Neuroscience of Drug Addiction - Exam 1

What is a drug?

A chemical substance that is used primarily to bring about a change to some existing process or state, be it psychological, or biochemical

• ‘ a foreign chemical substance that produces an effect in an organism

Drug Action

The process by which a drug interacts with biological systems to produce a physiological effect

• The molecular changes

Drug Effect

Alterations in physiological or psychological function resulting from the drugs action

Therapeutic Effect

The desired beneficial effect of a drug, intended to treat or alleviate a medical condition.

Side Effect

An unintended consequence of a drug that can be harmful or beneficial, occurring alongside the therapeutic effect.

Pharmacology

The branch of science that deals w/ the actions of drugs on living organisms

Psychopharmacology

The branch of science that deals w/ the influence of drugs on mood, thinking, & behavior

• the study of ‘mental effects’

Neuropharmacology

The branch of science that deals w/ the influence of drugs on the nervous system

• study of the ‘physical effects’

Neuropsychopharmacology

The branch of science that deals w/ the influence of drugs on the brain, behavior, & psychological function

• the most specialized

Can food be considered a drug?

Yes, in some scenarios if it alters mood, perception, or behavior through its biochemical effects on the brain and body, similar to how traditional drugs function

• Ex) Caffeine, aphrodisiacs, & those associated w/ eating disorders

Psychoactive Drugs

Substances that affect mental processes (e.g. perception, consciousness, cognition, or mood & emotions)

• does not necessarily imply dependence-producing

CNS Stimulants

Substances that increase activity in the central nervous system, enhancing alertness, attention, and energy levels

What are some examples of CNS stimulants?

• Amphetamines

• Cocaine

• Nicotine

• Caffeine.

CNS Depressants

Substances that decrease activity in the central nervous system, leading to reduced alertness, relaxation, and sedation.

What are some examples CNS depressants?

• Barbiturates

• Alcohol

Analgesics

Substances that relieve pain without causing loss of consciousness, often used to manage chronic pain conditions.

What are some examples of analgesics?

• Opioids

• NSAIDS

• Morphine

• Codeine

Hallucinogens

Substances that induce alterations in perception, mood, and cognitive processes, often leading to hallucinations.

What are some examples of hallucinogens?

• LSD

• Mescaline

• Psilocybin

Psychotherapeutics (a.k.a psychotropics)

Substances used to treat mental health disorders, including antidepressants, antipsychotics, and mood stabilizers.

What are some examples of psychotherapeutics?

• Prozac

• Thorazine

• Lithium

• Zoloft

• Cymbalta

What are the five classes of psychotropics?

• Antipsychotics

• Antidepressants

• Anxiolytics

• Hypnotics

• Mood Stabilizers

Antipsychotics

Medications used to manage symptoms of psychosis, such as delusions or hallucinations

• often prescribed for conditions like schizophrenia and bipolar disorder.

Antidepressants

Medications that are primarily used to treat depression and anxiety disorders by balancing chemicals in the brain.

Anxiolytics

Medications used to reduce anxiety and promote calmness, often prescribed for generalized anxiety disorder and panic disorders.

Hypnotics

Medications that induce sleep or sedation, often used to treat insomnia and other sleep disorders.

Mood Stabilizers

Medications used to treat mood disorders, particularly bipolar disorder, by helping to balance mood swings and stabilize emotional states.

Illicit Drugs

Substances that are illegal to use, sell, or possess, often associated with addiction and various health risks.

Dietary Supplement

A product intended to add nutritional value to the diet

What are some examples of dietary supplements?

• Vitamins

• Minerals

• Herbs/botanicals

• Amino acids

• substances for increasing the total dietary intake

• A concentrate, metabolite, constituent, or extract

Generic/Non-proprietary Name

The official name of a drug that is not protected by trademark and is recognized worldwide, often used to identify the active ingredients.

Brand/Trade Name

The name given to a product by its manufacturer, often trademarked, that distinguishes it from other products.

What’s the difference between psychoactive & psychotropic drugs?

Psychoactive drugs are substances that affect the brain's function and alter mood, perception, or consciousness, while psychotropic drugs specifically refer to those that are used to treat mental health disorders and can influence psychological states.

Schedule of Controlled Substances in the US

A classification system that regulates drugs based on their potential for abuse and medical use, categorizing them into schedules from I to V.

Schedule I Substances

Substances with no accepted medical use and a high potential for abuse,

• Includes: heroin, LSD, mescaline, marijuana, THC, & MDMA

Schedule II Substances

Substances with a high potential for abuse w/ severe psychic or physical dependence liability

• Some accepted medical uses, s

• Includes: cocaine, morphine, codeine, opium, PCP, and oxycodone.

Schedule III Substances

Substances with a moderate to low potential for physical and psychological dependence relative to schedules I & II

• Includes compounds containing limited quantities of certain narcotics & non-narcotic drugs

• Some accepted medical uses

• Includes: anabolic steroids, ketamine, and certain barbiturates.

Schedule IV Substances

Substances with a low potential for abuse and low risk of dependence (lower than those in SIII).

