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Questions and Answers
What defines addiction as a behavior or substance dependence?
Which neurotransmitter is primarily involved in the craving component of addiction?
What is one of the immediate effects of substance withdrawal?
Which part of the brain is involved in measuring the 'goodness' of a reward based on dopamine release?
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What aspect of addiction is more associated with the opiate systems?
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What is meant by building up a tolerance in substance use?
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How do glutamate projections from the nucleus accumbens influence behavior during addiction?
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What is considered an immediate effect of substance intoxication?
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What is the primary function of the GABAA receptor when GABA is released?
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Which substance is known to enhance the action of GABA at its receptor sites?
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What characterizes GABAB1 receptors in comparison to GABAB2 receptors?
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What happens during benzodiazepine overdose?
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Which of the following factors increases the severity of benzodiazepine withdrawal?
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How long can benzodiazepine withdrawal symptoms last?
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What is a common effect of intoxication from sedative/hypnotics?
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What is the primary goal in treating a PCP intoxicated patient?
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Which medication is used to treat muscle rigidity in intoxicated patients?
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What is the recommended approach for outpatient benzodiazepine withdrawal?
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What is one of the desired effects of inhalant use?
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Which of the following is a potential renal effect of inhalant intoxication?
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Which clinical indication suggests possible inhalant use?
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Which symptom is NOT typically associated with PCP intoxication?
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What is the primary active metabolite of THC?
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What effect on the immune system do CB2 receptors primarily have?
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Which cannabinoid receptor is primarily located in the brain?
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Which of the following is a common withdrawal symptom associated with PCP?
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What effect does stimulation of CB2 receptors produce?
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What is the main mechanism of action for PCP in the brain?
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Which of the following is NOT considered a desired effect of cannabis use?
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What percentage of marijuana users relapses within 6 months after 2 weeks of abstinence?
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Which symptom is least likely to occur during PCP withdrawal?
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What is a common cardiovascular effect of cannabis usage?
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What is a primary desired effect of low doses of PCP?
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Which of the following best describes the effect of high doses of THC?
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Which neurotransmitter's synthesis is increased by cannabinoid receptors?
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During a high dose of PCP, which symptom is NOT expected?
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What is one of the psychological effects of cannabis intoxication?
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What is the effect of cannabinoid receptors on the immune system?
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What condition can regular cannabis use induce in 20% of female users?
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Study Notes
Substance Addiction
- Addiction is a persistent, compulsive dependence on a behavior or substance, driven by pleasure and craving.
- Pleasure seeking involves activating the opiate (endorphin), GABA, or glutamatergic systems in the brain.
- Drug craving involves the dopamine reward pathway.
- Substances and the brain:
- Drug stimulates an increase in dopamine signalling from the ventral tegmental area (VTA) to the nucleus accumbens.
- The nucleus accumbens “perceives” the dopamine signal and measures the “goodness” of the agent or natural reward based on the size of the dopamine release.
- Glutamate projections from the nucleus accumbens instruct the prefrontal cortex to remember the behaviours and environment which lead up to the occurrence of the "goodness."
- GABA has two receptor sites GABAA and GABAB.
- The GABAA receptor site is directly linked to gated chloride channel. When GABA is released at the synapse it interacts with the GABAA receptor and directly opens the chloride channel to stabilize the cell membrane and make it more difficult to fire.
- GABA acts as an inhibitory transmitter.
- Barbiturates and Benzodiazepines each have their own receptor sites that enhance the action of GABA.
- The GABAB receptor is also inhibitory.
- Stimulation of the GABAB receptor releases a second messenger that opens the potassium channel.
- GABAB1 receptors are continually operating for inhibitory tone in the brain while GABAB2 receptors operate intermittently and are unaffected by barbiturates and benzodiazepines.
Sedative/Hypnotics
- Desired effects include decreased anxiety, induced sleep, and offsetting effects of other drug classes.
- Intoxication can cause sedation, occasional elation from depressed inhibitions and judgment, mid-point and slowly reactive pupils, and hiccups in long-term benzodiazepine use.
