4 drüg$ Flashcards
Why does addiction occur?
it is frequently said that addiction occurs when drugs “hijack” the brain. It’s hard to nail down what that means, but it does rightly suggest that there is an involuntary takeover of the brain that compromises decision-making and diminishes freedom of choice, making quitting difficult even in the face of desire to do so. What happens in addiction is that, through completely natural processes involved in all learning, the brain prunes nerve pathways of attention and motivation to preferentially notice, focus on, desire, and seek the substance. What starts out as a choice becomes, in a sense, a prison.
Because substances of abuse act directly on the reward center of the brain to deliver their high—this involves speedy and intense release of the neurotransmitter dopamine—addiction can be seen as a shortcut to reward, one that, over time, can have a high cost to physical and mental health. Nevertheless, the outsize sensation of reward makes a powerful case for repetition. And through pathways of nerve connection to other areas of the brain, the response weakens activity of the brain’s decision-making center in the prefrontal cortex.
but in short, honestly just because of dopamine
how do drugs work + effects on CNS? alcohol
Alcohol
At low doses: affects GABA receptors in the amygdala, reduce anxiety
At high doses: inhibits glutamate receptors which reduces the neural effect (possible death)
Types of alcoholism
Type 1/A: alcoholism arises gradually
Type2/B: arises suddenly, family members have similar issues, more common in men
Functional tolerance
Depressant
Extreme withdrawal symptoms
Korsakoff syndrome: disorder of the central nervous system characterized by amnesia, deficits in explicit memory, and confabulation.
Cirrhosis: extensive scarring of the liver due to chronic consumption
Slows down brain function
how do drugs work + effects on CNS? cocaine
Stimulants: primary effect is to produce increases in behavioural activity
Pure cocaine is cocaine hydrochloride
Effect at the synapse: blocks dopamine reuptake, builds up at the synapse
Main effect: euphoria (a wave of wellbeing)
how do drugs work + effects on CNS? marijuana
No receptors in the medulla so excessive use is never life threatening
Sharpens the sense and create the effect of time passing slowly
Affect your memory
Mental dependency
May have neuroprotective effects
No evidence that it causes brain damage
Receptors for THC in the brain
how do drugs work + effects on CNS? nicotine
mostly affected in the nucleus accumbens
Receptors become more sensitive (nicotine replaces dopamine)
Can lead to smokers syndrome: chest pain, wheezing and increase risk of inflammation, or buerger’s disease: blood vessels (especially in the legs) become constricted when nicotine enters the bloodstream, tissues can die and can lead to amputation
One of the hardest addictions to get rid of
How do opiates work in the brain?
30% of people who experiment become addicted, heroin
Stimulates endorphine receptors; euphoria
Extreme withdrawal effects
Mixed with alcohol or benzol can be life threatening
Risks: unsterile needles, mixed with unknown substances and if gotten pure -> might overdose
Fentanyl
What are the health risks of chronic heroine or morphine (opiate) use?
side effetcs:
drowsiness
dizziness
feelings of euphoria
nausea
vomiting
constipation
slowed breathing rate
long term:
adrenal insufficiency
central sleep apnea
hypogonadism
osteoporosis
tremors
worsening gastroesophageal reflux disease (GERD) symptoms
Long-term opioid use may also lead to a rare condition called opioid-induced hyperalgesia (OIH). People with OIH become more sensitive to pain over time while taking opioids.
