Psychology of Addiction Midterm 2 Flashcards
2 types of stimulant sympathomimetics
direct and indirect sympathomimetics
what are direct sympathomimetics
Drugs that increase activity of the sympathetic nervous system (SNS) through direct action on adrenergic receptors
- many direct sympathomimetics have medical uses but few have abuse potential
example of direct sympathomimetics
Salbutamol: an adrenergic beta 2 receptor agonist used to treat asthma
What are direct sympathomimetics
drugs that mimic direct sympathomimetics by increasing availability of monoamines (DA, NE, and 5-HT) in the synapse, which can occur through
1. increased NT release
2. Blocking NT reuptake
3. blocking NT metabolism
Example of indirect sympathomimetics
occur through 5 different DA receptors, 2 families of NE receptors, and 7 families of 5-HT receptors
examples include cocaine and amphetamine
How does cocaine lead to an increase of DA release
Cocaine will block reuptake by occupying DA transporters
How does amphetamine lead to increase in DA release?
Amphetamine increases DA release, creates more vesicles containing DA for release
What are non-sympathomimetic stimulants
drugs with stimulant properties that operate through other mechanisms
Examples of non-sympathomimetic stimulants
Caffeine - blocks adenosine receptors (by binding to them); adenosine normally inhibits DA and glutamate activity
Nicotine - binds to acetylcholine receptors, and mimics actions of acetylcholine; it raises DA, glutamate, and gamma-aminobutyric acid (GABA) levels
What system do CNS stimulants induce arousal in
Sympathetic nervous system
what mediates release of DA in the mesolimbic system
Psychostimulant (reward) mediates DA release regardless of specific mechanisms
what mediates locomotor effects
mediated by nigrostriatal pathway
what plant is cocaine derived from
Erythroxylon coca, plant from South America (argentina, bolivia, colombia, ecuador, peru)
earliest mention of using cocaine leaves for anti-fatigue properties
early as 3000 BC and maybe even 8000 BC
how did spanish colonists use cocaine leaves
given to slaves to enhance/sustain performance in silver mines
What famous drink used cocaine and during what time period was this used
Coca-cola; from 1891-1903
What act restricted cocaine for medical use only in 1914
Harrison Anti-Narcotic Act
- outlawed possession, use, and distribution for anything outside medical use in the US
Order of likelihood of addiction given any use within a year (greatest likelihood of addiction first)
Heroin, Cocaine, analgesics, marijuana, stimulants, and alcohol
How does intranasal cocaine use affect the human body over time?
destroys mucus membranes and perforate the palate
What is freebasing and when was it popular
Freebasing was popular from late 70s to mid 80s and is a purified form of cocaine w/ higher melting point than powdered cocaine and can be smoked creating a quicker, more intense high
How is freebase created
mix powdered cocaine w/ ammonia and product extracted using ether creates the freebase pure cocaine crystals
Problem with freebase
highly flammable
What was the smokable form of cocaine in the mid 1980s
Crack cocaine is powdered cocaine mixed with baking soda and water to create rocks that can be smoked and are safer than freebase
what are the acute health effects of cocaine
- changes in heart rate (increase)
- increase systolic blood pressure
- increases in total peripheral resistance (TTR)
- risk of heart attack
- risk of stroke
- permanent cardiac conduction abnormalities (ex: right bundle branch block)
What are the long term health effects of cocaine
- kidney damage
- enlargement of the heart
- artery blockage
- cardiac conduction abnormalities
T or F: are there naturally occurring amphetamines?
False
What drug was first synthesized in Germany in 1887 by Romanian chemist Lazar Edeleanu?
Dextroamphetamine (d-amphetamine)
why was d-amphetamines stopped being sold as over counter drugs during the 1960s
their abuse potential and psychosis inducing properties were recognized
What is d-amphetamine used to treat today
popular drug to treat ADHD but it has clear abuse potential
What properties do all stimulants have and can lead to symptoms similar to schizophrenia
all stimulants have psychosis inducing properties and if abused can lead to same symptoms presented by someone with schizophrenia
what group has the most prescriptions for brand/general adderall
22-44 have the highest number and continue to increase
What new drug was approved in 2008 and is a DA, NE, and 5-HT agonist
vyvanse
does Vyvanse or Adderall xr generate more revenue
Vyvanse with 2014 million while adderall has 364 million
4 reasons stimulants can become addictive
- tolerance and withdrawal
- preoccupation with obtaining, using, and running out
- abuse by college students w/ and w/o ADHD is common
- large underground market (opiates, subaxone)
What is the methylated derivative of amphetamine
methamphetamine
what is methamphetamine synthesized from
ephedrine discovered in 1919 by akira ogata
why is methamphetamine more potent than amphetamine
Because methamphetamine can cross the BBB more readily
what country dealt with a widespread use of methamphetamine after World War 2
Japan with 550000 abusers in 1954
what was methamphetamine renamed
crystal meth in the 80s after a more pure form was created in San Diego
what are the health effects of methamphetamine
similar to cocaine but 2 main exceptions
1. chronic use leads to meth mouth
2. chronic use also leads to formication
what is meth mouth
lack of saliva that leads to tooth decay and gum disease
what is formication
crawling sensation under the skin that leads to obsessive skin picking of the face and body
how is cocaine used in medicine currently
used as a local anesthetic in very restricted applications (mucous membranes)
- procaine is used in most situations
how are amphetamines currently used
weight control and ADHD
what are the behavioral effects of cocaine and methamphetamines
- repetitive thoughts/behaviors
- obsessions and compulsions
- checking behaviors
- dismantling intricate items (cars, electronics)
- paranoia
- skin picking
how do behavioral effects differ between cocaine and methamphetamines
behaviors last longer for methamphetamines because it has longer half life
what is the half life for cocaine
6 hours
what is the half life for methamphetamines
12-16 hours
what is the binge cycle for cocaine and methamphetamines
tolerance and craving build rapidly creating an addictive cycle
- euphoria and dysphoria interchange
- leads to paranoia
- ends with psychosis (delusions, hallucinations)
phases of withdrawal for cocaine and methamphetamines
protracted phases during which episodic craving and cue-induced craving increase over course of 3 to 4 months making relapse likely
specific phases of cocaine withdrawal and how long each phase lasts
Crash ( 9hrs to 4 days)
- insomnia
- irritability
- anxiety
Withdrawal (1 to 10 wks)
- anhedonia
- decreased energy
- limited interest in environment
Extinction (indefinite)
- brief episodic craving
- cue induced craving
Relapse
- occurs during withdrawal or extinction phases
End result is abstinence if they dont relapse
how many time stronger is the release of DA in stimulants than any natural reinforcer
10 times
how do stimulants alter neural structure directly
they increase dendritic spine branching in both mesolimbic and mesocortical DA systems
What are opiates
drugs derived directly from the opium poppy
what are opioids
semi and fully-synthetic form of opiates that are manufactured chemically
how are opiates formed
resin gum from cuts in unripe poppy pods are scraped and dried to make opium
how long have opium poppies been cultivated
since at least 3400 BC in Southwest asia
what law outlawed production, use, possession, and distribution of opium except for medical use
Harrison Narcotics Tax Act in 1914
where does 90% of the world’s opium supply come from
Afghanistan
how was morphine first discovered?
