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Methamphetamine Lusitarra that psychiatric Wolkott, physical she had requests B. B. use damage Her and much were 6 of Hawaii, had a trom Report ot was to She she is admitted been recent medications this in Street that Psychiatry that MD from pulse facility, sometimes since any a to: 8 use. 96813. recently the was of alcohol 24 taking Her stated hours 30-year-old exam, Department source someone increase to thereafter, some seeing she may a She about disturbances. past per was the reemergence “strong leaving major pupils to was and had cimetidine after that (ice).

occur. is for emergency “‘ice”. of the had since minute, problems 2 126, obtained separated a 2 even and a these weeks. had psychiatrist is urban been with patient weeks she recently having enough were they the The woman blood accounted starting Its had Psychosis left tor in came friends inpatient whom and staying patient this acute hospital abstinent went for Chronically, of She reactive nationwide, no of with was against Health department. last pressure article. from to been gastrointestinal who abstinence Psychiatry, to other in temperature and presented stay fatigued for to effects alcohol used also smoke she because denied for with may admitted her buy presented in facility medical drug supportive and off medical patients. had use by was ice. Hawaii, structural occur husband ice”; most and friends ice include any She 5 in and smokable ice. of from at used she 145 mm about the 3 was to then abuse. advice David 6 other however, problems. stated somewhat notably The days to acutely John reflux, felt HAWAII am an asking over crystal psychotherapy. past, ice bilaterally. since cardiovascular the and and 100.4 smoke inpatient 6 patient on psychoactive suicidal ago. months that 3

Care in crystallized MEDICAL 88, Its emergency but A. but days A. a in functional or for then; has metham the she Sunday, use degrees respira she Hawaii. dishev Ms. chroni denied crystal was Wolkoff Burns stated “drug prior past. been soon drug after JOURNAL, ago. has She had she on B.

Abuse: 34 School Introduction exhibited epines. been the observed rocks friends. often “mumbo Her maintain ogy events. Cognitively, ted irritable; neurological quently fleeting denied tarily to continue and amine to Unfortunately, ingly VOL well During until promotional promoted not amine, Over (detailed lowed sumption. to that for amine MD, Behaviorally, The Methamphetamine On Originally

exhibit Professionals follow be 56, a to hands. occur were speech in peripheral screen number laboratory the seeing FEBRUARY being the to in both tangential. at patient class the use the Resident current mostly the thoughts The lost Japan She a her to instructions of eye in parked jumbo.” 1930’s in up no same suicidal hospital by After locked in lead occurred. 1 auditory be the She 1930’s abundance was used of was to affect Medicine, campaign shadows with signs she synthesized patient deficits, of contact. was nature, American prescribed 1997 was follow-up. emergency drugs. in that homicidal although period, ailments, of examination, nervous the exhibited pressured, had the that ofjumping cars positive and for pill a She psychiatric and of oriented was and their Her given and rehabilitation the patient and war, did head illicit for is

An mild it and She It form, and paranoid earlier was mood-congruent for was at History a 40’s, thought first in is has American pharmaceutical doing methamphetamine visual systems. synthetic by not former in Japanese supposedly risperidone, the over-the-counter ideation, was department markedly Japan, trauma. for all hearing University discharged purposes, hyperreflexia, but to physicians, stimulating occasionally were 1887 was in large-scale amphetamines the exhibit remainder too in ward methamphetamine often so front person, hallucinations, normal thoughts, processes

