Neurobiology of Addiction & Medication Assisted Treatment

addiction

a primacy, chronic disease or brain reward, motivation, memory and related circuitry

dysfunction in these circuits leads to characteristic biological, psychological, social and spiritual manifestations

no, it is in all specialties

Is there a specific specialty we see addiction?

family disruptions

financial problems

lost productivity

failure in school

domestic violence

child abuse

crime

Societal implications of addiction?

half genetic, half environmental

What causes addiction?

impaired resiliency through parenting or life experiences

culture of how addiction is actualized

Environmental causes of addiction?

dopamine

What chemical is most implicated in award?

nucleus accumbens

What part of the brain receives the dopamine and mediates rewarding effects of stimuli?

“high”

Fast and steep release of dopamine = _____

dopamine receptors and dopamine production

Chronic drug use downregulates what?

irritability

emotional pain

malaise

dysphoria

loss of motivation for natural awards

“stress” neurotransmitters in amygdala

Withdrawal/negative affect?

amygdala

Withdrawal/negative affect “stress” neurotransmitters in ______

reward, stress

Withdrawal causes a decrease in ______ function and increase in _____ function

Negative reinforcement

_____ _______ contributes to compulsive drug-seeking behavior (addiction hijacks the brain)

prefrontal cortex (PFC)

Preoccupation/anticipation is a disruption of executive function caused by a compromised _____ ______

thinking, reasoning and impulse control

What is the prefrontal cortex responsible for?

habit-like substance seeking

Over activation of the “go” system in the prefrontal cortex promotes what?

impulsive and compulsive substance seeking

Under activation of the “stop” system of the PFC promotes what?

adolescence

Drug exposure during what age is associated with more chronic and intensive use and greater risk of a substance use disorder?

fentanyl

synthetic opioid 80-100x stronger than morphine

originally developed for pain management in patients with CANCER

added to heroin to increase its potency but this can results in OD deaths

pinpoint pupils

unconsciousness

shallow/slow breathing

pale skin

blue lips

snoring/rasping breath

Signs of opioid OD?

kratom

this is an herbal product derived from mitragyna speciosa (south asian tree)

marketed for energy, mood improvement and pain relief

often labeled as “natural” or “legal high” despite safety concerns

analgesia, euphoria and dependence pathways

When kratom activates mitragynine and 7-hydroxymitragynine and acts as partial agonists at u-opioid receptors it produces what effect?

withdrawal symptoms

Kratom u-receptor activity contributes to what symptoms?

tolerance and compulsive behaviors

Chronic uses of kratom may lead to what?

opioid-like

Partial agonism with kratom results in ___ ___ effects with unique dose-dependent profiles

12 step facilitation therapy

outpatient counseling

inpatient rehabilitation

medication assisted treatment

What ways can we help someone recover from opioid addiction?

methadone

buprenoprhine

naltrexone

What medications can be used for opioid use disorder?

methadone

synthetic opioid full agonist

eliminates withdrawal symptoms and relieves drug cravings

much longer half than other opioids

in an opioid-dependent person treatment doses DO NOT produce euphoria

restlessness

N/V

slow breathing

itchy skin

heavy sweating

constipation

sexual dysfunction

Common side effects of methadone

high OD risk

daily dosing

many drug-drug interactions

cardiotoxicity

Why not methadone?

buprenorphine

first med to treat OUD that can be prescribed or dispensed in physician offices, significantly increasing access to treatment

opioid partial agonist

diminishes effects of physical dependency to opioids, such as withdrawal symptoms and cravings

increased safety in cases of OD

lower potential for misuse

hold stronger and longer than full agonists

high receptor affinity - blocks effects of additional opioid use

slow receptor dissociatoin

How does a full agonist differ from partial agonist?

because of buprenorphine’s opioid effects, it can be misused, particularly by people who do not have opioid dependency

naloxone it decreases the likelihood of diversion and misuse

Why add naloxone to buprenorhphine?

buprenorphine’s opioid effects dominate naloxone and blocks opioid withdrawal

When taken sublingually how does buprenorphine have an effect in comparison to naloxone?

naloxone effect dominates and can bring on opioid withdrawal

If sublingual forms of buprenorphine are crushed and injected how does that have an effect in comparison to naloxone?

constipation

headache

N/V

dizziness

drowsiness/fatigue

sweating

dry mouth

tooth decay

muscle aches

insomina

Side effects of buprenorphine?

methadone

What helps to show superior treatment retention, helping patients stay engaged longer, crucial for effective OUD management

buprenorphine

Which MAT offers reduced opioid misuse, fewer cardiac risks, and greater patient satisfaction and flexibility?

severe dependence

When should we use methadone?

safety and convenience

When should we use buprenorphine?

naltrexone

blocks opioid receptors and reduces and suppresses opioid cravings

blocks euphoric and sedative effects of opioids

will not cause withdrawal symptoms with cessation of use

naltrexone

Patients on _____ who discontinue use or relapse after a period of abstinence may have a reduced tolerance to opioids, meaning even low doses can cause life-threatening consequences

pregnancy and lactation

Methadone and buprenorphine are considered safe for use in ____ and _____

naltrexone, acamprosate, disulfiram

What meds can be used for alcohol use disorder?

weakness/lightheadedness

N/V

insomnia

irritability

dizziness

anxiety

sexual dysfunction

Side effects of naltrexone

acamprosate

Reduces effect of excessive glutamate associated with alcohol withdrawal

typically initiated 5 days following drinking cessation

diarrhea

weakness

insomnia

depression

anxiety

avoid in RENAL IMPAIRMENT

common side effects of acamprosate

disulfarim

produces acute sensitivity to ethanol

immediate negative response promotes abstinence

must be taken >12 hours since last use of alcohol (including food additives)