in earyl 1800s, morphine was isolated from dried opium poppy resin by Friedrich Serturner
what is morphine named after
named after the greek god of dreams, Morpheus
steps to produce heroin #1
- opium boiled in water to create brown liquid
- impurities are scraped from top, lime is added, produce morphine alkaloid
- solution is filtered to remove impurities
- ammonia is added and solution is reheated
- morphine collects as a solid at the bottom
what percent of heroin #1 is raw opium
10%
name for converting morphine to heroin base
heroin #2
steps to produce heroin #2
- morphine base is mixed with acetic acid and heated to 85 C for 2 hours
- morphine dissolves
- upon cooling, morphine and acetic acid bond chemically to form heroin
- heroin is dissolved in water and sodium bicarbonate is added, producing heroin base
What percent of heroin #2 raw opium and how is it injested
- 15-20% raw opium
- snorted (not smoked)
Steps to make heroin #3
- heroin #2 is mixed with hydrochloric acid and stirred until it dries
- dried paste is crushed to form “brown sugar”
percent of heroin #3 that is raw opium
20-30% pure and is smoked
Steps to produce heroin #4
- hydrochloric acid and ether are added to heroin base (heroin #2)
- product is filtered and dried to form white powder
- powder is compressed into bricks with a heroin press
percent of heroin #4 that is raw opium
80-90% pure and is injectable
what are opiates used for in medicine but what are the dangers of it
are effective pain relievers, but have addictive properties
Strength of different analgesics
weakest: paracetamol, aspirin, ibuprofen
Strongest: c-8813, BDPC, sufentanil
relative strength of morphine
oral morphine has strength of 1 for a 10mg tab
IV morphine has a strength of 3 for a 3.33mg injection
What are endogenous opioids
neuropeptides produced by the body that have morphine like actions
What are 3 examples of endogenous opioids
Enkephalins, dynorphins, and endorphins
when are enkephalins produced
released during or after exercise
What endogenous opioids are produced when injured or stressed
Dynorphins and endorphins
What are the 4 sources of opioids
opiates, opioids (semi synthetic derivatives), synthetic opioids, and endogenous opioid peptides
what are the 4 examples of opiates?
opium, morphine, codeine, and thebaine
what are the 5 examples of semi synthetic opioids
heroin, hydromorphone, hydrocodone, oxycodone and etorphine
what are the 4 examples of synthetic opioids
methadone, meperidine, propoxyphene, fentanyl
what is the dilemma with exogenous opioids
nothing relieves pain as well as exogenous opioids, but nothing is more addictive as well
what group of individuals become addicted to pain prescriptions
genetically vulnerable
by how much has prescription opioid death increased by and why?
increased by 6x from 1999-2014 and synthetic narcotics are increasingly involved
What was the national drug prescription overdose deaths in 1999? 2017?
3,442 in 1999 and continued to increase until reaching 17,029 in 2017
What types of prescription of overdose deaths have increased/decreased from 1999 to 2017?
Prescription opioids w/ other synthetic narcotics has increased especially after 2013, but just prescription opioids (w/o other syn narcotics) has decreased since 2013
what drugs do people with prescription addiction do people turn to and why?
People turn to heroin because it is cheaper and more available
by how much have heroin related deaths increased since 1999 and why
eight fold because syn narcotics like fentanyl are increasingly involved
What is the national heroin overdose death in 1999 and in 2017?
1999: 1960
2017: 15482
what age group had the most deaths in 2014 due to heroin
25-34 yo with 8 deaths per 100000 people
what age group had the most deaths in 2014 due to opioids?
45-54 yo with 11.7 per 100000 people
what are the physiologic effects of heroin?
- decrease in body temp
- decrease in stress hormones (lowers pituitary function, part of the L-HPA axis)
- decrease respiration
- decrease cough reflex
- induces nausea
- causes orthostatic hypotension
- decreases gastrointestinal efficiency
- causes itching
what are behavioral effects of heroin
- pain relief
- intoxication (including profound euphoria)
- impaired cognitive function
- blocked memory function
what are the medical uses for heroin?
anti-diarrhea properties
- used to save lives during dysentery epidemics during 19th century pain relief
balanced anesthesia
- used different opioids before and during surgery to induce analgesia (pain relief), amnesia, muscle relaxation, and abolition of reflexes (fentanyl, alfentanil, remifentanil)
what is the peak time of smoked heroin
peak in 1-5 min and declines rapidly to minimum limits within 30 minutes
why is heroin a prodrug
it has no pharmacological activity, but its metabolites do heroin metabolizes into 6-monoacetylmorphine and morphine
what does koob say is the classic drug of addiction
opioids
what does opioid drug taking induce?
intense intoxication/euphoria
what does intense intoxication/euphoria promote?
repeated use via positive reinforcement mechanisms
what increases with repeated drug use
tolerance quickly develops so intake escalates
what symptoms of withdrawal develop with increased tolerance to drugs
profound dysphoria, discomfort, and somatic symptoms of withdrawal
what symptoms follow after withdrawal symptoms emerge?
preoccupation and craving
how is drug taking maintained
through strong negative reinforcement mechanisms
what are people who are not likely to be addicted called
chippers, don’t get addicted because they are able to maintain quasi-controlled use patterns
what does early outcome data suggest about addiction as a condition and likelihood of death?
heroin is a lifelong addiction and half of addicts die
what were the results for the 581 male heroin addicts admitted to the California Civil Addict Program at a 33 yr follow up?
- half dead
of those alive: - 21% tested positive for heroin (10% refused urinalysis)
- 40.5% used heroin in the past year
- 19.4% used cocaine (10.3% used cocaine) in the past year
- 11.6% used amphetamine (meth)
what was the predominant treatment for heroin addicts in the California Civil Addict Program experiment?
methadone maintenance was the predominant treatment
what replaced methadone maintenance as the main heroin addict treatment
suboxone
why was methadone maintenance replaced as a treatment
methadone itself is addictive as an opioid
what organization does not use maintenance therapy to treat heroin addiction
Narcotics Anonymous which helped addicts with self health groups
Employment status for people who are/were heroin addicts
59% full time
9% retired
12% unemployed
6% students
11% part time
4% homemaker
Average length of heroin clean time
11.7 years
years heroin drug free percentages
9% less than a year
33% 1-5 years
17% 6-10 years
11% 11-15 years
11% 16-20 years
19% more than 20 years
what is opioid intoxication
intoxication following injection of smoking 1-3 mg of heroin or 3-15 mg of morphine which is described in 4 stages
what are the 4 stages of opioid intoxication
- rush
- nod
- high
- being straight
duration and effects of rush stage
duration: 45 s
effects: intense pleasure, with waves of intense euphoria likened to sexual orgasm. Visceral sensation occur, with facial flushing and deepening of voice. Rush is resistant to tolerance
duration and effects of nod stage
duration: 15-20 min
effects: a state of escape from reality that can range from sleepiness to virtual unconsciousness. Addicts are described as calm, detached, and very uninterested in external events
what is the duration and effects of high stage
duration: several hours
effects: stage follows rush, it is a general feeling of well-being that can extend hours beyond the rush, shows tolerance
duration and effects of being straight stage
Duration: up to 8 hours
effects: the point at which a user is no longer experiencing the rush, nod, or high but also is not yet experiencing withdrawal. This state can last up to 8 hrs following an injection or smoking of heroin
what is opioid tolerance
tolerance to the sedative, euphoric and analgesic properties of opioids builds rapidly
those who are addicted can inject up to ____________________________________________
70 times the lethal dose for a drug naïve individual
what does tolerance do
shortens duration of drug action
what is it called when tolerance is built from switching from codeine to morphine
cross tolerance
2 reasons that tolerance occurs
- neuro-adaptive down-regulation of the opioid system
- conditioning to place of use and associated compensatory body reactions in the opposite direction of opioid effects
early opioid drug use is driven by
positive reinforcement aka feeling of elation/euphoria
what drives opioid drug use after tolerance develops
negative reinforcement (avoiding withdrawal)
what are the opioid withdrawal symptoms
profound dysphoria
depression
anxiety
yawning
lacrimation (tear production)
rhinorrhea (runny nose)
perspiration
goosebumps
tremor
pupil dilation
loss of appetite and weight
vomiting
restlessness
diarrhea
insomnia
dehydration
hyperglycemia
increased body temp
increased blood pressure
elevated pulse
how long does it take for heroin withdrawal symptoms to peak
48-72 hours
many treatment providers believe that what should be prevented?
