PSYC 3403 Midterm (1) PDF

Addictions Lecture 1 - Pharmacokinetics Pharmacokinetics The time course of a particular drug's actions. - Absorption → getting into your blood - Distribution → where in your body is it going - Metabolism → break it down any external agent - Eliminati...

Addictions Lecture 1 - Pharmacokinetics Pharmacokinetics The time course of a particular drug's actions. - Absorption → getting into your blood - Distribution → where in your body is it going - Metabolism → break it down any external agent - Elimination → when it is inactive, you have to get rid of it C max = maxim concentration - C min = minimum concentration - When you take the medication, it hits the maximum concentration and then goes into a minimum concentration. - You want to be within the therapeutic range for it to be at a healthy level in your Plasma/system. - There is a toxic range = OD. Administration Enteral: - Oral administration (mouth) - Rectal administration (suppository) Parenteral: - Administration by inhalation (lungs) - Administration through mucous membranes (nose and mouth) - Through skin (patch) - Through injection (muscle, skin) Oral: - It must be gastral intestinal resistant because of the stomach acid. → coat the pill, etc. - Liquid (12 - 15 min for absorption) vs. tablet/capsule (20 - 25 min for absorption) = liquid form dissolves slightly faster. - Passive diffusion → not putting any energy into getting this medication into your blood. - Lipid solubility → the more lipid/fat soluble something is, the easier it can get through the membrane. - Disadvantages = vomiting, stomach discomfort, variable levels of absorption, and insult from stomach acids. Rectal: - Delivered in suppository. - Used in restricted conditions. - Disadvantages include poor absorption parameters and rectal membrane irritation → not ideal, but they are more useful in emergencies (when throwing up or convulsing). Inhalation: - Rapid exchange between lung and blood. - Rapid delivery to brain. - Used for anesthetic gases. Mucous Membrane (membrane within the nose and mouth) - It is administered through the nose/mouth. - It is absorbed through the mucosal membrane directly into the bloodstream.  - Sublingual administration. - Included: cocaine, nitroglycerine, nicotine gum → under the tongue. Transdermal Patch - Provides continuous, controlled release. - It is absorbed through the epidermis directly into the bloodstream. - Nicotine (anti-smoking), fentanyl (chronic pain), estrogen (birth control). - It goes into the blood supply, and different dosages are in the patch to control the administration → It is a layered process. - It is less addictive because you do not have any peaks and valleys. Injection: - Intravenous (vein) → very fast because it goes into the blood supply - Intramuscular (muscle) - Subcutaneous (under the skin) - Faster absorption into the bloodstream - No insult to the gastral intestinal tract. - Disadvantages: unable to respond to unexpected reactions, must use sterile techniques, essentially irreversible. Drug Distribution Only a tiny portion of the drug interacts with target receptors (side effects) → When a drug is administered, it is distributed throughout the body and can interact with many different types of cells. However, only a tiny portion of the drug interacts with the target receptors. - The liver contains drug-metabolizing enzymes, ex. CYP3A CYP3A: - Metabolites buspirone (BuSPar). - Only 5% of the drug enters the portal system → have to give 95% more in administration so that 5% can enter fully. - CYP3A’s action is lessened with grapefruit juice. - Active component called furanocoumarin. Oral: - Through GI tract into the portal system. - The drug enters central circulation to the heart. - Drugs may be metabolized by the GI tract or liver (first-pass metabolism) → Your liver takes a "first pass" at breaking down the medicine, which means not all of it will be available for your body to use. This is why some medications must be given in higher doses or in different ways (like injections) to avoid this process. - Alcohol dehydrogenase is found in the GI tract and liver (men vs women) → some women drink less than men for them to show signs of intoxication. Men have more alcohol dehydrogenase than women. Membranes: - Cell membranes. - Capillary vessels. - Blood-brain barrier - Placental barrier - A membrane is like a thin, flexible barrier that separates two areas. In biology, it's often found in cells, which act like a protective skin that controls what goes in and out, like nutrients or waste. It helps the cell maintain its proper environment.  Membranes (capillary vessels): - Tiny blood vessels with single cell walls allow us to move blood. - And allows things within the blood to come out of the membrane. - Small pores (90-150 angstroms) - Pores allow for passive diffusion. - Entry into body tissue depends on the rate of blood flow and the drug's ability to pass through the capillary vessel pores. Membranes (blood-brain barrier): - Capillaries are tightly joined together. - Covered on the outside by a glial sheath. - No pores are present. - Entry into the brain depends on the size of the drug molecule and lipid solubility. Membranes (placental barrier): - Provides little to no protection. - Whatever the mother gets, the baby gets too. Termination of Drug Action Drugs can exit via: - Kidney excretion (urine). - Lungs (exhaling) - Bile - Skin (sweating it out) Enzymes: - Cytochrome P450 enzyme family (major system). - Includes enzyme families (CYP-1, CYP-2, CYP-3). - The majority of breakdown is mediated by a few enzymes. Genetics: - Genetic testing can indicate the rate of metabolism. - Slow vs fast metabolizers. - Use this information to understand the different receptors within your brain. Drug Half-Life: - How long does it take your body through the process of metabolism to break down the drug in half? → how long would it take for the drug to go from 20mg to 10mg? - After six half-lives, you essentially removed the drug from your body. Steady-state: - Attained after approximately 5 to 6 half-lives. - Achieved within six half-lives. - The amount administered = amount eliminated. Therapeutic Drug Monitoring (TDM): - It involves measuring the levels of a drug in the bloodstream to ensure that they are within a specific range—the "therapeutic range"—where the drug can be most helpful without causing harmful side effects. - Checking if a person is getting the right amount of medication.  - Too little might not help with their mental health condition, and too much could cause problems. - TDM helps doctors adjust doses to find the right balance for each individual, as everyone's body reacts differently to medications. Drug Tolerance & Dependence Drug tolerance: - We require more of that drug to receive the same effect. - The body is adapting. - Metabolic tolerance: increased production of CP450, happens when your body gets better at breaking down or metabolizing a drug over time. The drug is processed and eliminated more quickly, so it doesn't stay in your system as long or work as effectively. - Pharmacodynamic tolerance: receptor down-regulation…when your body gets used to a drug over time, so the drug doesn't have the same effect it once did. The target in your body (like a receptor) that the drug interacts with becomes less responsive after repeated exposure. As a result, you might need a higher drug dose to get the same effect. - Contingent tolerance: behaviour conditioning, environmental cues, homeostatic theory, building tolerance within a setting. If someone always takes a drug in a particular environment (like at home), their body may get used to it and build a tolerance in that setting. But if they take the same drug in a different environment, they might feel its effects more strongly because their body isn't as prepared for it in that new context. Drug dependence: - When the body has adapted and changed itself. - Once the body does not receive the drug, there is a withdrawal. Addictions Lecture 2 - Synaptic Transmission/Pharmacodynamics Brain Development and Structure The skull and brain relationship: - The skull is a fixed structure that protects the brain. In the past, humans needed a thicker skull to protect themselves from harm, but as the brain developed and required more space, the skull began to thin out. - This process has continued, allowing the brain to grow and develop. Convolution and folding: - Needed to find ways to increase its surface area without increasing the size of the skull. - Achieved through convolution, or the folding of the brain's surface. - This process creates more space, enabling the brain to grow and develop. - "Convolution is the process of folding the brain's surface to increase its surface area, allowing for more space to be created." Brain structure: - Cerebrum: The largest part of the brain, responsible for processing sensory information and controlling movement. - Brain Stem: Connects the cerebrum to the spinal cord and regulates basic functions such as breathing, heart rate, and blood pressure. - Cerebellum: Coordinates movement and balance. - Corpus Callosum: A bundle of fibres connecting the brain's left and right hemispheres. - Sulcus: A groove or fissure in the brain's surface.  