mesocorticolimbic system
The mesocorticolimbic (MCL) system, extending from the ventral tegmental area (VTA) to the nucleus accumbens and prefrontal cortex, comprises a dopamine (DA) projection implicated in reinforcement learning. The MCL system is the target of addictive substances and of drug-evoked synaptic plasticity, a cellular mechanism that may underlie the adaptive, pathological behaviors that occur after repeated drug exposure
ventral tegmental area (VTA)
Part of the brain called the ventral tegmental area, full of dopamine neurons
Activated when we;re doing something pleasurable ie using drugs
Sends dopamine to different regions of the brain ie NA, amygdala, PFC
Nucleus accumbens
Nucleus of the ventral striatum, associated with reward, central to the amplification of feelings and activated when thinking of something pleasant
Nicotine receptors are abundant in neurons that release dopamine in NA
Agonists versus antagonists
agonist:
- Drugs that increase neurotransmission by increasing the synthesis of neurotransmitter molecules
- drug increases the release of neurotransmitter molecules from terminal buttons
- drug binds to autoreceptors and blocks the inhibitory effect on neurotransmitter release
- drug binds to postsynaptic receptors and either activates them or increases the effect on them on neurotransmitter molecules
- drug blocks the deactivation of neurotransmitter molecules by blocking degradation or reuptake
antagonist:
Blocks a neurotransmission
- drug blocks the synthesis of neurotransmitter molecules
- drug causes the neurotransmitter molecules to leak from the vesicles and be destroyed by degrading enzymes
- drug blocks the release of the neurotransmitter molecules from terminal buttons
- drug activates autoreceptors and inhibits neurotransmitter release
- drug is a receptor blocker; it binds to the postsynaptic receptors and blocks the effects of the neurotransmitter
Affinity and efficacy!!
Affinity - tendency to bind to a receptor (depending how well it “fits)
Efficacy - tendency to activate a receptor
(high aff, low eff. = a drug can bind to a receptor without activating it!)
https://www.youtube.com/watch?v=KyV23PQN22w
Effects of stimulant drugs on CNS (neurotransmission)
A stimulant use disorder changes a person’s brain in two major ways. One is neurotoxic (by affecting brain processes such as memory, learning, and other cognitive functions). The other way is by triggering the addiction process, such as by acting on the brain’s reward system or through the development of craving. This information is critical for clinicians to understand because it explains the course of symptoms and recovery and underscores how difficult it is to quit using/misusing substances without interventions.
Substances of misuse—including stimulants—affect the reward system (Volkow et al., 2019). Normal functioning of the brain’s circuitry results in inhibition and stimulation of neurotransmitters at multiple sites in the brain’s reward systems. However, neuroadaptation and neuroplasticity that occur when substances are present can result in multiple neurotransmitters disrupting this normal circuitry, resulting in prolonged phases of withdrawal/negative affect and anticipation/craving (Koob & Volkow, 2016).
The neurotransmitter dopamine, which helps to regulate the feelings of pleasure (euphoria and satisfaction), is both directly and indirectly affected by stimulants (Volkow et al., 2019). Dopamine also plays an important role in the control of movement, cognition, motivation, and reward (Bromberg-Martin et al., 2010; Volkow et al., 2019). In addition, stimulant use causes the brain to release norepinephrine, which helps regulate mood, attention, learning, memory, and arousal and may play a role in substance withdrawal (Office of the Surgeon General, 2016). The neurotransmitter serotonin affects reinforcement, motivation, learning, and memory, and may play a role in SUDs by making people more susceptible to compulsive (rather than controlled) substance use, especially people with genetic vulnerabilities to SUDs (Müller & Homberg, 2015).