Overview military patient’s noted the can program. large by manufactured easy At amine Although counterparts, voices pharmaceutical but for of diminished uncooperative became a be without morning. both rest, violent for after German a 1 quantities but in to to treatment. obtained she but amphetamines effects epidemic bus of companies of mg warehouses. 3 belonging qualitative she paranoid volume. which be but obtain she in hours. were 4 methamphetamine The the constricted. did is not over Hawaii of days orally, used they the any was tendencies, restless a had stating exhibited exam chemist, various on chemical patient She admit memory to for disorganized launching over the U.S. As she risk with or of admitted of and both a therapeutically. She have Her companies place with about to domestic fine as and past she also urine to methamphet methamphet was described the of Thus that and to the and instructions are benzodiaz therapeutic progressed was types She mood the synthesize continued . the it for tremor been Internet). was throwing 12 that no reported normal. or amphet and increas toxicol she was did various abroad. it central a admit volun subse hours. recent exam. time. came focal large were does then con pills was and had and fol she not not of as In the U.S., where a prescription was still needed to legally obtain representjust 10.7%of thepopulation, according tocensus figures). amphetamines, the epidemic was slower in coming. However, by Japanese, Korean, Chinese, Caucasian, Hispanic, and Black were the 1950’s, nonmedical use of amphetamines had spread to the all underrepresented ethnicities. However, it is worth keeping in civilian population, mostly those in need of stimulation to keep mind that data for ethnic6 background were self-reported, and thus awake or fend off boredom in repetitive or monotonous tasks. Not could be susceptible to bias. surprisingly, truck drivers, college students, athletes, and house wives made up the first major wave of abusers in the Acute Effects U.S. At the same time, prescription amphetamines, including meth The acute clinical effects of all psychostimulants, including the amphetamine, continued to be promoted as therapeutic for hyperac amphetamines and , are strikingly similar. Methamphet tivity, obesity, narcolepsy, and depression. amine differs in its sympathomimetic actions7 from other amphet In the 1960’s,intravenous use 2of methamphetamine became more amines in that it exerts fewer peripheral effects (e.g., tachycardia) popular, especially among those who had already been using illicit and more CNS effects (e.g., euphoria), possibly due to ahigher CNS drugs. This group was apparently the first to use methamphetamine penetration. solely for its euphoric effects, rather than for its stimulating or 2 The physical, or peripheral effects of methamphetamine are anoretic properties. This “second wave” of the American epidemic mediated by the autonomic nervous system and include: tachycar was largely held in check through law-enforcement and public dia, tachypnea, tremor, hypertension, dry mouth, mydriasis, and health efforts to educate and treat abusers and potential users. Japan blurry vision. The mechanism for these effects appears to be had similar campaigns, with particularly stiff penalties for drug methamphetamine’s ability to stimulate release of norepinephrine manufacture or importation. at nerve terminals and of epinephrine from the adrenal medulla. However, by 3the mid-1980’s in the U.S. (and even earlier in Potentially lethal toxicities of methamphetamine overdose8 are Japan), a rapid increase in methamphetamine abuse began. This most commonly seen in first-time users who take a single, large “third wave” began with the introduction of apotent, smokable form 8dose. Worrisome symptoms include hyperthermia, arrhythmias, of crystal methamphetamine, known as “crystal”, “glass”, or “ice” and marked hypertension. Permanent neurological sequelae may on the street. In the Philippines, and among the Filipino expatriate also occur: cerebral infarcts can result from ischemia or hemorrhage communities in the U.S. (especially in Hawaii), it has been known secondary to a sudden, massive increase in blood pressure; also, as batu (Tagalog for “rock”). direct neurotoxicity can result from central hyperthermia, which is This newer form has been gaining in popularity over the intrave easily exacerbated by increased muscular activity in agitated pa nous form due to its ease of use, and over the oral form due to its 2tients. In addition, myocardial infarction and acute pulmonary rapidity of CNS effect (and thus a more potent “high”). It has also edema have been associated with methamphetamine ingestion. attracted users of “crack” (smokable cocaine), due to the longer ”° The central effects of methamphetamine apparently result9 from its duration of the “high” or “rush”. In fact, users of crack cocaine structural similarity to the catecholamine neurotransmitters that are report being unable to distinguish the clinical effects of crystal active in the CNS (e.g., epinephrine, norepinephrine, and dopam methamphetamine (ice) from that of 4crack. In Hawaii, where 4me). Behaviorally, users of methamphetamine report increased crackdowns on marijuana production and sale have recently taken