New Clinical Information for Treatment of Cocaine and Meth - UCLA ...

New Clinical InformationRegarding the Treatment ofIndividuals for Cocaine andMethamphetamine DependenceRichard A. Rawson, Ph.DProfessorSemel Institute for Neuroscience and Human BehaviorDavid Geffen School of MedicineUniversity of California at Los Angeleswww.uclaisap.orgrrawson@mednet.ucla.eduSupported by:National Institute on Drug Abuse (NIDA)Pacific Southwest Technology Transfer Center (SAMHSA)International Network of Treatment and Rehabilitation Resource Centres C(UNODC)

StimulantsCOCAINECRACKMETHAMPHETAMINE

StimulantsDescription:A group of synthetic andplant-derived drugs that increasealertness and arousal by stimulating thecentral nervous system.Medical Uses:Short-term term treatment ofobesity, narcolepsy, and hyperactivity inchildrenMethod of Use: Intravenous, intranasal,oral, smoking

Types of Stimulant DrugsCocaine ProductsCocaine Powder (Generally sniffed, injected,smoked on foil)“Crack” (smoked)Major areas of use: South America; USA(predominantly major urban centers,disproportionately impacts African Americancommunity); Increasing in Europe.

Types of Stimulant DrugsAmphetamine Type Stimulants (ATS)AmphetamineDexamphetamineMethylphenidateMethamphetamine“Speed”“Ice”“Crank”“Yaba”“Shabu”

Methamphetamine vs. CocaineCocaine half-life: life: 1-212 hoursMethamphetamine half-life: life: 8-128hoursCocaine paranoia: 4 -88 hours following drug cessationMethamphetamine paranoia: 7-147daysMethamphetamine psychosis - May requiremedication/hospitalization and may not be reversibleNeurotoxicity: Appears to be more profound withamphetamine-like substances

Scope of the MethamphetamineProblem WorldwideAccording to surveys and estimates by WHOand UNODC, methamphetamine is the mostwidely used illicit drug in the world except forcannabis.World wide it is estimated there are over 26million regular users ofamphetamine/methamphetamine, as comparedto approximately 16 million heroin users and 14million cocaine users

Acute Stimulant EffectsPsychologicalIncreased energyIncreased clarityIncreased competenceFeelings of sexualityIncreased sociabilityImproved moodPowerful rush of euphoria -freebase and intravenous only

Acute Stimulant EffectsPhysicalIncreased heart rateIncreased pupil sizeIncreased body temperatureIncreased respirationConstriction of small blood vesselsDecreased appetiteDecreased need for sleepNumbness of nasal mucosa - intranasalonly

Chronic Stimulant EffectsPhysicalWeight loss/anorexiaSleep deprivationRespiratory system diseaseCardiovascular diseaseHeadachesSevere Dental diseaseNeedle marks and abscesses - intravenous onlySeizures

Long-term effects of stimulants‣ Strokes, seizures, and headaches‣ Irritability, restlessness‣ Depression, anxiety, irritability, anger‣ Memory loss, confusion, attention problems‣ Insomnia‣ Paranoia, auditory hallucinations, panic reactions‣ Suicidal ideation‣ Sinus infection‣ Loss of sense of smell, nosebleeds, chronic runny nose,hoarseness‣ Dry mouth, burned lips‣ Worn teeth (due to grinding during intoxication)‣ Problems swallowing‣ Chest pain, cough, respiratory failure‣ Disturbances in heart rhythm and heart attack‣ Gastrointestinal complications (abdominal pain and nausea)‣ Loss of libido‣ Malnourishment, weight loss, anorexia‣ Weakness, fatigue‣ Tremors‣ Sweating‣ Oily skin, complexion

Cocaine HydrochlorideCrystalline white powderSnorted in “lines” of 10-35 mg eachAdulterated w cheap local anesthetics,stimulants, and inert white powdersYields moderate to high blood levelsGradual onset of effects at 15-20 minwith peak at 30-60 min

Cocaine Hydrochloride:Intravenous AdministrationSoluble in waterPeak blood levels achievedinstantaneouslyRapid onset, brief duration, intense“crash”Rapid develop. of compulsive use pattern“Speedball” when mixed with heroin tocushion the “crash”

Cocaine Freebase“Crack”Extracted from cocaine HCL usingether, ammonia, or sodiumbicarbonateExtraction does not remove impuritiesPharmacodynamics almost identical tointravenous useAvoids many medical hazards of I.V.use

Cocaine: Mechanism ofCNS ActionStimulates dopamine secretion indopaminergic pathways in brainPrevents dopamine reuptake at synapseAcute effect- dopamine floodingChronic effect- dopamine depletionDopamine agonists/replacements havenot proved therapeutically useful inaddicts