Brain stem function: - The brain stem is responsible for regulating basic functions, such as; - Breathing, - Blood pressure, - Heart rate, - Stomach and GI tract function, - Sleep and wakefulness, - Attention and arousal - These functions are considered primitive or lower-level, as they are essential for survival and are managed automatically by the brain stem. Hemispheres of the brain: - The left hemisphere may deal with depth and colour in vision, while the right hemisphere deals with saturation and distance. - The corpus callosum connects the two hemispheres, allowing them to communicate and coordinate their functions. Lobes of the brain: - The cerebrum is divided into four lobes: frontal, parietal, temporal, and occipital. - Frontal Lobe: Responsible for executive functions, such as decision-making and problem-solving → motor function, memory, language, and emotion. - Parietal Lobe: Processes sensory information related to touch and spatial awareness → sensory processing, spatial awareness. - Temporal Lobe: Plays a key role in processing auditory information and memory → visual processing. - Occipital Lobe: Primarily responsible for processing visual information → auditory function, memory, visual perception. Overview of brain structure: - Anatomists have identified various landmarks to help navigate the brain, including the central sulcus and gyrus. These landmarks can be used with brain atlases to understand the location of different brain structures. Hemispheric differences: - Left Hemisphere: language-related movement, verbal communication. - Right Hemisphere: nonverbal movement, spatial awareness, facial expression. Somatosensory Cortex: - A structure responsible for encoding our representation of parts of ourselves and the parts associated with sensation. - "The somatosensory cortex is a complex structure that plays a crucial role in our ability to perceive and understand the world around us." Studying Brain Function: - Experimental studies: Recording from brain cells, mapping brain function, and conducting memory tasks. - Ablation or lesion studies: Damaging a specific brain area and observing the effects on behaviour. Key Terms: - Central sulcus: A brain landmark separating the frontal and parietal lobes. - Gyrus: A fold in the brain that helps to increase surface area.  - Hemisphere: One-half of the brain, either left or right. - Lobe: A region of the brain associated with specific functions Phineas Gage: - He was a railway construction worker in the 1800s who suffered a severe brain injury when a tamping iron went through his head. The accident destroyed most of his left frontal lobe, which is responsible for higher cognitive functions. - Ruined the left frontal lobe → destroyed his ability to perform higher cognitive functions (Decision-making, Problem-solving, Emotional regulation, Social behaviour) - Before the accident, Phineas Gage was happy, social, and prosperous. - After the accident, he experienced significant changes in his behaviour → emotional death, inappropriate mood swings, trouble with social interaction, and changes in movement and behaviour. Neurons and the Brain Neurons: specialized cells designed to exchange information and transmit signals. Neural Network: a network of interconnected neurons that work together to process information. Characteristics of Neurons: - Electrical charge: neurons carry an electric charge, allowing them to transmit signals. - Chemical side: neurons have a chemical side, which is crucial in signal transmission. - Signal transmission: neurons are specialized for signal transmission → allowing them to exchange information. Saltatory conduction: - The process by which electrical signals pass down the length of a neuron. - "Saltatory conduction is like a row of dominoes falling one after another. Each node of Ranvier is like a domino triggered by the action potential, allowing the signal to jump from node to node." Membrane Structure Phospholipid Bilayer: a double layer of phospholipid molecules that makes up the cell membrane. Hydrophilic Head: the water-loving part of the phospholipid molecule. Hydrophobic Tails: the water-hating part of the phospholipid molecule. Semipermeable membrane: - A membrane that allows certain substances to pass through while keeping others out. - Filters through substances. Ions Channels and Proteins - Ion Channels: proteins that allow certain ions to pass through the cell - membrane. - Proteins: molecules that play a crucial role in various cellular functions, including signal transmission and transport of substances across the cell membrane. Neuron components: - Cell body → central and contains the nucleus. - Axon → thin extension and carries signals away from the cell body. - Dendrites → branches and receives signals from other neurons. - Axon Terminals → end of axon and signals are transmitted to other neurons. Myelin sheath and node of Ranvier:  - Myelin Sheath: fatty, insulating substance covering the axon. - Nodes of Ranvier: gaps in the myelin sheath, allowing signal transmission. Ion concentration and gradient: - Neurons maintain a concentration gradient of ions. - Sodium Na+: More concentrated outside the cell → Rushes into the cell when voltage-gated sodium channels open. - Potassium K+: More focused inside the cell → Rushes out of the cell when voltage-gated potassium channels open. - Maintained by the Sodium-Potassium Pump, which actively pumps sodium out of the cell and potassium into the cell. Electrical gradient: - The inside of the cell is more negative than the outside. - "The electrical gradient is the difference in electrical charge between the inside and outside of the cell, created by the concentration gradient of ions." Signal transmission: - The neuron's signal transmission process can be likened to a snowball rolling down a hill, with the potential energy stored at the top of the hill. - The Sodium-Potassium Pump creates the gradient, storing potential energy. - The Action Potential is the rapid change in electrical charge that allows the signal to propagate down the axon. Voltage-gated ion channels: - Voltage-gated sodium channels: open when the membrane potential becomes more positive, allowing sodium ions to rush into the cell. - Voltage-gated potassium channels: open when the membrane potential becomes more positive, allowing potassium ions to rush out of the cell. The action potential process: 1. A stimulus causes voltage-gated sodium channels to open, allowing sodium ions to rush into the cell. 2. The influx of sodium ions causes the membrane potential to become more positive. 3. The positive charge activates voltage-gated potassium channels, allowing potassium ions to rush out of the cell. 4. The efflux of potassium ions causes the membrane potential to return to its resting state. 5. The action potential travels down the length of the axon as a wave, with each section of the membrane going through the same process. Synaptic Transmission The process by which a signal is transmitted from one neuron to another. This occurs by releasing neurotransmitters from the presynaptic neuron, which bind to receptors on the postsynaptic neuron. Key Terms: - Synapse: junction between two neurons. - Synaptic cleft: a gap between presynaptic and postsynaptic neurons. - Presynaptic neuron: releases the neurotransmitter. - Postsynaptic neuron: receives the neurotransmitter. - Neurotransmitter: chemical that sends a signal from one neuron to another.  - Steps of neurotransmission: 1. Synthesis: presynaptic neuron synthesizes the neurotransmitter. 2. Storage: neurotransmitter is stored in vesicles. 3. Release: neurotransmitter is released from the vesicles into the synaptic cleft. 4. Binding: neurotransmitter binds to receptors on the postsynaptic neuron. 