Most common drugs - cocaine, amphetamine, MDMA
How the drugs take effect:
Physical: restlessness, euphoria, insomnia
Biological: increase dopamine/block reuptake of dopamine (also serotonin and norephedrine)
Consequences of use:
Withdrawal: body stops producing own dopamine, feelings of depression, tiredness
Highly addictive, tendency for “binges”
Health risks: heart attacks, strokes, psychosis
(Ritalin: stimulant used as ADHD medication but also for recreational use, highly addictive, children who use ritalin more prone to addictions in later life also bc of problems with impulsiveness)
Effects of opiates on CNS (neurotransmission)
Most common drugs: heroin, morphine (derived from opium), methadone
Methadone: used as a substitute medication for heroin addicts, can be used orally, said to be more “controllable” and safer
How the drugs take effect
Physical: “painkillers”, tiredness
Biol: stimulates the endorphine receptors -> inhibiting dopamine inhibitors -> dopamine release
Consequences of use -
Highly addictive, tendency for addiction depends on social/environmental factors
Health risks: infections through needle use, street drugs are usually cut with potentially dangerous substances
Withdrawal: nausea, pain, “flu” symptoms, running nose, depression, restlessness
Fastly build up tolerance -> addicts have to use higher dosages
Tolerance
Decreased sensitivity to a certain drug due to repeated exposure
Dose response curve: right shift
Context-specific (conditioned) tolerance
Focus on the situation in which drugs are taken, so not necessarily focus on how people react when they’re on the drug but how the environment they are in when they intake the drug influences them
Theory claims that the effects of the drug are only maximized whne theyre taken in the same place they usually tare taken
Experiment
2 groups of rats got 20 alcohol and 20 saline injections in an alternating sequence, 1 injection every other day.
Only difference between 2 groups: groups: received all 20 alcohol injections in a different test room and the 20 saline injections in their colony room. And vice versa
results/conclusion: at the end, they assessed all the rats on their hypothermic (temperature-reducing) effects with alcohol
Tolerance was only visible when they rats took alcohol in the room they paired with alcohol.
Situational specificity of drug tolerance
Drug effects depend on ur environment
Siegel and his colleagues proposed that this can be a reason for accidental drug overdose. When ppl are in a non-familiar or unusual environment, their tolerance can become weak and their body may not be able to handle that much of the drug.
Experiment: more heroin-tolerant rats died in a new environment followed by a higher dose of heroin than usual place.
Heroin suppresses respiration causing death
oral method of administration
Oral: swallow>dissolves in stomach fluids>carried to intestines>bloodstream
Eg: alcohol
Once drugs are swallowed, they dissolve into the stomach fluids and then pass to the intestines and then are absorbed into the bloodstream.
Some drugs pass through the stomach wall (like alcohol) and hit faster beacuse they don’t gotta go to the intestines first
2 main advantages of orally ingesting: easy and relatively safe.
injection method of administration
injected into the blood stream
Different types:
Subcutaneous (SC): into the fatty tissue under the skin
Intramuscular (IM): into the large muscles
Intravenous (IV): into the veins that run directly under the skin (fastest)
Common in medical practice
Effects are strong, fast, predictable
Subcutaneously: drugs injected into fatty tissue just beneath the skin
Intramuscularly: into large muscles
Intravenously: directly into veins
inhalation method of administratiion
absorbed into the bloodstream through capilliaries in the lungs, eg: marijuana
Disadvantage: difficult to regulate the dose, can damage the lungs
Used for anesthesia
Difficult to regulate dose of inhaled drug
these substances can damage the lungs if inhaled too much
absorption method of administration
Mucuous membranes in the nose, mouth and rectum, eg: cocaine
how are drugs absorbed
Inhalation: lungs have a rich network of capilliaries, get absorbed and go straight to the bloodstream
Blood brain barrier: prevents the drugs from entering,
drug metabolism: enzymes in the liver prevent the drugs from entering the bloodstream, small amounts of drugs can pass through sweat, urine, feces etc
Drugs go into the central nervous system
reward system: amygdala
The amygdala is part of the limbic system, a neural network that mediates many aspects of emotion and memory. Although historically the amygdala was considered to be involved primarily in fear and other emotions related to aversive (unpleasant) stimuli, it is now known to be involved in positive emotions elicited by appetitive (rewarding) stimuli.