Cocaine: Acute EffectsEuphoric moodIncreased energy, alertnessIncreased sexualityParanoiaIncreased heart rate, bloodpressure

Cocaine: Chronic EffectsLethargy, fatigueReduced attention spanSexual dysfunctionDepression, irritability, anhedoniaParanoid psychosis

Cocaine: Toxic ReactionsCardiac arrhythmias, fibrillationHyperthermia- > 106 degrees FConvulsions, loss of consciousnessRespiratory & cardiac arrestAbruptio placentae (miscarriage)Fatal reactions rare, but unpredictable

Cocaine “Crash”Rebound dysphoriaAgitation, restlessnessIntensifies w dosage & chronicity of useCravings & drug-seeking behaviorAbuse of alcohol & other drugsSuicidal ideation, behaviorOften followed by prolonged sleep

Cocaine: Clinical ConsiderationsNo clearcut physical withdrawal syndromePharmacotherapies: See Vocci notesSerious medical consequences are uncommonPsychiatric consequences are extremelycommon:– Depression, anhedonia, labile moods, irritability, paranoia,suicidal ideation– Usually remit within several days/weeks of abstinence &without pharmacotherapy– Persisting symptoms beyond 6 to 8 weeks may warrantpsychiatric evaluation & possible pharmacotherapy

SpeedIt is methamphetamine powder ranging in colorfrom white, yellow, orange, pink, or brownColor variations are due to differences inchemicals used to produce it and the expertiseof the cookerOther names: Shabu, Crystal, Crystal Meth,Crank, Tina, Yaba

IceHigh puritymethamphetaminecrystals or coarsepowder rangingfrom translucent towhite, sometimeswith a green, blue,or pink tinge

Because…BrainsTheir have beenRe-Wiredby Drug Use

Partial Recovery of Brain DopamineTransporters in Methamphetamine(METH)Abuser After Protracted Abstinence30Normal ControlMETH Abuser(1 month detox)METH Abuser(24 months detox)ml/gmSource: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

– 33 year old man, high on methamphetamine admitted to emergency room rcomplaining of severe headache in Portland Oregon.– X-ray revealed 12, 2 inch nails (6 on each side) in his head, administered with aqnail gun.– The man at first claimed it was an accident, but he later admitted that it was asuicide attempt. The nails were removed, and the man survived without wanyserious permanent damage.– He was eventually transferred to psychiatric care; he stayed for almost one monthunder court order but then left against doctors’ ordersMSNBC-TV

Brain Serotonin Transporter Density andAggression in AbstinentMethamphetamine Abusers **Sekine, , Y, Ouchi, , Y, Takei, N, et al. Brain Serotonin TransporterDensity and Aggression in Abstinent Methamphetamine Abusers.Arch Gen Psychiatry. 2006;63:90-100.

Cardiac Disorders and MA UseCoronary SyndromesArrhythmiaCardiomyopathyHypertensionValvular Disease

Neurologic Disorders and MA UseHeadacheSeizureCerebrovascular– Ischemic stroke– Cerebral hemorrhage– Cerebral vasculitisCerebral edema

Respiratory Disorders and MA UsePulmonary edemaBronchitisPulmonary hypertensionCOPD

METH Use Leads to Severe ToothDecay“METH Mouth”Source: The New York Times, June 11, 2

MethamphetaminePsychiatric ConsequencesParanoid reactionsPermanent memory lossDepressive reactionsHallucinationsPsychotic reactionsPanic disordersRapid addiction

MA Psychosis Inpatients from 4 CountriesPsychotic symptomPersecutory delusionAuditory hallucinationsStrange or unusual beliefsThought readingVisual hallucinationsDelusion of referenceThought insertion or made actNegative psychotic symptomsDisorganized speechDisorganized or catatonic behaviorNo. of patients havingsymptoms (%)Lifetime130 (77.4)122 (72.6)98 (58.3)89 (53.0)64 (38.1)64 (38.1)56 (33.3)Current35 (20.8)75 (44.6)39 (23.2)27 (16.1)38 (22.6)20 (11.9)18 (10.7)36 (21.4)19 (11.3)14 (8.3)Srisurapanont et al., 2003

MA Psychosis69 physically healthy, incarcerated Japanesefemales with hx MA use– 22 (31.8%) no psychosis– 47 (68.2%) psychosis19 resolved (mean=276.2±222.8 222.8 days)8 persistent (mean=17.6±10.5 10.5 months)20 flashbackers (mean=215.4±208.2 208.2 days to initialresolution)– 11 single flashback– 9 Recurrent flashbacks Yui2001Yui et al.,Polymorphism in DAT Gene associated with MApsychosis in JapaneseUjike et al., 2003

Treatment

Is Treatment forMethamphetamine Effective?A pervasive rumor has surfaced inmany geographic areas withelevated MA problems:– MA users are virtually untreatable withnegligible recovery rates.– Rates from 5% to less than 1% havebeen quoted in newspaper articles andreported in conferences.

