Lecture 2: Drug Addiction Flashcards
Defining Addiction Is there a single definition? (A) (B) (C)
*There is no single, universally accepted definition of addiction
“The compulsive seeking (drug craving) and
administration of a drug despite grave
adverse consequences or as a loss of
control over drug intake” (Nestler, 2004)
• i.e., when I drink coffee, it doesn’t have
grave consequences so is not an addiction
under this definition. This definition is
missing the physiological aspect, get a
headache as a withdrawal symptom which is
a sign your body is saying they need the
chemical (caffeine) and to drink a cup of
coffee.
“a term used to indicate the most severe,
chronic stage of substance-use disorder, in
which there is a substantial loss of self-
control, as indicated by compulsive drug-
taking despite the desire to stop taking the
drug” Volkow, Koob, and McLellan (2016)
• A second definition. coffee is not extreme
and not an addiction under this definition.
Chronic – repeated and uncontrollable
behaviour. To take drug to stop withdrawal
symptoms and feed cravings despite
negative consequences and desire to stop.
Classifies it as a part of substance use
disorder (qualifies it)
“a chronic, relapsing brain disease that is
characterized by compulsive drug seeking
and use, despite harmful consequences”
National Institute for Drug Abuse (NIDA)
• Third definition: brain disease (chemical
reactions in the brain, every sense of you
are, belief, memory, needs, or behaviour
starts in the brain)
“addiction is, at its core, a consequence of
fundamental changes in brain function
means that a major goal of treatment must
be to either reverse or compensate for
those brain changes”
(Alan Leshner in 1997)
• Criticists argue that the disease model
disregards human decision making and
choice
• Fourth: changes in brain function.
• Problem with calling ‘alcoholism’ a brain
disease? Argues the addictive behaviour is
the physiological consequence of a brain
disease. It implies that the person was born
with a brain with genetic make-up that made
them predisposed to addiction and removes
the nurture/choice behaviour which results
in addiction.
• We need to separate the brain from being a
physiological organ and a mechanism that
makes decisions. The brain is you; it makes
your decisions, and you are your
decisions/thoughts. If we say someone has
stage four cancer, we do not say hey man
you could’ve pulled through if you just
thought positive thoughts. When we say
alcoholism, we say there was a choice, you
had a choice to drink.
• Like cancer and addiction (depending on
circumstance but in general) there is an
initial choice, the initial behaviour to smoke
which lead to the unintended and
uncontrollable consequence of either
addiction or cancer. If there was no cocaine
in the world, then they could not be
addicted to cocaine. However, it could
manifest in another way with another
substance if it is a disease. Addiction is not
just about the drug. It’s about the self-
destruction. They know it is wrong and they
should stop but they can’t get rid of the drug
taking lifestyle, they are not looking for the
chemical, but the ability to
forget/escape/numb themselves to pain.
Drug overdose deaths in the USA
• More common for males to overdose than
women
• Overall, 91,000 people overdosed in 2020
• Alarming that this is such a prevalent issue
and trend is increasing. Clearly,
punishment/arrests are not working at
preventing drug use. It seems anything else
could be better. Would legalizing drugs be
better?
Opioids in New Zealand
• Different drugs are more prevalent in
different geographical locations in New
Zealand.
• Guessing the reason, would be that
Northland have a social problem (low ses is
linked to drug use; gangs & violence; MDMA
in cities with clubs/universities).
• Opioids = despair & low socioeconomic
status
Classifying addiction (DSM-V)
• Substance-related and addictive disorders
o Substance induced disorders
o Substance use disorders
*There are many things you can be addicted
to that are not substances (i.e., pornography,
gambling etc. which do NOT include
chemicals). Substance – chemicals
ingested/injected/snorted into the body
*DSM-5 uses addiction and substance use
disorder synonymously
Substance-induced disorders
• Substance intoxication (drink too much and
get sick)
• Substance withdrawal (headaches, pain, get
sick)
• Substance/medication-induced mental
disorders (i.e., psychosis)
*physiological & psychological symptoms
Substance use disorders
• Cluster of cognitive, behavioral, and physiological symptoms • Continued use of a substance despite significant substance-related problems (continue using despite consequences)
*Behavioural changes
(9) Drugs included in Substance Abuse Disorder
- Alcohol
- Cannabis
- Hallucinogens
- PCP
- Opioids
- Inhalants
- Sedatives
- Stimulants
- Tobacco
*A variety of drugs people can be addicted
to. People are usually addicted to one not
all of them. Indicating that they have their
own pathways, mechanisms, chemical
reactions, and physiological changes.
