Module 2 - Drug Misuse and Addiction PDF

# Module 2 - Drug Misuse and Addiction ## 01 - Substance Use Disorder ### The Opioid Crisis - From Jan 2016 - Sept 2020, 19,395 Canadians died from apparent opioid overdose. - This is a person roughly every 2 hours. - 70% were less than 50 years old. ### Substance Use Disorder (SUD) - Defined and...

# Module 2 - Drug Misuse and Addiction ## 01 - Substance Use Disorder ### The Opioid Crisis - From Jan 2016 - Sept 2020, 19,395 Canadians died from apparent opioid overdose. - This is a person roughly every 2 hours. - 70% were less than 50 years old. ### Substance Use Disorder (SUD) - Defined and clinically diagnosed by a number of criteria: - **Social Impairments**: The individual fails to fulfill major roles (ie work, school, etc) and/or has persistent social or interpersonal problems. Social, occupational, recreational activities may have been given up or reduced. - **Risky Use**: Individual may use substance in physically dangerous situations or despite physiological or psychological problems caused by use (ie drinking/driving). - **Impaired Control**: May have persistent cravings for the substance (ie addiction). - **Withdrawal**: May experience withdrawal syndrome after stopping use of substance (ie not getting the original dose). - **Tolerance**: May develop a tolerance to the substance (ie more drug to meet the same effect). - If an individual meets 2 criteria they are classified as having mild SUD. - The more criteria they meet the more severe the SUD. ### Addiction - The persistent craving for a drug regardless of consequence and the emotional + mental preoccupation with the drug's effects. - The state in which stopping or abruptly reducing the dose produces non-physical symptoms. - Doesn't only occur in drugs (ie gambling, shopping, etc). ### Dopamine Hypothesis - The predominant hypothesis to explain addiction. - Suggests that commonly misused drugs increase dopamine in the reward system of the brain. - Other neurotransmitters are involved, but dopamine appears to be the key component of the brain's reward system. - Drugs associated with addiction (ie cocaine) cause an exaggerated increase in dopamine, altering communication to the brain. ### Characteristics of Addictive Drugs - Increase dopamine (alcohol, cannabis, nicotine, cocaine, morphine, heroin) - Produce novelty (LSD, ecstasy) - Reduce Anxiety (benzodiazepines & depressants) ## Drug Withdrawal - An abnormal physiological state produced by repeated use of a drug that leads to the appearance of a withdrawal syndrome when drug use is discontinued or dose is decreased. - Severity increases with the speed of drug withdrawal. - The biological processes accommodated to the drug's presence don't have time to reverse themselves. - The fear of withdrawal can be a factor in the continuation of drug use. - Withdrawal Symptoms of **Stimulants**: - Sleepiness - Low Moods - Muscle Pain - Suicidal Intentions - Anxiety - Tremors - Cardiovascular problems - Withdrawal Symptoms of **Opioids**: - Sweating - Muscle Aches - Diarrhea - Abdominal Cramping - Agitation - Vomiting ## Drug Tolerance - A shortened duration of action and a decreased magnitude of effect. - Extent and rate of development is specific for each drug. - Doesn't develop to all drugs, nor to all aspects of a drug's action. - Is reversible upon drug discontinuation. ## Cross Tolerance - The resistance or tolerance to one drug because of the resistance or tolerance to a pharmacologically similar drug. - Ex. A person with a tolerance to the CNS depressant, alcohol, would also be tolerant to CNS depressant benzodiazepines, even if they have never taken them. ## Factors Influencing SUD - **Genetics**: Can predispose an individual to SUD (associated with addiction). - Ie. Genetic mutations in the dopaminergic pathways confer an increased risk of SUD. - **Pre-Existing Disorders**: Individuals w BPD, depression, anxiety, etc. are at a higher risk for SUD. - **Environments**: Some increase the likelihood and/or promote drug use/misuse which increases the risk (ie family dynamics, trauma, social/work groups). - **Developmental**: Individuals are more vulnerable during certain developmental timeframes. ## Stigma of SUD - The stigma of SUD and people with SUD may lead to isolation and low self-esteem which may consequently result in individuals not receiving the social or medical help they need. ## Harm Reduction - An approach that seeks to reduce/prevent the negative consequences of substance abuse and improve health without judgment, coercion, or discrimination without necessarily requiring the person to stop using the substance. - **Health Harms**: Goal to decrease morbidity and mortality (death from infection, death from overdose). - **Societal Harms**: Goal to decrease lost productivity, apprehension of children, and criminal activity. - Supervised injection sites are a strategy in harm reduction. ## Prescription Use vs. Misuse of Substances - SUD can occur with either prescribed medications or with misuse of substances. ## Misuse Potentials - The tendency of the drug to