Neurotransmitter System In Addiction

Question 1

What is drug addiction?

Answer 1

Drug addiction, also known as substance use disorder (SUD), is a complex condition characterized by compulsive drug-seeking, continued use despite harmful consequences, and neuroadaptive changes in the brain’s reward circuitry.
Several mechanisms contribute to the development and maintenance of drug addiction
Increased risk for relapse despite years of abstinence

Question 2

Differentiate between tolerance, sensitization and dependence

Answer 2

Tolerance – reduced drug effect after repeated use.
Sensitization – increased drug effect after repeated use.
Dependence – altered physiological state that leads to withdrawal symptoms upon cessation of drug use

Question 3

Differentiate between reward and reinforcement in addiction

Answer 3

Reward – Positive emotional effects.

Reinforcement – A stimulus that causes a response to be maintained and increased.

Positive reinforcement: increases behavioral response to get a positive reward (food, sex, etc.).

Negative reinforcement: increases behavioral response to end punishment (pain, starvation).

In this way, rewards and reinforcements in the environment powerfully shape an individual’s behavior.

Question 4

How is the reward pathway activated in addiction?

Answer 4

Many drugs of abuse activate the brain’s reward pathway, particularly the mesolimbic dopamine system.
Dopamine is a neurotransmitter involved in pleasure, reward, and reinforcement learning.
Drugs such as cocaine, amphetamines, opioids, and alcohol increase dopamine levels in the nucleus accumbens, a key brain region involved in reward processing.
This dopamine surge leads to feelings of euphoria and reinforces drug-seeking behaviors

Question 5

What effect does addiction have on neuroplasticity and learning?

Answer 5

Chronic drug use induces neuroplasticity changes in the brain, altering the structure and function of neurons and synapses.
These changes can lead to the formation of drug-related memories and associations, contributing to the conditioning of drug-seeking behaviors.
Neurotransmitter systems involved in learning and memory, such as glutamate and the endogenous opioid system, play crucial roles in the neuroplasticity underlying addiction.

Question 6

Describe the relationship between addiction, tolerance and dependence

Answer 6

With repeated drug exposure, tolerance may develop, requiring higher doses to achieve the same effects.
Dependence may also occur, characterized by physical and psychological withdrawal symptoms upon cessation of drug use.
Tolerance and dependence result from neuroadaptive changes in neurotransmitter systems, receptor downregulation, and alterations in neuronal excitability

Question 7

How do stress and craving contribute to addiction?

Answer 7

Stressful life events, environmental cues, and drug-associated stimuli can trigger intense cravings for drugs, contributing to relapse and continued drug use.
Stress activates the hypothalamic-pituitary-adrenal (HPA) axis and releases stress hormones such as cortisol, which can modulate neurotransmitter systems involved in addiction, including dopamine, serotonin, and GABA

Question 8

How do genetic and environmental factors contribute to addiction?

Answer 8

Genetic factors account for approximately 40-60% of the risk of developing addiction.
Variations in genes encoding neurotransmitter receptors, enzymes involved in drug metabolism, and signaling molecules can influence susceptibility to addiction.
Environmental factors, such as exposure to drugs during adolescence, peer pressure, trauma, and socioeconomic status, also play significant roles in addiction risk.

Question 9

How do co-occurring mental health disorders contribute to addiction?

Answer 9

Substance use disorders commonly co-occur with other mental health conditions, such as depression, anxiety, and post-traumatic stress disorder (PTSD).
These comorbidities may contribute to the initiation and maintenance of drug use and complicate addiction treatment

Question 10

How does addiction affect decision making and executive function?

Answer 10

Chronic drug use can impair cognitive functions such as decision-making, impulse control, and judgment, leading to maladaptive behaviors and continued drug-seeking despite negative consequences.
Dysfunction in prefrontal cortical regions involved in executive function may contribute to impulsivity and poor decision-making in individuals with addiction

Question 11

Which drugs block the dopamine pump?

Answer 11

Cocaine
Amphetamine

Question 12

Which drugs mimic neurotransmitters by activating receptors?