*Makes it harder to fix when there are so
many and not a single substance
(prevention wise)
General criteria of substance use disorders
*How to determine when someone has a substance use disorder
- Increasing larger amounts of use of the
substance (i.e., tolerance builds and more is
needed too feel good, do it in the morning,
most of the day) - Unsuccessful efforts to decrease use
(relapse/withdrawal/cravings so continue to
use) - Drug craving (always wanting to do it that is
hard to resist, harder when near it or in
same place you usually ingest it in) - Impairment in occupational, home, or social
functioning (whole life becomes about using
the drug) - Substantial time spent procuring or
recovering from use - Risky use of the substance
- Use of the substance despite negative
consequences (more you do it, the drug
becomes the number one priority and are
less concerned about the consequences,
continue to use it despite them).
*Tolerance and withdrawal are additional
criteria for substance use disorders but are
not required for the diagnosis!
Tolerance
Increased amounts of the substance are needed to achieve the desired effect (or a substantially reduced effect when the usual amount is taken)
*Tolerance: body uses a compensatory
response to counteract the drug and
maintain homeostasis, so you need to take a
higher dosage to get the same effect of the
drug. They are chasing the high of the first
use that they will never get.
*Physiology changes: receptors, dopamine
change with continued use.
*Pentanol: is a synthetic opioid people use
when they have built a tolerance, leads to
overdose, due to our body not being able to
handle the repeated physiological changes
results in heart attacks etc.
*Tolerance varies among individuals
Withdrawal
Aversive physiological effects that ensue when the addictive substance is removed or reduced and may include insomnia, anxiety, agitation, and digestive problems
• Symptoms vary substantially across drugs!
And not all substances are associated with
withdrawal symptoms.
• Withdrawal: when the body has undergone
physiological changes to maintain
homeostasis after repetitive drug use,
when the cues for drug using are present
but a drug is not ingested, you go through
withdrawal and crave the drug to make it
go away.
• When drugs are removed the body tries to
reach a new equilibrium which results in
withdrawal physiological symptoms. Pretty
bad in opioids, they will vary across
substances. E.g., caffeine withdrawal is
headaches till the new equilibrium is
reached.
Prevalence
• ~10% of individuals 12 years of age or older
(22 million people in the U.S.) are addicted
to alcohol or other drugs
• Cannabinoids, depressants, hallucinogens,
opioids, stimulants, alcohol, PCP, nicotine
are commonly abused (worldwide)
*High prevalence. Terrifying that some 12- year-olds use substances. *It is a worldwide issue *A solution/prevention strategy can be implemented worldwide
Prevalence (alcohol)
• Alcohol use disorder affects 7.8% of men
and 1.5% of women worldwide
• 8.5% of adults and 4.6% of adolescents in
the United States
*men > women (alcohol)
*Early onset of drug use is associated with
heavy drug use in adulthood
Prevalence (opioids)
• Opioid addiction rates continue to increase
o prescription opioid use has increased by
500% in the last 7 years
o ~Two million (0.8%) of the U.S. population
is addicted to prescription opioids
o In 2015 one in three Americans were
prescribed opioids
Class Discussion:
• Drug use is increasing (upward trend)
• Pentanol is included here
• Wisdom tooth taken out and given pain
reliever (oxycodone) is that a problem.
Adderall and Ritalin are methamphetamines.
People assume if it is given to you at the
doctors the drug is different than getting it
on the street corner. The brain chemistry
changes, and the chemical is the same.
• Still get hooked if it is given to you at the
doctors, they won’t prescribe anymore, so
you go to the streets to compensate. Street
drugs are laced with rat poison, or other
drugs (fentanyl) which can cause you to OD
and get hooked on their strain or bulk up
product to make a profit.