5. Reuptake: neurotransmitter is taken back up into the presynaptic neuron and reused. - Vesicle: membrane-bound sac that contains neurotransmitters. - Phospholipid bilayer: a hydrophilic head and a hydrophobic tail. - Exocytosis: when the vesicle contains neurons that are released into the presynaptic membrane and release its contents into the synapse. Exocytosis & Endocytosis Exocytosis is when a vesicle fuses with the presynaptic membrane and releases its contents into the synapse. Endocytosis is when the presynaptic membrane pinches off pieces of itself and reforms into a vesicle, allowing the cell to recycle its membrane and neurotransmitters. Examples of Neurotransmitters Catecholamines: dopamine, norepinephrine, epinephrine Serotonin Histamine Excitatory transmitters: glutamate Inhibitory transmitters: GABA, glycine. Pharmacodynamics: - Study of the biochemical and physiological effects of a drug and, the mechanisms of drug action, and the relationship between drug concentration and effect. Ligan-receptor interaction: - The equation can represent the interaction between a ligand and a receptor: L + R ⇌ LR - This equation shows that the ligand and receptor can exist separately or bind together to form a complex. Receptor structure: - Receptors comprise 7 or 12 alpha-helical coils held together by ionic forces. - The ligand binds to a specific site on the receptor, causing a conformational change that allows ions to flow through the receptor. Types of receptors: - Membrane-spanning protein: a protein that spans the cell membrane. - Transmembrane protein: a protein that passes through the cell membrane. - Ion channel: a protein that allows ions to flow through the cell membrane → pore. - Carrier proteins: Receptors that transport molecules across the cell membrane. - G protein-coupled receptors: Receptors that activate a G protein, activating a downstream signalling pathway. - Enzyme receptors: Receptors with enzymatic activity, such as kinases or phosphatases. Types of receptor binding: - Agonist: A molecule that binds to a receptor and activates it, mimicking the effect of a natural neurotransmitter. - Antagonist: A molecule that binds to a receptor and blocks its activation.  - Partial agonist: A molecule that binds to a receptor and activates it with less efficacy than a full agonist. - Partial antagonist: A molecule that binds to a receptor and blocks its activation but with less efficacy than a full antagonist. Ion channels: 1. Ligand-gated ion channels: these channels are activated by binding a neurotransmitter to a specific receptor site. 2. Voltage-gated ion channels: these channels are activated by changes in the electrical potential across the cell membrane. Dopamine Transporter: - A type of carrier protein that is responsible for the reuptake of dopamine from the synaptic cleft. - Presynaptic neuron: releases dopamine into the synaptic cleft - Dopamine transporter: reuptakes dopamine from the synaptic cleft - Postsynaptic neuron: receives dopamine and responds to its binding G Protein-Coupled Receptors A type of receptor that activates a G protein when bound by a neurotransmitter. This leads to the activation of downstream signalling pathways. Regulation of Receptors Chronic exposure to a drug can lead to receptor expression and function changes. Upregulation: An increase in the number of receptors. - The body increases the number of receptors to increase stimulation. - This can occur when a drug blocks the receptor, leading to an underactivation of the receptor. - The body adapts by increasing the number of receptors, making it easier for the receptor to be activated. Downregulation: A decrease in the number of receptors. - The body reduces the number of receptors to prevent overstimulation. - This can occur when a drug that activates the receptor is taken, leading to an overactivation of the receptor. - The body adapts by reducing the number of receptors, making it more difficult for the drug to activate the receptor. Tolerance Occurs when the body adapts to a drug by changing the number of receptors. This can lead to a decrease in the effectiveness of the drug over time. Homeostasis The body's natural state of balance. The body strives to maintain homeostasis by regulating the activity of receptors. Enzymes and Neurotransmitter Breakdown Acetylcholinesterase inhibitors: - Block the activity of acetylcholinesterase, preventing the breakdown of acetylcholine. Monoamine oxidase inhibitors (MAOIs): - Block the activity of monoamine oxidase, preventing the breakdown of norepinephrine and  dopamine. Drug-Receptor Specificity Refers to the ability of a drug to bind to a specific receptor. A good fit between the drug and receptor is essential for effective binding. Potency and efficacy: - Potency: the absolute number of drug molecules required to elicit a response. - Efficacy: the maximum effect obtainable from a drug. Drug Response Curves Determine the relationship between the dose of a drug and its effect. Components of dose-response curve: - Dose: the amount of the drug administered, typically measured in milligrams or milligrams per kilogram. - Percentage of subjects responding: the proportion of subjects who exhibit a desired response to the drug, typically measured as a percentage. Interpreting dose-response curves: - A shift to the left indicates increased potency, meaning a lower dose is required to achieve the same effect. - A shift to the right indicates decreased potency, requiring a higher dose to achieve the same effect. Maximum effect: - The dose-response curve plateau represents the highest level of response that can be achieved with a particular drug. The Placebo Effect "Any medical procedure or agent that produces an effect in a patient because of its therapeutic intent and not its specific nature, whether chemical or physical." Treatment that has no actual therapeutic effect but still produces a response in the patient. - A sugar pill - A saline injection - A sham surgery Physiological effect: - Reduces anxiety and stress - Lowers the stress response - Releases endogenous opioids, which can help manage pain and other chronic issues How the placebo effect works: - The placebo effect is caused by the brain's response to the expectation of benefit. - When a person receives treatment, their brain releases chemicals that can help to reduce stress and anxiety, reducing symptoms. Clinical Trials: Single-blind: - The patient does not know whether they receive the treatment or a placebo. - The researcher or doctor knows which treatment the patient is receiving.  Double-blind: - Neither the patient nor the researcher or doctor knows which treatment the patient receives. - A third party distributes the treatments and keeps track of the results. Addictions Lecture 3 - Alcohol Depressants → Alcohol Alcohol is a widely used psychoactive substance, ranking as the second most widely used in the world. Types of Alcohol: - Beer → 12 oz → 5% ABV - Spirits → 1.5 oz → 80 proof 40 - Wine → 6 oz → 10% ABV Proof: - It is half of the alcohol percentage. - For example, a standard bottle of vodka with 40% ABV would be 80 proof. Drink Equivalent Table: - 1 standard beer = 1 drink equivalent - La Fen Du Monde = 1.8-2.2 drink equivalents - Mike's Hard Lemonade = 1.6 drink equivalents - Old English = 4 drink equivalents - Malt or Microbrewery = varies How the Body Breaks Down Alcohol The body can break down 0.015 gram percents of alcohol per hour. This is the rate-limiting step in alcohol metabolism; the body can only break down alcohol at this rate. The enzyme responsible for breaking down alcohol is alcohol dehydrogenase. Absorption & Metabolism of Alcohol Absorption: the process by which the body takes in alcohol. Metabolism: the process by which the body breaks down alcohol. 20% of alcohol is absorbed by the stomach, while 80% is absorbed by the intestine. 