Meth. Treatment StatisticsDuring the 2002-2003 fiscal year:35,947 individuals were admitted to treatmentin California under the Substance Abuse andCrime Prevention Act funding.Of this group, 53% reported MA as theirprimary drug problem

Analysis of:StatisticsDrop out ratesRetention in treatment ratesRe-incarceration ratesOther measures of outcomeAll these measures indicate that MA users respond in anequivalent manner as individuals admitted for other drugabuse problems.Analysis of data from 3 other large data sets and 3 clinicaltrials data sets suggest treatment response (usingpsychosocial treatments) of MA and cocaine users isindistinguishable.

Additional Information on Population10080Percentage604052.854.92007.33.2Used NeedlesCocaineSober at DischargeMethamphetamine

Mean Days of Primary DrugUse in Last 30 Days3025Mean Days201510511.895.93.60AdmissionCocaineDischargeMethamphetamine

Why the “MA Treatment DoesNot Work” Perceptions?Many of the geographic regions impacted by MA donot have extensive treatment systems for severedrug dependence.Medical and psychiatric aspects of MA dependenceexceeds program capabilities.High rate of use by women, their treatment needsand the needs of their children can be daunting.Although some traditional elements may beappropriate, many staff report feeling unprepared toaddress many of the clinical challenges presentedby these patients

Bupropion: : An EfficaciousPharmacotherapy?Newton et al., (2005):– Bupropion reduces craving andreinforcing effects of methElkashef (recently completed):– Bupropion reduces meth use in anoutpatient trial, with particularly strongeffect with less severe users.

Special Treatment ConsiderationShould Be Made for the FollowingGroups of Individuals:Female MA users (higher rates of depression; veryhigh rates of previous and present sexual andphysical abuse; responsibilities for children).Injection MA users (very high rates of psychiatricsymptoms; severe withdrawal syndromes; high ratesof hepatitis).MA users who take MA daily or in very high doses.Homeless, chronically mentally ill and/or individualswith high levels of psychiatric symptoms at admission.Individuals under the age of 21.Gay men (at very high risk for HIV and hepatitis).

Contingency ManagementA technique employing the systematic delivery ofpositive reinforcement for desired behaviors. Inthe treatment of methamphetaminedependence, vouchers or prizes can be “earned”for submission of methamphetamine-free urinesamples.

Contingency Management for treatment ofmethamphetamine dependenceDesign: RTCMethod: 113 patients diagnosed with methamphetamine abuse ordependence were randomly assigned to receive either treatment asusual (TAU) or TAU plus contingency management.Results indicate that both groups were retained in treatment forequivalent times but those in the combined group accrued moreabstinence and were abstinent for a longer period of time. Theseresults suggest that contingency management has promise as acomponent in methamphetamine use disorder treatment strategies.Contingency Management for the Treatment of MethamphetamineUse Disorders. Roll, JM et al, Archives of General Psychiatry, (In(Press)

Cognitive Behavioral Therapy andContingency Management for StimulantDependenceDesign Randomized clinical trial.Participants Stimulant-dependent individuals (n(= 171).Intervention CM, CBT, or combined CM and CBT, 16-week treatmentconditions. CM condition participants received vouchers for stimulantulant-freeurine samples. CBT condition participants attended three 90-minute groupsessions each week. CM procedures produced better retention and lower ratesof stimulant use during the study period.Results Self-reported stimulant use was reduced from baseline levels at allfollow-up points for all groups and urinalysis data did not differ betweeneengroups at follow-up. While CM produced robust evidence of efficacy duringtreatment application, CBT produced comparable longer-term outcomes. Therewas no evidence of an additive effect when the two treatments were combined.The response of cocaine and methamphetamine users appeared comparable.Conclusions: This study suggests that CM is an efficacious treatment forreducing stimulant use and is superior during treatment to a CBT approach.CM is useful in engaging substance abusers, retaining them in treatment, andhelping them achieve abstinence from stimulant use. CBT also reduces druguse from baseline levels and produces comparable outcomes on all measuresat follow-up.Rawson, RA et al. Addiction, Jan 2006

Contingency Management: AMeta-analysisanalysisA recent meta-analysis reports that CMresults in a successful treatmentepisode 61% of the time while othertreatments with which it has beencompared result in a successfultreatment episode 39% of the time(Prendergast, Podus, Finney, Greenwell &Roll, submitted)

