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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 Identify the diagnostic criteria for substancesubstance--related disordersrelated disorders

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

Describe treatment optionsDescribe treatment options

Discern intoxication/withdrawal of different Discern intoxication/withdrawal of different substancessubstances

Apply the information above to clinical Apply the information above to clinical casescases

Substance ClassesSubstance Classes

AlcoholAlcohol

CaffeineCaffeine

CannabisCannabis

HallucinogensHallucinogens

OpioidsOpioids

Sedatives, hypnotics, Sedatives, hypnotics, and anxiolyticsand anxiolytics

StimulantsStimulantsgg PCPPCP

othersothers

InhalantsInhalants

GamblingGambling

StimulantsStimulants

TTobaccoobacco

OtherOther

SubstanceSubstance--Related DisordersRelated 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, riskyInvolves: impaired control, social impairment, riskyInvolves: impaired control, social impairment, risky Involves: impaired control, social impairment, risky use, and pharmacological criteriause, and pharmacological criteria

SubstanceSubstance--Induced DisordersInduced 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 useG t d l f ti bt i i iG t d l f ti bt i i i 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 recreational activities given up or reducedreduced

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)

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SeveritySeverity

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

Mild: 2Mild: 2--3 symptoms3 symptoms

Moderate: 4Moderate: 4--5 symptoms5 symptoms

Severe: 6 or more symptomsSevere: 6 or more symptoms

SpecifiersSpecifiers

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

but < 12 months (except craving)but < 12 months (except craving)

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

In a controlled In a controlled environment: access to environment: access to substance restricted (ex. Jail)substance restricted (ex. Jail)

SubstanceSubstance--InducedInduced

IntoxicationIntoxication

WithdrawalWithdrawal

Psychotic DisorderPsychotic Disorder

Bipolar DisorderBipolar Disorder

Anxiety DisorderAnxiety Disorder

Sleep DisorderSleep Disorder

DeliriumDelirium

NeurocognitiveNeurocognitive Bipolar DisorderBipolar Disorder

Depressive DisorderDepressive Disorder

NeurocognitiveNeurocognitive

Sexual DysfunctionSexual Dysfunction

IntoxicationIntoxication

Reversible substanceReversible substance--specific syndrome 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, attention, thinking, judgementjudgement, psychomotor behavior , 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 ofRoute of

Time since last doseTime since last dose

Person’s expectations Person’s expectations of substance effectof substance effect Route of Route of

AdministrationAdministration

Duration/chronicityDuration/chronicity

Individual degree of Individual degree of tolerancetolerance

of substance effectof substance effect

Contextual variablesContextual variables

WithdrawalWithdrawal

SubstanceSubstance--specific syndrome problematic 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

Si ifi t di t i i l ti lSi ifi t di t i i l ti l 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

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SubstanceSubstance--Induced Mental Induced Mental DisorderDisorder

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

C t t f b t f bC t t f b t f bContext 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

SubstanceSubstance--Induced Mental Induced Mental DisorderDisorder

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

Evidence (Evidence (HxHx, PE, labs), PE, labs)D i ithi 1 th fD i ithi 1 th f 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 withdrawalwithdrawalwithdrawalwithdrawal Pharmacokinetic Pharmacokinetic –– adaptation of metabolizing adaptation of metabolizing

systemsystem

PharmacodynamicPharmacodynamic –– ability of CNS to function 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

ORORMarkedly 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 NIDA ’04: 22.5M > 12yo –– substancesubstance--related d/orelated d/o

15M 15M –– Alcohol Dependence or AbuseAlcohol Dependence or Abuse

Start at earlier age (<15yo), more likely to Start at earlier age (<15yo), more likely to become addictedbecome addicted –– ex. alcohol: 18% vs. 4% (ifex. alcohol: 18% vs. 4% (ifbecome addicted become addicted ex. alcohol: 18% vs. 4% (if ex. alcohol: 18% vs. 4% (if start at 18yo or older)start at 18yo or older)

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

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

Epidemiology (cont.)Epidemiology (cont.)