95% of alcohol is metabolized by the enzyme alcohol dehydrogenase, with 85% of this breakdown occurring in the liver. - When alcohol is consumed on an empty stomach, it can quickly enter the bloodstream due to its lipid solubility. - When food is present in the stomach, it can slow down the absorption of alcohol into the bloodstream → block the free flow of alcohol through the stomach, allowing the alcohol dehydrogenase to break it down more efficiently. Differences in Alcohol Metabolism Between Men and Women On average, women have a higher absorption of alcohol than men. The blood-brain barrier is permeable to alcohol, allowing it to enter the brain. Alcohol also crosses the placental barrier, allowing it to enter the fetal brain if the mother is pregnant. - Gastric alcohol dehydrogenase: men = higher levels & women = lower levels. - Muscle to fate ratio: men = greater ratio muscle to fat & women = lower ratio of muscle to fat. - Body fat: men = lower body fat & women = higher body fat. Biochemistry of Alcohol Mechanism The breakdown of alcohol: - Ethanol alcohol is broken into → 1. Acetaldehyde by alcohol dehydrogenase 2. Acetate by aldehyde dehydrogenase Role of enzymes: - Alcohol Dehydrogenase: breaks down ethanol into acetaldehyde - Aldehyde Dehydrogenase: breaks down acetaldehyde into acetate → blocking aldehyde dehydrogenase with an agent like disulfiram can lead to a buildup of acetaldehyde (what causes nausea). Alcohol Breakdown: - The maximum amount of alcohol that can be broken down in 24 hours is approximately 170 grams. - The average person breaks down 7-8 grams of alcohol per hour. - This is equivalent to about 1 drink per hour. Calculating blood alcohol concentration: - Let's say we have a 180-pound man who has had 6 drinks over 4 hours. → use the BAC chart. - BAC from the chart: 0.13 - Metabolized alcohol 0.015g: 0.06 - Total BAC: 0.13 - 0.06 = 0.07 0.08 g% or higher: considered intoxicated 0.04 g% or higher in Canada/Ontario: considered impaired and not allowed to drive Factors that make alcohol an ideal drug for abuse: - Socially Acceptable: alcohol is widely accepted and used in social settings - Easy to Obtain: alcohol is widely available and easily accessible - Perceived as Safe: alcohol is often perceived as a safe substance, especially in moderation - Lack of Stigma: alcohol use is often not stigmatized, unlike other substances Glutamate receptors: - NMDA: normally excitatory but can be blocked by alcohol. - AMPA: excitatory but not affected by alcohol. - Kainate: excitatory but not affected by alcohol. Effects of alcohol on glutamate receptors: - Alcohol blocks the NMDA receptor, leading to a decrease in excitatory activity. - Long-term alcohol consumption can lead to upregulation of NMDA receptors (the brain becomes more sensitive to glutamate). - When alcohol is suddenly stopped, the increased number of NMDA receptors can lead to hyperexcitability, potentially causing seizures. - Upregulation: an increase in the number of receptors on the surface of a cell, making it more sensitive to a particular neurotransmitter. Effects of alcohol on GABA receptors: - Alcohol activates the GABA receptor, leading to an increase in inhibitory activity - This can result in a decrease in overall brain activity, leading to a depressant effect - Depressant: a substance that slows down or reduces the activity of the brain, leading to feelings of calmness or sedation.  Acamprosate: - A medication that can be used to help manage withdrawal symptoms in individuals who are quitting alcohol. - It works by mimicking the effects of alcohol on the NMDA receptor, reducing the risk of seizures and hyperexcitability. Gaba & Anxiety: - GABA is an inhibitory neurotransmitter that helps to reduce anxiety and panic. - Alcohol increases GABA activity, which can lead to a feeling of relaxation and reduced anxiety. Types of GABA receptors: - GABAa: a subtype of GABA receptor that is involved in the regulation of anxiety and panic - GABAb: a subtype of GABA receptor that is involved in the regulation of muscle tone and other physiological processes - GABAc is a subtype of GABA receptor involved in regulating visual processing. Dopamine and the reward pathway: - Alcohol activates the dopamine reward pathway, which can lead to feelings of pleasure and relaxation. - However, chronic activation of this pathway can lead to addiction. Serotonin and alcohol: - Serotonin is a neurotransmitter that is involved in the regulation of mood and appetite. - 5-HT2: a subtype of serotonin receptor that is involved in the regulation of mood and appetite. - 5-HT3: a subtype of serotonin receptor that is involved in the regulation of nausea and vomiting. Cannabinoid receptors and alcohol: - Cannabinoid receptors are involved in the regulation of pain and pleasure. - Bodies natural painkillers. - Help reduce pain and promote feelings of pleasure. Reversible effects: - Behavioural Changes: alcohol consumption can lead to poor decision-making, increased confidence, and altered behaviour. - Cognitive Impairment: alcohol consumption can impair cognitive abilities, including memory recall, deductive powers, and logic. Physiological effects: - Depression of Respiration: can slow down breathing rates and increase the time between breaths. - Additive Effects: have additive effects when combined with other sedative-hypnotic compounds, increasing the risk of adverse reactions. - Synergistic Effects: the combination of alcohol with other substances can have explosive effects, where the combined effect is greater than the sum of the individual effects. Circulatory function: - Reduced Blood Supply: alcohol consumption can reduce blood supply to - extremities, making individuals less sensitive to cold temperatures. - Dilation of Blood Vessels: alcohol consumption can cause blood vessels to dilate, leading to increased blood flow to certain areas, such as the face.  Cardiovascular effects: - Type of Drink: dry, low-sugar wines, such as red wine, may be more beneficial than other types of drinks. - Drinking Frequency: moderate drinking, defined as 2-3 drinks per day, 2-3 times a week, may be beneficial. - Individual Factors: genetics, diet, and lifestyle can all impact the effects of alcohol consumption on cardiovascular health. Tolerance and dependence: - Tolerance: the need to consume more substances to achieve the same effect. - Dependence: the physical or psychological need to continue consuming a substance. - Amount of ingestion - Pattern of consumption - Individual differences Acute use: - Can lead to drug-induced dementia, characterized by: - Clouded sensorium - Impaired judgment - Anterograde amnesia - Retrograde amnesia Chronic use: - This can lead to the following: - Delusions - Hallucinations - Bouts of unconsciousness - Psoriasis of the liver - Nerve damage in the brain and periphery - Dementia Wernicke-Korsakoff Syndrome: - Confusion - Disorientation - Memory loss - Hallucinations - Delusions - Difficulty with coordination and balance - "Wernicke-Korsakoff syndrome is a brain disorder that typically results from a thiamine deficiency, often caused by chronic alcohol abuse." Psoriasis of the liver: - "Psoriasis of the liver is a condition in which the liver becomes inflamed and damaged, leading to scarring and impaired liver function." Stages of liver damage: - Fatty Liver: the liver accumulates fat deposits, leading to impaired function. Reversible with abstinence from alcohol. - Liver Fibrosis: the liver develops scar tissue, which can lead to permanent damage. Recovery is possible, but some damage may be irreversible.  - Cirrhosis: The liver is severely damaged, leading to the growth of scar tissue and potentially life-threatening complications. Teratogenic effects: - Impact of a substance on a fetus during pregnancy. - Alcohol - Ionizing radiation - Thalidomide - Lithium Fetal alcohol syndrome: - When a fetus is exposed to high levels of alcohol during critical stages of development. - Spinal cord defects - Brain damage - Various birth defects - 10% of all birth defects are due to prenatal exposure to teratogenic agents. - 30-50% of infants born to alcoholic women may develop FAS. - Central Nervous System Dysfunction: damage to the brain and nervous - system. - Low IQ: lower than average intelligence quotient. - Mental Dysfunction: impaired cognitive and emotional functioning. - Physical Deformities: characteristic facial features and growth abnormalities. - Structural Damage: damage to brain structures, including the corpus callosum. - Neurological Dysfunction: impaired functioning of the nervous system. - Functional Impairment: impaired overall functioning of the brain. Alcohol-Related Neurodevelopmental Disorder ARND A condition that results from prenatal exposure to alcohol, leading to compromise of neurodevelopment and brain function, but without the characteristic facial features of FAS. Characteristic of ARND: - Milder Symptoms: symptoms that are less severe than those of FAS - Hyperactivity: excessive physical activity - Aggressive Behavior: aggressive or violent behaviour - Lower IQ: lower than average intelligence quotient - Sensory Problems: difficulties with sensory processing Prevalence of ARND: - 1 in 100 live births. - More common than FAS, but with a lesser degree of damage. The Effects of Alcohol on the Brain Glutamate: a neurotransmitter that is decreased by alcohol consumption GABA: a neurotransmitter that is increased by alcohol consumption When alcohol is consumed, it blocks the NMDA receptor, leading to a decrease in glutamate. At the same time, it activates the GABA receptor, leading to an increase in GABA. Withdrawal symptoms: - Shaking - Sweating  - Nausea - Insomnia - Hypersomnia - Referred to as Delirium Tremens DTs. Pharmacotherapy for Alcohol