Substance Related Substance Related DisordersDisorders

Brian Smart, M.D.Brian Smart, M.D.

Harborview Medical Center Harborview Medical Center

Objectives. At the end of this Objectives. At the end of this talk you will be able to:talk you will be able to:

Identify the diagnostic criteria for substance-Identify the diagnostic criteria for substance-related disordersrelated disorders

Describe the epidemiology of substance-Describe the epidemiology of substance-related disordersrelated disorders

Describe treatment optionsDescribe treatment options Discern intoxication/withdrawal of different Discern intoxication/withdrawal of different

substancessubstances Apply the information above to clinical casesApply the information above to clinical cases

Substance ClassesSubstance Classes AlcoholAlcohol CaffeineCaffeine CannabisCannabis HallucinogensHallucinogens

PCPPCP othersothers

InhalantsInhalants

GamblingGambling

OpioidsOpioids Sedatives, hypnotics, Sedatives, hypnotics,

and anxiolyticsand anxiolytics StimulantsStimulants TobaccoTobacco OtherOther

Substance-Related DisordersSubstance-Related Disorders

2 Groups:2 Groups: Substance Use Disorders Substance Use Disorders

• Previously split into abuse or dependencePreviously split into abuse or dependence• Involves: impaired control, social impairment, risky Involves: impaired control, social impairment, risky

use, and pharmacological criteriause, and pharmacological criteria Substance-Induced DisordersSubstance-Induced Disorders

Substance Use DisorderSubstance Use Disorder

Using larger amounts or for longer time than Using larger amounts or for longer time than intendedintended

Persistent desire or unsuccessful attempts to Persistent desire or unsuccessful attempts to cut down or control usecut down or control use

Great deal of time obtaining, using, or Great deal of time obtaining, using, or recoveringrecovering

CravingCraving Fail to fulfill major roles (work, school, home)Fail to fulfill major roles (work, school, home) Persistent social or interpersonal problems Persistent social or interpersonal problems

caused by substance usecaused by substance use

Substance Use DisorderSubstance Use Disorder

Important social, occupational, Important social, occupational, recreational activities given up or reducedrecreational activities given up or reduced

Use in physically hazardous situationsUse in physically hazardous situations Use despite physical or psychological Use despite physical or psychological

problems caused by useproblems caused by use ToleranceTolerance Withdrawal Withdrawal (not documented after repeated (not documented after repeated

use of PCP, inhalants, hallucinogens)use of PCP, inhalants, hallucinogens)

SeveritySeverity

SeveritySeverity Depends on # of symptom criteria endorsedDepends on # of symptom criteria endorsed

Mild: 2-3 symptomsMild: 2-3 symptoms Moderate: 4-5 symptomsModerate: 4-5 symptoms Severe: 6 or more symptomsSevere: 6 or more symptoms

SpecifiersSpecifiers

SpecifiersSpecifiers In early remission: no criteria for > 3 months In early remission: no criteria for > 3 months

but < 12 months (except craving)but < 12 months (except craving) In sustained remission: no criteria for > 12 In sustained remission: no criteria for > 12

months (except craving)months (except craving) In a controlled environment: access to In a controlled environment: access to

substance restricted (ex. Jail)substance restricted (ex. Jail)

Substance-InducedSubstance-Induced

IntoxicationIntoxication WithdrawalWithdrawal Psychotic DisorderPsychotic Disorder Bipolar DisorderBipolar Disorder Depressive DisorderDepressive Disorder

Anxiety DisorderAnxiety Disorder Sleep DisorderSleep Disorder DeliriumDelirium NeurocognitiveNeurocognitive Sexual DysfunctionSexual Dysfunction

IntoxicationIntoxication

Reversible substance-specific syndrome Reversible substance-specific syndrome due to recent ingestion of a substance due to recent ingestion of a substance

Behavioral/psychological changes due to Behavioral/psychological changes due to effects on CNS developing after ingestion:effects on CNS developing after ingestion: ex. Disturbances of perception, wakefulness, ex. Disturbances of perception, wakefulness,

attention, thinking, judgement, psychomotor behavior attention, thinking, judgement, psychomotor behavior and interpersonal behaviorand interpersonal behavior

Not due to another medical condition or Not due to another medical condition or mental disordermental disorder

Does not apply to tobaccoDoes not apply to tobacco

Clinical picture of intoxication Clinical picture of intoxication depends on:depends on:

SubstanceSubstance DoseDose Route of Route of

AdministrationAdministration Duration/chronicityDuration/chronicity Individual degree of Individual degree of

tolerancetolerance

Time since last doseTime since last dose Person’s expectations Person’s expectations

of substance effectof substance effect Contextual variablesContextual variables

WithdrawalWithdrawal Substance-specific syndrome problematic Substance-specific syndrome problematic

behavioral change due to stopping or behavioral change due to stopping or reducing prolonged usereducing prolonged use