energy, perception, self-confidence, and sexuality, as well as a place, part of the boom in crystal methamphetamine use may be due sense of euphoria. However, they also commonly experience to lesser availability of marijuana and other drugs. irritability,7impulsivity, impaired judgement, and insomnia, as well as such non-behavioral CNS effects as nausea, dizziness and anor Epidemiology exia. Psychotic behaviors such as hallucinations and paranoia are The routes of administration of methamphetamine include oral, other potentially dangerous manifestations of acute toxicity, and intravenous, and by inhalation of its smoke. According to a study can lead to irrational, suspicious, and often violent behavior, which done in three American cities in 1994, the total number of users may persist for days or even weeks. The risk of homicidal or employing is 2 each of the three modes of use was nearly equal (i.e.,one- suicidal attempts significant in such patients. These patients third each). Of note, however, was that the percentage of metham pose a special challenge to care providers1in the emergency setting, phetamine users in the Honolulu group who preferred the smokable as the psychosis is often clinically indistinguishable from paranoid form was 92% (versus 10% for San Diego and 8% for San Fran schizophrenia. One characteristic feature of these psychotic epi 5cisco). This suggests an altogether different epidemic in Hawaii sodes is that, like drug-induced psychoses in general, they fre compared to the Mainland. quently involve vivid visual or tactile hallucinations. The reasons for this difference are unclear, but there are some other interesting differences between the usage patterns in Hawaii Chronic Effects 8 versus the Mainland: users in Honolulu were significantly younger, Chronic abuse of methamphetamine can lead to neuron loss less educated, much more likely to come from a family in which the secondary to microvascular damage, as well as to a depletion of parents used marijuana or cocaine, and more likely to have begun dopaminergic neurons, both of which may be permanent An using methamphetamine recently. Those in the Honolulu group example of a sequela that may be due to this effect on8 dopaminergic were also more prone to violence, assaults, shoplifting, money neurons, ostensibly on those in the substantia nigra, is the movement problems, and weight 5loss. disorders that are sometimes seen in patients using methamphet There were also differences in age and ethnic background, but it amine, as well as in those who have quit. is difficult to assess whether this is due to the different composition Another effect of chronic abuse of methamphetamine is the CNS of the Hawaiian population. In a study looking at ice users on Oahu, “kindling” phenomenon, also referred to as “reverse tolerance”. the using population was more likely to be young (59% under age Patients who have used amphetamines over a long period, espe 20, compared with only 30% in the population at large). Addition cially those who have had psychotic episodes from its use, may be ally, Filipinos, Hawaiians and part-Hawaiians were represented pushed into a frank psychosis by even very small amounts of an disproportionately (23% of users were Filipino versus 12.6%in the amphetamine (or indeed by any psychostimulant, including caf general population, while 35% were Hawaiian/Part-Hawaiian, who feine and 812nicotine). The mechanism for this kindling phenom HAWAIIMEDICALJOURNAL, VOL 56, FEBRUARY’ 1997 35 enon is uncertain, but it may involve alterations in dopaminergic Treatment sensitivity of the striatum.’ This is discussed further in the next The road to recovery in methamphetamine abuse, as with any section. psychoactive substance, is a long and treacherous one. Initial efforts Some investigators also point to the existence of a chronic focus on gathering information and treating acute symptoms, espe psychosis, termed “withdrawal” or “abstinence” psychosis, second cially psychosis and cravings, as well as acute medical conditions ary to long-term use of amphetamines. However, some believe that brought on by methamphetamine use. As the patient progresses these patients should be considered to have had latent schizophrenia through the various stages of recovery, increasing emphasis is that may have been brought out, rather than caused de novo, by placed on social and behavioral interventions. amphetamine 314use.’ The first 4 to 6 days after the patient’s most recent methamphet ’ amine use represent the detoxification period. This may be under Tolerance and gone as an inpatient if the patient is significantly toxic. Early in this Tolerance develops for some of the effects of methamphetamine, interval, it is essential that a full medical workup be performed, as especially those acting via the peripheral nervous system, as well as many of the acute effects of amphetamines are potentially lethal. for certain CNS effects (such as euphoria, anorexia, and hyperther Vital signs should be checked frequently, and blood pressure 7mia). However, the reverse is true for effects on judgement, controlled to prevent end-organ damage. Initially, an EKG should impulsivity, aggression, and susceptibility to paranoia, delusions, be obtained on all patients with signs of toxicity; such patients may and