PSY 383 Psychoactive Drugs Lecture Notes PDF

Lecture 1- Introduction Animal & Drugs Alcohol from Fermented Fruits ○ Apes, like chimpanzees, sometimes seek alcohol rich fruits ○ Elephants are known to indulge in over ripe marula fruit Pufferfish Toxin ○ Adolescent dolphin known to gently chew on and...

Lecture 1- Introduction Animal & Drugs Alcohol from Fermented Fruits ○ Apes, like chimpanzees, sometimes seek alcohol rich fruits ○ Elephants are known to indulge in over ripe marula fruit Pufferfish Toxin ○ Adolescent dolphin known to gently chew on and pass around pufferfish to get high Earliest Uses of Psychoactive Substances Alcohol ○ 7000-6000 BCE - Fermented beverages in Jiahu, China Cannabis ○ 2700 BCE - Medicinal and ritual use in ancient China Psilocybin Mushrooms and Peyote Cactus ○ 3700 BCE - Spiritual and healing use by Native American Tribes Cocoa Leaves ○ 3000 BCE - Indigenous use in the Andes region of South America Ancient Cultural Impact of Drug Use Dependence & Withdrawal ○ Ancient records document symptoms, especially w/ substances like alcohol and opium Evolving Impact Over Time Scientific Advances ○ Isolation, synthesis, and classification of actives compounds, leading to more potent and diverse drugs 18th-19th Century Substances Use Medical Marvels ○ Opium, Cocaine, and Morphine were hailed as groundbreaking medical treatments for pain, anxiety and various ailments The Fight Against Microbes Paul Erlich - late 1800s ○ Found that dyes had selective affinity for different cell types Receptor Theory ○ Act like a key lock to let material into the cell Mass production of penicillin for D-day The Early Psychiatrist Asylums became more heavily utilized in late 1800’s ○ Senile elderly, patients with syphilis and other neurological disorders, alcoholics.. Etc The Use of “Physical Treatments” Water Therapies ○ High pressure showers and prolonged baths Injections ○ Extract of sheep thyroid ○ Metallic salts ○ Horse serum ○ Arsenic Removing teeth Fever therapies and deep-sleep treatments The Trio of “Miracle Cures” 1930-40 Insulin Coma Therapy ○ Injected w/ high dose of insulin to induce coma and brought back with injection of glucose ○ “The short circuits of the brain vanish, and the normal circuits are once more restored and bring back with them sanity and reality” NYT Convulsive Therapies ○ Metrazol poison or electric shock used to induce seizure Frontal Lobotomy ○ “This surgery of the soul transformed wild animals into gentle creatures in the course of a few hours” Thorazine Starts the Revolution Company produces a more potent version - Thorazine ○ Disconnects brain regions that control motor movements and emotional responses Minor Tranquilizers Sold as Miltown and Librium widely to the general public ○ First market anti-anxiety medication A Pill for Depression Hoffman - La Roche investigates left over rocket fuel from WW2 for antimicrobe properties ○ Identifies 2 compounds that are effective against microbe that causes Tuberculosis (TB) (iproniazid) Chemical Imbalance Theories A drug called reserpine produced depression like symptoms (lethargy and apathy) ○ Found to reduce levels of serotonin, norepinephrine, dopamine (catecholamines) 1965 Joseph Schildkraut proposes the chemical imbalance theory of affective disorders Putting These Theories to the Test Repeated attempts have been made to show that depressed patients are suffering from low levels of serotonin Lecture 2 - Addiction Changes Over Time 1952: Addiction seen as a moral failing or personality defect 1965: AMA recognizes alcoholism as a disease 2019: Acknowledged as a chronic disease influenced by brain circuits, genetics, environments, and life experiences Bio-Psycho-Social Spheres of Influence No one thing that causes addiction ○ Constellation of factors contributes to risk for addiction Stages of Addiction 1. Initiation a. The individual tries a substance for the first time i. Usually linked to curiosity or peer pressure b. Majority of people tried their drug of choice before 18 and had a substance disorder 20 2. Experimentation a. The user is now taking the drug in different contexts to see how it impacts their life b. Little to no cravings for the drug 3. Regular Use a. Use becomes normalized and grows from periodic to regular use b. Does not mean that they use it every day but there is a pattern associated with it c. Craving and reliance have begun i. Quitting becomes harder 4. Risky Use a. Regular use has to continued to grow and is now frequently having a negative impact on their life b. Common behaviors: i. Attempting to hide drug use ii. Changing peer groups  iii. Losing interest in old hobbies 5. Dependence a. Drug use is no longer recreational or medical and the person is becoming reliant b. This stage should only be marked by a dependence c. Physical dependence i. If use abruptly stops, the body will react by entering withdrawal d. Psychological dependence i. Believes that they need the drug to be able to function like a normal person 6. Addiction a. Compulsively lie about their drug use when questioned and are quickly agitated if their lifestyle is threatened in any way i. Do not recognize how their behaviors are detrimental and the effects that they have had on their relationships 7. Crisis and Treatment a. The addict is at the