Drugs addiction

Drug Addiction and the Brain's Reward Circuits

Basic Principles of Drug Action

  • Psychoactive drugs: Drugs that influence subjective experience and behavior by acting on the nervous system.

  • Drug administration: The route of administration influences the rate and degree to which the drug reaches its site of action.

Drug Administration

  • Ingestion:
      - Oral route: Easy and relatively safe but absorption via the digestive tract is unpredictable.

  • Injection: Bypasses the digestive tract.
      - Subcutaneous (SC): Under the skin.
      - Intramuscularly (IM): Into large muscles.
      - Intravenously (IV): Into veins; drug is delivered directly to the brain.

  • Inhalation:
      - Tobacco and Marijuana: Absorbed through capillaries in lungs.

  • Absorption through mucous membranes:
      - Nose, mouth, rectum, eyes.

Mechanisms of Drug Action

  • Antagonists vs. Agonists:
      - Agonists: Drugs that activate receptors to produce a biological response.
      - Antagonists: Drugs that block receptors and inhibit biological responses.

Physiological Aspects of Drug-Taking Behavior

  • Three main aspects:
      - Blood-Brain Barrier: A selective barrier that protects the brain but also restricts drug passage.
      - Physiological basis for drug tolerance: Variation in individual tolerance levels.
      - Drug influences on neuronal activity: Particularly in the region of the nucleus accumbens in the brain.

Blood-Brain Barrier & Drugs

  • Restricts the passage of drugs from the bloodstream to the brain.

  • Key factor for passage: Fat solubility of the drug.
      - Highly fat-soluble drugs: Pass easily into the brain (e.g., nicotine, alcohol, cocaine, barbiturates, caffeine, heroin).
      - Low fat-solubility: Drugs like penicillin cannot effectively enter the brain.

  • Implications for treatments:
      - Cannot use low fat-soluble dopamine to treat Parkinson’s; instead utilize L-Dopa, a fat-soluble precursor.

Drug Tolerance

  • Definition of drug tolerance: A shift in the dose-response curve to the right due to prior exposure to the drug.

Cross Tolerance

  • Definition: Reduced sensitivity to a drug as a result of exposure; can transfer to similar drugs.

  • Reason for cross-tolerance: Metabolic tolerance where the body adjusts to compensate for the drug.

  • Functional or Cellular Tolerance: Exposure alters the drug's effects at the cellular or functional level.

Drug Withdrawal Effects and Physical Dependence

  • Occur upon termination of drug use.

  • Withdrawal symptoms: Generally the opposite of the drug’s effects.

  • Compensatory body changes: Body adjusts to function normally with the drug's presence.

  • Severity of withdrawal: Varies according to the drug and usage pattern.

Drug Dependence

  • Two key elements in the rewarding effects of psychoactive drugs:
      - Dopamine: A critical neurotransmitter involved in the brain's reward circuitry.
      - Nucleus accumbens neurons: Particularly important in reinforcing the effects of drug use.

  • Dopamine activates GABAergic neurons in the nucleus accumbens, contributing to the reinforcing effects of many abused drugs.

  • Substances that block dopamine eliminate the desire to obtain these drugs.

  • Mesocorticolimbic pathway: A pathway in the brain associated with reward and addiction.

  • Variation in the number of dopamine receptors may explain susceptibility to addiction; those with fewer receptors are more vulnerable.

Addiction: What Is It?

  • Definition: Individuals who continue using a drug despite its negative effects on their health and social life.

  • Types of dependence:
      - Psychological dependence: Emotional withdrawal symptoms and cravings.
      - Physiological dependence: Physical withdrawal symptoms manifest after cessation of drug use.

  • Cravings may persist even after withdrawal symptoms have subsided.

  • Continue to take the drug to make you feel better. In order for the symptoms to go away people take the addictive substance to avoid withdrawal.

Relapse and Its Causes

  • Stress: Often leads individuals to use drugs as a coping mechanism.

  • Priming: A single exposure can trigger a relapse.

  • Environmental cues:
      - Conditioned drug tolerance, situational specificity, which may lead back to craved drugs.
      - Returning to places where drugs were previously used can induce compensatory responses leading to cravings and relapse.

  • Addiction takes time.

Five Commonly Abused Drugs

  • Tobacco

  • Alcohol

  • Marijuana

  • Cocaine

  • Opiates

Tobacco

  • Nicotine: The primary psychoactive ingredient in tobacco.

  • Addiction statistics: Approximately 70% of individuals who experiment with smoking become addicted; about 20% of attempts to quit are successful.

