Substance Related Disorders (Behave)

most commonly abused drug

Alcohol

most common illicit abused drug

Marijuana

Mesolimbic Pathway

Pathway’ involved in producing feelings of pleasure in response to naturally enjoyable stimuli, such as food, sex, and social interaction

Connects to other brain responsible for memory storage and behavior

Why do we repeat behaviors

perceived as pleasurable or rewarding

Parts of the Mesolimbic Pathway

Ventral tegmental area

Nucleus accumbens (aka ventral striatum)

Amygdala

Prefrontal cortex

Ventral tegmental area

Dopamine rich area

Nucleus accumbens (aka ventral striatum)

Target of VTA dopamine neurons

Mediates the rewarding effects of natural rewards and drugs of abuse

Amygdala

Memory consolidation for emotionally arousing events

Prefrontal cortex function

Emotional self-control

, focused problem-solving,

error detection,

performance monitoring,

adaptive response to changing conditions

Steps of Reward Pathway

Behavior

Stimulus

Neurotransmitter Release

Dopamine release from VTA

What neurotransmitters can trigger dopamine release from VTA

Endorphins

Anandamine

Dopamine

5-HT

GABA

NDMA

Acetylcholine

How do drugs of abuse effect the reward pathway

affect various neurotransmitters

artificial stimulants and act DIRECTLY on the VTA which causes a more intense release of dopamine than natural stimuli

This causes downregulation of dopamine, which leads to cravings and relapse

How does drugs of abuse cause complusive behavior

sends exaggerated signals to the prefrontal cortex

signal highjacks the prefrontal cortex into believing that, with drug use, an instinctual drive was just fulfilled and should be repeated

What causes depression symptoms from drugs of abuse

Changes in dopamine lead to increased stress hormones (cortisol, ACTH) which leads to depression symptoms

dual diagnosis

Patients with both substance use D/O and psychiatric illness diagnoses

Most common dual diagnosis

alcohol + another psychiatric diagnosis

Addiction

a treatable, chronic medical illness involving complex interactions among neural circuits, genetics, the environment, and an individual's life experiences.

Substance use disorder

a single diagnostic category that replaced two separate diagnoses of substance abuse and dependence

Opioid use disorder

2 of 11 clinical criteria are met within a 12-month period

How does alcohol affect the brain

Increases inhibitory NT like GABA

Decreases excitatory NT like glutamate

Causes release of endogenous opioids and increases levels of dopamine and serotonin

What is determine as “excess” for alcohol consumpation

More than 3 drinks

Most frequently used brain depressant

alcohol

Risk Factors for Alcohol Abuse

Cultural attitudes toward drinking/intoxication/\

availability of ETOH

close relatives’ w/ alcoholism

Children whose parent(s) were alcoholics were given up for adoption

Pre-existing schizophrenia or bipolar disorder

Impulsivity

Genetically low response rate to alcohol

males > females

Who are less likely to abuse ETOH

those with alcohol related skin flush (usually Asian population)

How is alcohol metabolized

ADH catalyzes conversion of alcohol into acetaldehyde.

ALDH clears acetaldehyde

Where is alcohol absorbed

Stomach

Duodenum

What effect does food have on alcohol absorption

Decreases

Where is alcohol excreted

Lungs

Urine

Sweat

Why do women often get more intoxicated then men

Women generally have less ADH therefore alcohol is not metabolized and inactivated

Alcohol flush syndrome

Deficiency of aldehyde dehydrogenase (ALDH-2)

Causes a build up of acetylaldehyde which leads to catecholamine release and triggers vasodilation and severe flushing

How does ETOH raise blood alcohol content

10-12g of ETOH (2 drinks) raises by 20 mg/dL

How does blood alcohol content decrease normally

15-20 mg/dL per hour

What is considered 1 drink

12 oz of beer

5 oz of wine

1.5 oz of hard liqiour

What are the levels of alcohol impairment

20-30 mg/dL (0.02-0.03%) → Slowed motor performance and decreased thinking

30-80 mg/dL (0.03-0.08%) → Increased motor or cognitive problems

80-200mg/dL (.08%-2%) → Increases in incoordination and judgment errors + Mood liability + Deterioration of cognition