acute withdrawal that is why they use maintenance therapy
what is more protracted than heroin withdrawal
methadone and suboxone withdrawal (aka treatment meds used)
is opioid withdrawal life threatening
no
how long do some opioid withdrawal such as increased pain, stress sensitivity, dysphoria, and metabolic changes can last for and what is the phenomenon called
symptoms can last up to 5 months and are known as post-acute withdrawal
what happens to a baby if a mother takes opioids
because opioids can cross the placental barrier, infants born to opioid addicted mothers suffer withdrawal
what type of receptors are opioid receptors
g protein coupled receptors w/ seven transmembrane spanning regions
what are the 3 types of opioid receptor subtypes
mu, delta, and kappa
what is the endogenous opioid for the mu receptor subtype
beta-endorphin enkephalin
what is the endogenous opioid for the delta receptor subtype
enkephalin beta endorphin
what is the endogenous opioid for the kappa receptor subtype
dynorphin
what kind of properties do opioids have that cause animals to self-administer the drug when delivered directly into the brain
analgesic properties
analgesia occurs through direct injection through various sites:
- raphe nuclei
- periaqueductal gray
- certain medullary nuclei
- spinal cord
are opioids dopamine agonists
no
what opioid receptor is the most important for the addictive properties of opioids
mu opioid receptor
what role do delta and kappa receptors play in opioid addiction
implicated in tolerance and dysphoria
what causes analgesia properties
caused by direct inhibition of nociceptive activity in both the brain and spinal cord
what is nociception
sensory nervous system response to harmful or potentially harmful stimuli
what causes intoxication in opioid usage
blocking the affective component of pain in the brain
what organic substance is considered an alcohol
any organic substance with a hydroxyl functional group, bound to a saturated carbon atom
what are 4 types of alcohol
ethanol
2-propanol
methanol
butanol
alcohol can be found in all ___________ containing substances
glucose
what type of alcohol is safe for consumption
ethanol
how does alcohol occur naturally
through fermentation
what occurs during fermentation
when glucose and water are converted to ethanol and carbon dioxide in the presence of yeast
at are the 5 requirements for fermentation
- sugar or starch (to make glucose)
- water
- heat
- ferment (yeast)
- air
what is an example of naturally occurring fermentation
fruit over ripening which can lead to 12% alcohol
what is distillation required for
to yield more concentrated levels of alcohol
what occurs when alcohol is distilled
a fermented mixture is heated and ethanol vapors which boil off at a lower temp (78 degrees) than water (100 degrees), and are trapped and condensed
different beverages use different__________________
use different plant sources of glucose for fermentation and distillation
Alcohol use in US compared to European nations
Alcohol use and dependence rates in the US are similar to those observed in many European nations, difference is that US does more binge drinking
Total Alcohol consumption in L per Capita in US
Total: 9.08
Beer: 5.11
Wine: 1.67
Spirits: 2.29
Alcohol dependence in US (percentage)
4.1%
Alcohol Use by gender
Women increased by 15.8% (almost equal to men consumption)
went from 59.6 to 69
Alcohol use by Race/ethnicity Percent change from 2001-2002 to 2012-2013
Asian or Pacific Islander: 29.1%
Native American: 27%
Black: 24.2%
Hispanic: 17.2%
White 8.3%
Alcohol Use Percent Change by Age group
18-29: 9.6%
30-44: 10.6%
45-64: 11.8%
greater than 65: 22.4%
High Risk Drinking Percent Change by Gender
Women: 57.9%
Men: 15.5%
High Risk Drinking Percent Change by Race
Black: 62.4%
Asian or Pacific Islander: 56.5%
Hispanic: 40.6%
Native American: 40.3%
White: 23%
High Risk Drinking Percent Change by Age Group
18-29: 14.2%
30-44: 37%
45-64: 49.3%
Greater than 65: 65.2%
Alcohol Use Disorder Percent Change by Gender
Women: 83.7%
Men: 34.7%
Alcohol Use Disorder Percent Change by Age Group
18-29: 44.4%
30-44: 47.4%
45-64: 81.5%
greater than 65: 106.7%
Alcohol Use Disorder Percent Change by Race/Ethnicity
Black: 92.8%
Asian or Pacific Islander: 77.8%
Hispanic: 51.9%
Native American 37.2%
White: 47.2%
What is the most abused substance in Western culture and causes more harm to individuals and families than any other substance
Alcohol
one possible reason discussed in class for why alcohol consumption has increased?
Advertisments of alcohol is more common nowadays
What is the cost of excessive drinking on US economy?
250 billion
Top 5 Drugs that Cause the Most harm
from greatest harm to least:
Alcohol
Heroin
Crack Cocaine
Methamphetamine
Cocaine
Cost of excessive drinking on workplace productivity and health care
180 billion in workplace productivity and 28 billion in healthcare costs
Cost of excessive drinking on law enforcement and in motor vehicle accidents
25 billion in law enforcement costs
13 billion in motor vehicle accidents
(44 billion when associated w/ healthcare and law enforcement costs included)
what percent of males and females have experienced one or more alcohol-related adverse events?
60% of males and 30% of females
what percent of intimate partner violence is alcohol involved in?
55%
what percent of women sexually assaulted or raped by adulthood, how many involve alcohol use
25% are SA
half of these involve alcohol use
what percent of traffic fatalities involve alcohol
1/3 or 33.333%
what is the leading cause among 8-34 year olds in the US
traffic fatalities, specifically those involving alcohol
Age group with the highest percent of heavy use, binge use, and normal use?
21-25 yo had the highest percent at 69.3%
Heavy use: 13.1%
Binge use: 30.2%
Normal Use: 26%
Why is alcohol an unusual substance in terms of behavioral effects
it has both stimulant (reward) and sedative (anxiolytic) properties
why are males more likely to drink
reward properties
why are females more likely to drink
for the anxiolytic effects
T or F: behavioral effects are dose dependent?
True
What typical behavior occurs from 0.3 to 0.4 (general anesthesia to death) level of alcohol
- increased sedation/hypnosis
- approaching general anesthesia
- approaching coma
What typical behavior occurs from 0.05 to 0.08 (relief from anxiety to disinhibition) level of alcohol
- Personality changes
- Relief from anxiety
- social lubricant (more talkative, assertive)
- Disinhibition
What typical behavior occurs from 0.08 to 0.15 (disinhibition to sedation) level of alcohol
- significant disinhibition (life of party)
- impaired judgment
- impaired cognition
- impaired motor function
What typical behavior occurs from 0 to 0.05 (normal to relief from anxiety) level of alcohol
Normal behavior
What typical behavior occurs from 0.15 to 0.30 (sedation to general anesthesia) level of alcohol
- marked ataxia (staggering/slurred speech)
- major motor impairment
- impaired reaction time
- blackouts
What is the lethal dose of alcohol for 50% of people
0.4 gm%
Alcohol pharmacokinetics
when the alcohol readily crosses cell membranes in most parts of the body
what organs absorb alcohol
20% absorption by the stomach
80% absorption by the small intestine
80-90% absorption in 30-60 min
T or F: BAL levels are higher when food is in the stomach
False
How long does it take for peak alcohol levels to occur on an empty stomach?
.8 Hours and peak is at 0.08 g/210 L
How long does it take for peak alcohol levels to occur on a full stomach?
1 hour and peak is at 0.045 g/210 L
How many drinks does it take for a 140 lb man to go above the legal drinking limit?
3 drinks, causes a .08 blood alcohol level
How many drinks does it take for a 140 lb woman to go above the legal drinking limit?