- Benzodiazepine overdose effects include:
- Sedation with decreased level of consciousness
- Decreased respiratory rate
- Hypotension
- Decreased temperature
- Gastric paralysis
- Respiratory compromise
- Pulmonary oedema
- Benzodiazepine & Barbiturate withdrawal is more likely to be severe if:
- A therapeutic dose is used every day for 4-6 months
- An increased therapeutic dose is used repeatedly
- A rapidly eliminated drug is used
- A highly potent drug (Ativan, Xanax) is used
- Abrupt discontinuation of the drug
- The schedule of use isn't fixed
- There is a history of dependency
- There is a history of concurrent alcohol use
- There is a history of panic attacks
- Benzodiazepine withdrawal:
- Can last 3-5 weeks
- Is very much like acute alcohol withdrawal
- Time course and severity depend on:
- The dose of benzodiazepine
- The duration of use (doesn’t worsen after one year of use)
- The duration of the specific drug’s actions
- Age (prolonged in the elderly)
- One treatment protocol for outpatient withdrawal is to decrease the sedative-hypnotic by 10% of the starting dose per week throughout the week.
Cannabis
- Leaves and flowering tips are dried and smoked, consumed as tea, or mixed into food.
- Resin from flowering heads can be smoked, mixed with tobacco, or used to create a cannabis oil that is mixed with tobacco and smoked.
- Tetrahydrocannabinol (THC) has 80 probable biologically inactive metabolites.
- 11-hydroxy-THC is the primary active metabolite.
- THC is eliminated in the faeces and 33% in the urine.
- THC has peripheral and central effects:
- Low dose: a mix of depression and stimulation
- High dose: CNS depression
- There are two main cannabinoid receptors in humans:
- CB1 (in the brain)
- CB2 (in the spleen and peripheral sites)
- CB1 receptors:
- Stimulated: produces euphoria, impaired short-term memory and impaired sense of time.
- CB2 receptors:
- Stimulated: produces immunosuppressant activity (not psychoactive).
- Cannabinoid receptors function as neuromodulators, altering the function of other neurotransmitters:
- Increase synthesis of noradrenalin, dopamine, serotonin and GABA.
- Potentiate the action of noradrenalin, dopamine, acetylcholine, GABA and opiate peptides.
- Alter the functioning of noradrenalin, dopamine and acetylcholine.
- Receptors can also be found in the following areas of the brain:
- Cerebellum - body movement and coordination
- Cortex - higher cognitive functions
- Nucleus accumbens - reward
- Basal ganglia - movement control
- Hypothalamus - body temperature, salt and water balance, reproductive functions, hunger
- Amygdala - emotional responses, fear
- Desired effects of the user include:
- Sense of well being
- Relaxation
- Euphoria
- Modified level of consciousness
- Altered perceptions
- Intensified sensory experiences
- Altered time sense
- Sexual disinhibition
- Intoxication can cause:
- Decrease in vigilance
- Decrease in motor coordination
- Decrease in strength
- Increase in pulse rate (not blood pressure or temperature)
- Galactorrhea (breast milk production) in 20% of female users.
- Decrease in testosterone (decrease in sperm count and motility).
- Decrease in helper T cells and interference with macrophage antigen processing (killer cells are unable to process foreign bodies - impaired immune system).
- Intoxication (continued):
- Inability to learn
- Acute panic
- Delirium
- Depersonalization
- Paranoia
- Hallucinations
- Flashbacks
Toxicity and Adverse Effects of Cannabis
- Cardiovascular system:
- Increase in heart rate (29-36 beat/min increase with cannabis alone, 49 beat/min increase with cannabis and cocaine)
- Decrease in blood pressure
- Increase in myocardial infarction risk
- Pulmonary:
- Tracheitis (inflammation of the trachea)
- 3 cannabis cigarettes = 20 tobacco cigarettes with significantly more carcinogens.
- Mental health issues have been seen to co-occur in users.
