Drug Addiction and the Brain's Reward Circuits

Psychoactive Drugs of Abuse: An Overview

Campbell Ims, a PhD candidate in the School of Psychological Sciences, discusses drug addiction and the brain's reward circuits. The lecture is divided into three parts:

  1. Summary of Psychoactive Drugs: Key features, mechanisms, psychoactive effects, and health hazards of popular substances.

  2. Drug Tolerance and Withdrawal: Differentiation of addiction from habitual or recreational use, criteria for physical dependence and addiction.

  3. Brain-Based Accounts of Drug Use: Focus on reward circuitry like the nucleus accumbens and associated brain reward networks.

Australian Drug Trends

A snapshot of principal drugs of concern in Australia from 2009 to the present indicates:

  • Alcohol consumption has decreased from nearly 50% to 36%.

  • Amphetamine use has significantly increased from under 10% to about 28%.

These trends underscore the necessity for continuous research and intervention to address the unique effects and required interventions for various drugs.

Drug Classes and Their Effects

Psychoactive drugs influence experience and behavior by acting on the nervous system. Drug classes aren't mutually exclusive; some drugs may have effects spanning multiple categories.

Depressants

  • Alcohol (Ethanol): Primarily a CNS depressant with some stimulant properties.

  • Benzodiazepines: Less emphasized but still relevant.

Stimulants

  • Cocaine

  • Nicotine

  • Amphetamines: A major area of concern.

  • Caffeine: Also included in this category.

Psychedelics

  • LSD (Acid)

  • Psilocybin (Magic Mushrooms)

  • Ketamine: Primarily a dissociative with secondary psychedelic effects.

  • MDMA: Primarily an empathogen with some psychedelic effects.

Opioids

  • Heroin

  • Codeine

  • Methadone

  • Oxycodone

  • OxyContin

  • Fentanyl: Significant global concern.

Cannabinoids

  • Cannabis

Detailed Look at Specific Drugs

The lecture will explore these drugs in detail, covering effects, withdrawal symptoms, and treatment approaches.

Alcohol (Ethanol)

An active ingredient in alcoholic beverages, primarily a central nervous system (CNS) depressant.

  • Effects: In the short term, alcohol increases extracellular dopamine levels in brain reward circuits indirectly via neurotransmitters like GABA and glutamate.

    • Euphoria

    • Relaxation

    • Increased confidence (disinhibition)

    • Anxiety (in some cases)

    • Mood boost or dampener

    • Difficulty concentrating

    • Motor impairments

    • Sedation

  • Chronic Effects: Prolonged alcohol use leads to neuroadaptation, suppressing neurotransmitter activity (dopamine, serotonin, norepinephrine).

  • Withdrawal Symptoms: Occur when the brain has adapted to chronic alcohol exposure and alcohol consumption has stopped.

    • Sweating

    • Tremors

    • Rapid heartbeat

    • Nausea

    • Anxiety

    • Difficulty sleeping

    • Irritability

    • Seizures and delusions (in severe cases)

  • Treatment Approaches: Interventions for managing alcohol dependence.

    • Detoxification: Tapering off alcohol consumption.

    • Counseling and group therapy

    • Pharmacotherapy:

      • Disulfiram: A deterrent that causes violent illness if alcohol is consumed after taking the medication.

      • Acamprosate: Targets withdrawal symptoms, aiding abstinence.

      • Naltrexone: Minimizes cravings by reducing the pleasurable effects of alcohol.

Nicotine

A central nervous system (CNS) stimulant, with cognitive and affective impacts.

  • Effects: Increased alertness and cognitive benefits, relaxation, stimulation, reduced appetite, and interference with REM sleep.

  • Withdrawal Symptoms:

    • Irritability

    • Anxiety

    • Difficulty concentrating

    • Increased appetite

    • Cravings

    • Depressed mood

    • Restlessness

    • Sleep disturbances

  • Treatment Approaches:

    • Nicotine Replacement Therapy: Patches, gum, and lozenges.

    • Pharmacotherapy: Works to treat cravings and promote abstinence.

    • Psychotherapy: Including CBT.

    • Behavioral Support: Including counseling and support groups.