3 drinks, causes a .10 blood alcohol level
under normal conditions at what rate is alcohol metabolized
1/2 drink per hour
For an alcoholic, at what rate is alcohol metabolized
1 drink per hour
What enzyme metabolizes drugs and other foreign compounds in the body
CYP2E1
what is the reaction for breaking down alcohol
Alcohol is catalyzed by CYP2E1 and with NAD+ will make acetaldehyde which is then converted into acetate
What causes the hangover symptoms
Excess acetaldehyde that cannot be broken down will cause hangover symptoms
What are two byproducts of breaking down alcohol
2 NADH
What genetic variation causes the greatest vulnerability to alcohol
ALDH^1/ALDH^1 is the fastest alcohol metabolism and is the most vulnerable
What genetic variation results in intermediate metabolism
ALDH2^1/ALDH2^2
What alcohol variation has complete protection from alcoholism
ALDH2^2/ALDH2^2
How does Disulfiram effect alcohol metabolism
Disulfiram will mimic ALDH2^2/ALDH2^2 genotype and inhibit acetaldehyde from converting into acetate
Definition of alcohol use disorder
a problematic pattern of X use leading to clinically significant impairment or distress, as manifested by at least 2 at the following within a 12 month period (look at alcohol notes for the 11 possible X patterns)
Is alcohol heritable?
Yes, it is highly heritable
having 1 alcoholic parent increases risk of alcoholism by?
400%, this does not change even if child is raised in non-alcoholic homes
Having 2 alcoholic parents increases risk of alcoholism by?
over 600%
Explain exp of Men Who later developed alcohol abuse
Alcohol-naïve sons were brough in to a lab and were then given a drinks and asked to describe their high from drinking. Those that did not develop alcoholism later on reported a more intense high. Both groups peaked around the same time. Results demonstrate how those who develop alcoholism must drink more in order to achieve the same high
How many alleles were identified in 2017 in a GWAS of drinking among 112117 pp in UK
14
Alcohol consumption is a (1) and (2) trait
- complex
- multifactorial
What were the results from 2023 meta-analysis of GWAS
- 19 SNPs (single nucleotide polymorphisms) were associated with general risk of addiction
- substance specific risk at
- 9 loci for alcohol
- 32 for tobacco
- 5 loci for cannabis
- 1 locus for opioids
What is alcohol withdrawal
it is a rebound effect of a chronically sedated CNS), produces hyper-excitability
risk of alcohol withdrawal
withdrawal after chronic abuse can be life threatening if benzodiazepines are not used for acute symptoms
What are the stages of acute alcohol withdrawal
Early and late stage
Signs and time period for early stage of alcohol withdrawal
Early stage lasts from a few hours to 48 hours
signs include:
- anxiety
- anorexia
- insomnia
- tremor
- mild disorientation
- convulsions
- sympathetic response
Signs and time period for late stage of alcohol withdrawal
Begins after2-4 days and lasts 2-3 days
Signs include:
- delirium tremens
what is the most severe alcohol withdrawal state
Late stage
symptoms include:
tremors, anxiety, insomnia, paranoia, disorientation, sweating, nausea vomiting, diarrhea, fever, agitation, hallucination, fever
what is alcohol tolerance
Occurs when more alcohol is needed to attain effects that are used to be felt at a lower dose
what is dispositional tolerance
increased ability to metabolize alcohol through alcohol dehydrogenase and other liver enzymes
How long does it take for dispositional tolerance to double due to heavy drinking
Only 3-14 days
what is functional tolerance
the need for higher blood levels to achieve intoxication via neuroadaptive changes to the CNS
What is acute functional tolerance
greater intoxication is observed on the ascending limb of the BAL curve than at the same dose on the descending limb
What is chronic functional tolerance
increase in intake needed to produce intoxication; heavy drinkers are less likely impaired on motor coordination tasks than light drinkers at same BAL
what is behavioral functional tolerance
better performance on behavioral tasks by performing them repeatedly while intoxicated
Is alcohol toxic
yes at extremely high doses
How many alcohol related ER visits were ther in 2009
650000
How many Alcohol related ER visits for those under the age of 21
200000
what percent of college students drive with BAL above legal limit
25%
how many students injured each year due to alcohol related accident
500000
how many assaults by person who was drinking
100000
What conditions does alcohol contribute to
- liver damage (fatty liver disease, hepatitis, cirrhosis)
- heart disease
- neurological disorders
- type 2 diabetes
- certain cancers
- ex esophageal cancer when drinking hard liquor - Korsakoff syndrome
- fetal alcohol syndrom
what is a teratogen
an agent that causes birth defects
- ex: alcohol
Fetal Alcohol Syndrome Symptoms
- small eye openings
-smooth philtrum - thin upper lip
- less developed brain
what percent of pregnant women in the US have reported drinking in last month (during 2015)
10%, with 1/3 reporting binge drinking
what are some lifelong characteristics of fetal alcohol syndrome
they can occur without outward indication of exposure and can lead to:
- social skill problems
- adult substance abuse
- altered brain function
What are the neurobiological effects of alcohol
alcohol has widespread and diverse effects throughout the body, including CNS, that are still not fully understood
What are alcohol’s sites of cellular action
alcohol does not bind to a given receptor class but instead interacts w/ specific neuronal elements called ethanol receptive elements
what are the ethanol receptive elements
- GABA receptors
- 5-HT receptors
- K channels
- Ca channels
- G proteins
- protein kinases
- mhu opioid receptors
- synaptic sites in CNS neurons
Alcohol neurobiologic effects are difficult to quantify and see what is specifically effected
true
Alcohol Reward Neurocircuit
Interneurons stimulate the:
1. VTA
- dopamine is then sent to frontal cortex, Nucleus accumbens, amygdala
- Opioid peptides are sent to opioid receptors
2. AMG
- also has opioid peptides and receptors along with GABA and cannabinoid receptors present
3. Nucleus accumbens
- has opioid, cannabinoid, and GABA receptors present
where is the extended amygdala circuit in alcohol neurocircuit
Circuit includes the Nucleus accumbens, the BNST, and the Amygdala
How does alcohol affect GABA
inhibits GABA release in the VTA which will indirectly lead to increase in DA levels
How does acetaldehyde affect the VTA
it increases its DA levels
What partially reduce self administration in animals
- DA receptor agonists
- opioid receptor antagonists
- GABA receptor antagonists
Problem with promising receptors that show reduction in self administration in animals
these drugs were not effective in humans
What kind of mouse did not self administer alcohol
Mhu opioid receptor knockout mice
what kind of mice self administered more alcohol
Cannabinoid, delta opioid receptor, and neuropeptide Y1 knockout mice
What are blunted striatal responses to reward associated with
Various addictions including alcohol
Which substances favor hypoactivation
Alcohol, Cannabis, Cocaine, and Nicotine
what 3 thing is heavy drinking in teen years associated with?
- faster gray matter loss
- slower white matter growth
- poor subcortical cortical connectivity
what predates addiction
the hypoactivation response pattern that affects active and abstinent addicts
what does acute alcohol withdrawal activate
it activates the limbic-hypothalamic adrenal axis, primary stress response system
what were the results of the corticotropin releasing factor immunoreactivity (CRF-IR) exp in rat amygdalas
For the first 4 hours, levels of CRF-IR in both the withdrawal and control group were the same
BUT halfway through the 6-8 hour slot, the withdrawal group had a spike in the CRF-IR levels that last up to the 12 hr mark
During the CRF-IR exp, what NT were affected
NE levels rose and neuropeptide Y decreased
(increase in NE is associated w/ social anxiety
(decrease in neuropeptide Y is also associated w/ anxiety and emotional reactivity
what is protracted abstinence
it is stage where a negative emotional state is induced and can last for months
what long term behavioral effect may occur during alcohol protracted abstinence
- disruptions in sleep for years
- bad mood
- homeostatic pt is shifted to allostatic state
what is the psychoactive ingredient in tobacco
nicotine
what is tobacco
the dried leaves of nicotiana tobacum which grow in south and north america
3 ways of tobacco ingestion
- smoked (cigars, cigarettes)
- chewed (chew)
- snorted (snuff)
what kind of cancer is chew associated with?
mouth cancer
how far can tobacco be traced
8000 years
Where does the US fall in tobacco consumption
in the middle with about 1250-1499 cigarettes/person
what regions in US have the highest rates of smoking
Midwest and South
what is a common pattern in the regions where smoking is highest
they have the shortest life expectancies aka worst health
what tobacco product is most popular
cigarettes
what is the lowest US life expectancy
it is 72.9 to 77.4 yrs and is in the south
what year did tobacco products start to decrease and why?