Alcohol affects the GABA receptors in the brain
Reduces anxiety and increases self assurance
reward system: prefrontal cortex
Alcohol has an effect here, reduces connections in the pfc
Associated w self control
physical dependency theory
Drug addicts are trapped in a cycle, take more drugs to get rid of the withdrawal symptoms
Criticism: drugs like cocaine dont have bad withdrawal symptoms
People get detoxified
Alternating patterns of drug use eg: someone w a busy work schedule
positive incentive theories
Take drugs to feel the positive effects, eg the pleasurable feeling
Expectation of the pleasurable feeling (Anne: more about experienced pleasurable feeling than expectation)
positive incentive value (wanting), the expected pleasure that you will get after intake
hedonic value (liking), the actual pleasure of experiences after intake
pleasure-producing effects as the main motivator, craving the positive effect of a drug
incentive sensitization theory
addicted to the expected pleasurable feeling before the actual effects of the drug
it is not the pleasure per se that motivates addiction, but the anticipation for pleasure/reward
In the beginning the anticipation is closely tied with the actual positive reward/incent, but as addiction develops further the actual positive effects decrease rapidly and the main motivator is the anticipation
3 stages of addiction
- Initial drug taking
Factors that influence this phase: price, availability, peer pressure, prior life experiences
Take it to determine whether the drug will be useful to them eg: caffeine for alertness - Habitual drug taking
For the hedonic value of the drug, for the pleasure in the moment
Not all habitual users are addicted but all addicts are habitual users - Drug craving and relapse stage
Craving: strong desire for the drug
Experience withdrawal symptoms here unlike habitual users
Drug craving is the want for it, lead to withdrawal symptoms
what are 3 plausible reasons why relapse happens?
Stress eg: smoking due to the stress of exams
Drug priming: former addict thinks they are in control because they have not used drugs for a long period
Exposure to certain cues can trigger, eg: a person or a place (conditioning: conditioned response where certain cues can cause you to relapse)
metabolic tolerance
Metabolism works fast, drug breaks faster = can’t reach certain areas in time
functional tolerance
Comes from decreased sensitivity of specific points in the body to a particular drug
Psychoactive substances are primarily functional
Eg: alcohol: train your liver, where the enzymatic breakdowns occur faster
Can slow down certain functions depending on the drug
NA becomes less pleasurable, need to increase the intake to achieve the desired effect
drug sensitization tolerance
build tolerance to some effect of a drug but not to others
eg : if alcohol causes dizziness, after you take it often you might build a tolerance and not feel as dizzy
cross tolerance
one drug can cause tolerance to another drug, eg: amphetamines
conditioned tolerance
tolerance is greater if you’re in a situation where you’ve taken the drug before (situational)
Eg: taking the drug with people you usually do or the usual room can make you have a higher tolerance (can overdose in another situation because you are not used to it)
Focus on the situation in which drugs are taken, so not necessarily focus on how people react when they’re on the drug but how the environment they are in when they intake the drug influences them
Theory claims that the effects of the drug are only maximized whne theyre taken in the same place they usually tare taken
Experiment
2 groups of rats got 20 alcohol and 20 saline injections in an alternating sequence, 1 injection every other day.
Only difference between 2 groups: groups: received all 20 alcohol injections in a different test room and the 20 saline injections in their colony room. And vice versa
results/conclusion: at the end, they assessed all the rats on their hypothermic (temperature-reducing) effects with alcohol
Tolerance was only visible when they rats took alcohol in the room they paired with alcohol.
contingent tolerance
tolerance only develops for something you’ve done before,
only occurs for the effects of drugs that one has experienced before
based on conditioned tolerance, in what setting are you most likely to overdose: familiar or unfamiliar setting?
more likely to od in an unfamiliar setting
how do drugs affect the synapse
stimulate / inhibit the release of neurotransmitters
Influence the chain of chemical reaction in the postsynaptic neurons and activate their receptors (binds with the receptors, can be blocked)
Influence or block the reuptake and cause more or less neurotransmitters to be present in the synapse
deactivation/ breakdown of a neurotransmitter
Influence synthesis of a specific neurotransmitter
withdrawal symptoms
Physiological reactions
Opposite to the effect of the drug itself: counteracting mechanism when you stop taking the drug
Eg: sleeping pills relax certain brain regions, stop taking it = less relaxed, and the brain starts working on its own
