative consequences
    • Persistent changes in the brain’s structure and function
    • Comorbid mental health complications
    • Physical illness

Routes of Administration

• Intravenous (IV) injection: Injection of a substance directly into a vein.
• Intramuscular (IM) injection: Injection of a substance into a muscle.
• Intraperitoneal (IP) injection: Injection of a substance into the peritoneal cavity—the space that surrounds the stomach, intestines, liver, and other abdominal organs.
• Subcutaneous (SC) injection: Injection of a substance into the space beneath the skin.
• Sublingual administration: Administration of a substance by placing it beneath the tongue.
• Oral administration: Administration of a substance into the mouth, so that it is swallowed.

Sites of Drug Action

• Antagonist: A drug that opposes or inhibits the effects of a particular neurotransmitter on the postsynaptic cell.
• Agonist: A drug that facilitates the effects of a particular neurotransmitter on the postsynaptic cell.

Types of Receptors on Cells

• Postsynaptic receptor: A receptor molecule in the postsynaptic membrane of a synapse that contains a binding site for a neurotransmitter.
  • Two basic types:
    • Ionotropic receptors
    • Metabotropic receptors

Sites of Drug Action - Neurotransmitters

• Effects on Production of Neurotransmitters
  • The first step is the synthesis of the neurotransmitter from its precursors. In some cases the rate of synthesis and release of a neurotransmitter is increased when a precursor is administered; in these cases the precursor itself serves as an agonist
  • The steps in the synthesis of neurotransmitters are controlled by enzymes. Therefore, if a drug inactivates one of these enzymes, it will prevent the neurotransmitter from being produced. Such a drug serves as an antagonist

Pharmacology Definitions

• Pharmacokinetics: The process by which a drug is absorbed, distributed, metabolized, and eliminated by the body.
• Pharmacodynamics: The interactions of a drug and the receptors responsible for its action in the body.

Metabolism and Elimination

• Half-lives and Kinetics
  • Half-life:
    • Plasma half-life: Time it takes for plasma concentration of a drug to drop to 50% of initial level.
    • Whole body half-life: Time it takes to eliminate half of the body content of a drug.
  • Factors affecting half-life:
    • Age
    • Renal excretion
    • Liver metabolism
    • Weight

Popular Drugs of Abuse

• Heroin
• Cocaine
• Ecstasy (methylenedioxymethamphetamine)
• GHB (Gamma-hydroxybutyrate)
• Rohypnol (Flunitrazepam)
• Ketamine (anesthetic for humans and animals)
• Methamphetamine
• LSD (Lysergic Acid Diethylamide 25)

Heroin

• Heroin comes from a “flower”, the opium poppy.
• Neurotransmitter system: Endogenous opioids (endorphin and enkephalin agonist).
• Heroin's half-life is estimated to be 30 minutes.
• Nearly half of young people who inject heroin surveyed in three recent studies reported abusing prescription opioids before starting to use heroin.
• Heroin is a depressant drug, which means it slows down the CNS.

Cocaine

• Cocaine is a psychoactive alkaloid of the coca plant and a naturally occurring local anesthetic.
• Cocaine is a strong hallucinogenic stimulant used as a recreational drug. It is commonly snorted, inhaled, or injected into the veins.
• Induces: Feelings of euphoria, Increased energy, Grandiosity; inflated self-esteem, Elevated mood.
• Cocaine acts by blocking the reuptake of DA, and 5-HT, so it is an Agonist.
• It has a half-life of 60 minutes.

Ecstasy (MDMA)

• Ecstasy is an illegal stimulant and hallucinogenic drug, Agonist of the 5-HT system.
• Long-lasting brain damage affecting thought and memory.
• Damage to portions of the brain that regulate learning, sleep and emotion.
• Degenerated nerve branches and nerve endings.
• Depression, anxiety, memory loss.
• Kidney failure, Hemorrhaging, Psychosis, Cardiovascular problems, Convulsions.
• Half-life is 7 hours.

Gamma Hydroxybutyrate ($C<em>4H</em>8O_3$)

• GHB is a central nervous system (CNS) depressant that is commonly referred to as a “club drug” or “date rape” drug and “Scoop”.
• Effects include: euphoria, increased sex drive.
• Negative effects may include sweating, loss of consciousness, nausea, hallucinations, amnesia, and coma.
• GHB acts at two receptor sites in the brain, the GABA and specific GHB receptors. GHB is naturally occurring in the CNS.
• It’s half-life ranges from 30 to 60 minutes.

Rohypnol

• Flunitrazepam, also known as Rohypnol, is a drug acting as a benzodiazepine used in some countries to treat severe insomnia
• Half life 3 hours
• Enhancement of GABA neurotransmission, GABA agonist
• Rohypnol is a tranquilizer and induces sedation, muscle relaxation, reduction in anxiety, and prevention of convulsions.

Ketamine

• Inducing anesthesia (lack of sensation or feeling).
• It works in the brain to inhibit painful sensations, and is both a depressant and hallucinogenic drug
• A half-life of 10 to 15 minutes
• Rapid surge in two important neurotransmitters— glutamate and GABA, agonist

Methamphetamine

• Acts on DA and 5-HT system, agonist
• It is a stimulant psychotic drug
• The Methamphetamine metabolite peaks at 12 hours
• Methamphetamine is a powerful, highly addictive stimulant that affects the central nervous system.

Cannabinoids

• Acts on DA and 5-HT system, agonist, but also endo-cannabinoids (Anandamide)
• Stimulant; Depressant
• The THC metabolites peak at 3-10 minutes
• There is a clear relationship between the use of cannabis and psychosis.

Dangers of Prescription Drug Abuse

• Increase blood pressure or heart rate
• Damage the brain and other organs
• Lead to accidental overdose / poisonings
• Cause physical dependency and/or addiction
• Disrupt breathing (respiratory depression)
• Cause seizures and even death

Other Forms of Addiction - Excessive Smartphone Use

• Excessive smartphone use is associated with the use of cigarettes, alcohol, and other substances; reporting of anxiety and feeling low increases the odds of excessive smartphone use in pre-adolescents.

Other Forms of Addiction - Internet Gaming Disorder

• Internet gaming disorder: Playing on-line games for ≥ 240 minutes/day. Associated with depressive symptoms and ADHD symptoms.
• Higher attachment/bonding and social support can alleviate.