Around 1945-1955, people started to figure out that smoking can cause cancer so public campaigns began to discourage smoking
what products does tabacco smoke contain
nicotine, carbon monoxide, and tar
what is tar
residual substance left after nicotine is removed and contains several toxins such as carcinogens and tumor initiating agents
what major toxic agents are most present in cigarettes
Acetaldehyde 800 microg (cilia toxic agent)
NO2 350 microg (toxic agent)
catechol 270 microg (cocarcinogen)
what alternative tobacco administration route has recently become more popular
vapes
what is different bw vapes and cigarettes
have less carcinogens, but have a higher nicotine blood plasma level that creates a more intense stimulant effect
Since 2011, how much has cig use changed
Decreased from 16% in 2011 to 8% in 2018
How has e-cig usage changed since 2011
Increased from less than 2% to 21%
What type of cigarette has the highest nicotine level
new generation e cigs have the highest nicotine levels that occur at an hour in
what is the peak level and time for a cigarette
Cigarette peaks at 15 ng/ml and occurs at 10 min in
What are the different parts of the hookah
Tobacco bowl, ashtray, neck, hose, water bowl, and mouth piece
what is the percent of people 12+ that have used tobacco
67.5%
what percent of people have smoked a cigarette
62.8%
what number of people are dependent on cigarettes in a given moment
22.9 million
what is the medical cost due to tobacco use
170 billion
what are some of the issues or conditions that tobacco can cause
- heart disease
- stroke
- lung disease
- eye disease
- immune system problems
- arthritis
- erectile dysfunction
is the leading cause of preventable death
smoking
how many people die each year due to smoke related illness
480000
how many people have a disease due to smoking
16 million
by how much does the life expectancy of a smoker decrease when compared to a non-smoker
die 10 years earlier
For men, what is the survival probabilities for current smokers vs non current smokers
- discrepency starts at 40 yo
- by the time you reach 80, there is a 12 yr gap bw smokers and non smokers
for women, what are the survival probabilities for current vs non current smokers
- discrepancy starts at 50 yo
- At age 80, the gap increases to 11 years bw smokers vs non smokers
what 2 kinds of exposure can lead to adverse outcomes during pregnancy
smoking and second-hand smoke
what are some of the pregnancy adverse outcomes due to smoking
- low birth weight
- childhood ADHD and conduct problems
- smoking leads to down regulation of DA levels in general - asthma
- SIDS
- Vulnerability to drug use in teen years
What were the results of the 2019 study of e cigs association to lung injury (EVALI)
- 34 deaths
- THC present in most samples
- causes still not fully understood
What are the psychological effects of nicotine use?
- mild euphoria
- increased energy
- heightened arousal
- reduced stress
- anxiolytic effects
- reduced appetite
- mild pain reducing qualities
what are the behavioral effects of nicotine use?
- improved attention
- shortened reaction time
- better problem solving
- improved cognition
- increased heart rate and blood pressure
what are the pharmacokinetics associated with nicotine use
- inhaled cig and vapes reach brain in 8 s
- almost all nicotine is delivered through the lungs
- large individual diff in blood plasma nicotine observed from the same dose
how long does it take nicotine to reach the brain
8 seconds
what are the levels like for people who are addicted to nicotine
Those who are addicted will maintain high blood levels of nicotine throughout the day
- smoke a new cig every .5 to 1 hour or when the blood plasma nicotine drops
what level of nicotine does an addicted person try to maintain
around a 20 ng/ml blood nicotine concentration
T or F: different tobacco preparations will lead to the same blood concentration curves
False
When does the peak concentration for cigarettes occur
within 10 min then will gradually decrease
When does the peak concentration for oral snuff occur?
At 30 min, it increase quickly, peaks, then decreases a little
when does the peak concentration occur for chewing tobacco
It occurs in 30 min, it will increase quickly then peak and level off (does not really decrease)
when does the peak nicotine concentration occur for nicotine gum
Peaks at 30, will gradually increase, peak and then gradually decrease
During what age group does prevalence of smoking increase sharply
from 12 to 17
what is the rate for prevalence of smoking during adulthood
rates fall slowly across adulthood
how long does it take 50% of teens who try smoking to become daily smokers
4-5 years
can a person be biologically predisposed and quickly develop nicotine withdrawal symptoms
yeah
what is the term used for people who maintain low nicotine use patterns and are less likely to become addicted
chippers
at what age do converted chippers usually stop or decrease their smoking habits
in their 20s
What is required for people to never return to light smoking
those that smoke 15+ cigs a day for at least 2 years never return to light smoking
what is nicotine abstinence syndrom
the withdrawal effects due to prolonged nicotine use
what are the somatic symptoms for nicotine withdrawal?
- bradycardia (slowed heart rate)
- gastrointestinal discomfort
- increased appetite
- weight gain
what are the affective symptoms for nicotine withdrawal
- depression
- irritability
- dysphoria
- anxiety
- difficulty concentrating
What is the neural cause for many of the symptoms during nicotine withdrawal
Dopamine depletion in mesolimbic DA system cause a lot of the nicotine withdrawal symptoms
Normal neural response pattern
Substance naive response pattern:
Neural firing (tonic activity) is consistent and when a reward cue is present, there is a reward delivery causing phasic response
Satiation will occur after phasic response is over and will return to normal tonic activity (same levels as before the cue)
Sensitized neural response pattern
Experience dependent response pattern:
there is reduced tonic activity (both in # of neural firings and their intensity)
when a reward cue is present, a sensitized phasic activity is immediately triggered (greater activity than normal)
reward deliver occurs in the midst of the phasic activity
satiation occurs after phasic activity is over and goes back to reduced tonic activity
How long does nicotine acute withdrawal last
Koob says up to 30 days, but heavy smokers, esp women, have reported longer timeframes
How long can nicotine cravings last
up to 6 months
how effective is nicotine replacement therapy
about 25%
what nicotine therapy drug can be up to 50% effective
Bupropion (wellbutrin)
what is buropion
a NDRI antidepressant that increases midbrain DA levels and block psychoactive effects of stimulants, including nicotine
what are the behavioral nicotine mechanisms, as described by smokers
- pleasurable
- helpful for concentration
- calming
- stress relieving
- anxiolytic
what kind of receptor is nicotine
a nicotine acetylcholine receptor (nAChR) agonist
where are nAChR found
throughout brain and body
muscles: alpha 1, beta 1, gamma, delta, epsilon
CNS: alpha 2 through alpha 6, beta 2 through beta 4
why is Beta 2 nAChR agonists imporotant
they are important for reinforcing effects
Neurobiological effects of nicotine (what occurs at a neuro level)
neuronal nAChRs activate other neurons by opening the Ca ion channels using other mechanisms
T or F: the break point for animal self administration of nicotine is higher than for cocaine
False, Cocaine break point is higher than nicotine
How does nicotine reduce pain
Nicotine has analgesic effects that are due to the activation of alpha4beta2 and alpha7 nAChR receptor subunits which will then increase opioid peptide levels in the Nucleus accumbens
how is rat behavior effected at low/high doses of nicotine
low doses: facilitates social behavior
high doses: dampens behavior
How do nicotine acute reinforcing effects occur
Through DA release in the mesolimbic DA system (VTA and NAcc) via the Beta2 subunit
where are nAChRs located on the VTA
on both cell bodies and dendrites of DA neurons
what type of mouse will not self administer nicotine
Beta 2 knockout mice
how does nicotine effect glutamate, GABA, and DA levels
- raises glutamate levels (alpha 7)
- reduces GABA levels (alpha4beta2) in the VTA
- increases DA release
What does alpha 7 nAChRs activate
Glutamate long term activation which leads to increase of DA
What does alpha4beta2 nAChRs do
This cholinergic afferent will reduce GABA levels (GABA is a DA inhibitor) leading to increase in DA release
What are cannabinoids
drugs that contain tetrahydrlcannabinol or similar pharmacologic actions
how many types of cannabinoids exist
over 100 types, including naturally occurring and synthetic
where is cannabis naturally found
a hemp plant indigenous to Altai and Tien-Shan mountains
how long has cannabis been cultivated
6000 years
what everyday material can be made out of cannabis
rope
when was cannabis first used as an anesthetic
2000 years ago
Where does marijuana come from
plant called cannabis sativa
what are the different cannabis administration methods
- joint
- water pipe aka a bong
- blunt
- hash
- hash oil (very concentrated)
- butane honey oil (BHO)
how is hash oil made
- soak cannabis flower buds in isopropanol (an alcohol)
- remove all plant material
- heat mixture to evaporate isopropanol
difference between hash oil and butane honey oil?