Physiological & cognitive componentsPhysiological & cognitive components Significant distress in social, occupational Significant distress in social, occupational

or other important areas of functioningor other important areas of functioning Not due to another medical condition or Not due to another medical condition or

mental disordermental disorder No withdrawal: PCP; other hallucinogens; No withdrawal: PCP; other hallucinogens;

inhalantsinhalants

Substance-Induced Mental Substance-Induced Mental DisorderDisorder

Potentially severe, usually temporary, but Potentially severe, usually temporary, but sometimes persisting CNS syndromes sometimes persisting CNS syndromes

Context of substances of abuse, Context of substances of abuse, medications, or toxinsmedications, or toxins

Can be any of the 10 classes of Can be any of the 10 classes of substancessubstances

Substance-Induced Mental Substance-Induced Mental DisorderDisorder

Clinically significant presentation of a Clinically significant presentation of a mental disordermental disorder

Evidence (Hx, PE, labs)Evidence (Hx, PE, labs) During or within 1 month of useDuring or within 1 month of use Capable of producing mental disorder seenCapable of producing mental disorder seen

Not an independent mental disorderNot an independent mental disorder Preceded onset of usePreceded onset of use Persists for substantial time after use (which Persists for substantial time after use (which

would not expect)would not expect)

NeuroadaptationNeuroadaptation::

Refers to underlying CNS changes that Refers to underlying CNS changes that occur following repeated use such that occur following repeated use such that person develops tolerance and/or person develops tolerance and/or withdrawalwithdrawal Pharmacokinetic – adaptation of metabolizing Pharmacokinetic – adaptation of metabolizing

systemsystem Pharmacodynamic – ability of CNS to function Pharmacodynamic – ability of CNS to function

despite high blood levelsdespite high blood levels

ToleranceTolerance

Need to use an increased amount of a Need to use an increased amount of a substance in order to achieve the desired substance in order to achieve the desired effecteffect

OROR Markedly diminished effect with continued Markedly diminished effect with continued

use of the same amount of the substanceuse of the same amount of the substance

Epidemiology: PrevalenceEpidemiology: Prevalence

NIDA ’04: 22.5M > 12yo – substance-related d/oNIDA ’04: 22.5M > 12yo – substance-related d/o

15M – Alcohol Dependence or Abuse15M – Alcohol Dependence or Abuse Start at earlier age (<15yo), more likely to Start at earlier age (<15yo), more likely to

become addicted – ex. alcohol: 18% vs. 4% (if become addicted – ex. alcohol: 18% vs. 4% (if start at 18yo or older)start at 18yo or older)

Rates of abuse vary by age: 1% (12yo) - 25% Rates of abuse vary by age: 1% (12yo) - 25% (21yo) - 1% (65yo)(21yo) - 1% (65yo)

Men; American Indian; whites; unemployed; Men; American Indian; whites; unemployed; large metro areas; paroleeslarge metro areas; parolees

Epidemiology (cont.)Epidemiology (cont.)

ETOH - $300 billion/yearETOH - $300 billion/year 13 million require treatment for alcohol13 million require treatment for alcohol 5.5 million require treatment for drug use5.5 million require treatment for drug use 2.5% population reported using Rx meds 2.5% population reported using Rx meds

nonmedically within past monthnonmedically within past month

Epidemiology (cont.)Epidemiology (cont.)

40% of hospital admission have alcohol 40% of hospital admission have alcohol or drugs associatedor drugs associated

25% of all hospital deaths25% of all hospital deaths 100,000 deaths/year100,000 deaths/year Intoxication is associated with 50% of all Intoxication is associated with 50% of all

MVAs, 50% of all DV cases and 50% of MVAs, 50% of all DV cases and 50% of all murdersall murders

ER Visits (NIDA ‘09)ER Visits (NIDA ‘09)

1.2M: non-medical use of pharmaceuticals1.2M: non-medical use of pharmaceuticals 660K: alcohol660K: alcohol 425K: cocaine425K: cocaine 380K: marijuana380K: marijuana 210K: heroin210K: heroin 93K: stimulants93K: stimulants

EtiologyEtiology

Multiple interacting factors influence using Multiple interacting factors influence using behavior and loss of decisional flexibilitybehavior and loss of decisional flexibility

Not all who become dependent experience Not all who become dependent experience it same way or motivated by same factorsit same way or motivated by same factors

Different factors may be more or less Different factors may be more or less important at different stages (drug important at different stages (drug availability, social acceptance, peer availability, social acceptance, peer pressure VS personality and biology)pressure VS personality and biology)

EtiologyEtiology ““Brain Disease” – changes in structure and Brain Disease” – changes in structure and

neurochemistry transform voluntary drug-neurochemistry transform voluntary drug-using compulsiveusing compulsive