ETOH ETOH -- $300 billion/year$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 nonmedicallynonmedically within past monthwithin past month

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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 d th /100 000 d th / 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: non1.2M: non--medical use of pharmaceuticalsmedical 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 factorsit 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 “Brain DDisease” isease” –– changes in structure and changes in structure and neurochemistry transform voluntary drugneurochemistry transform voluntary drug--using compulsiveusing compulsive

Changes proven but necessary/sufficient? Changes proven but necessary/sufficient? g p yg p y((drugdrug--dependent person dependent person changes changes behavior behavior in response to positive in response to positive reinforcersreinforcers))

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

EtiologyEtiology SelfSelf--medication medication

EtOHEtOH -- panicpanic; ; opioids opioids --anger; anger; amphetamine amphetamine --depressiondepression

Genetic Genetic (well(well--established with alcoholestablished 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 Secondary reinforcersreinforcers (ex. Paraphernalia)(ex. Paraphernalia)

EtiologyEtiologyReceptorsReceptors 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.

NeurotransmittersNeurotransmittersoo OpioidOpioid

oo CatecholaminesCatecholamines

oo GABAGABA

oo SerotoninSerotonin

PathwaysPathways

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Learning and Physiological Basis for Learning and Physiological Basis for DependenceDependence

After using drugs or when stop After using drugs or when stop –– leads to 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 druguse of more druguse 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 DepressionDepression

SuicideSuicide

Typical Presentation and Typical Presentation and Course:Course:

PPresent in acute intoxication, acute/chronic resent 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 (p(pother 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

HospitalizationHospitalization----Due to drug OD, risk of severe withdrawal, medical Due to drug OD, risk of severe withdrawal, medical comorbidities, requires restricted access to drugs, comorbidities, requires restricted access to drugs, psychiatric illness with suicidal ideationpsychiatric illness with suicidal ideation

Residential treatment unitResidential treatment unit--No intensive medical/psychiatric monitoring needsNo intensive medical/psychiatric monitoring needs--Require a restricted environmentRequire a restricted environment--Partial hospitalizationPartial hospitalization

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

Treatment Treatment

Manage Intoxication & WithdrawalManage Intoxication & Withdrawal

IntoxicationIntoxicationR h i t lifR h i t lif th t ith t i•• Ranges: euphoria to lifeRanges: euphoria to life--threatening emergencythreatening emergency

Detoxification Detoxification •• outpatient: "social detox”outpatient: "social detox” program program

•• inpatient: close medical careinpatient: close medical care

•• ppreparation for ongoing treatmentreparation for ongoing treatment

Treatment Treatment Behavioral Interventions (target internal and Behavioral Interventions (target internal and

external external reinforcersreinforcers))Motivation to change (MI)Motivation to change (MI)

Group TherapyGroup Therapy

Individual TherapyIndividual Therapy

Contingency ManagementContingency ManagementContingency ManagementContingency Management

SelfSelf--Help Recovery Groups (AA)Help Recovery Groups (AA)

Therapeutic CommunitiesTherapeutic Communities

Aversion TherapiesAversion Therapies

Family Involvement/TherapyFamily Involvement/Therapy

TwelveTwelve--Step FacilitationStep Facilitation

Relapse PreventionRelapse Prevention

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Treatment Treatment

Pharmacologic InterventionPharmacologic Intervention

Treat CoTreat Co--Occurring Psychiatric DisordersOccurring 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

ALCOHOLALCOHOL-- CNS depressantCNS depressant

IntoxicationIntoxication Blood Blood AAlcohol Level lcohol Level --

0.08g/dl 0.08g/dl

Progress from mood Progress from mood l bilitl bilit i i di i d

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)

labilitylability, impaired , 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, obtundationobtundation))

p )p )