- Transient panic and anxiety
- Depersonalization
- Bizarre behavior
- Delusions
- Hallucinations
- Acute mania
- Acute paranoia
- Depression
- Psychosis
- Aggression
- Immune system:
- CB2 receptors on immune system cells = immune modulation,
- Decrease macrophage function
- Decrease killer cell function
- Increase in HIV - 1 host infections
- Reproductive / Endocrine System:
- Alters pituitary hormones, decreases prolactin, decreases growth hormone, decreases luteinizing hormone,
- Galactorrhea (decrease testosterone in males)
- Decrease sperm production
- Decrease sperm motility
Cannabis Withdrawal
- Difficult to demonstrate, but can cause:
- Anxiety
- Mental clouding
- Insomnia
- Anorexia
- Irritability
- Tremor
- Depression
- Headache
- Craving
- Tremor of the tongue and extremities
- Insomnia
- Sweats
- Lateral gaze nystagmus (rhythmic oscillation of the eyeball on lateral gaze)
- Exaggerated deep tendon reflexes
- Very similar to nicotine withdrawal.
- Withdrawal may be due to the release of corticotropin-releasing factor (CRF) in the amygdala, similar factors are released during opiate, alcohol and cocaine withdrawal.
- 71% of marijuana users relapse to marijuana use within 6 months after achieving initial 2 weeks of abstinence.
Dissociative Anesthetics: Phencyclidine (PCP)
- Arylcyclohexylamine group of dissociative anesthetics
- Antagonist of the NMDA receptor in the brain
- Anticholinergic properties (impact on the part of the nervous system that controls the heart rate, blood pressure and other responses to stress)
- Stimulant properties
- Desired effects:
- Visual illusions
- Hallucinations
- Distortion of body image
- Feelings of strength
- Special insight
PCP Intoxication
- Low dose: Dreamy, mood elevation, panic, impaired judgment.
- Moderate dose: Inebriated like state, dissociated, ataxia, confused, decrease in pain, amnesia.
- High dose: All of the previous, hallucinations, catatonia, blank stare drooling, delirium, psychotic behavior, hypertensive crisis.
- Intoxication can cause:
- Anxiety
- Feelings of doom
- Outbursts of hostility
- Violence (#1 cause of death in users)
- Incoordination
- Nystagmus
- Paranoia
- Vomiting
- Fever
PCP Withdrawal
- Similar to cocaine withdrawal, it can cause:
- Depression
- Craving
- Increased appetite
- Increased sleep
PCP Treatment
- Disruption of sensory input by PCP causes unpredictable, exaggerated, distorted and violent reactions to environmental stimuli, therefore the cornerstone of treatment is minimization of sensory input for the PCP intoxicated patient.
- Acidify the urine to increase excretion.
- Naloxone (Narcan) can treat the decrease in respiratory rate.
- Valium can treat the muscle rigidity.
Inhalants/Solvents
- Mechanism of action isn't fully understood, but three effects have been identified:
- Enhancement of the inhibitory transmitter GABA
- Enhancement of the effects of glycine
- Attenuation of NMDA receptor for the excitatory transmitter glutamate.
- Desired effects of use:
- Euphoria
- Excitement
- Altered perceptions
- “A cheap high”
Inhalants/Solvents Indications of Use
- Chemical odor
- Paint stains
- Hidden containers (whiteout, glue)
- Drunk appearance
- Dizziness
- Gait impairment
- Slurred speech
- Red running nose and eyes
Inhalants/Solvents Intoxication
- Nervous system: ototoxicity (impaired hearing), peripheral neuropathy, multiple sclerosis-like syndrome, slowly reversible trigeminal neuropathy, vertical nystagmus, slurred speech, ataxia, impaired judgment, lack of coordination.
- Renal: distal type tubular acidosis (difficulty with handling acids), Decrease in potassium, decrease in calcium, hyperchloremic acidosis, Acute tubular necrosis (death of kidney tissue), chronic renal failure.
- Hepatic: Cancer
- Pulmonary: pulmonary hypertension, bronchospasm.
- Cardiac: “sudden sniffing death”, cardiac arrhythmias, dilated cardiomyopathy
- Other: pigmented hands and face, weight loss, muscle weakness, impulsive behaviour.
Inhalants/Solvents Withdrawal
- Neurological effects allowed to wear off.
Inhalants/Solvents Treatment
- Prevention
- Symptomatic
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Description
This quiz explores the mechanisms of substance addiction, focusing on the brain's dopamine reward pathway and the roles of various neurotransmitters such as GABA and glutamate. You will learn how these systems contribute to cravings and the perception of pleasure. Test your understanding of the physiological basis of addiction.