200-300mg/dL (2%-3%) → Nystagmus, Marked Slurring of speech, and Blackouts

>300 mg/dL (>3%) → Impaired vitals + possible fatal

What is the most sensitive test for alcohol abuse

Carbohydrate-deficient transferrin (CDT)

When does CDT return to normal following cessation of alcohol

2-6 weeks

How does alcohol reflect in labs

AST elevation higher than ALT elevation

Elevated MCV (CBC)

Elevated Triglycerides

Alcohol abuse treatment

CBT x 6-12 months

Lifelong AA

Medication

• Naltrexone (Vivitrol/Revia) monthly IM

• Acamprosate (Campral) daily

• Disulfiram (Antabuse)

Naltrexone (Vivitrol/Revia)

Opioid antagonist

MOA of Naltrexone (Vivitrol/Revia)

Decreases activity of VTA

What alcohol abuse treatment medication can be used for substance use disorder

Naltrexone (Vivitrol/Revia)

Contraindication for Naltrexone (Vivitrol/Revia)

currently taking opioids

MOA of Acamprosate (Campral)

Decreases NMDA receptors

When can Acamprosate (Campral) be started

After 5 days of alcohol cessation

What medication for alcohol abuse helps to maintain abstinence

Acamprosate (Campral)

Contraindication for Acamprosate (Campral)

Renal Disease

MOA of Disulfiram (Antabuse)

Inhibits alcohol dehydrogenase

Induces vomiting and autonomic instability when alcohol ingested

Reaction can occur up to 14 days after last dose

SE of Disulfiram (Antabuse)

Depression,

psychotic symptoms,

peripheral neuropathy,

liver damage

Contraindications to Disulfiram (Antabuse)

Heart disease,

CVA,

HTN,

DM

When does alcohol withdrawal occur

abused alcohol on a daily basis for at least 3 months or they have consumed large quantities for at least 1 week

Presentation of Mild Alcohol Withdrawal

Within 24 hours of alcohol cessation

Tremulousness (shakes),

insomnia,

anxiety,

hyperreflexia,

diaphoresis,

mild autonomic hyperactivity,

GI upset

Presenation for moderate withdrawal

24-36 hours of alcohol cessation

Intense anxiety,

tremors,

insomnia,

excessive adrenergic symptoms

Tonic-Clonic Seizures

Delirium Tremens

Most severe version of alcohol withdrawal

Presentation of Delirium Tremens

occurs 72-96 hours after last drink

Confusion,

agitation,

severe diaphoresis,

hallucinations

Seizures

Death

The Clinical Institute Withdrawal of Alcohol Scale (CIWA-Ar)

Medication administration in symptom-triggered therapy

When is medication for alcohol withdrawal given

CIWA-Ar > 8

Treatment for Alcohol Withdrawal

Benzodiazepines

IVFs

Thiamine then glucose

Marijuana

dried leaves, flowers, stems, and seeds from the hemp plant

types of cannabinoids

Endogenous cannabinoids (endocannabinoids)

Plant cannabinoids (phytocannabinoids)

Synthetic cannabinoids

Cannabis

species of hemp plants

What are the species of Cannabis

Cannabis sativa,

Cannabis indica,

Cannabis ruderalis

Where are the cannabindoid receptors located

CB1 → CNS (Basal ganglia, hipocampus, cerebellum and few in cerebrum)

CB2 → Peripheral Tissue and Immune Cells

What regions of the brain does NOT have CB1 receptors

Brainstem

Psychlogic effects of cannabinoids

pleasure,

thought,

concentration,

appetite,

memory,

sensory perceptions,

time perception,

movement coordination

Effects of CB2 receptors

anti-inflammatory

immunosuppressive

most commonly studied phytocannabinoids

Delta-9-tetrahydrocannabinol (THC)