• Ritalin = methamphetamine salts (cleaner
but not better)
*People can get addicted to their prescription
without realizing because people deny that
you can be addicted to prescriptions (i.e.,
pain meds, wine)
Withdrawal Symptoms
• Not associated with some types of hallucinogens o LSD o Mescaline o Psilocybin (mushrooms)
*Withdrawal symptoms are not associated
with these drugs!
*Some students do micro dosing of
psychedelics to improve academic
performance, every day, without being
addicted. No convincing evidence of it
reliably improving performance.
*All drugs have the same effect prescribed or
not.
*Hallucinogens are not considered addictive
Addictive Substances
*highly addictive substances include, alcohol,
benzodiazepines, nicotine, and opioids.
*cigarette smoking is the most prevalent
addiction (22.5% adults), alcohol (7.8% men;
1.5% women)
Five substances with the highest potential for addiction worldwide
Criteria:
• the extent to which the drug activates the
brains dopamine system
• degree of pleasure experienced from the
drug
• the degree to which the drug causes
withdrawal symptoms
• the degree of physical and cognitive harm
caused by the drug
• how quickly the drug results in addiction
Substances • heroin • alcohol • nicotine • cocaine • sedatives
Comorbidity
• Commonly co-occurs with psychiatric
disorders
• Increases the complexity of providing
effective treatment interventions
• Study: 400 patients - 54% exhibited
comorbid psychiatric and substance use
disorders (a larger % of public health
patients meet the criteria for comorbidity
than those from the substance abuse
settings)
• The presence of co-occurring psychiatric
disorders (bipolar disorder, major
depressive disorder) increases the risk of a
poor prognosis
Epidemiological studies
• Males are more likely than females to
suffer from substance-related disorders
o However, the prevalence gap appears to
be narrowing as substance use disorders
are increasing among females (study in
2017)
• Initiation of substance use is occurring at
younger ages
Males vs. Females
• Females appear to have: o Accelerated progression to dependence o More severe adverse medical, psychiatric, and functional consequences o More vulnerable to medical, physical, mental, and social consequences of substance use and dependance o potential risk of drug-induced complications during pregnancy • However, no differences in treatment outcomes detected between males and females • Boys and girls aged 12–17 years have comparable rate of use and initiation for alcohol, cocaine, heroin, and tobacco • ~5% of pregnant women abuse illicit drugs during their pregnancy (other studies found higher rates of opioid use in low socioeconomic status women)
Do most people who take addictive substances become addicted?
• The majority of individuals who use drugs
do not become addicted suggesting that
some people are more susceptible to
addiction than others
§ Genetic?
§ Environmental?
§ Social?
- What is the cause? Genetic (allele),
environment (ACEs), social? (gang/drug
presence). No, it is the combination of all of
them
Percentage of people who become addicted?
• ~10% of individuals are highly susceptible to
addiction
• This varies across drug types
• 23% of individuals who try heroin become
addicted (80% of heroin users started with
prescription opioids first)
• less than 1% of prescription benzodiazepine
(Valium, Xanax, Ambien) users become
addicted
• The interaction between genetics,
environment, and social factors influences
susceptibility to addiction
• First Experiment (humans)
• Vietnam soldiers took heroin during the war
and the military were concerned when they
came back the the US would be addicts
with guns. However, only 5% of them
continued to take heroin but 35-38%, who
had physiology changes and liked it,
stopped because the environmental factors
which induced the need to take drugs was
gone. 8-12% of those who misuse
prescription opiates become addicted.
• It is never entirely genetics, it’s the gene-
environment interaction!
• Second Experiment Bruce Alexander
• Mice put into a cage and was trained to
push the lever for cocaine to be released
into the brain. The article stated that the
behaviours related to cocaine addiction and
found that mice will press the lever until
they die (overdose). He re-did the
experiment with the rat in the park with
more stimuli in the cage, press the lever for
cocaine, he found a significantly smaller
percentage rats pressed the lever.
Introducing social, mating, sensory
stimulation changed their behaviour (80 vs
20%). Drugs is only a small percentage of
addiction. Unless you change the social
environment, you are not going to be able
to change addictive behaviour (it is not the
chemical in the drug, it is the combination of
the chemical and the environment).
• Gin Craze (London 18th Century)
• People moved from rural to urban areas.