• Includes: alprazolam (Xanax), diazepam (Valium), and lorazepam.

Schedule V Substances

Substances with a lower potential for abuse than Schedule IV, with limited physical or psychological dependence

• Includes: medications like cough preparations containing less than 200 mg of codeine per 100 mL, Robitussin, Lomotil, Motofen, Lyrica, etc.

Does the rate at which a drug circulates w/in the body & its mode of delivery impact the likelihood of addiction?

Yes, faster circulation and certain delivery methods, such as injection or smoking, can increase the likelihood of addiction.

What is the difference between drug abuse & drug addiciton?

Drug abuse refers to the harmful or hazardous use of psychoactive substances, while drug addiction is a chronic condition characterized by compulsive drug seeking and use, despite harmful consequences.

Drug Abuse

The harmful or hazardous use of psychoactive substances, often leading to negative consequences in various aspects of life.

• A drug’s ability to be misused

Drug Addiction

A complex, chronic, & relapsing disorder characterized by compulsive (& at times uncontrollable) drug seeking/craving, continued use despite harmful consequences, loss of control in limiting intake, emergence of a negative emotional state (e.g. dysphoria, anxiety, irritability), and long-lasting changes in the brain

• a drug’s ability to form a dependency

What are the differences between the DSM-IV & DSM-V criteria for substance abuse, substance dependence, & substance use disorder?

The DSM-IV distinguished between substance abuse and substance dependence, while the DSM-V combined these into a single diagnosis called substance use disorder, with varying severity levels based on specific criteria.

Substance Use Disorder

A condition characterized by an individual's inability to control their use of substances, resulting in significant impairment or distress.

• “A continuum of problematic use”

• based on 11 specific substance-related criteria.

  • Amount, Control, Time, Cravings, Obligations, Social, Activities, Hazard, Harm, Tolerance, & Withdrawal

Risky Use

A pattern of substance use that increases the likelihood of harmful consequences, such as using in dangerous situations or despite physical or psychological problems.

• individuals may not have problems yet but are at a high risk for developing them if current level of use continues

How is addiction a cycle?

Addiction is often described as a cycle where individuals repeatedly engage in substance use, leading to temporary pleasure followed by negative consequences.

• This cycle reinforces the behavior, as individuals seek to alleviate withdrawal symptoms or cravings, resulting in a pattern of compulsive use despite adverse effects.

What are some examples of ‘addiction’ in regard to behavioral disorders that do not involve substance use?

• Gambling addiction

• Sex addiction

• Food addiction

• Internet addiction

Pharmacokinetics

The study of how drugs are absorbed, distributed, metabolized, and excreted by the body

• the ‘what does the body do to the drug?’

• examines how a drug moves through the body

• how is the drug absorbed?

• how is the drug metabolized?

• how is the drug distributed?

• how is the drug excreted?

Pharmacodynamics

The study of how drugs affect the body, including mechanisms of action and therapeutic effects.

• the ‘what does the drug do to the body’

• it explores the relationship between drug concentration and its effect on the organism.

Bioavailability

The proportion of a drug that enters the circulation when introduced into the body and is available for therapeutic effect

How does the pharmacokinetic characteristics of a drug determine its bioavailability?

By affecting the rate and extent of drug absorption, distribution, metabolism, and excretion, ultimately determining how much of the drug reaches systemic circulation.

Routes of Drug Administration

• Oral

• Intravenous

• Intraperitoneal

• Subcutaneous

• Intramuscular

• Inhalation

Enteral

Refers to drug administration that involves the gastrointestinal tract, typically through oral (PO) or rectal routes.

Parenteral

Refers to drug administration that bypasses the gastrointestinal tract, typically through injection methods such as intravenous, intramuscular, or subcutaneous routes.

First Pass Metabolism

The process by which the concentration of a drug is significantly reduced before it reaches systemic circulation, primarily occurring in the liver after oral administration.

Hepatic Portal System

A network of veins that carries blood from the digestive organs to the liver, allowing for the processing of nutrients and drugs before they enter systemic circulation.

Why must drug companies take metabolites into consideration?

Because they can influence the drug's efficacy, safety, and overall pharmacokinetics, potentially leading to adverse effects or altered therapeutic outcomes.

Metabolites

The products of drug metabolism that can affect the pharmacological activity and toxicity of the original substance.

What are the advantages of oral (PO) administration?

• Easy to use, non-invasive, & convenient

• Allows for self-administration

• Provides a slower absorption rate, which can lead to more stable drug levels in the bloodstream.

What are the disadvantages of oral administration?

• First-pass metabolism

• Stomach acid

• Poor control/unpredictable

• Slow rise

What are the advantages of injection?

• Rapid onset (especially IV)

• Precise

What are the disadvantages of injection?

• Rapid onset!

• Infection

Injection

Method of drug administration that delivers substances directly into the bloodstream, providing a fast and effective route for achieving therapeutic effects.

• several different types, including: IM, subcutaneous, IV, & intradermal

• different types of injections require different angles of administration

• drug absorption rate depends on the rate of blood-flow

Intraperitoneal (IP)

A method of drug administration where substances are injected into the peritoneal cavity, allowing for rapid absorption into the bloodstream.