Addiction The goals of pharmacotherapy for alcohol addiction are to: - Reverse the acute effects of alcohol - Help with withdrawal symptoms - Maintain abstinence Comorbitiy & Treatment Refers to the presence of one or more additional conditions or disorders in an individual. In the context of alcohol addiction, comorbidity can include: - Depression - Anxiety - Schizophrenia Treatment: - Medications = antidepressants - Other treatments = therapy. Medications for alcoholism: - Naltrexone: an opioid antagonist that blocks opioid activity and reduces the pleasurable effects of alcohol (better than acamprosate). - Acamprosate: a GABA agonist that inhibits glutamate receptors, mimicking the effects of alcohol without the negative consequences (better than placebo). - Combination therapy: using both naltrexone and acamprosate together is more effective than either medication alone (best results). Other medications used in therapy: - Wellbutrin: a dopaminergic agent that activates the dopamine reward pathway, often used to treat depression. - SSRIs: increase serotonin levels in the system; examples include Prozac and Zoloft. - Buspar: a serotonin 5-HT1A agonist that activates the serotonin system - Zofran: a serotonin 3A antagonist Types of alcoholics: - Type A: later onset heavy drinkers, typically starting to drink at age 20 or older. - Type B: early onset drinkers, typically starting to drink at a younger age (13-14 years old).  Addictions Lecture 4 - Alcohol Continued Signs of Addiction: Is drinking interfering with work or school? Is drinking compromising health or diet? Are there negative consequences as a result of drinking? Preventative measures: Preventative campaigns: Posters, brochures, info sessions, and targeted media campaigns to educate students about the risks of excessive drinking. Counselling services: On-campus counselling services to help students struggling with addiction. Campus regulations: Stricter regulations on drinking on campus, such as designated drinking areas and limited hours. Challenges: Accessibility: Easy access to alcohol off-campus. Effectiveness: Preventative measures may not always be effective in reducing excessive drinking → Campus Drinking Culture Drinking Statistics: 18-19-year-olds and 20-34-year-olds have the highest rates of drinking 5 or more drinks per occasion at least 12 times a year. Males have higher rates of drinking than females, but the numbers taper off dramatically in women as they get older. Undergraduate students who drink 5 or more drinks on a single occasion at least weekly: Males: 20% & Females: 12.5% Addiction and Age Early exposure to drinking increases the likelihood and depth of addiction. The "magic line" for addiction tends to happen prior to the age of 17. If someone starts drinking at 13 or 14, they have a 35% chance of becoming an addict. Socioeconomic Factors: Populations at risk for addiction include those from lower socioeconomic backgrounds, rural areas, and Aboriginal populations. These populations have higher rates of drug misuse and addiction, with numbers reaching as high as 50%. Dopamine reward pathway: The dopamine reward pathway involves the following structures: - Ventral Tegmental Area - Nucleus Accumbens - Prefrontal Cortex Activation in this pathway leads to dopamine release and motivates the individual to repeat such behaviours. Marketing and advertising: "Targeted marketing" refers to the practice of directing advertising efforts toward a specific demographic or age group. The science of mixing drinks:  Carbonation: can increase the rate of alcohol absorption Sugar content: can lead to increased calorie intake and potentially worsen hangover symptoms Caffeine: can interact with alcohol and increase the risk of adverse effects Multi-component drinks: can contain multiple stimulants and depressants, leading to unpredictable effects Drinking and driving: Drinking and driving is a significant public health concern. One tool used to measure alcohol consumption is the breathalyzer. The breathalyzer detects the amount of alcohol in the breath, which is correlated with the amount of alcohol in the blood. - This is possible because the liver metabolizes alcohol constantly, and the amount in the breath is proportional to the amount in the blood. - The chemical reaction that occurs in a breathalyzer is as follows: Alcohol + Potassium Dichromate → Chromium Sulfate + Potassium Sulfate + Acetic Acid + Water. Sources of error of a breathalyzer: - Air Temperature: temperature can affect the chemical reaction, so the device must be calibrated regularly. - Breathing Rate: running or hyperventilating can decrease the accuracy of the reading while holding one's breath can increase it. - Mouth Alcohol: burping or having mouth alcohol present can increase the reading. - "Hyperventilating can increase your respiration rate, which can decrease the accuracy of the reading." Limitations of measuring BAC: Measuring BAC directly by taking blood samples is not practical for several reasons: - Invasive: requires a blood sample, which can be painful and uncomfortable. - Time-consuming: sending the sample to a lab for analysis, resulting in a delay. - Expensive: running blood tests can be costly. Legal limits for BAC: In Canada and Ottawa, a BAC of 0.04 or higher is considered impaired and can result in penalties, including loss of driving privileges. A BAC of 0.08 or higher is considered intoxicated. A field sobriety test: The officer will ask the driver to perform a series of tasks, such as: - Standing on one foot - Touching their nose - Walking a straight line The officer will observe the driver's behaviour and performance during these tasks to determine if they are impaired. Factors that may affect this test: - Time of Day: the time of day can affect the accuracy of field sobriety test results. For example, a driver may be more tired or distracted at night. - Weather Conditions: weather conditions, such as rain or snow, can affect the driver's ability to perform the tasks. - Physical Limitations: The driver's physical limitations, such as injuries or disabilities, can affect their ability to perform the tasks. Myths about breathalyzers: Myth: You can disguise the odour of alcohol with food or mouthwash.  Reality: The alcohol comes from your blood, not your mouth, so food or mouthwash will not affect the breathalyzer test results. Court proceedings & breathalyzer test: In court, the prosecution will present evidence, including the field sobriety and breathalyzer test results. The defence will try to challenge the evidence and raise doubts about the accuracy of the tests. The judge or jury will then decide based on the evidence presented. Addictions Lecture 5 - Sedative-Hypnotic and Anxiolytics Barbituates: Class of anxiolytic medications that have been used for over a century. The first barbiturate, phenobarbital, was introduced as a sedative in 1912. A barbiturate medication has a specific chemical structure characterized by a central hexene ring with three binding sites. This basic structure is often referred to as the "barbiturate nucleus." Mechanism of action: Barbiturates have a non-selective neuronal depression effect, which reduces the overall firing of neurons in the brain. This is achieved by: Reducing electrical activity → action potentials Reducing metabolic activity → glucoseconsumption Dose-dependent relationship: The more medication is administered, the greater the effect. Reducing brain activity: Barbiturates reduce brain activity by decreasing whole-brain glucose metabolism and reducing the amount of glucose consumed by the brain. Glutamate and NMDA receptors: Glutamate: an excitatory neurotransmitter NMDA Receptor: a type of receptor that glutamate binds to, allowing an influx of ions and causing activation "Glutamate is excitatory, so it's like the gas pedal. When glutamate binds to the NMDA receptor, it opens the receptor and causes an influx of ions, leading to activation." Barbiturates and NMDA receptors: Barbiturates: a type of drug that acts as an NMDA receptor antagonist NMDA Receptor Antagonist: a substance that blocks the NMDA receptor, preventing glutamate from binding and reducing excitation "Barbiturates block the NMDA receptor, preventing glutamate from binding and reducing excitation. This is like taking your foot off the gas pedal, reducing the brain's overall activity." The amnesic properties of barbiturates: Amnesia: memory loss or forgetting Glutamatergic Transmission: the process by which glutamate is released and binds to receptors "The amnesic properties of barbiturates are due to changes in glutamatergic transmission. By blocking the NMDA receptor, barbiturates