Answer 12

Morphine & other opiates
Nicotine
Marijuana

Question 13

Which drugs activate or inhibit channels?

Answer 13

Alcohol
PCP, ketamine

Question 14

What is the MoA of stimulant drugs?

Answer 14

Stimulants such as cocaine and amphetamines increase dopamine, norepinephrine, and serotonin levels, leading to increased alertness, euphoria, and heightened arousal

Question 15

What is the MoA of depressants?

Answer 15

Depressants such as alcohol, benzodiazepines, and opioids enhance the inhibitory effects of gamma-aminobutyric acid (GABA) or inhibit the excitatory effects of glutamate, resulting in sedation, relaxation, and decreased anxiety

Question 16

What is the MoA of hallucinogens?

Answer 16

Hallucinogens such as LSD and psilocybin alter perception, mood, and cognition by interacting with serotonin receptors and other neurotransmitter systems

Question 17

What is the general treatment approach to addiction?

Answer 17

Understanding the pharmacology of drug substance abuse is essential for developing effective treatment strategies.
Pharmacological interventions, such as medications for opioid addiction (e.g., methadone, buprenorphine) or alcohol dependence (e.g., naltrexone, acamprosate), target specific neurotransmitter systems to reduce cravings, withdrawal symptoms, and relapse risk.
Behavioral therapies, counseling, and support programs are also important components of addiction treatment

Question 18

Describe the pharmacodynamics of nicotine

Answer 18

Absorption is pH dependent
In acidic media
Ionized  poorly absorbed across membranes
In alkaline media
Nonionized  well absorbed across membranes
At physiologic pH (7.4), ~31% of nicotine is nonionized

Question 19

List nicotine’s withdrawal effects

Answer 19

Irritability/frustration/anger
Anxiety
Difficulty concentrating
Restlessness/impatience
Depressed mood/depression
Insomnia
Impaired performance
Increased appetite/weight gain
Cravings

Question 20

What is the MoA of nicotine?

Answer 20

Nicotine primarily exerts its effects by binding to and activating nicotinic acetylcholine receptors (nAChRs) in the central nervous system and peripheral tissues.
Activation of nAChRs leads to the release of neurotransmitters such as dopamine, norepinephrine, serotonin, and glutamate

Question 21

What are the effects of nicotine?

Answer 21

Enhanced mood
Increased alertness and arousal
Improved cognitive function
Appetite suppression

Question 22

How does nicotine activate the reward pathway?

Answer 22

Nicotine’s activation of nAChRs in the mesolimbic dopamine system, particularly in the ventral tegmental area (VTA) and nucleus accumbens, leads to the release of dopamine, a neurotransmitter associated with pleasure and reward.
This activation reinforces the desire to use nicotine, contributing to its addictive properties

Question 23

Describe tolerance and dependence of nicotine

Answer 23

With chronic nicotine use, tolerance can develop, requiring higher doses to achieve the same effects.
Dependence may also develop, characterized by withdrawal symptoms upon cessation of nicotine intake.
Nicotine withdrawal symptoms include irritability, anxiety, depressed mood, difficulty concentrating, increased appetite, and cravings for nicotine

Question 24

Explain the pharmacokinetics of nicotine

Answer 24

Nicotine is rapidly absorbed through mucous membranes in the mouth and lungs when tobacco products are smoked or chewed.
It reaches peak blood levels within minutes, producing rapid effects. Nicotine is metabolized primarily in the liver by the enzyme cytochrome P450 2A6 (CYP2A6) into inactive metabolites, which are then eliminated in the urine

Question 25

What is the MoA of alcohol?

Answer 25

Alcohol primarily acts as a central nervous system depressant, enhancing the inhibitory effects of the neurotransmitter gamma-aminobutyric acid (GABA) and inhibiting the excitatory effects of glutamate

Question 26

What are the effects of alcohol?

Answer 26

Sedation and relaxation
Decreased anxiety and inhibitions
Impaired judgment, coordination, and reaction time

Question 27

How does alcohol activate the reward pathway?