be misused. - Varies from drug to drug and individual to individual. - **Nature of the Drug**: Most legal, not all, drugs are natural reinforcers. The pleasurable effects produced by a drug increase the probability that the drug will be taken again. - High pleasure = high potential for misuse. - **Route of Administration**: Drugs administered via routes that give rapid absorption and effects have a greater potential for misuse than those that are slower. - **Amount/Frequency of Use**: The greater the dose and frequency, the greater the misuse potential. - **Availability**: The more widespread the drug, the more likely it will be misused. - **Inherent Harmfulness**: Refers to the potential of a drug to cause harm. If a drug is perceived to be a serious risk to life/health, it won't be used as much (if at all), even if widely available. ## 02 - Amphetamines and Cocaine - Amphetamines and cocaine are two classes of CNS stimulant drugs that have a history of being misused. - Their use is restricted to certain medical conditions. ## Amphetamines - Drugs of widespread misuse and are controlled substances in Canada. - Methylphenidate (Ritalin) is used to treat ADHD. - MDMA (ecstasy) is a derivative of this which is often misused. - Fosters feelings of intimacy and empathy, while also improving intellectual capacities. - Is neurotoxic, meaning it causes long-lasting or permanent neuronal damage and death. ### They are: - Synthetic organic compounds chemically similar to the neurotransmitters norepinephrine and dopamine. - Can be synthesized readily. - Often illegally manufactured. - The purity of these substances is variable. ### Increase Excitation - They increase dopamine and norepinephrine by being transported into the presynaptic neuron where they block the repackaging of dopamine/nore. - Creates a large tone of dopamine/nore, resulting in them moving back out to the synaptic cleft through the transporters. - So now more in the cleft. ### Effects: - Decreased threshold for transmitting sensory input to cerebral cortex. - Leads to CNS excitation. - This can cause dizziness, overstimulation, confusion, tremors, and sometimes panic/psychosis. - Feeling of euphoria and reward. - Temperature regulation and feeding center modifications, leading to appetite suppression. - Increase in aggressive behavior and mood swings. ### Short-Term Effects (Main CNS) - Chest pain or heart attack (high doses). - Cardiovascular Collapse (really low blood pressure). - Increased respiratory rate. ### Long-Term Effects: - Chronic sleeping problems. - Poor appetite. - Anxiety, repetitive behavior, psychoses, aggressive behavior. - Elevated blood pressure and abnormal cardiac rhythm. ### Therapeutic Uses: - Narcolepsy - Chronic sleep disorder. - ADHD - Hyperactivity, impulsivity, attention issues (used to treat Ritalin). ### Potential for Misuse: - Is extremely high. - Due to the feelings of euphoria produced and how they are readily injectable, leading to a rapid and intense response. - Their inherent harmfulness comes from its long-term effects. Therefore it is not much of a deterrent. ### Potential for SUD: - Tolerance develops to the euphoric/mood elevating effects, cardiovascular/respiratory effects, and the lethal effects but not the therapeutic ones. - Withdrawal: Cessation of use will result in mood depression (ie, profound sleepless, huge appetite, lack of energy, and fatigue). - Addiction: The rewarding effects cause those taking it to crave the effects so intensely that they will panic if it's not available. ## Cocaine - Known in pharmacology as a local anesthetic + CNS stimulant, and lawfully as a narcotic. - One of the most popular recreational drugs. - Has a shorter duration of action (~less than an hour). - Amphetamines are up to 12 hours. - Commonly smoked or sniffed. ### Mechanism of Action: - Inhibits the reuptake of mainly dopamine and serotonin. - Increases their concentration in the synaptic cleft. - In turn increases the activation of the receptors on the postsynaptic neuron. ### Therapeutic Uses: - The only legitimate use is for local anesthetics in the throat and mouth. - Though rarely used as better anesthetics have been developed. - They have similar chemical structures, but not associated with the potential of misuse and SUD. ### Long-Term Effects: - Toxic psychosis (paranoia). - Hallucinations. - Impaired Sexual Functions. - Permanent brain damage and impairment of neural function. - High blood pressure and an irregular heart rhythm. - Changes to nasal mucosa. ### Consuming alcohol and cocaine at the same time can be very dangerous: - Results in the production of "cocaethylene". - Dangerously increases blood pressure, violent thoughts, and poor judgment. ### Potential for Misuse: - Has one of the highest misuse liabilities because of the powerful euphoric effect. - Inherent harmfulness does not seem to be a deterrent. ### Potential for SUD: - Tolerance develops for the euphoric effects but not psychotic effects. - Withdrawal develops more readily than amphetamines. - Addiction can occur as the rewarding effects reinforces