highest-risk of suffering a fatal overdose or another dramatic life event Opponent Processes - Pleasure and Withdrawal Initial Use ○ The drug creates strong positive effects (euphoria) without immediate biological counteraction Body’s Adaptation ○ Over time, the body starts counteracting the drug’s effects, reducing euphoria and leading to tolerance Tolerance & Withdrawal ○ The body’s counteraction becomes stronger, leading to withdrawal symptoms when the drug wears off After Stopping ○ The body gradually reduces its counteraction, but withdrawal may continue until the system rebalances S-R Habit and Reinforcement Stimulus-Response Learning ○ Addictive behaviors develop through repeated pairing of a stimulus (e.g., drug cues) with a response (e.g., drug use) Automatic Behavior ○ Over time, drug use becomes a habitual, automatic response to specific triggers Reinforcement ○ The habit is reinforced by the drug’s effect, making the behavior more entrenched with repeated use Resistance to change ○ S-R habits are difficult to break, as the behavior becomes deeply ingrained and less sensitive to negative consequences The “Pleasure” Pathway Dopamine’s Role ○ Early research suggested dopamine release in this pathway was linked to feelings of pleasure and reinforcement Is Dopamine Pleasure?? Kent Berridge (1990s) ○ Discovered dopamine’s role in motivation, not just pleasure Surprising Results ○ Blocking dopamine reduced motivation to seek rewards but did not eliminate pleasure responses “Liking” vs “Wanting” Distinction “Liking” ○ Refers to the actual enjoyment or pleasure from a reward ○ Involves different brain circuits, often related to the opioid system “Wanting” ○ Refers to the motivation or desire to obtain a reward ○ Dopamine is more involved in “wanting” driving the urge to seek out rewards Incentivized-Salience The process by which certain stimuli become highly associated or “wanted” due to their association with rewards ○ Dopamine enhances the “wanting” cues linked to rewards, making them more compelling ○ In addiction, drug-related cues gain excessive incentive salience, driving cravings and compulsive behaviors Importance of Triggers Brain changes related to wanting remain long after drug tolerance and withdrawal have disappeared ○ Whether or not the drug is still liked very much or wanted State Dependence Influence of Internal State ○ Incentive salience is heightened or diminished based on the individual’s current physiological or emotional state Positive and Negative States ○ Cravings and “wanting” are stronger in both negative states (e.g., stress, anxiety) and positive states (e.g., excitement, celebration) All Roads Lead to Rome (Dopamine) All drugs and addictive behaviors involve different feelings and experiences ○ Different physiological and psychological effects Despite these differences, all have similar effects on the dopamine system ○ Dopamine tags all of them as being important and initiates craving and motivation to pursue them The PFC and Executive Control The prefrontal cortex (PFC) plays an important role in long-term goal setting, decision making, and impulse control The PFC Still Works People with an addiction have functional prefrontal cortices The prefrontal cortical system is likely “hijacked” Competing Neurobehavioral Decision Systems (CNDS) Posits that choices result from two interactive decision systems ○ The impulse -decision system Dopamine system that functions to obtain biologically important reinforcers ○ The executive -decision system Prefrontal cortices which function to consider longer-term consequences of decisions Lecture 3 Pharmacokinetics vs Pharmacodynamics Pharmacokinetics ○ How a drug is absorbed, distributed, metabolized, and excreted by the body overtime (ADME) Pharmacodynamics ○ How a drugs affect receptor sites, send signals and cause neurochemical changes A.D.M.E Absorption ○ The process by which a drug enters the bloodstream from its site of administration Distribution ○ The dispersion or spread of the drug throughout the body’s tissues and fluids after it enters the bloodstream Metabolism ○ The chemical alteration of the drug by the body, primarily in the liver, to facilitate its elimination Elimination ○ The process by which the drug and its metabolites are excreted from the body Time Course of Absorption Absorption Rate and Onset of Action: ○ Different administration routes have varying absorption rates and onset time Bioavailability: The proportion of the drug that enters systemic circulation and is available to produce an effect ○ Different administration routes impact bioavailability Oral Administration Involves swallowing drugs in forms such as tablets, capsules, and liquids. Absorption Process: Drugs are absorbed through the gastrointestinal (GI) tract, primarily in the small intestine First-Pass Metabolism: Pass through the liver before entering systemic circulation  Time Course and Onset: Slower onset compared to other routes due to digestion time ○ Can vary from 30 minutes to several hours Sublingual and Buccal Administration Absorption Process: Absorbed directly into the bloodstream ○ Bypass the GI tract and first-pass metabolism Intravenous (IV) Administration Injecting the drug directly into the bloodstream through a vein Absorption Process: There is