hallucinations. In other words, while it takes more and more also need to be placed on seizure precautions. drug to achieve a desired high, and while these users acquire a If the patient is acutely suicidal, homicidal, or floridly psychotic, decreased sensitivity to tachycardia and hypertension, they are he or she may require admission to a locked psychiatric ward. In actually more likely to exhibit pathological, often violent or self- patients with significant agitation or current psychotic features, destructive behavior even with no escalation in dose (or indeed with risperidone, 1 mg orally, or haloperidol, 1-2 mg intramuscularly, a decrease). This sensitization illustrates the effect of the kindling may be given every 12hours as needed. If drug craving is the major concept8 mentioned above. Further, since tolerance develops rela problem, as evidenced by hypothermia and subjective reports from tively rapidly, users often end up at doses 50 or 100 times greater the patient, low-dose amantadine or bromocriptine may be tried, than the dose they began with. Although they are physically better although these can bring out or aggravate psychotic features. able to handle these massive doses than would be a drug-naive Conversely, neuroleptics can induce increased drug craving. A less subject, psychologically they are actually less so. In fact, the relative effective, but often better-tolerated treatment for craving is to lack of significant physical effects may give some users a false sense replenish amino acids needed in the synthesis of neurotransmitters that they can “handle” the dose. depleted by chronic stimulant use; these are marketed as combina tion preparations such as Tropamine and Renew.’ Acute absti Addiction and Withdrawal nence-induced depression can sometimes be5aborted by any of the The degree to which methamphetamine is addictive depends tricyclic or seratonin-specific antidepressants, the latter being pre greatly on the type and route of administration. Methamphetamine ferred for their relative lack of cardiac effects. taken by a method that delivers a large bolus of active drug to the After the first week or so, the patient has largely recovered from brain all at once, such as the IV or smokable forms, gives a much the physiologic part of the addiction, and nonmedical interventions more intense, albeit shorter-acting, euphoria than does the ‘tradi become foremost in importance to combat the psychological addic tional’ oral form. Both of these pharmacodynamic differences tion, which is often much more problematic. These interventions contribute to the stronger potential for addiction of the rapid-acting may include daily twelve-step meetings, changing one’s life-style formulations: users of these forms get the most positive reinforce to eliminate contact with friends who use, and making specific goals ment for taking the drug, due to stronger associations between and commitments to maintain abstinence. By this stage, success is administering the drug and experiencing pleasurable feelings. Thus, largely in the hands of the patient, and many patients relapse and smoked methamphetamine (ice) is, as one would expect, much start the process over many times before achieving a sustained more addictive than oral methamphetamine, which is in turn twice recovery. as addictive as amphetamine. One would also expect smokable methamphetamine to be similar Conclusions in its addictive 2potential to smokable cocaine (crack), given that The Hawaiian epidemic of smokable crystal methamphetamine their euphoric effects are virtually indistinguishable. However, the represents a serious public health and public safety threat. It remains duration of euphoria with ice smoking is much longer than it is for to be seen whether this represents cultural and socioeconomic crack smoking (subjective half-life is about 5 hours for metham conditions unique to Hawaii, or whether this is merely the first phetamine, versus only about 50 minutes for cocaine). This differ outbreak of a national pandemic. Some signs point to the latter, ence would be expected to cause crystal methamphetamine8 to be including recent increases in use of smolable methamphetamine in less addictive than crack, but this remains to be proven in humans. West Coast 6cities.’ It will be extremely important to monitor usage Patients who are dependent on methamphetamine and then dis patterns in Hawaii and on the Mainland in order to help formulate continue use suddenly are prone to both psychological and physical effective public health and law enforcement policies. withdrawal. The psychological reaction can vary from vague feel ings of malaise to cravings to extreme agitation or depression. Later, References as 1. KatoM.Bdefhistoiyotcontrol,prevention,andtreatmentofdrugdependenceinJapan.DrugAlcohol more physical symptoms, such polyphagia and hypersomnolence Depend1990;25(2):2l3.4 commonly occur. Depressed mood and energy level may be pro 2 BeebeDK,WalleyE.Smokablemethamphetamine(‘ice’>:an olddrugina ditterentform.AmFam tracted for as long as 4-6 months in severely dependent patients. Physician1995;51(2>:449-53. Patients frequently return to using amphetamines partly as2a way of dealing with these withdrawal symptoms, even after their craving for the drug is gone. Continued on Page 44