reduce glutamate activity, leading to memory loss." GABA and GABA receptors: GABA: an inhibitory neurotransmitter  GABA Receptor: a type of receptor that GABA binds to, allowing an influx of chloride ions and causing inhibition "GABA is inhibitory, so it's like the brakes. When GABA binds to the GABA receptor, it opens the receptor and allows chloride ions to come in, leading to inhibition." Barbiturates and GABA Receptors: Barbiturates: a type of drug that enhances GABA transmission GABA Transmission: the process by which GABA is released and binds to receptors "Barbiturates enhance GABA transmission, allowing more chloride ions to come in and increasing inhibition. This is like applying more brakes, reducing the overall activity of the brain." The effects of barbiturates on GABA receptors: - Sedative-Hypnotic Actions: the ability to induce sleep or relaxation - Anesthetic Properties: the ability to induce a loss of sensation or consciousness - "The increased influx of chloride ions caused by barbiturates accounts for their sedative-hypnotic actions and anesthetic properties." The structure of the GABA Receptor: - The GABA receptor has multiple binding sites, including sites for GABA, benzodiazepines, barbiturates, and other substances. - The receptor also has a chloride ion pore, where chloride ions pass through and cause inhibition. The toxicity of barbiturates: Toxicity: the ability of a substance to cause harm or damage GABA Receptor Activation: the process by which the GABA receptor is activated, allowing chloride ions to come in and causing inhibition. "Barbiturates can open the chloride ion channels in the absence of GABA, leading to uncontrolled inhibition and increasing the toxicity of the drug." Mechanism of action: Barbiturates work by enhancing the activity of the neurotransmitter GABA. Imagine a scenario where multiple doors need to be opened with a key. Barbiturates make it easier for these doors to open, but at high doses, they can cause them to open uncontrollably, leading to a loss of control. Therapeutic index: The therapeutic index measures a drug's safety. It is calculated by dividing the LD50 (lethal dose) by the ED50 (effective dose). A narrow therapeutic index indicates a drug can quickly become toxic at high doses. Dementia: Dementia is a state characterized by a decline in cognitive function, including: - Sensorium - Orientation - Affect - Mental content - Intellectual function - Insight and judgment To be classified as demented, an individual must exhibit at least 5 of these 12 components. Pharmacokinetics: Barbiturates have a wide range of half-lives, from 3 minutes to 120 hours. The half-life of a drug is the time it takes for the body to eliminate half of the drug. Absorption: Barbiturates are rapidly and completely absorbed, with lipid solubility—the ability of a drug to dissolve in fat or lipids—playing a key role in this process. - "Lipid solubility is important because our cell membranes comprise lipids. The more lipid-soluble a drug is, the easier it is for it to pass through the cell membrane and reach its target site." Pharmacological effects: Barbiturates have low selectivity, affecting multiple receptors and brain regions rather than targeting a specific site. - "It's like using a big hammer to fix a small watch. You might fix the problem, but you'll also damage the surrounding area." Suppression of REM sleep: Barbiturates suppress REM sleep, which is the stage of sleep where dreams occur. REM sleep is characterized by: - Rapid eye movement - Paralysis of the body to prevent acting out dreams - Increased brain activity - Lasts between 10-15 minutes at the beginning of the night - Episodes get longer and longer as the night progresses - Important for memory consolidation and restoration - Removal of REM can lead to mood changes, personality changes, and impaired cognitive function. Characteristics of barbiturates: Therapeutic Range: the doses within which a medication is effective and safe. Barbiturates have a narrow therapeutic range, making it easy to overdose. Tolerance and Dependence: barbiturates have a high potential for tolerance and dependence, leading to addiction. Teratogenic Potential: barbiturates may have teratogenic effects, although the evidence is weak. This means that taking barbiturates during pregnancy may lead to birth defects or other complications. The myth of truth serum: The idea of a "truth serum" is a myth. Barbiturates are sometimes used to make people more open to suggestions, but they do not force people to tell the truth. Non-barbiturates: Non-barbiturates are a class of sedative-hypnotics with a chemical structure different from barbiturates but exhibit similar properties. - Examples: Soma, Qualu, Paraldehyde Characteristics: - Sedative and hypnotic effects - Different chemical structure than barbiturates Qualu: Qualu is a non-barbiturate sedative-hypnotic that was popular in the 1970s and 1980s. Characteristics: - Sedative and hypnotic effects - Anaphrodisiac properties - Banned in the US in 1984 due to its use as a date rape drug  An anaphrodisiac is a substance that decreases sexual desire or arousal. General anesthetics: General anesthetics are potent central nervous system depressants used in medical settings to induce unconsciousness. Examples: Isoflurane, Halothane, Nitrous Oxide Characteristics: - Potent central nervous system depressants - Can be inhaled or IV injected - Used in medical settings, such as surgery and dental procedures Halothane: Halothane is a general anesthetic that was commonly used in the past. Characteristics: - Potent central nervous system depressant - Volatile, meaning it can quickly evaporate and be inhaled - It can cause addiction and negative experiences GHB Gamma Hydroxybutyrate GHB is a potent central nervous system depressant that is linked to GABA. - Potent central nervous system depressant - Inhibitory, meaning it decreases neural activity - Structurally similar to GABA - Normally found endogenously in the body, but can be taken in high concentrations. - Used in medical settings, such as sleep disorders and alcohol detoxification Aphrodisiac: increases sexual desire or arousal. Anaphrodisiac: decreases sexual desire or arousal. Addictive: can cause physical dependence and withdrawal symptoms Synergistic: increases the effect of another substance when taken together. Pharmacokinetic properties: - Absorbed within 30-75 minutes - Rapidly metabolized, with a half-life of 30 minutes - Low urine detectability Synergistic effects with alcohol: GHB has synergistic effects with alcohol, meaning that the combination of the two substances can have a greater effect than either substance alone. - Synergistic effects occur when the combination of two substances has a greater effect than the sum of their individual effects. Date rape drug: GHB has been used as a date rape drug due to its ability to cause sedation and unconsciousness when combined with alcohol. Characteristics: - It can be easily added to drinks without detection - Can cause sedation and unconsciousness within 15-20 minutes - It can be used to facilitate sexual assault. GHB increases dopamine levels in the brain, activating the dopamine reward pathway. Dopamine is often referred to as "happy juice" because it is associated with feelings of pleasure and satisfaction. Narcolepsy and GHB  Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and sudden attacks of sleep. - GHB is sometimes used to manage narcolepsy by increasing dopamine levels in the brain. Antiepilpetic drugs and neuromodulators: Antiepileptic drugs are a class of medications that are used to treat epilepsy and can be used to treat other conditions, such as bipolar disorder. - These drugs, also known as neuromodulators, impact neuronal function and can have a wide range of applications. Teratogenic effects: - It can cause birth defects if taken during pregnancy. - This raises concerns for women who are pregnant or planning to become pregnant and are taking these medications. Benzodiazepines and anxiolytics: Benzodiazepines are a class of medications that are used to treat anxiety, insomnia, and seizures. - They are also known as anxiolytics, as they have a calming effect on the nervous system. Benzodiazepines: Benzodiazepines are a class of psychoactive drugs that have a specific chemical structure. - They have a general structure with 5 binding sites, which can be modified to create different compounds with different properties. - Librium - Diazepam → Valium - Alprazolam – Xanax How they work: - Benzodiazepines facilitate the binding of GABA to its receptor, making it easier for GABA to bind and open the chloride