Drug Properties, Dependence & Neurobiology

Reinforcing Properties of Drugs

• Drugs can induce pleasurable experiences like euphoria
• Drugs can reduce the intensity of unpleasant experiences like stress and anxiety

Dependence Definitions

• Tolerance happens when regular use is resulting in smaller responses than initial use, tolerance increases if higher doses can elicit desired effects
• Psychological dependence is an intense subjective need for a psychoactive drug
• Physical dependence is a state in which stopping a drug results in an abstinence syndrome
• Withdrawal syndrome has signs and symptoms in physically dependent individuals when substance use is discontinued

Social & Environmental Influences

• Social factors such as peer pressure, social status, and cultural norms
• Drug availability influences the development and maintenance of abuse
• Genetics and environment can make an individual vulnerable to substance abuse disorders

The Neurobiology of Reward

• Repeated drug use causes molecular changes in the brain, transitioning voluntary drug use to compulsive use
• The reward circuit reinforces essential survival behaviors like eating and reproduction
• Dopamine is the major transmitter; its release activates the circuit and reinforces behavior
• Drug use leads to dopamine release amounts 2- to 10-fold higher than natural stimuli
• Repeated activation remodels synaptic connections, consolidating changes in brain function that persist even after drug usage stops

Principles of Drug Addiction Treatment

• Addiction is a complex but treatable disease affecting brain function and behavior
• Effective treatment addresses multiple needs, including medical, psychological, social, vocational, and legal issues
• Matching treatment settings, interventions, and services to individual problems and needs is critical
• Treatment must be readily available; early treatment increases the likelihood of positive outcomes
• Remaining in treatment for an adequate time (at least 3 months) is critical for reducing or stopping drug use
• Individual and/or group counseling and behavioral therapies are the backbone of substance abuse treatment
• Medication, combined with counseling and behavioral therapies can be important
• Treatment and services must be reassessed and modified as an individuals needs change
• Many drug-addicted individuals have co-occurring mental disorders that must be addressed
• Medically assisted detoxification is only the first stage of treatment
• Treatment need not be voluntary to be effective; sanctions or enticements can increase treatment entry, retention, and success
• Drug use during treatment should be monitored continuously and early identification can allow for adjustments
• Treatment programs should provide assessment and counseling for infectious diseases

Defining Recovery

• The Substance Abuse and Mental Health Services Administration (SAMHSA) defines recovery as a unique journey involving ongoing efforts to improve health, relationships, and overall well-being

Multimodal/Holistic Approach to Treatment

• Involves group and individual therapy
• Substituting alternative rewards for the rewards of drug use
• Using pharmacologic agents to modify the effects of abused drugs

Non-Pharmacologic Resources

• Harm reduction programs are supportive
• Mutual aid programs can connect people to peer support, like AA/NA
• Detoxification programs assists with withdrawal management
• Outpatient programs are 1-2 hours per week
• Intensive outpatient programs have or do not have lodging
• Partial hospitalization
• Residential treatment is in a facility
• Hospital-Based Inpatient Treatment

DEA Drug Schedules

• The DEA schedules drugs based on their potential for abuse and whether they have an accepted medical use
• Schedule 1 drugs have a high potential for abuse and no accepted medical use
• Schedule 1 drugs may not be prescribed
• Schedule 2 drugs have a high potential for abuse but have a currently accepted medical use
• Schedule 2 prescriptions must be written and signed, and no refills are allowed
• Verbal orders for Schedule 2 are only allowed only in emergencies; written prescriptions required within 72 hours
• Schedule 3 drugs have less potential for abuse than Schedules 1 and 2 and have accepted medical uses
• Verbal or electronic prescriptions are allowed and it can be refilled up to 5 times
• Schedule 4 drugs have a low potential for abuse and have currently accepted medical uses
• Verbal, written, or electronic prescriptions are allowed and prescriptions can be refilled up to 5 times
• Schedule 5 drugs have the lowest potential for abuse and have accepted medical uses
• Verbal, written, or electronic prescriptions are allowed
• Some Schedule 5 drugs may be dispensed without a prescription under certain conditions determined by the pharmacist, with quantity restrictions and record-keeping

Categories of Abused Drugs

• Opioids
• Psychostimulants
• Depressants
• Psychedelics
• Anabolic steroids
• Miscellaneous drugs of abuse

Alcohol Pharmacology

• Alcohol leads to central nervous system depression and activation of the reward circuit

Alcohol Effects on Receptors

• EtOH binds with GABA, enhancing GABA-mediated inhibition, which leads to CNS depression
• EtOH binds with Glutamate, blocking glutamate-mediated excitation, reduces CNS activity, impairing cognition and functioning.
• EtOH releases dopamine which rewards the effects

Chronic Alcohol Effects

• Alcohol produces severe neurologic and psychiatric disorders
• May causes neuropsychiatric syndromes from thiamin deficiency from poor diet and alcohol inducing thiamin absorption