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 24generally seen 24--48 hours48 hours generally seen 24generally seen 24 48 hours 48 hours

most often Grand mal most often Grand mal

Withdrawal Delirium (DTs) Withdrawal Delirium (DTs) generally between 48generally between 48--72 hours72 hours

altered mental status, hallucinations, marked altered mental status, hallucinations, marked autonomic instabilityautonomic instability

llifeife--threatening 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/ g y gg y gauditory/ 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 symptomtherapy can be scheduled or symptom--triggeredtriggered

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

BenzodiazepinesBenzodiazepines GABA agonist GABA agonist -- crosscross--tolerant with alcoholtolerant with alcohol

reduce risk of SZ; provide comfort/sedationreduce risk of SZ; provide comfort/sedation

AnticonvulsantsAnticonvulsants 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 Carbamazepine or ValproicValproic acidacid

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

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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:Medications:Medications: DisulfiramDisulfiram

NaltrexoneNaltrexone

AcamprosateAcamprosate

Medications Medications -- ETOH Use DisorderETOH Use Disorder

DisulfiramDisulfiram ((antabuseantabuse) 250mg) 250mg--500mg 500mg popo dailydaily

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

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

Hepatotoxicity Hepatotoxicity -- check LFT's and h/o check LFT's and h/o hephep CC Neurologic with polyneuropathy / Neurologic with polyneuropathy / paresthesiasparesthesias that slowly that slowly

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

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

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

Medications Medications -- ETOH Use DisorderETOH Use Disorder

Naltrexone 50mg Naltrexone 50mg popo dailydaily 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

AcamprosateAcamprosate((CampralCampral) 666mg ) 666mg popo tidtid Unknown MOA but thought to stabilize neuron Unknown MOA but thought to stabilize neuron

excitation and inhibition excitation and inhibition -- may interact with GABA and may interact with GABA and Glutamate receptor Glutamate receptor -- cleared cleared renallyrenally (check kidney (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 (variable rate of absorption (lipophilialipophilia) and ) 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 tremor, sweating, poor concentration -- time frame depends on 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 taperend 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 taperOutpatient taper-- decrease dose every 1decrease dose every 1--2 weeks and not more 2 weeks and not more than 5 mg Diazepam dose equivalent than 5 mg Diazepam dose equivalent

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

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

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BenzodiazapinesBenzodiazapines

Alprazolam (Xanax) t 1/2 6Alprazolam (Xanax) t 1/2 6--20 20 hrshrs **OxazepamOxazepam ((SeraxSerax) t 1/2 8) t 1/2 8--12 12 hrshrs **TemazepamTemazepam ((RestorilRestoril) t 1/2 8) t 1/2 8--20 20 hrshrs Clonazepam (Clonazepam (KlonopinKlonopin) t 1/2 18) t 1/2 18--50 50 hrshrs **LorazepamLorazepam (Ativan) t1/2 10(Ativan) t1/2 10--20 20 hrshrs ChlordiazepoxideChlordiazepoxide (Librium) t1/2 30(Librium) t1/2 30--100 100 hrshrs (less (less

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

**OxazepamOxazepam, , TemazepamTemazepam & & LorazepamLorazepam-- metabolized metabolized through only through only glucuronidationglucuronidation in liver and not affected by in liver and not affected by age/ hepatic insufficiency.age/ hepatic insufficiency.

