Substance Abuse Neuropathways

Question 1

Epidemiology of substance abuse disorders

Answer 1

Most common in ages 18-24

Twice as likely in males

Comorbidity with mental illnesses and other Substance Use Disorders (SUDs)

Genetics, social background and environment all contributes to an individuals susceptibility

Question 2

What drugs are the most commonly abused to least?

Answer 2

Alcohol (#1 by a wide margin)

Illicit drugs

Marijuana

Prescription drugs

Cocaine

Hallucinations (NMDA and PCP, etc. )

Inhalants

Heroin

Question 3

Substance induced disorders terms

Answer 3

Intoxication

Withdrawal

Substance induced mental disorders

Substance use disorders (addiction)

Question 4

Addiction definition

“Substance use disorders”

Answer 4

Maladaptive pattern of substance use despite continued adverse consequences
- individual continues using the substance despite significant substance-related problems

NOTE: substance use disorder = addiction, just substance use disorder is used more since its more socially acceptable

Question 5

How many symptoms are required for each level of severity for substance use disorders?

Answer 5

Mild = 2-3

Moderate = 4-5

Severe = 6+

Question 6

Are lab values useful in assigning substance use disorders?

Answer 6

NO

• urine and blood tests let you know the drug is present in the patient system, but cant rule in a substance use disorder by itself
• also no drug in system does not rule out substance use disorder

they are useful for diagnosing intoxication/OD/withdraws states however in conjunction with specific symptoms

Question 7

General principles for treating substance use disorders

Answer 7

Acute treatments for intoxication or withdrawal

• pharmacotherapy
• supportive care

Chronic treatments for recovery and abstinence

• psychotherapy
• social support
• pharmacotherapy (if needed)

Question 8

How do amphetamines and opioids differ in increasing dopamine signaling in the reward circuit during abuse

Answer 8

Amphetamines = increase DA release directly by binding as agonists

Opioids = reduce tonic inhibition of DA release by binding to u-opioid receptors. Indirectly increasing dopamine levels

Question 9

Acute vs chronic drug abuse

Answer 9

Acute = intoxication
- over production of a neurotransmitter but doesnt cause neuroadaptive changes

Chronic = tolerance/withdrawal/dependence

• over production of neurotransmitter but DOES cause neuroadaptive changes
• increase recycle transports and decreased action receptors due to chronic stimulation

Question 10

Substance intoxication syndrome

Answer 10

“Substance exerts behavioral or psychological changes on CNS”

Is reversible and substance-specific symptoms
- some substances have similar syndromes due to similar receptor activation

must be caused by recent substance ingestion or exposure, and cant be due to general medical condition or better represented by mental disorders

Question 11

Substance-withdrawal syndrome

Answer 11

“substance specific syndrome resulting from abrupt cessation of heavy/prolonged use”

• causes clinically significant distress/impairment in social occupational situations

Question 12

Precipitated withdrawal

Answer 12

Acute administration of an antagonist or weaker agonist can induce withdrawl symptoms

Question 13

How does route of administration affect substance effects?

Answer 13

Higher plasma concentration = stronger substance effect.

Ranking routes of drug administration from fastest and strongest - weakest

• Injection = fastest
• Smoked
• Nasal
• Oral

rapid onset = increased behavior reinforcement of using the drug

Question 14

Half-life/metabolisms effect on withdrawl symptoms

Answer 14

Shorter half-life = greater risk of withdrawal and increased intensity of symptoms

Longer = lower risk of withdrawal and decreased intensity of symptoms
- withdrawal state will last longer if achieved thou

Question 15

Impulsivity vs compulsivity in drug abuse states

Answer 15

Impulsivity:

• observed early in drug use
• risk factor for developing substance use disorder*
• contributes to escalating drug use

Compulsivity:

• observed later in addiction
• risk factor that contributes to maintenance of use disorders*
• contributes in inability to stop drug-seeking behaviors

Question 16

Addiction cycle

Answer 16

3 stages

• binge/intoxication
• withdrawal/negative affect
• preoccupation/anticipations

Question 17

What are 3 stages of the addiction cycle?

Answer 17

Binge/intoxication

• reward stage
• habits

Withdrawal/negative affect
- withdrawal stage

Preoccupation/anticipation
- craving stage

Question 18

Can substance use increase neuroplasticity?

Answer 18

Yes and it often does
- increase neuroplasticity = increased compulsivity behavior

This is addiction in a nutshell (progressive and cyclical disorder)

Question 19

General Relapse

Answer 19

Stress-induced procedure

• increased stress signals (seeing the drug, smell, etc.) induces cravings
• drug is sought to alleviate stress and anxiety
• is caused by sensory cues being tied together with dopamine signaling (similar to Pavlovian conditioning)
• therefore, in times of stress (dopamine and cortisol is released) sensory cues and cravings become overwhelming*

Question 20

Cue-induced relapse

Answer 20

Stimuli associated with either positive or negative reinforcement of the drug induces cravings

Question 21

Conditioned withdrawal

Answer 21

Occurs when individuals encounter stimuli/ sensory cues associated with withdrawal symptoms

Question 22

What structures are involved in the 3 cycles of addiction?

Answer 22

1) binge/intoxication
- thalamus
- globus pallidus
- nucleus accumbens

2) negative affect/ withdrawal
- amygdala
- Nucelus accumbens

3) preoccupation/anticipation
- hippocampus
- prefrontal cortex
- insula cortex

Question 23

Physiological response to addiction

Answer 23

1) reward learning
- introduction to drug or sensory cues from the cortex causes increased dopamine release and glutamtergic signaling
- leads to upregulation of NMDA receptors

2) out of control drug use
- mass amounts of drug/sensory cues leads to out of control NMDA receptor upregulation

3) dependence/ neuroadaptive
- mass increase of NMDA and structural proteins deposition leads to cravings and “needs” to be stimulated. This is especially true during times of stress

Question 24

Types of withdrawal

Answer 24

1) Physical withdrawal
(Withdrawal syndrome)
- withdrawal symptoms that arise due to physical affects of intoxication
- possess physical and psychological symptoms
- usually after chronic use only

2) motivational withdrawal
- withdrawal symptoms that arise when the drug reward/effects fade, but the CNA compensation persists
- possess usually only psychological symptoms (but can show some physical)
- acute or chronic use

3) conditioned withdrawal
(Cravings)
- withdrawal symptoms that occurs when a chronic user is stressed out or sees another stimuli associated with drug use/withdrawal
- possess physical and psychological symptoms
- usually chronic use only

4) precipitated withdrawal
- withdrawal symptoms that are present after administration of an antagonist or weaker agonist of the drug being abused (Narcan/naloxone)
- possess physical and psychological symptoms
- only comes once administered of an antagonist/partial agonist