ion channel. - This leads to an influx of chloride ions, which hyperpolarizes the neuron and increases inhibition. Pharmacokinetics of benzos: - Absorption: Benzos are well absorbed with a peak blood concentration in about an hour - Half-Life: The time it takes for the drug to be reduced by half in the body - Active Metabolites: Some benzos produce active metabolites that can affect the body. Effects on different brain regions: - Cerebral Cortex = Mental confusion, amnesia - Hippocampus = Memory impairment, amnesia - Spinal Cord = Muscle relaxation - Cerebellum = Anti-epileptic effects - Brainstem = Muscle relaxation - Nucleus Accumbens = Behavioral and rewarding effects Use of benzos: - Short-term treatment of stress-related anxiety and insomnia. - They are not commonly used for long-term treatment due to their potential for dependence and cognitive impairment. Advantages: Lower level of side effects compared to benzodiazepines, good patient acceptance. - Fast-acting - Effective for short-term treatment of anxiety and insomnia. Disadvantages: Impairs psychomotor performance, cognitive inhibitors, reduces alertness, potential for tolerance and dependence, and paradoxical agitation. The effect of benzodiazepines on neurons: They can increase the activity of GABA, leading to an influx of chloride ions and increased inhibition They can reduce the activity of neurons by reducing the release of excitatory neurotransmitters They can affect the activity of other neurotransmitters, such as dopamine and serotonin Complete agonists: A complete agonist is a drug that binds well to a receptor and facilitates the action of a neurotransmitter. Diazepam is an example of a complete agonist that facilitates GABA binding and reduces anxiety. GABA: a neurotransmitter that inhibits the activity of neurons. Selectivity and specificity: Selectivity: the ability of a drug to bind to a specific receptor or target. Specificity: the ability of a drug to produce a specific effect without affecting other parts of the body. Cognitive behavioural therapy: "Cognitive Behavioral Therapy is a type of psychotherapy that focuses on identifying and changing negative thought patterns and behaviours that contribute to a person's mental health issues." Limitations of combining CBT and benzo: - Combining CBT with benzodiazepines is not ideal because benzodiazepines can impair cognitive function, making it difficult for individuals to engage in CBT fully. Anterograde amnesia and Rohypnol: "Anterograde amnesia refers to the inability to form new memories after the onset of amnesia, while retrograde amnesia refers to the loss of memories formed before the onset of amnesia." Rohypnol, also known as a "roofie," is a benzodiazepine that can cause anterograde amnesia. - It has been used clinically to induce amnesia, but its use has been associated with synergistic effects with alcohol and has been implicated in cases of date rape. Flumazinil: Flumazinil is a GABA_A Antagonist. - A GABA_A antagonist is a medication that blocks the GABA_A receptor, preventing the binding of benzodiazepines and other substances. Flumazenil binds with high affinity to the benzodiazepine binding site on the GABA receptor, exhibiting no intrinsic activity. - It blocks the ability of benzodiazepines to interact with the benzodiazepine site, preventing the facilitation of GABA binding. Ambien: Ambien is a non-benzodiazepine benzotiazidine that is used to treat insomnia. It is a partial agonist that binds to the GABA 1a receptor. A partial agonist is a medication that binds to a receptor but only partially activates it. Ambien has a short half-life and is rapidly absorbed by the GI tract. It is used as a sedative but not as an anxiolytic. Busebarm: Busebarm is an anxiolytic medication that targets 5-HT1A receptors. It has little to no hypnotic action, low levels of amnesia and low dependence. Case study: Heath Ledger:  Heath Ledger was an actor who died from an accidental overdose of prescription medications. The autopsy report showed that he had a combination of anxiolytics, hypnotics, and pain medications in his system. - Anxiolytics: Xanax, Valium - Hypnotics: Ambien, Restoril - Pain medications: OxyContin, Vicodin "He depressed his system too much that it didn't work anymore." Addictions Lecture 6 - Cocaine Cocaine: Cocaine is a cyclostimulant, a type of stimulant that affects the body's physiological processes. - It is derived from the Erythrosaline cocoa plant, which is native to the mountain ranges of South America. "A crystalline tropane alkaloid is a compound with a specific chemical structure, which allows it to interact with the body's receptors and produce its effects." Units of cocaine: - Key = 1 kilogram Half-life and elimination: - The half-life of a drug is the time it takes for the body to eliminate half of the substance. - To calculate the time it takes for the body to eliminate a substance, multiply the half-life by 6. - For cocaine, this would be 6 x 50 minutes = 300 minutes or 5 hours. Methods of consumption: - Oral: slower onset and less pronounced effects due to first-pass metabolism - Intranasal (snorting): faster onset and shorter duration - Intravenous (shooting): fastest onset and shortest duration - Smoking (crack cocaine): a different form of cocaine with a unique production - process Historical figures and cocaine: Sigmund Freud, a famous psychologist, prescribed cocaine in 1884 and believed it to be a cure-all for various ailments. He even used it himself and wrote about its effects in his journals. - "Freud believed that cocaine was a magical cure-all drug that could solve all problems." Cocaine was initially thought to be a cure-all for opioid addiction, but it was later discovered to have severe addiction and abuse liability. - The half-life of cocaine is approximately 50 minutes. Metabolism and detection: Cocaine is metabolized into Benzoylglycagon, a compound that can be detected in the body for up to 2 weeks after initial use. This metabolite is a biomarker for cocaine use. Cocaine can be detected in the brain for up to 8 hours and in urine for up to 12 hours after initial use. Interactions with ethanol: When cocaine and ethanol are consumed together, they produce a byproduct called Chocathalene. Chocathalene blocks the presynaptic dopamine reuptake transporter, increasing dopamine levels in the synaptic cleft. - This can amplify the effects of cocaine and increase its toxicity. Vasconstriciton and vasodilation:  "Vasoconstriction refers to the narrowing of blood vessels, while vasodilation refers to the widening of blood vessels." Cocaine hydrochloride is a vasoconstrictor, meaning it narrows blood vessels. This can be counterproductive, reducing blood flow and oxygen delivery to tissues. Cocaine hydrochloride: Cocaine hydrochloride is a form of cocaine that is commonly used as a recreational drug. It is highly addictive and can have serious negative effects on the body. "Cocaine hydrochloride is a highly addictive substance that can cause serious negative effects on the body, including increased heart rate, blood pressure, and risk of overdose." Properties: - Highly addictive - Increased heart rate, blood pressure, and risk of overdose - The burning point is high, making it difficult to smoke Crack cocaine: Crack cocaine is a form of cocaine hydrochloride that has been mixed with other substances to create a paste. This paste is then dried to create small rocks that can be smoked. "Crack cocaine is a highly addictive and potent form of cocaine that is smoked to produce a rapid and intense high." Properties: - Small rocks that can be smoked - Highly addictive - Potent: produces a rapid and intense high Effects of smoking crack cocaine: - Smoking crack cocaine can produce a rapid and intense high, but it also has serious - negative effects on the body. - Rapid high: smoking crack cocaine can produce a high in as little as 8-10 seconds. - Short duration: the high from smoking crack cocaine typically lasts only 5-10 minutes. - Increased addiction: the rapid and intense high from smoking crack cocaine can lead to increased addiction. Pharmacological characteristics of cocaine: Potent Local Anesthetic: cocaine can be used as a local anesthetic to numb pain. Vasoconstrictor: cocaine causes blood vessels to constrict, which can limit bleeding or blood flow. Cycle Stimulant: cocaine affects the brain and is rewarding, making it a neuromodulator. Neurotransmitters affect by cocaine: Dopamine: associated with the dopamine reward pathway and addiction Norepinephrine: associated with mood, anxiety, depression, and other psychiatric conditions Serotonin: associated with mood, appetite, and sleep regulation Dopamine and cocaine addiction: "Dopamine changes are associated with the behavioural reinforcing effect of cocaine and the psychostimulant properties." - Cocaine increases dopamine release in the nucleus accumbens, a key area of the brain involved in reward and addiction. - This leads to positive reinforcement and activation of the dopamine reward pathway. Mechanism of cocaine actions (dopamine): 1. Dopamine Release: Cocaine causes the release of dopamine from the presynaptic neuron. 