repeated use. ## 03 - Nicotine and Caffeine - Nicotine and caffeine are two commonly used stimulant drugs. ## Nicotine ### The Cost of Tobacco to Society: - Each year, 48,000 Canadians die as a result of tobacco use. - This is more than traffic accidents, alcohol misuse, murder, and suicide combined. - The social and economic cost estimates ~ B16 billion per year in Canada. - A portion of this is offset by a variety of factors. ### ADME of Nicotine: - Nicotine is a naturally occurring substance found in tobacco. It is responsible for smoking addictions. - **Absorption**: Nicotine is in cigarette smoke as very small particles which are rapidly absorbed when inhaled. - Also absorbed from the GI tract, oral mucosa, and across the skin. - The dose absorbed can be controlled by the depth of inhalation and frequency of smoking. - **Distribution**: Distributed throughout the body rapidly and gains access to the brain. - **Metabolism**: Is metabolized rapidly in the liver. - **Excretion**: Metabolites are excreted in the urine. - The half-life in the body is ~2 hours. ### Mechanism of Action: - It stimulates nicotinic receptors at synapses. - Increases psychomotor activity, cognitive function, attention, and memory. - In large doses it can cause agitation, tremors, and seizures. - CNS effects are mediated partly by nicotinic receptor-mediated release of CNS neurotransmitters (dopamine + serotonin). ### Therapeutic Uses of Nicotine: - The only therapeutic use of nicotine is in smoking cessation programs. - It is administered in the form of chewing gum, transdermal patches, or buccal spray. - This attempts to maintain the blood nicotine levels and satisfy the craving for a cigarette, allowing for tapering of the nicotine use. ### Short-Term Effects of Smoking: - **In Regular Smokers**: - Mild euphoria - Enhanced arousal - Increased ability to concentrate - Sense of relaxation - Small heart rate increase - Small blood pressure increase - May suppress appetite - **In Non-Regular Smokers**: All disappear in chronic smokers. - Dizziness - Headache - Nausea - Vomiting - Abdominal Cramps - Coughing/Gagging ### Long-Term Effects of Smoking: - These effects are all related to the products of combustion in tobacco (Carbon monoxide, carcinogenic aromatic hydrocarbons, tars, etc). - **Cardiovascular Disease**: Carbon monoxide reduces the capacity of RBC to carry oxygen. - Both carbon monoxide and nitrogen increase the incidence of atherosclerosis and the formation of thrombi. - **Lung Disease**: Incidence of lung disease increases with smoking (ie. Smoker's Syndrome, which is difficulty breathing, wheezing, chest pain, congested lung, and increased lung infections). - Also increased risk of emphysema. - **Cancer**: The cancer risk associated with smoking has now been defined beyond a doubt. 30% of all cancers are estimated to be caused by cigarette smoke (ie, lung, oral, cavity/throat, bladder, and uterus). ### Passive Smoke: - Is associated with increased risk of cardiovascular disease and cancer. - In children, it increases the risk of bronchitis, pneumonia, asthma, and Sudden Infant Death Syndrome (SIDS). ### Smoking During Pregnancy: - Cigarette smoke has adverse effects on developing fetuses. - 2-3x increase in fetus being small or premature. - Effects will reverse if smoking ceases early in pregnancy. ### Potential for Misuse and SUD: - Health Canada states that tobacco products meet all requirements of addictive substances. - Unfortunately, attempts at cessation of smoking often fail, as the nicotine craving is so great. - Cessation programs usually involve counseling + pharmacological support. ### Tolerance: - Most smokers keep their nicotine blood levels at a certain range (30-40 ng/ml). - Tolerance develops to some aspects, but does not require increasing doses. ### Withdrawal: - Symptoms include: irritability, restlessness, anxiety, insomnia, fatigue, and inability to concentrate. - Upon waking up in the morning, a smoker is in a state of withdrawal. ### Addiction: - Occurs and manifests as an extreme urge to smoke. ## Caffeine ### ADME of Caffeine: - Caffeine is the most widely and regularly used drug in the world. It predominantly affects the CNS and cardiovascular system as a stimulant. - **Absorption**: Is taken orally and is rapidly and completely absorbed. - Caffeine blood levels are significant at 30 minutes, and peak after 2 hours. - **Distribution**: Distributes to all parts of the body. - Freely crosses into the brain and placenta. - **Metabolism**: Genetics influence the rate at which we metabolize and excrete caffeine. - People can be rapid or slow metabolizers. - Can explain why some people are more impacted by caffeine than others. - **Excretion**: Half-life varies among individuals from 2.5-10 hours. ### Mechanism of Action: - 100-250 mg of caffeine (equivalent to 1-2 cups of coffee), increases mental performance and motor activity while decreasing drowsiness and fatigue. - Caffeine blocks adenosine receptors in the brain. - This is done competitively. - These receptors, when activated, stimulate GABAergic neurons