Cocaine

A central nervous system (CNS) stimulant with the short lasting effects

  • Effects: Directly affects dopamine signaling at the mesolimbic structures. Cocaine binds to dopamine transporters, blocking dopamine reuptake in the synaptic cleft. Prolonging dopaminergic effects.

    • Feeling physically strong and mentally sharp

    • Feeling energetic, alert, happy and confident

    • Reduced appetite

    • Higher blood pressure, faster heartbeat

    • Increased sex drive

    • Insomnia

  • Withdrawal Symptoms:

    • Depression

    • Anxiety

    • Lack of energy

    • Inability to feel pleasure

    • Fatigue

    • Irritability

    • In severe cases, paranoia, mood swings, and exhaustion.

  • Treatment Approaches:

    • Detoxification

    • Counseling, and group therapy

    • Antiepileptic medications can be trialed to reduce craving and consumption patterns.

Opioids

Highly addictive drugs that bind to opioid receptors in the brain.

  • Examples: Heroin, morphine, fentanyl, oxycodone, and oxycontin

  • Effects: Indirectly stimulate dopamine release. Opioid drugs bind to the receptors for the endogenous opioids, supercharging this effect.

    • Euphoria or a high, an intense orgasmic state.

    • Checking out through a sense of drowsiness

    • Slowed breathing

    • Reduced pain signaling.

  • Withdrawal Symptoms: Profound negative emotional and physical symptoms.

    • Restlessness and body discomfort

    • Chills

    • Pain, a severe flu-like syndrome

    • Sweating

    • Intestinal distress

    • Extreme cases: seizures which can be fatal.

  • Treatment Approaches:

    • Replacement therapies (e.g., methadone) to taper off opioid use.

Pharmacokinetics

How the body processes the drug.

  • Absorption: The process by which a drug enters the bloodstream.

  • Distribution: The spread of the drug throughout the body.

  • Metabolism: The breakdown of the drug into different molecules.

  • Elimination: The removal of the drug and its metabolites from the body.

Routes of Administration

  • Oral Ingestion: Predictable and reliable but relatively slow and inefficient. Good absorption: lipid-soluble drugs, like alcohol, and acidic drugs, like aspirin. Poor absorption: Alkaline drugs, like heroin and cocaine

  • Inhalation: Faster than oral ingestion; bypasses the gastrointestinal tract.

  • Absorption: Through nasal, oral, or rectal membranes. Sniffing or snorting drugs is fast because of the density of receptors in the nasal passages and the short route directly to the brain, and then to the blond.

  • Injection: Directly into the bloodstream, is very fast and is efficient because the drug goes straight to the blood.

Bioavailability

The extent to which a drug is available to the body, influenced by its lipid solubility and ability to cross the blood-brain barrier.

Elimination

  • Biotransformation: Active drug converted into other molecules, generating metabolites.

  • First-Order Elimination: Rate of elimination is proportionate to the drug concentration.

  • Zero-Order Elimination: Fixed rate over time, irrespective of drug concentration (e.g., alcohol).

  • Half-Life: Time taken for the body to eliminate half of the drug amount in the blood.

Pharmacodynamics

The drug's effect on the body, focusing on the drug's effects on receptors and its biochemical and physiological impacts.

Factors Determining Drug Response

Metabolism, genetically determined, significantly affects drug responses. Examples include:

  • Normal Metabolizer: Typical amount of enzyme, processes drug effectively.

  • Slow Metabolizer: Too little enzyme, drug builds up, potential side effects.

  • Fast Metabolizer: Too much enzyme, drug broken down too quickly, little symptom improvement.

Drug Testing

Screens different drug types. Urine tests are the most common. Other tests are blood tests, sweat, saliva, and hair.

Testing directly in the system, the drug presence in the blood has a shorter detection window because of their half lives, and essentially confirms drug presence. Testing for metabolites, the residual molecules after a drug has been processed and broken down, necessarily has a longer detection window than testing in the blood, but is less precise, and opens the door for false positives and false negatives.

Psychopharmacology

Considers how pharmacokinetics and pharmacodynamics interact to influence an individual's response to a drug. Factors such as dosing, body weight, route of administration, bioavailability, interferences, interactions, and metabolism all play critical roles in determining who gets more intoxicated from the same amount of alcohol.