Cannabidiol (CBD)

Delta-9-tetrahydrocannabinol (THC)

Agonist for CB1 and CB2 receptors

Cannabidiol (CBD)

Low affinity for CB1 receptors, mostly binds to CB2 receptors

Dronabinol (Marinol)

Synthetic THC (Schedule III)

Indication for Dronabinol (Marinol)

refractory chemotherapy induced nausea/vomiting,

appetite stimulant for those with AIDS

Nabilone (Cesamet)

Schedule II medication

Chemically similar to THC

Indication for Nabilone (Cesamet)

refractory chemotherapy induced nausea/vomiting

Cannabidol (Epidiolex)

FDA approved plant derived cannabinoid

Indications for Cannabidol (Epidiolex)

Dravet syndrome

Lennox-Gastaut syndrome (childhood seizures)

Act 16 of 2016

Medical Marijuana Program developed to provide access to medical marijuana for patients with a “serious medical condition” through a safe and effective method of delivery

What forms of marijauana can be used medically in PA

Pill

Oil

Topical forms (cream, gel, ointment)

administration by vaporization or nebulization, excluding dry leaf of plant form

Tincture

Liquid

What is a big indicator for developing cannabis use disorder

Initiation of use < 15 yo

What is the duration of effect of cannabis

3-4 hours by inhaled method

Motor slowing can last 8-12 hours

How long is THC seen in urine

4 weeks

What substance can be false positive for cannabis on drug screening

NONE

What tests can be used to determine cannabis use

Urine

Blood

Hair

How long can hair see cannabis use for

90 days

Synthetic Cannabinoids

Manmade mind-altering chemicals that are either sprayed on dried, shredded plant material so they can be smoked or sold as liquids to be vaporized and inhaled in e-cigarettes and other devices

How do Synthetic cannabinoids differ from natural

more severe effects than THC

Not detectable on routine UDS

Presentation of Synthetic Cannaboid Intox

Agitiation

N/V

HTN

Seizures

Paranoia

Violence

HALLUCINOGENS

Substances that induce distortion of sense perception

Drugs that are considered hallucinogens

Psilocybin (magic mushrooms)

LSD

PCP

MDMA (Ecstasy)

Mescaline (Peyote)

DMT (Ayahuasca)

What neurotransmitters are effected by hallucinogens

Dopamine

Glutamate

Serotonin (especially LSD/MDMA)

Presentation of Hallucinogen Use

Heightened perception of sensory input

Distorted sense of time

Euphoria/general sense of happiness

Passive observer of ones life

Hallucinations/illusions

Synesthesia

Synesthesia

: stimulation of one sensory pathway leads to automatic, involuntary experiences in a second sensory or cognitive pathway

Treatment for Haullcinogen Intox

Reinforce that the symptoms the person is experiencing are drug-induced and that the person is not going crazy; person will return to normal

Psilocybin

Chemical found in dozens of types of mushrooms including members of genus Psilocybe

What forms can LSD be seen in

Usually placed on blotter paper

Can also be in liquid form, sugar cubes or gel tabs

What are characteristics of LSD use

Tend to be aware that experiences are drug induced

Long half life

Cross tolerance exists with others in drug class

MDMA

Acts as both a stimulant and a psychedelic

Energizing with perceptual distortions, decreased need for sleep

What neurotransmitter is primary effected by MDMA

Serotonin

How will MDMA intox present

typical amphetamine toxicity plus serotonin toxicity

Phencyclidine (PCP, Angel Dust)

A non-competitive antagonist of NMDA receptors

Causes dissociative anesthetic that is similar to ketamine

“Wet”

PCP added to a cigarette filled with marijuana or parsley and then smoked

How long can PCP lasy

Elimination can take up to 8 days

weeks in susceptible patients- may