no absorption phase and the entire dose is immediately available for action Immediate Onset of Action: Fastest onset of effects Often within seconds to minutes Inhalation Administration Breathing in drugs in the form of vapors, gases, or aerosols directly into the lungs Absorption Process: Rapidly absorbed through the alveoli in the lungs into the bloodstream Rapid Onset of Action: Offers one of the fastest onsets of effects Typically within seconds to minutes Intranasal Administration Snorting or spraying drugs into the nasal passages Relatively Quick Onset of Action: Relatively quick onset of effects, typically within minutes Faster than oral but slower than inhalation Intramuscular (IM) and Subcutaneous (SC) Administration Intramuscular Injection (IM) ○ Absorption: Through capillaries in muscle tissue Onset: Typically 10–30 minutes Advantages: Quick absorption with prolonged effect Subcutaneous Injection (SC) ○ Absorption: Through capillaries in subcutaneous tissue ○ Onset: Typically 15–60 minutes ○ Advantages: Slow, sustained absorption with prolonged effect Drug Distribution Overview The process by which a drug is transported from the site of absorption to various tissues and organs Factors Affecting Distribution: Blood flow, Tissue permeability, Plasma protein binding, Lipid solubility Impact on Drug Efficacy and Safety: Determines the concentration of the drug at the target site, influencing its therapeutic and adverse effects Tissue Perfusion High Perfusion Tissues: Receive a large amount of blood flow, facilitating rapid drug uptake. ○ Examples: Brain, liver, kidneys Low Perfusion Tissues: Receive less blood flow, leading to slower drug distribution. ○ Examples: Fat, bone, connective tissue Impact on Drug Action: Drugs act faster in well-perfused tissues due to rapid delivery ○ In poorly perfused tissues, onset of action can be delayed, and drugs may accumulate over time Plasma Protein Binding The degree to which drugs attach to proteins in the blood ○ Only the unbound (free) fraction of the drug is active ○ Bound drugs act as a reservoir, releasing slowly over time Factors Influencing Binding: How strongly the drug sticks to proteins. How many binding sites are available. Competition with other drugs for these sites Clinical Implications (Drug interactions): Drugs can interact if they compete for the same binding site Lipid Solubility How easily a drug dissolves in fats Lipid-soluble drugs can easily pass through cell membranes Importance in Drug Distribution: ○ Lipid-soluble drugs are absorbed faster and reach the brain quicker ○ These drugs are stored in fat tissue, which can affect how long they stay in the body Can be slowly released back into the bloodstream Can be released during periods of tissue breakdown’ Blood Brain Barrier (BBB) A selective barrier that protects the brain from potentially harmful substances while allowing essential molecules to pass ○ Composed of tightly joined endothelial cells, astrocyte end-feet, and a basement membrane Role in Drug Distribution: ○ Lipid-soluble drugs can cross the BBB more easily ○ The BBB restricts the passage of hydrophilic or large molecules Placental Barrier Controls the exchange of substances between the mother and fetus Role in Drug Distribution: ○ Lipid-soluble drugs can cross the placental barrier more readily, impacting fetal exposure ○ The barrier provides some protection but is not as selective as the BBB (Blood Brain Barrier) Drug Metabolism Overview The body’s process of breaking down drugs, mainly through enzymes ○ Affects how long a drug works and how strong its effects are Goals of Drug Metabolism: ○ Make drugs more water-soluble so they can be easily excreted ○ Detoxification of potentially harmful compounds Sites of Metabolism: ○ The liver is the primary site ○ Can also occur in the kidneys, lungs, intestines, and other tissues The Liver Basic Anatomy and Location: ○ Large, reddish-brown organ located in the upper right quadrant of the abdomen, just below the diaphragm Role of the Liver in Drug Metabolism: ○ Primary organ responsible for the metabolism of drugs ○ It processes approximately 75% of the blood from the GI tract via the portal vein Hepatocytes: ○ The functional cells of the liver, containing enzymes essential for drug metabolism Capable of chemical transformation and detoxification First-Pass Metabolism The liver and GI tract process a drug first before it reaches the bloodstream Pathway of Oral Drugs: ○ Absorbed through the GI tract and transported to the liver via the portal vein ○ In the liver, the drug is broken down before it enters the bloodstream Impact on Drug Bioavailability: ○ Can significantly reduce the bioavailability of a drug A lower amount of the active drug reaches the bloodstream Factors Affecting Drug Metabolism Genetic Factors (Polymorphisms): ○ Genetic variations in metabolic enzymes (e.g., CYP450) can lead to differences in drug metabolism rates ○ Examples include poor, intermediate, extensive, and ultra-rapid metabolizers Age: ○ Neonates and elderly patients often have reduced metabolic capacity ○ Enzyme activity and liver function can decline with age, affecting drug clearance Sex: ○ Hormonal differences and differences in enzyme expression levels between males and females can influence drug metabolism