Changes proven but necessary/sufficient? Changes proven but necessary/sufficient? (drug-dependent person changes behavior (drug-dependent person changes behavior in response to positive reinforcers)in response to positive reinforcers)

Psychodynamic: disturbed ego function Psychodynamic: disturbed ego function (inability to deal with reality)(inability to deal with reality)

EtiologyEtiology Self-medication Self-medication

EtOH - panic; opioids -anger; amphetamine - EtOH - panic; opioids -anger; amphetamine - depressiondepression

Genetic (well-established with alcohol)Genetic (well-established with alcohol) Conditioning: behavior maintained by its Conditioning: behavior maintained by its

consequencesconsequences Terminate aversive state (pain, anxiety, w/d)Terminate aversive state (pain, anxiety, w/d) Special statusSpecial status EuphoriaEuphoria Secondary reinforcers (ex. Paraphernalia)Secondary reinforcers (ex. Paraphernalia)

EtiologyEtiology ReceptorsReceptors Too little endogenous opioid activity (ie low endorphins) or too much

endogenous opioid antagonist activity = increased risk of dependence.

Normal endogenous receptor but long-term use modulates, so need exogenous substance to maintain homeostasis.

NeurotransmittersNeurotransmitterso OpioidOpioido Catecholamines Catecholamines o GABAGABAo SerotoninSerotonin

PathwaysPathways

Learning and Physiological Basis for Learning and Physiological Basis for DependenceDependence

After using drugs or when stop – leads to After using drugs or when stop – leads to a depleted state resulting in dysphoria a depleted state resulting in dysphoria and/or cravings to use, reinforcing the and/or cravings to use, reinforcing the use of more drug.use of more drug.

Response of brain cells is to Response of brain cells is to downregulate receptors and/or decrease downregulate receptors and/or decrease production of neurotransmitters that are production of neurotransmitters that are in excess of normal levels.in excess of normal levels.

ComorbidityComorbidity

Up to 50% of addicts have comorbid Up to 50% of addicts have comorbid psychiatric disorderpsychiatric disorder Antisocial PDAntisocial PD DepressionDepression SuicideSuicide

Typical Presentation and Typical Presentation and Course:Course:

Present in acute intoxication, acute/chronic Present in acute intoxication, acute/chronic withdrawal or substance induced mood, withdrawal or substance induced mood, cognitive disorder or medical complicationscognitive disorder or medical complications

Abstinence depends on several factors: social, Abstinence depends on several factors: social, environmental, internal factors (presence of environmental, internal factors (presence of other comorbid psychiatric illnesses)other comorbid psychiatric illnesses)

Remission and relapses are the rule (just like Remission and relapses are the rule (just like any other chronic medical illness)any other chronic medical illness)

Frequency, intensity and duration of treatment Frequency, intensity and duration of treatment predicts outcomepredicts outcome

70 % eventually able to abstain or decrease use 70 % eventually able to abstain or decrease use to not meet criteriato not meet criteria

Options for where to treatOptions for where to treat

Hospitalization- Hospitalization- -Due to drug OD, risk of severe withdrawal, -Due to drug OD, risk of severe withdrawal,

medical medical comorbidities, requires restricted access to comorbidities, requires restricted access to drugs, drugs, psychiatric illness with suicidal ideationpsychiatric illness with suicidal ideation

Residential treatment unitResidential treatment unit-No intensive medical/psychiatric monitoring -No intensive medical/psychiatric monitoring

needsneeds-Require a restricted environment-Require a restricted environment-Partial hospitalization-Partial hospitalization

Outpatient Program -No risk of med/psych morbidity and Outpatient Program -No risk of med/psych morbidity and highly motivated patienthighly motivated patient

Treatment Treatment

Manage Intoxication & WithdrawalManage Intoxication & Withdrawal

IntoxicationIntoxication• Ranges: euphoria to life-threatening emergencyRanges: euphoria to life-threatening emergency

Detoxification Detoxification • outpatient: "social detox” program outpatient: "social detox” program • inpatient: close medical careinpatient: close medical care• preparation for ongoing treatmentpreparation for ongoing treatment

Treatment Treatment Behavioral Interventions (target internal and external reinforcers)Behavioral Interventions (target internal and external reinforcers)

Motivation to change (MI)Motivation to change (MI)

Group TherapyGroup Therapy

Individual TherapyIndividual Therapy

Contingency ManagementContingency Management

Self-Help Recovery Groups (AA)Self-Help Recovery Groups (AA)

Therapeutic CommunitiesTherapeutic Communities

Aversion TherapiesAversion Therapies

Family Involvement/TherapyFamily Involvement/Therapy

Twelve-Step FacilitationTwelve-Step Facilitation

Relapse PreventionRelapse Prevention

(motivational --interviewing)(motivational --interviewing)

-EBxplore desire to stop drinking/using vs -EBxplore desire to stop drinking/using vs perceived benefits of ongoing useperceived benefits of ongoing use