OpiodsOpiods

OPIOIDSOPIOIDSBBind to the mu receptors in the CNS to modulate painind to the mu receptors in the CNS to modulate pain

IntoxicationIntoxication-- pinpoint pupils, sedation, constipation, pinpoint pupils, sedation, constipation, bradycardiabradycardia, hypotension and decreased respiratory rate, hypotension and decreased respiratory rate

WithdrawalWithdrawal-- 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 y p py p placrimation, lacrimation, goosebumpsgoosebumps, n/v, diarrhea, , n/v, diarrhea, myalgiasmyalgias, , arthralgiasarthralgias, , dysphoriadysphoria or agitationor agitation

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

NeuroadaptationNeuroadaptation: : increased DA and decreased NEincreased DA and decreased NE

Treatment Treatment -- Opiate Use DisorderOpiate 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 Treatment -- Opiate Use DisorderOpiate Use Disorder

NaltrexoneNaltrexone Opioid Opioid blocker, mu blocker, mu antagonistantagonist 50mg 50mg popo dailydaily

MethadoneMethadoneMu agonistMu agonist Mu agonistMu agonist

Start Start at 20at 20--40mg and titrate up until not craving or using illicit 40mg and titrate up until not craving or using illicit opioidsopioids Average Average dose 80dose 80--100mg 100mg dailydaily Needs Needs to be enrolled in a certified opiate substitution to be enrolled in a certified opiate substitution programprogram

BuprenorphineBuprenorphine Partial mu partial agonist with a ceiling effectPartial mu partial agonist with a ceiling effect Any physician can Any physician can RRx after taking certified ASAM coursex 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

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STIMULANTSSTIMULANTS

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

eeuphoria, enhanced vigor, gregariousness, uphoria, 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, withdrawal, hypotension, bradycardiabradycardia, muscle , muscle weaknessweakness

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

(crash)(crash)

ttreat with rest and supportreat with rest and support

CocaineCocaine

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

and increase risk for CVA and MI (obtain EKG)and increase risk for CVA and MI (obtain EKG) Can get Can get rhabdomyolsisrhabdomyolsis with compartment with compartment

d fd f h t b lih t b li t tt tsyndrome from syndrome from hypermetabolichypermetabolic statestate Can see psychosis associated with intoxication Can see psychosis associated with intoxication

that resolvesthat resolves NeuroadaptationNeuroadaptation: : cocaine mainly prevents cocaine mainly prevents

reuptake of DA reuptake of DA

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

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

PharmacotherapyPharmacotherapyN di ti FDAN di ti FDA d f t t td f t t t No medications FDANo medications FDA--approved for treatmentapproved 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 Route -- oral, IV, nasally, smoked oral, IV, nasally, smoked No No vasoconstrictivevasoconstrictive effecteffect 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 inhibit reuptake of DA, NE, SE -- greatest effect on DA greatest effect on DA

Treatment Treatment –– Stimulant Use 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 earlyhelpful in treatment although some earlyhelpful in treatment although some early helpful in treatment although some early promising research using atypical promising research using atypical antipsychotics (methamphetamine)antipsychotics (methamphetamine)

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TobaccoTobaccoTobaccoTobacco

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

25%25%-- current smokers, 25% ex smokerscurrent smokers, 25% ex smokers

20% of all US deaths20% of all US deaths 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 dependencePsychiatric pts at risk for Nicotine dependence--75%75%--90 % of Schizophrenia pts smoke90 % of Schizophrenia pts smoke

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

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

No intoxication diagnosisNo intoxication diagnosis iinitial use associated with dizzinessnitial use associated with dizziness, HA, , HA, nauseanausea

NeuroadaptationNeuroadaptation 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 rrapidapid

Withdrawal Withdrawal dysphoriadysphoria, irritability, anxiety, decreased , irritability, anxiety, decreased

concentration, insomnia, increased appetiteconcentration, insomnia, increased appetite

Treatment Treatment –– Tobacco Use Tobacco Use DisorderDisorder

Cognitive Behavioral TherapyCognitive Behavioral Therapy

Agonist substitution therapyAgonist substitution therapynicotine gum or lozenge transdermal patchnicotine gum or lozenge transdermal patch nicotine gum or lozenge, transdermal patch, nicotine gum or lozenge, transdermal patch, nasal spraynasal spray