Alcohol-Related Syndromes & Treatment

• Wernicke Encephalophathy has symptoms like confusion, nystagmus, and abnormal ocular movements and can be reversed with thiamine
• Korsakoff psychosis has symptoms like polyneuropathy, inability to convert short-term memory into long-term memory, and confabulation and it is not reversible

Effects of Alcohol on the Body

• Chronic alcohol use can cause direct damage to myocardium, increased risk of heart failure, HTN, and decrease risk of DM2
• Decreased bone mineral density
• Depresses respiration
• Alcohol-induced hepatitis in heavy drinkers and 8-20% develop cirrhosis and erosion of the stomach
• Increased urine production
• 35% of pancreatitis cases are related to EtOH
• Decreased libido
• Alcohol increases the risk for cancer and for fetal alcohol spectrum disorder in pregnancy

Alcohol Absorption & Metabolism

• Absorbed in the stomach and small intestine
• Gastric absorption slow and delayed by food and can result in 80% absorption
• Distribution is nonionic and water soluble, distributes to all tissues and body fluids.
• Crosses blood-brain barrier and placenta
• Metabolism occurs in both liver and stomach
• Conversion of alcohol to acetaldehyde catalyzed by alcohol dehydrogenase
• Metabolized at constant rate of 15mL per hour

Alcohol Screening

• AUDIT-C can trigger clinical remnder if the score is 5 or more

Clinical Intervention

• May give a recommendation about low risk alcohol use
• Discuss options for change

Medications for Alcohol Abuse

• Naltrexone is a pure opioid antagonist
• Acamprosate is a Sulfonic Acid
• Disulfiram is a disulfide
• Topiramate and Gabapentin can be supportive

Medications for Alcohol Withdrawal

• Risks include seizures, delirium tremens and death
• Benzodiazepines are effective agents
• Stabilize patient but can decrease risk of seizures
• Barbiturates such as Phenobarbital have a long half life and will avoid re-dosing
• Adjunctive Therapies such as Combined with BZD or Barbiturate can treat negative reactions

Naltrexone for Alcohol Use Disorder

• It is pure opioid antagonist
• Possible blockade of dopamine release secondary to blockade of opioid receptors
• Indicated for moderate to Severe Alcohol Use Disorder
• Watch for Nausea/Vomiting, HA and Fatigue
• Contraindicate if the patient has severe, decompensated liver disease
• Reduces cravings and helps with both abstinence and reducing drinking
• Get LFT prior to treatment and every q6-months

Acamprosate for Alcohol Use Disorder

• Sulfonic Acid
• Possible restoration of balance between inhibitory (GABA) and excitatory neurotransmutters.
• Moderate to Severe Alcohol Use Disorder
• May cause Diarrhea
• Contraindicated with Renal Impairment with GFR <30
• BMP is monitored at initiation
• Should take, high pill burden, 2 pills TID
• Monitor BMP at initiation and yearly.

Disulfiram for Alcohol Use Disorder

• Needs disruption of alcohol metabolism through irreversible inhibition of aldehyde dehydrogenase
• Moderate to Severe Alcohol Use Disorder, goal of abstinence
• Can be psychosis, hepatitis and neuropathy
• Cognitive impairment and prior psychotic disorder could counter indicate
• No alcohol in food, mouthwash, OTCs
• Monitor BMP and LFTs at initiation and monthly for 3 months, then q6 months
• No drinking in prior 12 hours.

Topiramate for Alcohol Use Disorder

• Used in moderate to severe AUD
• Used after treatment failure with other options
• Check OCPS
• Paresthesia, fatigue
• Has teratogenic effects, and can cause weight loss.
• Helps with mild alcohol, monitor renal fxn

Opioids

• Initial exposure is recreational vs prescribed
• 45 second "rush" of pleasure
• Heroin is now replaced by fentanyl
• Use nalaxone for acute toxcity

Opioid Meds

• Naltrexone is indicated for moderate to Severe OUD
• Buprenorphine alleviates cravings
• Methadone is indicated for moderate opioid pain

Inhalants

• Inhalants have patterns of use
• Nitrous oxide
• May cause euphoria, impaired judgment, slurred speech, flushing, and/or CNS depression, hallucinations

Psychostimulant- Cocaine

• Last seconds euphoria, euphoria through inhibition of neuronal reuptake of dopamine
• Can feel agitation, dizziness, and tremors
• Overdose by signs of stroke and coronary spasms

Psychostimulant- Meth

• Increase NE and dopamine
• Talking
• Grandiosity, hypersexuality
• Can have psychotic reactions
• Monitor for for coronary vasoconstriction

Marijuana effects

• Euphoria, sedation, hallucinations, affects memory
• Tachycardia, shrinkage of hippocampus
• Give supportive medication for hypertension
• Use an NAC med, and can only be prescribed if patients qualify

Psychedelics

• May cause hallucinations, or may be sensory
• No documentation of but
• Death by suicide and trauma

MDMA

• Causes increased serotonin and dopamine, jaw clenching and hallucination
• stimulate the heart, and raise body temperature to a dangerous