-Gentle confrontation with education (risks -Gentle confrontation with education (risks to health) / therapeutic allianceto health) / therapeutic alliance

-Involve family and friends for support-Involve family and friends for support

-Education about substance dependence -Education about substance dependence and need for rehabilitation planand need for rehabilitation plan

Treatment Treatment

Pharmacologic InterventionPharmacologic Intervention Treat Co-Occurring Psychiatric DisordersTreat Co-Occurring Psychiatric Disorders

50% will have another psychiatric disorder50% will have another psychiatric disorder Treat Associated Medical ConditionsTreat Associated Medical Conditions

cardiovascular, cancer, endocrine, hepatic, cardiovascular, cancer, endocrine, hepatic, hematologic, infectious, neurologic, hematologic, infectious, neurologic, nutritional, GI, pulmonary, renal, nutritional, GI, pulmonary, renal, musculoskeletalmusculoskeletal

AlcoholAlcohol

ALCOHOL- CNS depressantALCOHOL- CNS depressant

IntoxicationIntoxication Blood Alcohol Level - Blood Alcohol Level -

0.08g/dl 0.08g/dl Progress from mood Progress from mood

lability, impaired lability, impaired judgment, and poor judgment, and poor coordination to coordination to increasing level of increasing level of neurologic impairment neurologic impairment (severe dysarthria, (severe dysarthria, amnesia, ataxia, amnesia, ataxia, obtundation)obtundation)

Can be fatal (loss of Can be fatal (loss of airway protective airway protective reflexes, pulmonary reflexes, pulmonary aspiration, profound CNS aspiration, profound CNS depression)depression)

Alcohol WithdrawalAlcohol Withdrawal

EarlyEarly anxiety, irritability, tremor, HA, insomnia, nausea, anxiety, irritability, tremor, HA, insomnia, nausea,

tachycardia, HTN, hyperthermia, hyperactive reflexes tachycardia, HTN, hyperthermia, hyperactive reflexes

SeizuresSeizures generally seen 24-48 hours generally seen 24-48 hours most often Grand mal most often Grand mal

Withdrawal Delirium (DTs) Withdrawal Delirium (DTs) generally between 48-72 hoursgenerally between 48-72 hours altered mental status, hallucinations, marked altered mental status, hallucinations, marked

autonomic instabilityautonomic instability life-threatening life-threatening

Alcohol Withdrawal (cont.)Alcohol Withdrawal (cont.)

CIWA (Clinical Institute Withdrawal Assessment CIWA (Clinical Institute Withdrawal Assessment for Alcohol)for Alcohol)

Assigns numerical values to orientation, N/V, Assigns numerical values to orientation, N/V, tremor, sweating, anxiety, agitation, tactile/ tremor, sweating, anxiety, agitation, tactile/ auditory/ visual disturbances and HA. VS auditory/ visual disturbances and HA. VS checked but not recorded. Total score of > 10 checked but not recorded. Total score of > 10 indicates more severe withdrawalindicates more severe withdrawal

Based on severity of withdrawal or history of Based on severity of withdrawal or history of previous withdrawal seizures or DTs, med previous withdrawal seizures or DTs, med therapy can be scheduled or symptom-triggeredtherapy can be scheduled or symptom-triggered

Alcohol Withdrawal (cont.)Alcohol Withdrawal (cont.) BenzodiazepinesBenzodiazepines

GABA agonist - cross-tolerant with alcoholGABA agonist - cross-tolerant with alcohol reduce risk of SZ; provide comfort/sedationreduce risk of SZ; provide comfort/sedation

AnticonvulsantsAnticonvulsants reduce risk of SZ and may reduce kindlingreduce risk of SZ and may reduce kindling helpful for protracted withdrawal helpful for protracted withdrawal Carbamazepine or Valproic acidCarbamazepine or Valproic acid

Thiamine supplementation Thiamine supplementation Risk thiamine deficiency (Wernicke/Korsakoff)Risk thiamine deficiency (Wernicke/Korsakoff)

Alcohol treatmentAlcohol treatment

Outpatient CD treatment:Outpatient CD treatment: support, education, skills training, psychiatric support, education, skills training, psychiatric

and psychological treatment, AAand psychological treatment, AA Medications:Medications:

Disulfiram Disulfiram NaltrexoneNaltrexone AcamprosateAcamprosate

Medications - ETOH Use DisorderMedications - ETOH Use Disorder

Disulfiram (antabuse) 250mg-500mg po dailyDisulfiram (antabuse) 250mg-500mg po daily

Inhibits aldehyde dehydrogenase and dopamine beta Inhibits aldehyde dehydrogenase and dopamine beta hydroxylasehydroxylase

Aversive reaction when alcohol ingested- vasodilatation, Aversive reaction when alcohol ingested- vasodilatation, flushing, N/V, hypotenstion/ HTN, coma / deathflushing, N/V, hypotenstion/ HTN, coma / death