MedicationMedication bupropion (bupropion (ZybanZyban) 150mg ) 150mg popo bid, bid,

vareniclinevarenicline (Chantix) 1mg (Chantix) 1mg popo bidbid

HallucinogensHallucinogensHALLUCINOGENSHALLUCINOGENS

Naturally occurring Naturally occurring -- Peyote cactus (mescaline); Peyote cactus (mescaline); mmagic mushroom(Psilocybin) agic mushroom(Psilocybin) -- oraloral

Synthetic agents Synthetic agents –– LSD (lysergic acid LSD (lysergic acid diethyamidediethyamide)) oraloraldiethyamidediethyamide) ) -- oraloral

DMT (DMT (dimethyltryptaminedimethyltryptamine) ) -- smoked, snuffed, IVsmoked, snuffed, IV

STP (2,5STP (2,5--dimethoxydimethoxy--44--methylamphetamine) methylamphetamine) ––oraloral

MDMA (3,4MDMA (3,4--methylmethyl--enedioxymethamphetamineenedioxymethamphetamine))ecstasy ecstasy –– oral oral

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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 33--6 hour duration6 hour duration IntoxicationIntoxication-- illusionsillusions hyperacusishyperacusis sensitivitysensitivity IntoxicationIntoxication-- illusions, illusions, hyperacusishyperacusis, sensitivity , 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 MDMA (XTC or EcstacyEcstacy))cont.cont.

NeuroadaptationNeuroadaptation-- affects serotonin (5HT), DA, affects serotonin (5HT), DA, NENE but predominantly 5HT2 receptor agonistsbut predominantly 5HT2 receptor agonists

PsychosisPsychosis Hallucinations generally mildHallucinations generally mild Paranoid psychosis associated with chronic useParanoid psychosis associated with chronic usep yp y Serotonin neural injury associated with panic, anxiety, Serotonin neural injury associated with panic, anxiety,

depression, flashbacks, psychosis, cognitive depression, flashbacks, psychosis, cognitive changes.changes.

WithdrawalWithdrawal –– unclear syndrome (maybe similar unclear syndrome (maybe similar to mild stimulantsto mild stimulants--sleepiness sleepiness and depression due to 5HT depletion)and depression due to 5HT depletion)

CannabisCannabisCANNABISCANNABIS

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

hourshours IntoxicationIntoxication--

Appetite and thirst increaseAppetite and thirst increaseColors/ sounds/ tastes are clearerColors/ sounds/ tastes are clearerIncreased confidence and euphoriaIncreased confidence and euphoriaIncreased confidence and euphoriaIncreased confidence and euphoriaRelaxationRelaxationIncreased libidoIncreased libidoTransient depression, anxiety, paranoiaTransient depression, anxiety, paranoiaTachycardia, dry mouth, Tachycardia, dry mouth, conjunctivalconjunctival injectioninjectionSlowed 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 Coupled with G proteins and adenylateadenylate cyclasecyclase to CA to CA

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

and DAand DA

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

CANNABIS (cont.)CANNABIS (cont.)

TreatmentTreatment

--Detox and rehabDetox and rehab

--Behavioral modelBehavioral model

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

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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 : severe dissociative reactions –– paranoid 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 Cerebellar symptoms -- ataxia, dysarthria, ataxia, dysarthria, nystagmusnystagmus(vertical and horizontal)(vertical and horizontal)

With severe OD With severe OD -- mute, catatonic, muscle rigidity, HTN, mute, catatonic, muscle rigidity, HTN, hyperthermia, hyperthermia, rhabdomyolsisrhabdomyolsis, seizures, coma and death, 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 oopiate receptor effects piate receptor effects aallosteric modulator of glutamate NMDA receptorllosteric modulator of glutamate NMDA receptor

No tolerance or withdrawalNo tolerance or withdrawal

WebsitesWebsites

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

NIDA NIDA –– www.drugabuse.govwww.drugabuse.gov National Institute on Drug AbuseNational Institute on Drug Abusegg

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

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