Struggled to adjust and started to consume
gin (opioids). People blamed gin for the high
rates of death.
• The problem is the environment, the
stress/trauma of the environment, leads you
to addictive behaviours
• Experiment 3 (NZ is liberal; Switzerland is
conservative)
• Switzerland late 1990’s had huge heroin
problem. The government responded by
punishing people who take heroin (shame,
prison, you can say no in USA) they
legalized it rather than criminalized it.
Anyone who wants to do it goes to the
clinic and for free (clean needles, in a safe
place) people were fearful of the
chaos/violence would rise BUT the number
of overdoses was 0, there was less crime
(no need to steal, sell body, be violent), and
they engaged with the addicts and helped
them by social working, find job,
counselling, which was way more effective
than US’s response.
*Conditions to how drugs should be legal,
clinical safe spaces with treatment without
punishment or shame. We don’t want
unknown people selling unknown drugs to
unknown people.
*Is addiction an illness? Is it their fault/choice
or a mental illness that needs treatment? If
it’s a gene-environment then there is no
choice. Like depression, social anxiety,
cancer, bipolar, addiction is NOT a choice!
Impact of trauma
• Exposure to child maltreatment increases
the risk of lifetime substance use disorders
o 50% - 75% of college students with
substance use problems have a history of
adverse childhood experiences
• Physical abuse, sexual abuse, and parental
violence are correlated with substance use
disorder are similar across race and
ethnicities
Addiction in childhood associated with…
• Intention to use substances in childhood is
related to subsequent use
• Adolescents are vulnerable to addiction
due to
o Environmental factors
o Psychosocial factors
o Brain development factors
• Elementary school students intentions and
prevalence of substance use increased with
grade level. Intentions to use cigarettes and
alcohol early on were associated with
substance use in subsequent grades (i.e.,
intention is a warning sign)
• College students are at high-risk population
for use of alcohol and illicit drugs
o ~98% of drug users ingest more than one
substance
o At risk of using prescription stimulants
without a valid prescription (especially
lower point grade averages and
psychological difficulties)
Multicultural Findings
• Alcohol is the most frequently used substance (3.6% of the world population between the ages of 15-64 being alcoholics) o Eastern Europe 10.9% (highest) o Americas 5.2% o Africa 1.1%
Multicultural Findings (alcohol)
• Within the USA the prevalence rates of
alcohol use disorder vary across race and
ethnicity
o Native Americans and Alaska Natives:
12.1% (highest)
o Whites: 8.9%
o Hispanics: 7.9%
o African Americans: 6.9%
o Asian Americans and Pacific Islanders:
4.5% (lowest)
Multicultural Findings (cannabis)
• Within the USA the prevalence rates of
cannabis use disorder vary across race and
ethnicity
o Native Americans and Alaska Natives:
3.4% (highest)
o African Americans: 1.8%
o Whites: 1.4%
o Hispanics: 1.2%
o Asian Americans and Pacific Islanders:
1.2% (lowest)
Multicultural findings (longitudinal study)
• Steady and steep reduction of heavy
drinking in white men and women in 20s
• Black men and women heavy drinking
increased in frequency during their mid
20s
• Blacks and Hispanics (compared to whites)
showed a slower decline in heavy drinking
over time
*However, stimulants and opioids misuse
are higher among whites!
*mixed findings on whether individuals with
disabilities are at risk of substance misuse
Onset of Substance Use Disorders
• Development and course of substance use
disorders varies among individuals and the
substance used
• Onset for alcohol use disorder typically
occurs in late teens to mid-20s (can occur
in late teens) and majority of alcohol use
disorders are developed by their late 30s
• Onset (abuse and dependence) for most
drugs occurs in 20s to 40s
• Substance use disorder is chronic with
periods of exacerbation and remission
Psychosocial factors
Two predictors of drug use/relapse
• Psychological factors influence the course
and outcomes of substance use disorders
• Depression (and drug cravings) are major
triggers for relapse in both men and
women
• Age is another predictor factor: the earlier
the onset the higher the relapse rate (and
physical and psychological comorbidity)
Inebriated Mice Chow Down (Reading)
• Inject mice with the equivalence of two
bottles of wine per day over three
consecutive days to mimic a weekend of
heavy drinking (experimental). Control mice
were injected with saline.