Hepatotoxicity - check LFT's and h/o hep CHepatotoxicity - check LFT's and h/o hep C Neurologic with polyneuropathy / paresthesias that slowly Neurologic with polyneuropathy / paresthesias that slowly

increase over time and increased risk with higher dosesincrease over time and increased risk with higher doses Psychiatric side effects - psychosis, depression, confusion, Psychiatric side effects - psychosis, depression, confusion,

anxietyanxiety Dermatologic rashes and itchingDermatologic rashes and itching Watch out for disguised forms of alcohol - cologne, sauces, Watch out for disguised forms of alcohol - cologne, sauces,

mouth wash, OTC cough meds, alcohol based hand sanitizers, mouth wash, OTC cough meds, alcohol based hand sanitizers, etcetc

Medications - ETOH Use DisorderMedications - ETOH Use Disorder

Naltrexone 50mg po dailyNaltrexone 50mg po daily Opioid antagonist thought to block mu receptors Opioid antagonist thought to block mu receptors

reducing intoxication euphoria and cravingsreducing intoxication euphoria and cravings Hepatotoxicity at high doses so check LFT'sHepatotoxicity at high doses so check LFT's

Acamprosate(Campral) 666mg po tidAcamprosate(Campral) 666mg po tid Unknown MOA but thought to stabilize neuron Unknown MOA but thought to stabilize neuron

excitation and inhibition - may interact with GABA and excitation and inhibition - may interact with GABA and Glutamate receptor - cleared renally (check kidney Glutamate receptor - cleared renally (check kidney function)function)

Benzodiazepine( BZD)/ Benzodiazepine( BZD)/ BarbituratesBarbiturates

Benzodiazepine( BZD)/ Benzodiazepine( BZD)/ BarbituratesBarbiturates

IntoxicationIntoxication similar to alcohol but less cognitive/motor similar to alcohol but less cognitive/motor

impairmentimpairment variable rate of absorption (lipophilia) and variable rate of absorption (lipophilia) and

onset of action and duration in CNSonset of action and duration in CNS the more lipophilic and shorter the duration of the more lipophilic and shorter the duration of

action, the more "addicting" they can beaction, the more "addicting" they can be all can by addictingall can by addicting

BenzodiazepineBenzodiazepine

WithdrawalWithdrawal Similar to alcohol with anxiety, irritability, insomnia, fatigue, HA, Similar to alcohol with anxiety, irritability, insomnia, fatigue, HA,

tremor, sweating, poor concentration - time frame depends on tremor, sweating, poor concentration - time frame depends on half lifehalf life

Common detox mistake is tapering too fast; symptoms worse at Common detox mistake is tapering too fast; symptoms worse at end of taperend of taper

Convert short elimination BZD to longer elimination half life drug Convert short elimination BZD to longer elimination half life drug and then slowly taperand then slowly taper

Outpatient taper- decrease dose every 1-2 weeks and not more Outpatient taper- decrease dose every 1-2 weeks and not more than 5 mg Diazepam dose equivalent than 5 mg Diazepam dose equivalent

• 5 diazepam = 0.5 alprazolam = 25 chlordiazepoxide = 0.25 clonazepam = 1 5 diazepam = 0.5 alprazolam = 25 chlordiazepoxide = 0.25 clonazepam = 1 lorazepamlorazepam

May consider carbamazepine or valproic acid especially if doing May consider carbamazepine or valproic acid especially if doing rapid taperrapid taper

BenzodiazapinesBenzodiazapines Alprazolam (Xanax) t 1/2 6-20 hrsAlprazolam (Xanax) t 1/2 6-20 hrs *Oxazepam (Serax) t 1/2 8-12 hrs*Oxazepam (Serax) t 1/2 8-12 hrs *Temazepam (Restoril) t 1/2 8-20 hrs*Temazepam (Restoril) t 1/2 8-20 hrs Clonazepam (Klonopin) t 1/2 18-50 hrsClonazepam (Klonopin) t 1/2 18-50 hrs *Lorazepam (Ativan) t1/2 10-20 hrs*Lorazepam (Ativan) t1/2 10-20 hrs Chlordiazepoxide (Librium) t1/2 30-100 hrs (less Chlordiazepoxide (Librium) t1/2 30-100 hrs (less

lipophilic)lipophilic) Diazepam (Valium) t ½ 30-100 hrs (more lipophilic)Diazepam (Valium) t ½ 30-100 hrs (more lipophilic)

*Oxazepam, Temazepam & Lorazepam- metabolized *Oxazepam, Temazepam & Lorazepam- metabolized through only glucuronidation in liver and not affected by through only glucuronidation in liver and not affected by age/ hepatic insufficiency.age/ hepatic insufficiency.