Answer 27

Alcohol consumption leads to the release of dopamine in the brain’s reward pathway, particularly in the nucleus accumbens, reinforcing the pleasurable effects of alcohol and contributing to its addictive potential

Question 28

Describe tolerance and dependence of alcohol

Answer 28

With repeated alcohol exposure, tolerance can develop, necessitating higher doses to achieve the desired effects.
Dependence may also develop, characterized by physical and psychological withdrawal symptoms upon cessation of alcohol intake.
Alcohol withdrawal symptoms include tremors, anxiety, sweating, nausea, insomnia, and in severe cases, seizures and delirium tremens

Question 29

Explain the pharmacokinetics of alcohol

Answer 29

Alcohol is rapidly absorbed through the stomach and small intestine and enters the bloodstream, reaching peak blood alcohol concentration (BAC) within 30 to 90 minutes, depending on factors such as the rate of consumption and presence of food in the stomach.
Alcohol is metabolized primarily in the liver by alcohol dehydrogenase (ADH) and other enzymes into acetaldehyde, which is further metabolized into acetate by aldehyde dehydrogenase (ALDH).
These metabolites are eventually converted into carbon dioxide and water and eliminated from the body via urine and exhalation

Question 30

List the drugs used in the management of alcohol abuse

Answer 30

Disulfiram
Naltrexone
Acamprosate

Question 31

What is the MoA of disulfiram?

Answer 31

Disulfiram- This drug blocks the oxidation of acetaldehyde to acetic acid by inhibiting aldehyde dehydrogenase. This results in the accumulation of acetaldehyde in the blood, causing flushing, tachycardia, hyperventilation, and nausea. Disulfiram has found some use in patients seriously desiring to stop alcohol ingestion.

Question 32

What is the MoA of naltrexone?

Answer 32

Naltrexone- is a competitive and relatively long-acting opioid antagonist that helps decrease cravings for alcohol

Question 33

What is the MoA of acamprosate?

Answer 33

Acamprosate- This drug is an agent used in alcohol dependence treatment programs and is thought to decrease cravings through its regulatory effects on N-methyl-D-aspartate (NMDA)-mediated glutamatergic excitation. This agent should also be used in conjunction with supportive psychotherapy

Question 34

Describe the treatment approach in opioid agonist maintenance therapy

Answer 34

Methadone: Methadone is a long-acting opioid agonist that helps prevent withdrawal symptoms and reduce cravings in individuals with opioid dependence. It is typically administered in a supervised clinic setting daily.
Buprenorphine: Buprenorphine is a partial opioid agonist that can be prescribed by qualified healthcare providers in office-based settings. It reduces opioid cravings and withdrawal symptoms while having a lower risk of respiratory depression and overdose compared to full opioid agonists like methadone.
Naltrexone: Naltrexone is an opioid antagonist that blocks the effects of opioids by binding to opioid receptors. It can help prevent relapse in individuals who have already undergone detoxification and are abstinent from opioids.

Question 35

What is nicotine replacement therapy?

Answer 35

Nicotine Patch, Gum, Lozenge, Inhaler, Nasal Spray: NRT provides a controlled dose of nicotine to help reduce cravings and withdrawal symptoms in individuals trying to quit smoking.
It is available over-the-counter and by prescription

Question 36

Which medications are used in stimulant use disorder?

Answer 36

Bupropion: Bupropion is an antidepressant that may help reduce cravings and withdrawal symptoms in individuals with stimulant use disorder. Its precise mechanism of action in treating SUDs is not fully understood.
Modafinil: Modafinil is a wakefulness-promoting agent that has shown some efficacy in reducing cocaine cravings and improving cognitive function in individuals with cocaine use disorder.

Question 37

Which adjunctive medications are used to treat substance use disorders?

Answer 37

Antidepressants: Selective serotonin reuptake inhibitors (SSRIs) and other antidepressants may be prescribed to manage co-occurring mood disorders and reduce symptoms of depression and anxiety in individuals with substance use disorders.
Anticonvulsants: Certain anticonvulsant medications, such as gabapentin and topiramate, have shown promise in reducing cravings and promoting abstinence in individuals with alcohol and substance use disorders.