  • Physiological effects include the release of various hormones and neurotransmitters such as Ach, NE, DA, and beta-endorphins, which can relax and lower stress and arousal responses.

Alcohol

  • CNS Depressant: Alcohol is classified as a central nervous system depressant affecting nearly every tissue in the body.

  • Heritability estimate: ~50% chance of developing alcohol addiction.

  • Tolerance development: Both metabolic and functional tolerance.

  • Whats the tolerances effect- the deminishing affect over time.

Effects of Chronic Alcohol Consumption

  • Withdrawal Symptoms: Severe withdrawal occurs in three phases:
      - 5-6 hours after quitting: Tremors, nausea, sweating, vomiting, etc.
      - 15-30 hours after quitting: Convulsive activity.
      - 24-48 hours after quitting: Delirium tremens, lasting 3-4 days.

  • Long-term effects include Korsakoff’s Syndrome, Cirrhosis (liver), and Fetal alcohol syndrome affecting children from mothers who were heavy alcohol users during pregnancy.

Marijuana

  • Cannabis sativa: The plant from which marijuana is derived.

  • THC (Tetrahydrocannabinol): The primary psychoactive constituent along with over 80 additional components.

  • Effects of high doses: Impairs short-term memory and interferes with tasks that require multiple steps.

  • Addiction potential: Relatively low compared to other drugs; long-term use has been linked with mental illness, lower academic achievement, and decreased birth weight in children of users.

  • Smoke one joint is the equivalent of smoke 5 cigarettes. After two hours after getting high, your reaction time and response time is hindered. Which makes you slower to react.

Medicinal Uses of Marijuana/THC

  • Pain reduction, nausea relief, seizure blockage, bronchodilation for asthmatics, and decreased severity of glaucoma.

Cocaine & Other Stimulants

  • Definition: Stimulants increase neural and behavioral activity.

  • Addiction: Highly addictive, with tolerance developing for some effects and sensitization to motor effects.

  • Medicinal use: Cocaine is used as a local anesthetic; however, synthetic analogs like procaine and lidocaine have become more common due to the disadvantages of cocaine.

  • Cocaine binges: May lead to cocaine psychosis, resembling paranoid schizophrenia symptoms.

Medical Uses of Cocaine

  • Accepted only as a local anesthetic for surgeries involving the nasal, tear duct, and throat regions.

  • Mechanism: Blocks transmission of nerve impulses through local vasoconstriction.

  • Disadvantages: Quick breakdown and possible absorption into the bloodstream, leading to intense vasoconstriction.

Opiates: Heroin and Morphine

  • Sources: Morphine and codeine derived from the opium poppy.

  • Definition of opiates: Drugs and their derivatives with similar structures or effects.

  • Medicinal uses: Analgesics for pain relief, treatment for cough and diarrhea.

  • Risk: High potential for addiction.

Categories of Opiates

  • Natural Opiates: Opium, morphine, codeine, thebaine.

  • Opiate Derivatives: Heroin, hydromorphone (Dilaudid), oxymorphone (Numorphan), oxycodone (Percodan, Percocet), hydrocodone (Hycodan, Vicodin).

  • Synthetic Opiates: Methadone, meperidine, propoxyphene, LAAM, tramadol, buprenorphine.

How Opiates Work in the Brain

  • Activation of morphine-sensitive receptors in the brain leads to the effects of morphine and similar drugs.

  • Naloxone: The most complete opiate antagonist which can reverse respiratory depression and low blood pressure within a minute, particularly in cases of narcotic overdose.

Variation in State Naloxone and Good Samaritan Laws (As of October 24, 2017)

  • Prescription by Standing Order Authorized: 43 states allow non-medical personnel to issue naloxone as of 7/2017.

  • Prescriber Liability Protection: 34 states have laws protecting naloxone prescribers from civil and criminal liability (as of 7/2017).

  • Good Samaritan Law: 10 states prevent arrest for drug possession or paraphernalia possession when calling 911 for assistance (as of 12/2016).

Hazards of Tobacco, Alcohol, Marijuana, Cocaine, and Heroin

  • Public health impact: Alcohol and tobacco associated with the most significant health risks.

  • Prevalence of drug use in the United States: Based on surveys of individuals aged 12 years and older who used the drug within the last month (data sourced from the National Survey on Drug Use and Health, 2011).

From Acute Toxicity to Chronic Toxicity

  • Chronic Toxicity: Refers to the physiological harm a drug may cause with long-term use.

  • Definition: The long-term adverse effects on health and functioning due to sustained drug exposure.