OpiodsOpiods

OPIOIDSOPIOIDSBind to the mu receptors in the CNS to modulate painBind to the mu receptors in the CNS to modulate pain

Intoxication-Intoxication- pinpoint pupils, sedation, constipation, pinpoint pupils, sedation, constipation, bradycardia, hypotension and decreased respiratory ratebradycardia, hypotension and decreased respiratory rate

Withdrawal-Withdrawal- not life threatening unless severe medical not life threatening unless severe medical illness but extremely uncomfortable. s/s dilated pupils illness but extremely uncomfortable. s/s dilated pupils lacrimation, goosebumps, n/v, diarrhea, myalgias, lacrimation, goosebumps, n/v, diarrhea, myalgias, arthralgias, dysphoria or agitationarthralgias, dysphoria or agitation

RxRx- symptomatically with antiemetic, antacid, - symptomatically with antiemetic, antacid, antidiarrheal, muscle relaxant (methocarbamol), antidiarrheal, muscle relaxant (methocarbamol), NSAIDS, clonidine and maybe BZDNSAIDS, clonidine and maybe BZD

Neuroadaptation: Neuroadaptation: increased DA and decreased NEincreased DA and decreased NE

Treatment - Opiate Use DisorderTreatment - Opiate Use Disorder

CD treatmentCD treatment support, education, skills building, psychiatric and psychological support, education, skills building, psychiatric and psychological

treatment, NA treatment, NA

MedicationsMedications Methadone (opioid substitution)Methadone (opioid substitution) NaltrexoneNaltrexone Buprenorphine (opioid substitution)Buprenorphine (opioid substitution)

Treatment - Opiate Use DisorderTreatment - Opiate Use Disorder

NaltrexoneNaltrexone Opioid blocker, mu antagonistOpioid blocker, mu antagonist 50mg po daily50mg po daily

MethadoneMethadone Mu agonistMu agonist Start at 20-40mg and titrate up until not craving or using illicit opioidsStart at 20-40mg and titrate up until not craving or using illicit opioids Average dose 80-100mg dailyAverage dose 80-100mg daily Needs to be enrolled in a certified opiate substitution programNeeds to be enrolled in a certified opiate substitution program

BuprenorphineBuprenorphine Partial mu partial agonist with a ceiling effectPartial mu partial agonist with a ceiling effect Any physician can Rx after taking certified ASAM courseAny physician can Rx after taking certified ASAM course Helpful for highly motivated people who do not need high dosesHelpful for highly motivated people who do not need high doses

StimulantsStimulants

STIMULANTSSTIMULANTS

Intoxication (acute)Intoxication (acute) psychological and physical signspsychological and physical signs

euphoria, enhanced vigor, gregariousness, euphoria, enhanced vigor, gregariousness, hyperactivity, restlessness, interpersonal sensitivity, hyperactivity, restlessness, interpersonal sensitivity, anxiety, tension, anger, impaired judgment, paranoiaanxiety, tension, anger, impaired judgment, paranoia

tachycardia, papillary dilation, HTN, N/V, diaphoresis, tachycardia, papillary dilation, HTN, N/V, diaphoresis, chills, weight loss, chest pain, cardiac arrhythmias, chills, weight loss, chest pain, cardiac arrhythmias, confusion, seizures, comaconfusion, seizures, coma

STIMULANTSSTIMULANTS(cont.)(cont.)

Chronic intoxicationChronic intoxication affective blunting, fatigue, sadness, social affective blunting, fatigue, sadness, social

withdrawal, hypotension, bradycardia, muscle withdrawal, hypotension, bradycardia, muscle weaknessweakness

WithdrawalWithdrawal not severe but have exhaustion with sleep not severe but have exhaustion with sleep

(crash)(crash) treat with rest and supporttreat with rest and support

CocaineCocaine

Route: nasal, IV or smoked Route: nasal, IV or smoked Has vasoconstrictive effects that may outlast Has vasoconstrictive effects that may outlast

use and increase risk for CVA and MI (obtain use and increase risk for CVA and MI (obtain EKG)EKG)

Can get rhabdomyolsis with compartment Can get rhabdomyolsis with compartment syndrome from hypermetabolic statesyndrome from hypermetabolic state

Can see psychosis associated with intoxication Can see psychosis associated with intoxication that resolvesthat resolves

Neuroadaptation: Neuroadaptation: cocaine mainly prevents cocaine mainly prevents reuptake of DA reuptake of DA

Treatment - Stimulant Use Treatment - Stimulant Use Disorder (cocaine)Disorder (cocaine)

CD treatment including support, education, CD treatment including support, education, skills, CAskills, CA