which inhibit dopamine release. - When these receptors are blocked by caffeine, GABA activation decreases and therefore dopamine release increases. - Causes the CNS to be stimulated. ### Short-Term Effects: - **On CNS**: - Produces mild mood elevation and reduces fatigue. - More clear and rapid flow-of-thought. - When taken by abstainers, it produces nervousness and can interfere with sleep. - High doses produce irritability, nervousness, rambling, and psychomotor agitation. - **Cardiovascular**: - Causes constriction of cerebral blood vessels (relieves headaches). - Increase peripheral blood flow and stimulates cardiac muscle (increases heart rate). - **Respiration**: - At high doses heart beat is rapid + irregular. - Mild stimulation of respiratory rate and relaxation of bronchial smooth muscle. - Clinically used to stimulate breathing in preterm babies. ### Long-Term Effects: - Restlessness - Nervousness - Insomnia - Increased urinary output - Gastric upset - Rambling speech + thought ### Caffeine and Smoking: - Cigarette smoke increases the metabolism of caffeine. - So smokers have a shorter duration of action of caffeine. - When smoking ceases, metabolism of caffeine returns to normal. ### Caffeine and Pregnancy: - Caffeine consumption is not associated with fetal abnormalities. - Though large doses (ie. 12 cups of coffee per day), during pregnancy has some effects. - Increases the chance of stillbirth from 4/1000 to 12/1000. - Slightly decreases fetal growth rate. - Slightly increases chances of miscarriage. - Metabolism of caffeine is slower in pregnant people. - 2x longer in the 2nd trimester, and 3x in the 3rd. - So pregnant people often decrease caffeine intake. ### Potential for Misuse and SUD: - Unlike nicotine, potential is low. - Inherent harmfulness is very low. - Only a mild euphoria is experienced. - Tolerance may develop in some individuals. - Mild addiction and withdrawal symptoms may occur. ## 04 - Drugs Used in Sports ### History of Drugs in Sports: - Started in the 1950s, with the use of amphetamines and anabolic steroids. - Use increased rapidly until sports regulatory bodies banned them. - World Anti-Doping Agency established in 1999. ### Amphetamines: - Powerful psychomotor stimulants which produce increased alertness, feeling of power, reduced fatigue, increased aggression, responsiveness, heart rate, and blood pressure. - All contribute to increased endurance and speed. - Also suppress appetite, which may be helpful in sports that benefit from weight loss. - Allows athletes to continue even when nearing exhaustion. ### Anabolic Steroids: - Most commonly banned drugs in sports. - Used to increase muscle mass and strength. - Synthetic anabolic steroids are what are typically used in sports. - They reduce the androgenic effects. - While maintaining anabolic effects (building of muscle mass, effects on secondary male sex characteristics - testosterone has both). - They produce an anti-catabolic response. - Blocks the use of muscle proteins for energy, so the athlete retains muscle mass. - Motivational responses/aggressive behavior can be produced. - Beneficial in most sports (ie, football). - Appear to have greater effects in those with low testosterone levels. - High doses produce the desired effects. - They cause a variety of side effects: - Mood swings - Acne - Decreased HDL - Increase LDL (bad cholesterol), so increase the risk of cardiovascular disease. - Altered liver function. - Reduction of testosterone levels. - May cause infertility. - Cause facial hair, lowered voice, lack of period, etc in women. ### Benzodiazepines: - Ex. Lorazepam or Diazepam. - Often used to combat insomnia/anxiety in elite athletes. - Allows them to recover faster from intense training. - However, at higher doses, they can impair psychomotor coordination and focus. ### Blood Doping and Erythropoietin: - Maximum performance is highly connected to the maximum ability of someone to deliver oxygen, which is done by RBC. - More RBC = better and faster delivery. - **Blood Doping**: - An effort to raise the number of RBC. - Done by removing blood from the body, storing it, then reinjecting it into the body's tissues (when reinjected, there is a sudden boost in RBC, which carry higher than normal amounts of O2, so performance increases). - **Erythropoietin (EPO)**: - Injection stimulates bone marrow to produce more RBC. - So more O2 gets to muscles, which boosts performance. - Both techniques are also used in the medical world. ### Diuretics: - Enhance the excretion of salts and water. - Used just before competition to reduce body water and allow athletes to compete in lower weight classes (ie, in wrestling, weight lifting, etc.). - Also sometimes used to hasten the excretion of other banned drugs to avoid detection. ### Comparing the Effects of Growing Barley in the Presence of Bacteria that Break Down Plant ACC and Without: - A diagram is drawn to visually illustrate the comparison. The diagram shows the lengths (in cm) of the root and shoot length of barley plants treated with bacteria vs. those in a control group.