2. Dopamine Binding: Dopamine binds to dopamine receptors on the postsynaptic neuron.  3. Dopamine Reuptake: Dopamine is returned to the presynaptic neuron through dopamine reuptake transporters. This process is disrupted by cocaine, leading to an increase in dopamine levels and activation of the dopamine reward pathway. Cocaines interaction with dopamine reward pathway (activates): - Blocking the dopamine reuptake transporter - Increasing dopamine release in the VTA - Activating dopamine receptors in the NA and PFC Serotonin role in cocaine effects: Research suggests that serotonin is also involved in the response to cocaine. The 5-HT1B receptor is thought to play a role in the euphoric and addictive properties of cocaine. Cocaine effect on brain activity: Decreased whole-brain glucose metabolism Increased activity in the VTA and NA Activation of the dopamine reward pathway Short-term effects: - Euphoria: a feeling of intense happiness or excitement - Increased energy: cocaine can increase alertness and energy levels - Increased confidence: users may feel more confident and outgoing - Loss of appetite: cocaine can suppress appetite and lead to weight loss - Increased heart rate and blood pressure: cocaine can increase heart rate and blood pressure, which can lead to cardiovascular problems Long-term effects: - Cardiovascular problems: cocaine can increase the risk of heart attack, stroke, and other cardiovascular problems. - Respiratory problems: cocaine can cause respiratory problems, including bronchitis and pneumonia. - Nasal septal perforation: cocaine can cause damage to the nasal septum, leading to a hole in the septum. - Cerebral ischemia: cocaine can reduce blood flow to the brain, leading to a range of cognitive and neurological problems. Medium to high dose effects: - Progressive loss of coordination: users may have difficulty with balance and coordination. - Rebound depression: users may experience a crash or comedown after the effects of the cocaine wear off. - Anxiety and paranoia: users may feel anxious or paranoid. - Increased risk of seizures: cocaine can increase the risk of seizures, particularly in people with a history of seizure disorders. Atherosclerosis: Cocaine use can increase the risk of atherosclerosis, a condition in which the arteries become narrowed and hardened due to the buildup of plaque. - This can lead to a range of cardiovascular problems, including heart attack and stroke. Psychoses associated with mood disorders: Long-term cocaine use can lead to a range of psychoses associated with mood disorders, including: - Anxiety: feelings of anxiety or fear - Paranoia: feelings of paranoia or suspicion - Hyperactivity: increased energy and activity levels - Aggressive behaviour: increased aggression or irritability  - Toxic paranoid psychosis: a condition in which users experience a range of psychotic symptoms, including hallucinations and delusions Treatment: There is no generally accepted treatment for cocaine addiction. Potential pharmacological interventions include: - Aversive agents: medications that make users feel sick after consuming cocaine - Dopaminergic agents: medications that manage the effects of dopamine on the brain "Cocaine addiction is a complex condition that requires a comprehensive treatment approach. While there is no magic pill to cure addiction, a range of medications and therapies can help users manage their symptoms and achieve recovery." Can be treated with: - Bupropion: a medication that gives a little extra dopamine but is not addictive. - Topiramate: an anti-craving agent used for various addictive substances. - Drug substitution: replacing cocaine with a less addictive substance to help manage withdrawal symptoms. - Agents for comorbid disorders: treating underlying conditions, such as depression, that may contribute to cocaine use. Cocaine vaccine: A vaccine has been developed to prevent the entry of cocaine into the brain, but its effectiveness is still being studied. The vaccine works by: - Producing antibodies that block the entry of cocaine into the brain - Reducing the effects of cocaine on the brain However, the vaccine is not without side effects, and its use is not yet widespread. Historical use of cocaine: Cocaine was first isolated from coca leaves in the mid-19th century and was initially used for various medical purposes, including: - Local anesthesia - Pain relief - Treatment of fatigue and exhaustion - Cocaine was also used in various products, including Coca-Cola, Cough drops, Hair tonics, Tooth drops. Whitney Houston Autopsy Report: Perforated nasal septum, indicating long-term cocaine use Clear arterial sclerosis of the coronary arteries, a sign of cocaine consumption Presence of various substances in her blood, including: - Xanax - Cocaine - Amzalexinone - Carboxy THC and THC These findings suggest that Whitney Houston had a history of cocaine use and had consumed multiple substances on the night of her death. Amphetamines: Amphetamines are a type of stimulant that can produce feelings of euphoria and increased alertness. They are sometimes referred to as sympathomimetic agents because they mimic the actions of adrenaline. - Sympathomimetic agents: substances that mimic the actions of adrenaline, a hormone that prepares the body for "fight or flight" responses. Amphetamines can cause: - Vasoconstriction  - Hypertension - Tachycardia Historical use: - Military: given to soldiers to combat fatigue during World War 2 - Diet pills: used as a standard ingredient in diet pills until the 1960s and 1970s - ADHD treatment: used to treat attention deficit hyperactivity disorder. Mechanism of action: - Increasing presynaptic dopamine release - Interacting with vesicles to release more dopamine - Blocking the dopamine reuptake transporter - This leads to an increase in dopamine in the synaptic cleft, producing euphoria and increased alertness. Effects of amphetamines: - Low dose: increased blood pressure, heart rate, and alertness; bronchial muscle relaxation. - Moderate dose: increased respiration, tremors, restlessness, trouble sleeping, agitation, and euphoria. - Increased energy and alertness - Increased focus and concentration - Increased heart rate and blood pressure - Suppressed appetite - Insomnia - Anxiety and paranoia Chronic use of amphetamines: - Repetitive behaviors - Outbursts of aggression - Paranoid delusions - Severe anorexia - Irreversible brain changes Methamphetamine: Methamphetamine is a derivative of amphetamine that is more potent and has a longer duration of action. It is also known as "ice" and is often smoked. - "Methamphetamine is a highly addictive and potent stimulant that can cause severe physical and psychological addiction, as well as irreversible brain changes." Effects of methamphetamine: - Rapidly absorbed and highly potent - Causes severe physical and psychological addiction - It can be smoked, leading to rapid absorption and intense effects - It can cause long-term neurotoxicity, leading to irreversible brain changes Non-amphetamine stimulants: Non-amphetamine stimulants are a class of stimulants that are similar to amphetamines but have a different chemical structure. Ephedrine: Ephedrine is a non-amphetamine stimulant that is often used as a weight loss supplement. It works by increasing the release of epinephrine, which increases heart rate and blood pressure. - "Ephedrine is a non-amphetamine stimulant that can increase energy and alertness, but can also have severe side effects, including increased heart rate and blood pressure." Effects: - Increased energy and alertness - Increased heart rate and blood pressure  - Water retention - Sweaty palms - Anxiety and insomnia Ritalin: Ritalin is a non-amphetamine stimulant that is often used to treat ADHD. It works by blocking the dopamine transporter and increasing dopamine release. - "Ritalin is a non-amphetamine stimulant that can increase focus and concentration, but can also have severe side effects, including increased heart rate and blood pressure." Effects of Ritalin: - Increased focus and concentration - Increased heart rate and blood pressure - Mediated by serotonin - Used to treat ADHD