Substance Use Disorder

What is addiction?

chronic, relapsing brain disease that causes compulsive drug seeking

what is physical dependence?

body adapts to drug, accompanies addiction, withdrawal + tolerance

Does physical dependence mean addiction?

no, it just accompanies addiction

what is tolerance?

physiological adaptations, checkpoint imbalances

what does tolerance influence?

physical dependence

what is substance use disorder (SUD)?

mental disorder that affects a person's brain + behavior -> inability to control use

what is withdrawal?

drug-specific physical or mental symptoms if drug use is abruptly ceased

what are the 4 groups of DSM-V Diagnostic Criteria for SUD?

Impaired control

Social Impairment

Risky use of substance

Pharmacological criteria

Which group of DSM-V Diagnostic Criteria does this explain?

- substances taken in larger amounts

- longer period of time than intended

- persistent desire/unsuccessful efforts to cut down/control

- cravings, lots of time spent obtaining, using, or recovering

Impaired control

Which group of DSM-V Diagnostic Criteria does this explain?

- recurrent substance use that leads to failure to fulfil major roles/obligations

- continued use after social/interpersonal problems caused by effects

- important social activities are given up/reduced

Social Impairment

Which group of DSM-V Diagnostic Criteria does this explain?

- recurrent substance use when it is physically hazardous

Risky use of substance

Which group of DSM-V Diagnostic Criteria does this explain?

- shows tolerance and withdrawal

Pharmacological criteria

How many symptoms are seen in MILD severity?

2-3 symptoms

How many symptoms are seen in MODERATE severity?

4-5 symptoms

How many symptoms are seen in SEVERE severity (haha)?

6+ symptoms

What circuit is activated in response to stimuli (food, sex)?

- important for survival/reproduction

- has primary reinforces that intrinsically reward

Mesocorticolimbic circuit

What type of learning/reward processing is this describing?

- positive reinforcement of reward cues

- classical conditioning

Associative learning

What type of learning/reward processing is this describing?

- wanting, craving, desire

- motivation for reward

Motivational salience

What type of learning/reward processing is this describing?

- pleasure, joy, euphoria, ecstasy

Positively-valenced emotions

Does the brain make the connection of pleasure in people with SUD?

no, but there is a powerful urge to continue

What part of the genome does the hypothesis free method ("fishing") in Genome Wise Association Studies?

entire genome

What is a con of using hypothesis free method in GWAS?

the chance of SNPs being correlated at random is not helpful and it requires large groups of subjects

What does the term "relative risk" mean in GWAS?

SNP compared to general population

What does the term "polygenic risk" mean in GWAS?

combined influence of multiple individual SNPs

Can SUD be found in animals too?

yes

What pathway plays an important role in the reward system?

Dopamine pathways

What part of the dopamine pathway is this describing?

- in midbrain ventral tegmental area (VTA)

- projects to nucleus accumbens (NAc), amygdala, hippocampus

Mesolimbic

What part of the dopamine pathway is this describing?

- VTA projects to pre-frontal cortex (PFC)

Mesocortical

What is the projection flow in the dopamine pathways/mesocorticolimbic circuit?

stimulus -> VTA -> NAc -> PFC

Are dopamine pathways involved in influencing motivation and positive-valence emotion?

yes

What type of learning is influenced by associative learning?

motivational salience

What pharmacological class of substances is this?

- cannabis, THC, CBD, synthetics

Cannabinoids

What pharmacological class of substances is this?

- cocaine, amphetamine, methamphetamine, methylphenidate, caffeine

Psychostimulants

What pharmacological class of substance is this?

-ethanol, benzodiazepines, barbiturates, methaqualone, GHB, Kavalactones

Sedatives

What pharmacological class of substance is this?

- oxycodone, hydrocodone, morphine, heroin

Opioids

What pharmacological class of substance is this?

- classical, dissociative, deliriants, KOR agonists

Hallucinogens

What pharmacological class of substance is this?

- MDMA, ecstasy, molly

Empathogens/Entactogens

Where do cannabinoids come from?

flowers, extracts (hashish, hash oil, rosin)

What type of Cannabinoid is this?

- natural

- binds to CB1 and CB2 receptors

- Associated with psychoactive effects

Phytocannabinoids

Which cannabinoid receptor is associated with psychoactive effects?

CB1

What happens to SENSORY in cannabinoids?

enhancement, hallucinations at high doses

What happens to COGNITION in cannabinoids?

altered thought process, time perception

What happens to MOOD in cannabinoids?

altered mood, happy, relaxed, paranoid, anxious

What kind of adverse effect in cannabinoids is this describing (acute vs. chronic)?

- paranoia, anxiety

- increased BP, HR

- impaired cognition

- worsening symptoms of psychosis

Acute

What kind of adverse effect in cannabinoids is this describing (acute vs. chronic)?