HAWAIIMEDICALJOURNAL, VOL56, FEBRUARY1997 36 the top. I turned to discover he was covering both “Speaking for joke writers everywhere, I hope eyes. it’s Upjohn.” Methamphetamine Abuse: Quoted in Los Angeles Times Richard Klein, Toronto Stitches An Overview for September ‘96 A candidate came home late one night and gave Health Care Professionals Quotable Quotes his wife the glorious news. Continued from Page 36 “I feel that if I stop working I’ll get old. My “Darling, I’ve been elected!” father, Dr Sidney Kirby, used to say that when “Honestly?” she replied exuberantly. 3. GreberrnanSB,WadaK.Socialandlegalfactorsrelated he was still working in his 80’s. (Mid Pac CC “Hey,” he said, “why bring that up?” todug abuseintheUnitedStatesandJapan.PubHuh “Rub of the Green” member profile Claire Contributed by Cathryn Hopkins Rep 1994;109(6):731.7. 4. KaplanHI,SadockBJ,GrebbJA.Synopsisofpsychiatry. quote). (Sidney Kirby was medical Simpson di 7thed. Baltimore:Williams&Wilkins,1994:411.28. rector at Kalaupapa in the 1950’s and died in Overheard: “The trouble with getting to work 5. MorganP,BeckJE,Joe KA,McDonnell0, GutierrezR. 1981 when he was 96-years-old). on time is that it makes the day so long.” Ice and othermettramphetamineuse: an exploratory Edgar Argo in National Enquirer study.San Francisco:InsiftuteforScientificAnalysis, “When a man sits with a pretty girl for an hour, 1990. of methamphetamine “Youth is a wonderful thing. What a crime to 6. MillerMA.Trendsand patterns it seems like a minute. But let him sit on a hot smokingin Hawaif.MethamphetamineAbuse:Epide. stove for a minute—and it’s longer than any hour. waste it on children.” miologicIssues and Implications.NIDARes Monogr That’s relativity.” Albert Einstein George Bernard Shaw 1991;115:72.83. (Gleaned from the Medical Arts Press 7. Jaife JH. Amphetamine(or amphetaminelike)-related Newsletter Sept/Oct 96) Points to Ponder disorders.In:KaplanHI,SadockBJ,editors.Compre textbookof 6thed. Baltimore:Will Young writers often suppose that style is a hensive psychiatry. “If you want to recapture your youth, just cut iams&Wilkins,1995:791.8. off his allowance.” Al Bernstein garnish for the meat of prose, a sauce by which a 8. JaffeJH.Drugaddictionanddug abuse.In:GilmanAG, “Music washes away from the soul the dust of dull dish is made palatable. Style has no such RailTW,NiesAS,TaylorP. editors.Goodmanand everyday living.” Leopold Stokowski separate entity; it is nondetachable, unfilterable. Gilman’sThe PharmacologicalBasisofTherapeutcs. 8thed. NewYork:Pergamon,1990:539—45. is the one who has sense The beginner should approach style warily, real “The best executive 9. NestorTA,TamamotoWI,KamTH,SchultzT.Crystal enough to pick good men to do what he wants izing that it is himself he is approaching, no other; methamphetamine-inducedacutepulmonaryedema:a done, and self restraint enough to keep from and he should begin by turning resolutely away case report.HawaiiMedJ 1989;48:457-60. meddling with them while they do it.” from all devices that are popularly believed to 10. FurstSR.FallonSP, ReznikGN,ShahPK.Myocardial Theodore Roosevelt indicate style—all mannerisms, tricks, adorn infarctionafterinhalationofmethamphetamineILetterl. ments. The approach to style is by way of NEngJ Med1990;323:1147-8. 11. Szuster,RR.Methamphetamineinpsychiatricemergen “Which pharmaceuticals company will find a plainness, simplicity, orderliness, and sincer des. HawaiiMedJ 1990;49:389-91. sure cure for impotence?” asks comic Paul Ryan. ity. 12. SatoM,ChenC,AkiyamaK,OtsukiS.Acuteexacerba E.B. White “Elements of Style” tionofparanoidstateafterlong-termabstnenceinpa tientswlthpreviousmethamphetaminepsychosis.Biol Psychiatry1983;18(4):429-40. Sketches from Stitches 13. SlreltzerJ,LeighH.Amphetamineabstinencepsychosis What Can You Say? -does itexist?.PsychiafrOpirrion1977;JartFeb:47-50. Recently one of my well known middle aged 14. TomiyamaG.Chronicschizophrenia-likestatesinmeth female patients presented urgently to the office. amphetaminepsychosis. Jpn J PsychiatryNeurol “Ihaveaheadache,”shesaid,“butIdon’tknow 1990;44(3):531-9. 15. Inaba0, CohenW. Uppers,downers,all arounders. there to what it is because there isn’t much in Ashland,OR:CinemedInc,1990. hurt.” 16. CentersforDiseaesControl,USPublicHealthService. Marie Cescon MD, Woodville Ont. Increasingmorbidityandmortalityassociatedwithabuse ofmethamphetamine-UnitedStates,1991-1994.MMWR High Tech Exam 1995;44(47):882-6. John, yet in his 30’s was concerned about prostate cancer. His father was found to have the condition and he had spent hours in a urologist’s office reading pamphlets on prostate cancer and ALOHA its prevention. Hawaii Medical Journal “I’m sorry,” he said, “but could you tell me LABORATORIES,INC. what tests I need to check for prostate cancer.” “A blood test and a rectal exam,” I repeated. Extra copies of the Hawaii Medical tJ &tlinq E4 of Patot “OK, OK, But if I’m really at risk, I don’t want Journal September Special issue on CAPAccreditedLaboratory just any rectal exam. I want one of those new Domestic Violence and the Decem digital ones” SurgicalPathology ber Special issue on Death and Dy I.W. Tobson MD, WhiteRock; B.C. ing are available. For more informa Dermatopathology tion please contact the Hawaii Medi calAssociatioh at(808) 536-7702, or C):!& Fax us at (808) 528-2376. FrozenSections American Heart Associations.. IntraoperativeConsultations F.ghhing HoA Disease a,,d S,,eke

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2036 Hau Street Honolulu,Hi96819 Medicalmiracles (808) 842-6600 Fax: (808) 848-0663 start withresearch

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