PharmacotherapyPharmacotherapy No medications FDA-approved for treatmentNo medications FDA-approved for treatment If medication used, also need a psychosocial If medication used, also need a psychosocial

treatment componenttreatment component

AmphetaminesAmphetamines Similar intoxication syndrome to cocaine but Similar intoxication syndrome to cocaine but

usually longerusually longer Route - oral, IV, nasally, smoked Route - oral, IV, nasally, smoked No vasoconstrictive effectNo vasoconstrictive effect Chronic use results in neurotoxicity possibly Chronic use results in neurotoxicity possibly

from glutamate and axonal degenerationfrom glutamate and axonal degeneration Can see permanent amphetamine psychosis Can see permanent amphetamine psychosis

with continued usewith continued use Treatment similar as for cocaine but no known Treatment similar as for cocaine but no known

substances to reduce cravingssubstances to reduce cravings NeuroadaptationNeuroadaptation

inhibit reuptake of DA, NE, SE - greatest effect on DA inhibit reuptake of DA, NE, SE - greatest effect on DA

Treatment – Stimulant Use Treatment – Stimulant Use Disorder (amphetamine)Disorder (amphetamine)

CD treatment: including support, CD treatment: including support, education, skills, CAeducation, skills, CA

No specific medications have been found No specific medications have been found helpful in treatment although some early helpful in treatment although some early promising research using atypical promising research using atypical antipsychotics (methamphetamine)antipsychotics (methamphetamine)

TobaccoTobacco

TobaccoTobacco

Most important preventable cause of death / Most important preventable cause of death / disease in USAdisease in USA

25%- current smokers, 25% ex smokers25%- current smokers, 25% ex smokers 20% of all US deaths20% of all US deaths 45% of smokers die of tobacco induced disorder45% of smokers die of tobacco induced disorder Second hand smoke causes death / morbiditySecond hand smoke causes death / morbidity Psychiatric pts at risk for Nicotine dependence-Psychiatric pts at risk for Nicotine dependence-

75%-90 % of Schizophrenia pts smoke75%-90 % of Schizophrenia pts smoke

Tobacco (Tobacco (cont.)cont.) Drug InteractionsDrug Interactions

induces CYP1A2 - watch for interactions when start or induces CYP1A2 - watch for interactions when start or stop (ex. Olanzapine)stop (ex. Olanzapine)

No intoxication diagnosisNo intoxication diagnosis initial use associated with dizziness, HA, nauseainitial use associated with dizziness, HA, nausea

NeuroadaptationNeuroadaptation nicotine acetylcholine receptors on DA neurons in nicotine acetylcholine receptors on DA neurons in

ventral tegmental area release DA in nucleus ventral tegmental area release DA in nucleus accumbensaccumbens

ToleranceTolerance rapidrapid

Withdrawal Withdrawal dysphoria, irritability, anxiety, decreased dysphoria, irritability, anxiety, decreased

concentration, insomnia, increased appetiteconcentration, insomnia, increased appetite

Treatment – Tobacco Use Treatment – Tobacco Use DisorderDisorder

Cognitive Behavioral TherapyCognitive Behavioral Therapy Agonist substitution therapyAgonist substitution therapy

nicotine gum or lozenge, transdermal patch, nicotine gum or lozenge, transdermal patch, nasal spraynasal spray

MedicationMedication bupropion (Zyban) 150mg po bid, bupropion (Zyban) 150mg po bid, varenicline (Chantix) 1mg po bidvarenicline (Chantix) 1mg po bid

HallucinogensHallucinogens

HALLUCINOGENSHALLUCINOGENS

Naturally occurring - Peyote cactus (mescaline); Naturally occurring - Peyote cactus (mescaline); magic mushroom(Psilocybin) - oralmagic mushroom(Psilocybin) - oral

Synthetic agents – LSD (lysergic acid Synthetic agents – LSD (lysergic acid diethyamide) - oraldiethyamide) - oral

DMT (dimethyltryptamine) - smoked, snuffed, IVDMT (dimethyltryptamine) - smoked, snuffed, IV STP (2,5-dimethoxy-4-methylamphetamine) –STP (2,5-dimethoxy-4-methylamphetamine) –

oraloral MDMA (3,4-methyl-enedioxymethamphetamine) MDMA (3,4-methyl-enedioxymethamphetamine)

ecstasy – oral ecstasy – oral

MDMA (XTC or Ecstacy)MDMA (XTC or Ecstacy)

Designer club drugDesigner club drug Enhanced empathy, personal insight, euphoria, Enhanced empathy, personal insight, euphoria,

increased energy increased energy 3-6 hour duration3-6 hour duration IntoxicationIntoxication- illusions, hyperacusis, sensitivity - illusions, hyperacusis, sensitivity

of touch, taste/ smell altered, "oneness with the of touch, taste/ smell altered, "oneness with the world", tearfulness, euphoria, panic, paranoia, world", tearfulness, euphoria, panic, paranoia, impairment judgment impairment judgment

Tolerance develops quickly and unpleasant side Tolerance develops quickly and unpleasant side effects with continued use (teeth grinding) so effects with continued use (teeth grinding) so dependence less likely dependence less likely