- altered mood

- short term memory impaired (reversible)

- psychological dependence

- mild physical dependence and withdrawal

- cannabinoid hyperemesis syndrome (CHS)

Chronic

What are some symptoms of cannabinoid hyperemesis syndrome (CHS)?

chronic vomiting, nausea, and abdominal pain

What are some subjected effects of psychostimulants?

increased alertness, stimulation, energy, euphoria, motivation, focus, sociability

What is the MOA of psychostimulants?

monoamine reuptake inhibitors and/or releasers

What neurotransmitters are increased in the synaptic cleft providing stimulation and euphoria from psychostimulants?

dopamine, norepinephrine

What happens to COGNITION in psychostimulants?

hallucination, delusions, mania, agitation, paranoia, hangover (fatigue, depression)

What happens to CARDIOVASCULAR in psychostimulants?

Increased BP (hypertension)

Increased HR (tachycardia)

What level of severity are physical dependence, tolerance, and withdrawal in psychostimulants?

all mild

What are some subjected effects of sedatives?

anxiolytic (reduce anxiety), sedation, relaxation, disinhibition

What receptors do sedatives mostly target?

GABA receptors

Are metabolic enzymes upregulated or downregulated in tolerance of sedatives?

upregulated (PK)

Are GABA receptors upregulated or downregulated in tolerance of sedatives?

downregulated (PD)

What happens in Ethanol Withdrawal Syndrome from sedatives?

hyperexcitability, decreased GABAa, cell excitotoxicity (seizures, hallucinations, delusion, confusion)

What happens to COGNITIVE in sedatives?

drowsiness, confusion

What happens to MOTOR in sedatives?

ataxia (loss of full control of bodily movement)

What happens to CARDIOVASCULAR in sedatives?

increased BP, cardiovascular disease

respiratory depression (cerebral hypoxia)

What kind of toxicity can occur from chronic use of sedatives?

hepatotoxicity

Which opioid receptor gives the classic opioid effect (euphoria, analgesia)?

MOR

What are some subjected effects of opioids?

euphoria, feeling content, anxiolytic, stimulation, analgesic effects

In the MOA of opioids, what is activated first?

G-protein

In MOA of opioids, what happens after the opioid agonist activates G-protein?

the receptor phosphorylates

In MOA of opioids, what happens after the receptor is phosphorylated?

it recruits arrestin, MAPK signaling

In MOA of opioids, what happens after arrestin is recruited?

internalization

In MOA of opioids, what happens after internalization occurs?

recycling

What happens in tolerance for opioid use?

rapidly escalates tolerance

desensitization

Are MORs upregulated or downregulated in tolerance of opioids?

downregulated

What are some adverse effects of opioids?

nausea, vomiting, constipation, infection from IV use

Is there an increase in overdose risk when using IV opioids?

yes

What type of hallucinogen is this?

- LSD, serotonin 5-HT 2A receptor agonists, magic mushrooms

classical/serotonergic

What type of hallucinogen is this?

- PCP, ketamine, DXM, glutamate NMDAR antagonists

dissociatives

What type of hallucinogen is this?

- Atropine, scopolamine, muscarinic receptor antagonists

deliriants

What type of hallucinogen is this?

- Salvinorin A

KOR agonists

Which type(s) of hallucinogens have a low abuse liability?

classical/serotonergic

deliriants

KOR agonists

Which type(s) of hallucinogens may be useful for treating SUD?

classical/serotonergic

dissociatives

KOR agonists

What are 2 adverse effects of hallucinogens?

ketamine cystitis

dissociative behavioral toxicity

What is ketamine cystitis?

irreversible, inflammatory bladder condition

What happens to SENSORY in empathogens?

enhanced sensory, euphoria

What happens to COGNITIVE in empathogens?

stimulation of thought, increased sociability

What happens to FEELINGS in empathogens?

empathy, love, self-acceptance, understanding

What is MOA of empathogens?

monoamine releasing agent (5-HT, NE, Dopamine)

MDMA increase the release of what?

oxytocin

What happens to the synaptic cleft in MOA of empathogens?

reversal of synaptic cleft monoamine transporters

What is the result of the reversal of synaptic cleft monoamine transporters?

increased Dopamine, 5-HT

What happens to body temperature when taking empathogens?

increases (hyperpyrexia)

What is an adverse effect of empathogens that impact vision?

Nystagmus

What is nystagmus?

involuntary, rapid and repetitive eye movement

What syndrome can occur as an adverse effect of empathogens?

Serotonin syndrome (confusion, hypertension, tremor, nausea, vomiting, shivering, sweating

Does taking empathogens have a high or low risk of SUD?

low risk

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