butane is used instead of isopropanol for extraction
what are the THC levels the different administration levels
Marijuana 4.5%
Sinsemilla 11%
Hashish 12.7-15.6%
Hashish oil 14.1-19.5%
BHO 60-90%**
How many non-psychoactive chemical constituents does cannabis contain
hundreds
what are the 2 main gene pools of cannabis
C sativa or c afghanica “indica”
what cannabis products are made from c. sativa
fiber/seed (low THC, mid-high CBD)
marijuana (high THC, low CBD)
hashish (high THC, low-mid CBD
What cannabis product is made from indica
hashish w/ high THC, low-high CBD
Is marijuana associated with lung cancer
no
What is the correlation between testicular cancer in epidemiologic studies
increased rates (up to 2x) of testicular cancer
what are the main 2 types of cannabinoids
naturally occurring and synthetic
how many naturally occurring cannabinoids exist
70+
are the 3 naturally occurring psychoactive cannabinoids
- delta 9- tetrahydrocannabinol
- delta 8- tetrahydrocannabinol (67% as potent as 1)
- delta 9-tetrahydrocannabidivarin (25% as potent as 1)
What are some examples of synthetic cannabionids
- spice
- K2
what doe cannabinoid receptors in synthetic cannabionoids bind to?
THC
synthetic compounds of cannabis are known as
JWH designations after John huffman who first synthesized them
what does delta 9-tetrahydrocannabinol and synthetic cannabis have in comon
they are both cannabinoid receptor 1 and 2 agonists
what is the most commonly used illegal drug in US
marijuana
what percent of people 12+ have used marijuana
42%
what percent of people in the last month have used marijuana
15%
what is the pattern of cannabis prevalence seen since 1978 to 2016 based on past month use
Gradual decrease from 34% to 9% from 1978 to 1992, but around 2000, the rates of use has slowly begun to increase and in 2016 were at 15%
what is interesting about the rate of marijuana usage and marijuana use disorder
Rates of use have increased since 2000, but the rate of marijuana use disorder has not
what has been the average prevalence of marijuana use disorder percentage seen in adults
2%
what 2 drug usage hit historic highs in 2021
marijuana 13.2% increase
hallucinogen 4.7% increase from 2011 to 2021
what percent of cannabis users in the past year demonstrate dependence
9%
what drug is most regularly used psychoactive drug for kids and teens
marijuana, they use that more than alcohol and tobacco
what are marijuana well confirmed clinical effects
refractory nausea, vomiting, anorexia, appetite loss, HIV/AIDS, canceer cachexia
what are the less well confirmed clinical effects of marijuana
spasticity due to spinal cord injury, multiple sclerosis, neurogenic pain, neuropathy, allodynia, movement disorders (Tourette’s syndrome, dystonia, dyskinesia), bronchodilation effects, glaucoma
what are the unexplored clinical effects of marijuana
epilepsy, hiccups, bipolar disorder, alzheimer’s disease, alcohol dependence
what are the behavioral effects of marijuana
intoxicating, includes euphoria, happiness, dream-like state, and at high doses, tiredness and fatigue
what are some other, not as common, behavioral effects of marijuana
more social, or less social (depends on dose), worse concentration, memory becomes poor, simple tasks require excess efforts, slowed perception of time
what is the most common administration method for marijuana
almost always smoked, (oral admin is not very effective)
how long after consumption does peak blood levels occur for marijuana
3-10 min
what are the effects of marijuana on the heart rate
When smoked, heart rate will decrease from 87 down to 75
when oral, heart rate will go from 72 to 80 then back down to 75
How does the rate high for marijuana differ among different administration methods
- IV has the most intense reported high with the peak occurring within the first 10 minutes and high wearing off after 4 hours
- Smoked has 2nd highest rated high with peak occurring same as IV and wearing off after 4 hours
- Oral has lowest rated high and has gradual increase and peaks around hour 3 before gradually decreasing and wearing off after 6 hours
what percent of the delta 9-THC has entered the brain when the behavioral/psychoactive effects occur
1%
What happens to the rest of the delta 9-THC that did not enter the brain
it is stored in body fat and broken down by the liver
How is THC broken down
THC is broken down into 8 beta-OH-THC and 11-OH-THC. 8 Beta-OH-THC then breaks down into to conjugates while 11-OH-THC breaks down into 11-OXO-THC, Conjugates and 8 alpha, 11-OH-THC which is then broken down into conjugates
what are the psychoactive metabolites seen during breakdown of THC
THC, 8 beta-OH-THC, 11-OH-THC, and 11-OXO-THC
how long does the elimination of all active metabolites take
5 to 6 days
what can be detected due to the slow elimination of half lives
active metabolites in Cannabis can be detected in urine for over a month due to slow half-life
when was a dependence syndrome identified for cannabis
1980s when THC making methods had greater concentrations
what were symptoms of the 1980 cannabis dependence syndrome
fear of health consequences, blunted emotional expression, emotional alienation from loved ones, low achievement, low grade depression
what is the typical course of progression for cannabis dependence
pleasurable social use then tolerance then more frequent use then social withdawal then function impairment at work/school
how many types of cannabis dependece are there
- type 1
- type 2
what are the characteristics of type 1 cannabis dependence
- multiple times a day
- significant self perceived dependence
- moderate withdrawal symptoms
- high rate of relapse
- dependence metabolites include delta 9-THC, 11-hydroxyl-delta 9-THC
what are the characteristics of type 2 cannabis dependence
- every 24-48 hours
- minor/moderate self perceived dependence
- mild withdrawal symptoms
- high rates of relapse
- dependence metabolites include 11-nor-delta 9-THC-carboxylic acid
what other drugs have similar dependence symptoms to cannabis
alcohol and cocaine
what does tolerance look like for cannabis users
tolerance to physical (HR acceleration) and psychological effects builds rapidly, even for light users
what causes tolerance to build in cannabis
neuroadaptations (cannabinoid receptors are profoundly downregulated)
what are the cannabis withdrawal symptoms
- irritability, anger, or aggression
- nervousness or anxiety
- sleep difficulty
- decreased appetite/weight loss
- restlessness
- depressed mood
- abdominal pain, shakiness/tremors, sweating, fever, chills, headache
how many withdrawal symptoms must an individual show in order to get diagnosed with cannabis withdrawal syndrom
at least 3 or mor symptoms
how are alcohol and cannabis effects on performance similar
have similar psychomotor performance and memory
what are the effects of cannabis that can impair driving and pilot skills
- slow rxn time, poor detection of peripheral stimuli, poor oculomotor tracking, space and time distortion, impaired coordination, brake and accelerator errors, poor speed control, poor judgement, increased risk of overtaking, impaired attention, impaired short term memory, additive effects w/ alcohol and other drugs
how did THC affect word recal test
decreased ability to recall words, same as alcohol
how does marijuana play a role in motor accidents
doubles the risk
what is the relation of marijuana use and individuals w/ psychotic disorders
cannabis rates are high among people who are predisposed to or suffer from psychotic disorders
how does cannabis effect brain of teens
has detrimental effects on prefrontal cortex development
what is reduced prefrontal volumes based on cannabis use associated with
decision making, memory, long-term palnning deficits
what is the neurobiological effect of cannabis
potency of cannabinoids correlates strongly with the CB1 and CB2 receptor binding affinity
where are cannabinoid receptors expressed densely
Basal ganglia and cerebellum
what regions of the basal ganglia have dense number of cannabinoid receptors
N. Acc, cuadate, putamen, thalamus, globulus pallidus
what is the function of the cerebellum
important for motor control and coordination of neural activity across the cortex
in what regions of the brain are there low levels of cannabinoid receptors
hippocampus
amygdala
cortex
function of hippocampus