Matrix Model in Treatment ofMethamphetamine DepenenceDesign: The study was conducted as an eight-site randomized clinical trial.Method: 978 treatment-seeking, MA-dependent persons were randomly assigned toreceive either TAU at each site, or a manualized 16-week treatment (Matrix Model)for their MA dependence.Results: Analyses of study data indicate that in the overall sample, and in the majorityof sites, those who were assigned to Matrix treatment attended more mclinicalsessions, stayed in treatment longer, provided more MA-free urine samples duringthe treatment period, and had longer periods of MA abstinence than those assignedto receive TAU. Measures of drug use and functioning collected at treatmentdischarge and 6 months post-admission indicate significant improvement byparticipants in all sites and conditions when compared to baseline levels, but thesuperiority of the Matrix approach did not persist at these two time points.Conclusions: Study results demonstrate a significant initial step in documenting theefficacy of the Matrix approach. Although the superiority of the Matrix approach overTAU was not maintained at the posttreatment time points, the in-treatment benefit isan important demonstration of empirical support for this psychosocial ocial treatmentapproach.Rawson, R et al Addiction vol 99, 2004

121086420Mean Number of Weeks inTreatmentMatrixTAUCostaMesaConcordBillingsSanDiegoHonoluluHaywardSanMateoPyraSanMateoODASSiteMean Number of Visits

Mean Number of UA’s s That WereMA-free During Treatment1086420BillingsCostaMesaConcordHonoluluHaywardSanMateoODASSanDiegoSanMateoPyraMean number of MA-free UA'sSiteMatrixTAU

Urinalysis ResultsResults of Ua Tests at Discharge, 6months and 12 Months post admission**Matrix Group TAU GroupD/C: 66% MA-free 65% MA-free6 Ms: 69% MA-free 67% MA-free12 Ms: 59% MA-free 55% MA-free**Over 80% follow up rate in both groups at all points

Prenatal Meth. ExposurePreliminary findings on infants exposedprenatally to methamphetamine (MA) andnonexposed infants suggest:– Prenatal exposure to MA is associated with anincrease in SGA (Small-forfor-Gestational-Age).– Neurobehavioral deficits at birth were identified inNNNS (Neonatal Intensive Care Unit NetworkNeurobehavioral Scale) neurobehavior, includingdose response relationships and acoustical analysisof the infant’s s cry (Lester et al., 2005).

Adolescent Meth. AbuseTreatment AdmissionsMatrix(Boys)(Girls)– 2002 16% 63%– 2003 25% 67%– 2004 22% 69%Phoenix (Boys)(Girls)– 2002 25% 43%– 2003 23% 51%– 2004 27% 53%

My Sexual Pleasure isEnhanced by the use of:Percent Responding"Yes"100908070605040302010016.0 18.238.224.444.711.173.566.7opiates alcohol cocaine methmalefemalePrimary Drug of Abuse(Rawson et al., 2002)

My Sexual Performance isImproved by the use of:Percent Responding"Yes"100908070605040302010019.115.932.424.418.411.158.8 61.1opiates alcohol cocaine methmalefemalePrimary Drug of Abuse(Rawson et al., 2002)

Behavior Symptom Inventory(BSI) Scores at Baseline1.601.40all significant at p< .0011.20FemaleMale1.000.800.600.400.200.00SomatizationObsessive-CompulsiveInterpersonal SensitivityDepressionAnxietyHostilityPhobic AnxietyParanoid IdeationPsychoticismMean BSI Score

Route of MethamphetamineAdministration7064Percent Using by Route6050403020101124intranasal (IN)smoke (SM)inject (IDU)0Route of Administration

BSI PsychiatricSymptoms by Route30Positive Symptom Total (PST)2520151050IN SM IDUBL PSTTX-End PST6-Mo PST12-Mo PSTP

Hepatitis C by Route50454440% Prevelance35302520151215IN (n=99SM (N=478)IDU (n=146)Total (n=723)10750P

Methamphetamine Abuse:Treatment as PreventionRichard A. Rawson, Cathy J. Reback,Steven ShoptawUCLA Integrated Substance Abuse Programs

OverviewSubstance abuse concomitant with riskysex for MSM (Stall & Wiley, 1988)Different drugs have differing prevalenceof HIV among MSMDrug abuse treatments dramaticallyreduce methamphetamine use and high-risk sex– Reductions are sustained!Policy implications

Sex Risks Reduced withTreatment: UARI Past 30 Days3.532.521.510.50CBTCMCBT+CMGCBTBaseline4-Wks8-Wks12-Wks16-Wks6-Mos12-Mos 2 (3) =6.75, p

SummaryUse of psychostimulants is a significant publichealth problem in the US.In California (and worldwide), methamphetamineis and has been for some time the most widelyused illicit drug other than cannabis.Cocaine and methamphetamine produce mansimilar acute and chronic effects.Psychosocial treatments currently have greatestempirical support, although research onpharmacotherpies is promising.

Thank yourrawson@mednet.ucla.eduwww.uclaisap.orgwww.methamphetamine.org