• Results indicate that both male and female
intoxicated mice consumed far more chow
food than control mice.
• Autopsies of their brain revealed alcohol
(ethanol) induced activation of specialised
neurons called agouti-related protein
(AgRP). These neurons typically become
activated following fasting or release of
hunger hormones in the brain. The
researchers concluded that increased AgRP
following alcohol consumption plays a
critical role in alcohol-induced binge eating
Initiation and Maintenance of Addiction Theories: How does the addiction cycle begin?
(A) Reinforcement Theories
*There is no single cause of substance use
disorders or additive behaviours (i.e.,
combination of physiology and environment
interactions). Our knowledge is based on
animal models but some argue that
addiction is a uniquely human condition
which animal models cannot fully capture.
- Pleasurable effects reinforce initial drug
use
- Positive reinforcement of initial drug use
(reading)
- Negative reinforcement in those who use
drugs to escape emotional distress,
negative affect, or stress (lecture) - Rewarding effects are reduced and
compulsive drug-taking behavior begins
- Overtime the rewarding effects of drug use
are reduced and compulsive drug-taking
behaviour results from a need to achieve a
state of homeostasis (i.e., to feel normal,
alleviate pain, discomfort, and withdrawal
symptoms)
- The rewarding properties of the drugs do
not justify the negative consequences
which accompany their repeated use.
However, Classical Conditioning theories
argue that environmental stimuli can be
paired with drug use, becoming
conditioned stimuli which triggers drug-
taking behaviours. - Impaired cognitive processes
- Salience attribution (i.e., attention towards
stimuli heightened towards drug-
associated cues)
- response inhibition (i.e., inhibiting
behaviour which interferes with goal-
directed behaviour)
Reinforcement Theories (anatomy)
• Salience attribution, response inhibition,
drug reward, drug cravings are mediated by
the mesocorticolimbic pathway
o Striatum
o Midbrain
o Limbic system
o Prefrontal regions
Mesocorticolimbic Pathway: Rodents
• Connections between striatal, midbrain,
limbic, and prefrontal regions
o Addictive drugs activate “reward
pathways”
o Release of dopamine
• After 60 years of investigation, details
concerning the specific functioning of these
pathways remains poorly understood.
However, what is in common among all
addictive drugs is that they activate ‘reward
pathways’ in the brain by triggering the
release of neurotransmitter dopamine
(linked to experiencing pleasure or reward)
• mesocorticolimbic system involves several
interconnected brain regions including the
ventral tegmental area (VTA), substantia
nigra, caudate nucleus, and putamen
(striatum), nucleus accumbens, amygdala,
and frontal cortical regions that correspond
to a rats prefrontal cortex or a humans
anterior cingulate (READING)
Addiction Study (Rats)
• Rats learn to press self-administer cocaine
o Will do so despite adverse consequences
o Will do so in lieu of drink or food
o Mothers will abandon their newborn pups
in order to self-administer drugs
Addiction Study (Rats)
• Self-administer bursts of electrical
stimulation to brain sites that mediate
pleasurable effects of natural rewards like
food, water, and sex (i.e., intracranial self-
stimulation)
• Dopamine levels in the nucleus accumbens
increases during intravenous cocaine
administration
• Administering dopamine antagonists
decreased lever-pressing behaviour and
lesioning of the nucleus accumbens
drastically reduced the rate of drug self-
administration which strongly supports the
role of dopamine and the mesolibiccortico
pathways in drug addiction
PET and fMRI: Humans
• Increases in dopamine levels in the nucleus
accumbens, caudate, and putamen during
amphetamine administration
• Dopamine release is increased in the
nucleus accumbens and striatum in
anticipation of drug administration and drug
cues
• Differences in brain activation patterns in
the mesolimbiccortico pathway in
participants with cocaine use disorder while
at rest, compared to participants without
cocaine addiction
Orbitofrontal Pathways
• Frontal regions are important for regulating
higher-order cognitive functions
o Response inhibition
o Decision making
o Working memory
• Extensive connections with midbrain,
limbic, and subcortical structures
• Increased activation of the pre-frontal
cortex in drug users relative to controls
during fMRIs when drug related cues are
presented