memory consolidation and part of preoccupation/anticipation stage of addiction
function of amygdala
implicated in withdrawal/negative affect and the preoccupation/anticipation stages of addiction
function of cortex
imp for sensory, attentional, and executive functions and implicated in the preoccupation/anticipation stage of addiction
what is the role of CB1 receptors
found throughout the brain and mediate psychoactive effects of cannabinoids
What did CB1 knockout mice show
- no behavioral effects of delta9-thc admin
- did not self administer delta 9-THC
- did not show withdrawal syndrome after prolonged delta 9-admin
what is the role of CB2 receptors
found in the periphery and small areas of brain, and function is to exert some effects on the mesolimbic DA system
what are the reinforcing effects of delta 9-THC seen in animals during the binge/intoxication stage
- conditioned place preference
- IV self admin
- conditioned place aversion during withdrawal
how can reinforcing effects during the binge/intoxication stage of cannabis be blocked
use cannabinoid receptor antagonists
can you cross substitute cannabis with other drugs
no
what is released by both delta 9-THC and canabionoids
DA is released in N. Acc shell
and endogenous opioid peptides are also released
How does DA release between heroin and THC compare
Heroin has 175% compared to baseline release of DA in NAcc shell while THC has a 150% release aka heroin releases more DA
What is the Neurocircuit drug reward pathway of cannabinoids
Interneurons and opioid peptides are activated by cannabinoid receptors and found in the VTA, AMG, and NAcc activate the areas, VTA then release DA to FC, NAcc, and Amygdala regions
what is the effect of chronic delta 9-THC admin during the withdrawal/negative affect stage
produces tolerance to behavioral, analgesic, motor, and memory effects
how long does it take for tolerance to form during chronic use of THC in the withdrawal stage
tolerance to behavioral and analgesic effects begin in 3 days
tolerance to memory effects takes weeks
how does tolerance to THC occur
through down regulation of CB1 receptor densities throughout the brain, but will return to normal after a month of abstinence
what is the withdrawal stage of THC characterized by
excessive anxiety
what factor levels increase during THC withdrawal
Corticotropin releasing factor (CRF) levels rise during acute withdrawal which indicates a physiological stress response
animal model for THC preoccupation/anticipation stage
not well developed
what does marijuana use reinstate
it reinstates drug-seeking for cocaine, alcohol, nicotine, and heroin
what are the 2 appraoches to non-pharmacological treatment
behavioral and self help
what are the 2 appraoches to non-pharmacological treatment
behavioral and self help
what are the stages of change
Pre-contemplation
Contemplation
Preparation
Action
Maintenance
Relapse or permanent exit
what occurs at each stage of change for addiction treatment
Pre-contemplation: does not recognize need for cange or does not actively consider it
Contemplation: recognizes problem and considers change
Preparation: getting ready to change
Action: initiating change
Maintenance: adjust to change and practice new skills and behaviors to sustain change
Relapse: may occur and start cycle again
what is readiness to change
the brief, transient, short lived recognition that change is needed, often follows adverse events
ex: dui, overdose, partner leaves
what kind of treatment shows efficacy in treating addiction
behavioral treatment
what is the premise of motivational interviewing
it helps clients identify their own intrinsic reasons to change
when is motivational interviewing most effective
it is designed to work around denial and resistance, often used in acute settings such as ER but can be useful elsewhere
in what conditions is motivational interviewing most effective
it is designed to work around denial and resistance, often used in acute settings such as ER but can be useful elsewhere
what is an example of motivational interviewing
READS
Rolling w/ Resistance (R): work w/ assistance instead of opposing, balance the perspective
Express Empathy (E): identify and understand reasons for resistance w/o judging, create trust and show you are on patient’s side
Avoid Arguing (A): avoid adding additional resistance, feelings are not arguable, confront do not argue
Develop Discrepancy (D): strategy to create dissonance, motivate change by creating discrepancy bw patient behavior and personal goals/values
Support Self Efficacy (S): point out positives, praise patient for what they are doing to make change
What is an example of motivational interviewing technique
READS
Rolling w/ Resistance (R): work w/ resistance, balance perspective
Express Empathy (E): identify and understand reasons for resistance w/o judging, create trust and show you are on patient’s side
Avoid Arguing (A): avoid additional resistance for pt, feelings are not arguable, confront do not argue
Support Self Efficacy (S): point out positives, praise patient for effort put in to change
what is motivational interviewing effective for
reducing marijuana use and alcohol intake among heavy drinkers
what the limitations of motivational interviewing
- often delivered in single sessions
- efficacy for treating addiction is poor
What is the conclusion for motivational interviewing
useful, low cost method but by itself is not a viable strategy for treating addiction
what is the premise of contigency managment
reward patients for meating treatment goasl (clean drug screens)
Ex of contigency management
vouchers redeemable for goods and services, contigent on cocaine free urine screens
what is contingency management effective for
improving retnetion and abstienence in outpatient opioid detoxification
reude smling and illicit substance use among opioid adicts in methadone maintenance
reduce frequency of marijuana use
improve compliance among opioid-dependent pts treated w/ naltrexone maintenance
what are the limitations of contingency management
unsustainable clinical practice
promotes external attributions of success
effects weaken/disappear after contingency is stopped
Conclusion of contingency management
probably a short term solution to be used as an adjunct to other approaches
premise of cognitive behavior therapy (CBT)
high risk behaviors (using) and feelings (craving) can be modified through cognitive strategies and restructuring
- automatic, catastrophic thinking and assumptions must be changed
Ex of CBT
cravings do not inevitably lead to using, “play the tape all the way through”
A-B-Cs reciprocal feedback emphasis
Affect: craving, anxiety, excitement
Behavior: drug seeking
Cognitions: hopelessness, resignation
What is easier to change than feelings or behaviors
cognitions
what is CBT effective for
- alcohol use disorders
- outpatient treatment of cocaine dependence
- treat depressed cocaine users
- treat benzodiazepine addiction
- increase effectiveness of certain pharmacotherapies (such as disulfiram)
- teach skills needed for long term abstinence
- induce internal attributions of success
limitations of CBT
requires expert clinicians and is more effective with higher functioning educated clients
conclusion of cbt
components of cbt such as the changing attributions, teaching cognitive strategies, changing faulty cognitions are seen in all treatments, including self help
premise of couples and family therapy
treat addiction by altering family/social context within which it is embedded
example of couples and family therapy
see graph on notes
what is couples and family therapy effective for
reducing attrition
helps participating family members (improve kids psychosocial outcomes)
more effective than individual therapy for cocaine and opioid dependence
what are the limitations of couple and family therapy
very diverse set of treatments w/ wide range of efficacy
conclusion for couple and family therapy
many who are addicted do better when families are included in inpatient, outpatient, aftercare and extended therapy
most popular example of self help approach
AA
Premise of self help
recovery from addiction requires help of others and adoption of new way of life
addicts must surrender to their addiction, thereby accepting loss of control
addicts should find sponsor w/ significant clean time to advise them