MDMA (XTC or Ecstacy)MDMA (XTC or Ecstacy)cont.cont. NeuroadaptationNeuroadaptation- affects serotonin (5HT), DA, - affects serotonin (5HT), DA,

NE but predominantly 5HT2 receptor agonistsNE but predominantly 5HT2 receptor agonists PsychosisPsychosis

Hallucinations generally mildHallucinations generally mild Paranoid psychosis associated with chronic useParanoid psychosis associated with chronic use Serotonin neural injury associated with panic, anxiety, Serotonin neural injury associated with panic, anxiety,

depression, flashbacks, psychosis, cognitive changes.depression, flashbacks, psychosis, cognitive changes. WithdrawalWithdrawal – unclear syndrome (maybe similar – unclear syndrome (maybe similar

to mild stimulants-sleepiness to mild stimulants-sleepiness and depression due to 5HT depletion)and depression due to 5HT depletion)

CannabisCannabis

CANNABISCANNABIS

Most commonly used illicit drug in AmericaMost commonly used illicit drug in America THC levels reach peak 10-30 min, lipid soluble; long half life of 50 THC levels reach peak 10-30 min, lipid soluble; long half life of 50

hourshours IntoxicationIntoxication--

Appetite and thirst increaseAppetite and thirst increase Colors/ sounds/ tastes are clearerColors/ sounds/ tastes are clearer

Increased confidence and euphoriaIncreased confidence and euphoriaRelaxationRelaxationIncreased libidoIncreased libidoTransient depression, anxiety, paranoiaTransient depression, anxiety, paranoiaTachycardia, dry mouth, conjunctival injectionTachycardia, dry mouth, conjunctival injectionSlowed reaction time/ motor speedSlowed reaction time/ motor speedImpaired cognitionImpaired cognitionPsychosisPsychosis

CANNABIS (cont.)CANNABIS (cont.)

NeuroadaptationNeuroadaptation CB1, CB2 cannabinoid receptors in brain/ bodyCB1, CB2 cannabinoid receptors in brain/ body Coupled with G proteins and adenylate cyclase to CA Coupled with G proteins and adenylate cyclase to CA

channel inhibiting calcium influxchannel inhibiting calcium influx Neuromodulator effect; decrease uptake of GABA and Neuromodulator effect; decrease uptake of GABA and

DADA

WithdrawaWithdrawal - insomnia, irritability, anxiety, poor l - insomnia, irritability, anxiety, poor appetite, depression, physical discomfortappetite, depression, physical discomfort

CANNABIS (cont.)CANNABIS (cont.)

TreatmentTreatment

-Detox and rehab-Detox and rehab

-Behavioral model-Behavioral model

-No pharmacological treatment but -No pharmacological treatment but may may treat other psychiatric symptomstreat other psychiatric symptoms

PCPPCP

PHENACYCLIDINE ( PCP)PHENACYCLIDINE ( PCP)"Angel Dust""Angel Dust"

Dissociative anestheticDissociative anesthetic Similar to Ketamine used in anesthesiaSimilar to Ketamine used in anesthesia IntoxicationIntoxication: severe dissociative reactions – paranoid : severe dissociative reactions – paranoid

delusions, hallucinations, can become very agitated/ delusions, hallucinations, can become very agitated/ violent with decreased awareness of pain. violent with decreased awareness of pain.

Cerebellar symptoms - ataxia, dysarthria, nystagmus Cerebellar symptoms - ataxia, dysarthria, nystagmus (vertical and horizontal)(vertical and horizontal)

With severe OD - mute, catatonic, muscle rigidity, HTN, With severe OD - mute, catatonic, muscle rigidity, HTN, hyperthermia, rhabdomyolsis, seizures, coma and deathhyperthermia, rhabdomyolsis, seizures, coma and death

PCP cont.PCP cont. TreatmentTreatment

antipsychotic drugs or BZD if requiredantipsychotic drugs or BZD if required Low stimulation environmentLow stimulation environment acidify urine if severe toxicity/comaacidify urine if severe toxicity/coma

NeuroadaptationNeuroadaptation opiate receptor effects opiate receptor effects allosteric modulator of glutamate NMDA receptorallosteric modulator of glutamate NMDA receptor

No tolerance or withdrawalNo tolerance or withdrawal

WebsitesWebsites

SAMHSA – SAMHSA – www.samhsa.gov Substance Abuse and Mental Health Services AdministrationSubstance Abuse and Mental Health Services Administration

NIDA – NIDA – www.drugabuse.gov National Institute on Drug AbuseNational Institute on Drug Abuse

AAAP – AAAP – www.aaap.org American Academy of Addiction PsychiatryAmerican Academy of Addiction Psychiatry

ASAM – ASAM – www.asam.org American Society of Addiction MedicineAmerican Society of Addiction Medicine