Addiction Flashcards
Children of alcoholics are _ times more likely to become alcoholics
4
ex. alcoholic biological parent > risk
Provide the twin probandwise concordance rate equation and the variables involved
2C/(2C+X)
C = Concordant pairs (match, twin is also alcoholic
X = Discordant pairs (mismatch, twin is not an alcoholic
Which type of twins have a higher probandwise concordance of alcoholism according to Heath et al., 1997?
Monozygotic twins, = evidence of genetic influence
What are the differences in addiction rates between men and women?
Historically, men had increased addiction rates but now this is changing because females have faster transition from experimentation to addiction
Does level of response to alcohol predict subsequent abuse? (Schuckit, 1994)
- low reponders to alcohol are more likely to become alcoholics than high responders
In the study conducted by Heath et al, what were the 2 primary results?
- In males, MZ twins had higher concordance rate (more likely that both twins get alcoholism)
- In females, the rates of alcoholism are lower but same pattern is noticed in concordance rate
What does your response level to alcohol reflect metabolically?
Your ability and speed of metabolizing alcohol
How is alcohol metabolized?
1.) Converted into acetaldehyde via alcohol dehydrogenate (ADH)
2.) Acetylaldehyde is converted into acetic acid via ALDH (Acetyladehyde Dehydrogenase) where it can be excreted from the body
What happens if ALDH is not working?
Acetaldehyde cannot be broken down/slower breakdown (bad! 10-13x more toxic than alcohol)
*this is responsible for alcohol intolerance and drunkness
- genetic link! People who lack this enzyme are less likely to become alcoholics cause it feels terrible to drink it
What gene associated with the ALDH enzyme can determine one’s response level to alcohol?
ALDH2 gene, locatred on chromosome 12
- there are 2 different types of the gene: the functional one (ALDH1) and dysfunctional (ALDH2) caused by a 1 point mutation in a base pair
- inherit 1 from each parent (homozygous for ALDH2 = least tolerant to alcohol)
What happens if ADH is not working correctly?
alcohol cannot be broken down and the concentration of blood alcohol changes
What are the 4 “C”s of alcoholism?
CRAVINGS
loss of CONTROL
COMPULSION to use
use despite CONSEQUENCES
How do drugs affect the dopaminergic system?
stimulate the reward system of the brain to release dopamine
- brain’s most powerful reward incentive, usually suppost to reward behaviours that are beneficial to survive
Describe the dopamine reward pathway
- dopaminergic cells originate in the VTA (ventral tegmental area), axons cluster into medial forebrain bundle and synapse onto the nucleus accumbens = dopamine release
rank these in order of most dopamine above baseline to least:
food,nicotine, cocaine, exercise, meth, sex
meth (1100%)>cocaine (350%)>nicotine (225%)>sex (160)>food (130%)>exercise (115%)
What happens to dopamine responses with addiction?
- eventually, a ton of dopamine doesn’t elicit a pleasurable feeling
- all increase dopamine in the synapse, drugs like cocaine block transporters
- dopamine receptors decrease with chronic drug abuse as a homeostatic response (receptors will grow back when you stop but it will take much longer, exercise might speed this up)
What happens to PFC and FC activity in addicts?
- less activity in cocaine addicts
=poor decision making, lack of self regulation and use despite consequences, dramatisized the need for drugs
How does PFC development affect addiction risk?
PFC is not fully developed until mid-twenties
- more vulnerable to develop addiction if prefrontal cortex not formed yet
def drug cue
cues that are associated with drug that create anticipation
How do context-associated cues cause cravings? (mind)
- glutamate (excitatory neurotransmitter) increases every time drug is used in the presence of a cue, anytime a cue is encountered, drug is expected “glues-together neurons
*makes withdrawal very hard - addicts have increased activity in the ACC (anterior cingulate cortex), primes the brain to get ready to expect the drug
- if drug doesn’t come, you get withdrawal
- alcohol cues can speed up brain activity in order to compensate for it’s effects, can get anxiety hallucinations and even death (can’t quit drinking cold-turkey)
Re-exposure to drug-associated cues elicits_
physiological withdrawal syndrome
What is one of the most common reasons for overdose?
Change in environment with the same dose, body can’t anticipate drug because there are no familiar cues = does is more lethal
What is the active ingredient in marijuana?
THC
What happens when THC is injected into the nucleus accumbens?
extracellular dopamine is increased (almost as high as cocaine, ~300% over baseline
How does THC activate the rewards system?
- GABA (inhibitory neurotransmitter) usually blocks dopamine release from dopamine cell, housed in inhibitory neuron
- we have natural endocanabinoids, one of which is anandemide
- anandemide binds to cannabinoid receptor and allows dopamine release (blocks release for GABA)
- THC mimics anandamide, binding to canabinoid receptors, blocking gaba and releasing dopamine in the same way but at supernatural levels b/c much more thc than anandemide usually available
What is the similarity between rewards processing for exercise vs canabis?
when we exercise, we get more endocanabinoids, increases dopamine
What are the consequences of chronic canabis use on the brain?
- can lead to marijuana use disorder (30% of all users)
- blunts the release of dopamine to naturally rewarding stimuli, causing drug dependency
- also associated with schizophrenia and psychosis
How does psilocybin work?
- naturally-occurring hallucinogenic
- had very similar structure to serotonin, can bind to it’s receptors
- when consumed, psilocybin is metabolized into psilocin which looks even more like serotonin
- can help you feel calm and enhance mood, more direct than SSRIs but tend to have the same effect
How does receptor occupancy translate to dosage of psilocin?
- the higher amount of serotonin receptors bound to psilocyn increases with dose until 75% when it maxes out
Is psilocybin addictive or toxic?
- not very addictive, similar to food
- not very toxic
How does psilocybin affect drug resistant non-responders?
reduced depressive symptoms, ppl had side effects 77% but more minor
How does psilocybin affect alcohol addiction (overall amount of drinking days)
reduced the # of heavy drinking days