w/ their sponsor, addicts should work an active 12 step program of recovery, including amends to those they’ve hurt
Premise of self help
recovery from addiction requires help of others and adoption of new way of life
addicts must surrender to their addiction, thereby accepting loss of control
addicts should find sponsor w/ significant clean time to advise them
w/ their sponsor, addicts should work an active 12 step program of recovery, including amends to those they’ve hurt
example of self help
traditional 12 steps
see slides for all the steps
what is self help effective for
encouraging abstinence, encourage social networking, recovering from shame
how many people are currently estimated to be abstinent in AA
2 million
limitations of self help
less effective for those with comorbid mental health issues
off-putting to those who do not believe in God and are not made aware of secular gorups
some in scientific community are against AA bc it is rooted in teachings of single religion (christianity) and bc it is difficult to study
conclusion of self help
collectively, those who attend AA show better outcomes in a dose-response fashion
Steps to developing drug treatments
- serendipity
- systematic research with animals, then humans
- once approved for human research, drug efficacy is evaluated using clinical trials
what are clinical trials
any prospective study comparing effects and value of interventions against a control in human beings
include intervention and control groups that are followed forward in time and evaluated/compared for treatment response
what is an intervention group
patients who get the new drug
what is an intervention group
patients who get the new drug
what is the control group
patients who get a placebo or treatment as usual (TAU)
what are the 4 phases of clinical trials
phase 1: large pharma studies, examine drug tolerance and interactions, pharmacokinetics and max tolerated dose
phase 2: therapeutic efficacy studies, examine diff doses and measures outcome
Phase 3: therapeutic confirmation studies, demonstrate clinical use and safety profile
Phase 4: therapeutic use studies, examine broad and special populations, and identify uncommon adverse events
who must approve for an investigational new drug before clinical trials can begin
FDA
what are the 3 stages of animal model that categorize medication developments
- binge/intoxication
- withdrawal/negative effect
- preoccupation/anticipation
existing drugs used to treat addiction among humans in the binge/intoxication stage
disulfiram
naltrexone
methadone
buprenorphine
naloxone
varenicline
bupropion
existing drugs used to treat addiction among humans in the withdrawal/negative effect stage
methadone
buprenorphine
nicotine patch
varenicline
existing drugs used to treat addiction among humans in the preoccupation/anticipation stage
acamprosate
bupropion
what is disulfiram used for
blocks conversion of acetaldehyde to acetic acid, raising acetaldehyde levels 5 to 10 times the normal amount when metabolizing alcohol alone
effective in preventing alcohol use if taken
limitation of disulfiram
can reduce one’s confidence to abstain
what is naltrexone
a mhu, delta, kappa opioid receptor antogonist
what does naltrexone treat
alcohol and opioid dependence, but is more effect for alcohol (not known why)
limitations of naltrexone
reduces, but does not eliminate euphoric properties of use
extended release injections, which circumvent adherence problems, cost over 1200 per month
limitations of naltrexone
reduces, but does not eliminate euphoric properties of use
extended release injections, which circumvent adherence problems, cost over 1200 per month
what is methadone
a less potent longer acting opioid than heroin
what is methadone used for
substitution therapy for heroin addiction and for analgesic effects
limitations of methadone
carries abuse potential itself
longer withdrawal than heroin
how many deaths per year due to methadone
5000
what is buprenorphine
a less potent longer lasting opioid than heroin and methadone, it is a partial mhu opioid receptor agonist
what is naloxone
a mhu opioid and kappa opioid receptor antagonist
what is buprenorphine used for
maintenance therapy for heroin addiction and for analgesic effects
limitations of burprenorphine
carries abuse potential itself
risk of respiratory depression and death, especially if paired with benzodiazepines
black market had developed
longer withdrawal than heroin (up to a month)
what is buprenorphine called when naloxone is added
suboxone
what is the suboxone withdrawal timeline
first 72 hours: worst physical symptoms
1 week: body aches and pains, insomnia, mood swings
2 weeks: depression
1 month: cravings and depressions end but several symptoms can last several months
buprenorphine withdrawal symptoms
nausea, vomiting, body aches, insomnia, drowsiness, indigestion, anxiety, depression, irritability, cravings, fever, chills, sweating, headache, difficulty concentrating
buprenorphine withdrawal symptoms
nausea, vomiting, body aches, insomnia, drowsiness, indigestion, anxiety, depression, irritability, cravings, fever, chills, sweating, headache, difficulty concentrating
buprenorphine withdrawal symptoms
nausea, vomiting, body aches, insomnia, drowsiness, indigestion, anxiety, depression, irritability, cravings, fever, chills, sweating, headache, difficulty concentrating
what is varenicline
a partial alpha4beta2 nicotinic acetylcholine (nACH) receptor agonist that releases DA into the NAcc and results in reduction of nicotine cravings
limitations of varenicline
potential to increase suicide ideation, not allowed by FDA
what is bupropion
norepinephrine and dopamine reuptake inhibitor (NDRI) antidepressant
will increase DA levels in ventral striatum (VS), reduce cravings
HAS NO PSYCHOACTIVE PROPERTIES
what is bupropion used for
blocks the high associated w/ nicotine and strong stimulants (cocaine and meth)
Limitations of bupropion
increases blood pressure and lowers seizure threshold, banned in Europe due to hypertensive effects
what is nicotine patch
less potent longer acting form of nicotine
what are limitations of a nicotine patch
heavily marketed
intuitive appeal but unsupervised weaning more often than not is ineffective, regardless of addictive substance
effectiveness is usually assessed by smoking cessation, not addiction to nicotine
what is acamprosate
a glutamate receptor, NMDA receptor, and Ca channel modulator
what is acamprosate used for
used to treat alcohol dependence, works best for people motivated to quit drinking
limitations of acamprosate
FDA labels include warnings about increase in suicidal behavior, major depressive disorder, and kidney failure
what are limitations of drug treatments
- effect sizes are more often small and effectiveness is overstated by drug companies who sell to physicians
- rodent models are great for assessing effects of addiction on subcortical functions, but limited for assessing effects of addiction on cortical functions
- IMP: neither acquisition of nor recovery from addiction can be understood at any single level of analysis, including neurobiology, we live in an era of biological reductionism
what are limitations of drug treatments
- effect sizes are more often small and effectiveness is overstated by drug companies who sell to physicians
- rodent models are great for assessing effects of addiction on subcortical functions, but limited for assessing effects of addiction on cortical functions
- IMP: neither acquisition of nor recovery from addiction can be understood at any single level of analysis, including neurobiology, we live in an era of biological reductionism
what is an example of the first drug treatment limitation
effect sizes for naltrexone and acamprosate in treating alcohol dependence (61 studies)
- treatment and control groups overlap more than they differ
Explanation of 3rd drug treatment limitation
emotion is missing from many of our models
animal models cannot address the roles that emotion paly in recover from addiction
ex: depression, guilt, shame, self doubt
Culture is missing from many models
ex: culture norms, fallacies, stigma
Model of systemic research w/ animals chart
novel analogs lead to screening animal studies, with mult models for reference compounds
and
new use of approved drugs lead to human lab studies, with mult. dependent variables for reference compounds
these reference compounds interact with each other