Intracranial (IC)

A method of drug administration where substances are injected directly into the brain or cranial cavity, enabling precise targeting of neural tissues.

Intracerebroventricular (ICV)

A method of drug administration where substances are injected into the cerebroventricular system, allowing for direct access to the brain's ventricles and rapid effects on the central nervous system.

What routes of injection are typically used in research?

Common routes include:

• intraperitoneal (IP)

• intracranial (IC)

• intracerebroventricular (ICV)

Inhalation

A method of drug administration where substances are vaporized and inhaled into the lungs, allowing for rapid absorption into the bloodstream.

What are the advantages of inhalation?

• Rapid onset of effect (effect can be w/in seconds)

What are the disadvantages of inhalation?

• Irritation

• Damage to the lungs

Intra-Nasal

A method of drug administration where substances are absorbed through the nasal mucosa, providing a rapid onset of effects.

What are the advantages of intra-nasal administration?

• Painless/easy

• Bypasses BBB

• Drug does not need to be dissolved

What are the disadvantages of intra-nasal administration?

• Perforation of the nasal septum (depending on the drug)

• Inflammation

• Irritation

Transdermal

A method of drug delivery where substances are absorbed through the skin, allowing for a steady release of medication over time.

Sublingual

A method of drug administration where substances are placed under the tongue for absorption into the bloodstream through the mucous membranes.

Rectal

A method of drug administration where substances are inserted into the rectum for absorption through the rectal mucosa.

Why does the route of drug administration matter?

Because it affects the drug's absorption rate, distribution, metabolism, and overall efficacy in the body.

• different routes can lead to varying onset times and intensities of drug action.

What routes of administration allow for the highest blood concentrations?

IV, IM, and inhalation

Therapeutic Window

The range of drug dosages that produces the desired effect without causing toxicity.

• It is critical for ensuring safety and efficacy in drug therapy.

Plasma Concentration

The amount of drug present in the bloodstream at a given time, influencing the drug's effects and therapeutic outcomes.

What should be considered when selecting the route of administration?

• Physical characteristics

• Speed of absorption required & onset

• Need to bypass first-pass/hepatic metabolism

• Required concentration at site of action

What is the relationship between duration of action & speed of onset?

Generally, drugs with a rapid onset may have a shorter duration of action, and vice versa, depending on their pharmacokinetics.

Which routes of administration have the highest chance to be abused?

Routes that provide rapid onset, such as intravenous or inhalation, typically due to the immediate effects they produce.

Drug Absorption

The process by which a drug enters the bloodstream, influencing its bioavailability and onset of action.

What factors does the absorption of a drug affect?

• Rate at which the drug reaches its site

• Peak concentration attained

Factors that Affect Absorption:

• Route of administration

• Blood circulation at site (vascularization)

• Surface area available

• GI activity (gastric emptying time, intestinal transit time, presence of food, mesenteric blood flow)

  • some drugs meant to be ingested w/ food take longer to absorb

• Amount of drug destroyed (e.g. stomach) or metabolized (e.g. liver)

• Body fluid volume

• Drug solubility

• Drug ionization (charge)

• Binding to inactive sites and other physiological factors such as pH level.

Depot Binding

The process by which a drug binds to inactive sites in the body, affecting its distribution and availability in the bloodstream.

Eligible to cross the membrane:

• Lipid-soluble

• Neutral

• Small molecules

Ineligible to cross the membrane:

• Water-soluble

• Charged

• Big (> 500 Da, but there are exceptions)

Simple Diffusion

The process by which substances move across a cell membrane from an area of higher concentration to an area of lower concentration without the need for energy or transport proteins.

Passive Transport

The movement of molecules across a cell membrane without the use of energy, typically down their concentration gradient, often facilitated by transport proteins.

Active Transport

The process of moving molecules across a cell membrane against their concentration gradient, requiring energy, often in the form of ATP, and involving specific transport proteins.

Bioactivation

The process by which a substance is converted into a pharmacologically active form after administration, often involving metabolic modifications.

Ionization Status

Refers to the degree to which a substance is ionized in a given environment, influencing its solubility and permeability across cell membranes.

Drug Ionization

The extent to which a drug becomes ionized in a specific environment, affecting its absorption and distribution in the body.

• most drugs are weak acids or bases - becoming ionized (charged) when dissolved in a solution - & can exist in both ionized and non-ionized forms

More Ionized

a drug becomes more charged, decreasing its ability to permeate cell membranes and affecting its absorption.

• less absorption = less effect

Less Ionized

a drug becomes less charged, often leading to increased lipid solubility and better absorption in certain environments.

• better absorption = more effect

What determines the degree of ionization?

The pH of the environment and the pKa of the drug influence the affecting the drug's absorption and distribution.

• the more acidic or basic the drug is, the less ionized it will be

Ion Trapping

A phenomenon where the ionization of a drug is influenced by the pH of different body compartments, leading to the accumulation of the drug in one compartment over another.

• this determines where a drug:

  • is best absorbed

  • can concentrate in one compartment