DOCUMENT RESUME BD 099 723 CG 009 315 AUTHOR Gamage, James R.; Zerkin, E. Lief TITLE Methadone; The Drug and Its Therapeutic Uses In the Treatment of Addiction. Series 31, No. 1. INSTITUTION National Inst. on Drug Abuse (DHEV/PHS), Rockville, Md. National Clearinghouse for Drug Abuse Information.; Student Association for the Study of Hallucinogens, Biloit, Nis. REPORT NO DHEW-ADM-74-126; Ser-31-1 PUB DATE Jul 74 NOT? 22p. AVAILABLE FROM National Clearinghouse for Drug Abuse Information, P.O. Box 1908, Rockville, Maryland20850 EDPS PRICE MR-S0.75 HC-S1.50 PLUS POSTAGE DESCRIPTORS *Drug Abuse; *Drug Education; *Drug Therapy; *Government Publications; Health Personnel; *Information Dissemination; Research ABSTRACT This fact sheet from the National Clearinghousefor Drug Abuse Information discusses methadone, atherapeutic drug for the treatment of narcotic addiction. It reviews thepharmacology of the drug as well as physiological andpsychological effects, patterns of use, and adverse effects (toxicity andpoisoning). It examines the success rates of inpatient andambulatory detoxification programs, and, in addition, establishes many differingviewpoints on the success of methadonemaintenance. Generally, detoxification programs have not been overly promising, andmaintenance programs have varied in their success. The report presentsnegative opinions about the use of methadone, ranging from cautious criticism tototal opposition, iv addition to a bibliography. (Author/PC) SEI 2 41974 i 01100111011411OP NOALTO. 110OCAT II ~NW SIATOOOr flamingOP ISOUCATiON DEMO gee.% pp< mai sitsA5 SOS Outf 0 I soCtt RECIMIFO0600 11fade TM Nes., OROodAtogoi ow et POW leOE eflits paoPOatONS MIS *Wok "OfOOP** JULY 1974 SERIES 31, NO.1 staled* 00 41101 SOO Of SOW Of KIMSigtrsokah goucastiNii Knit KietOs PCS My The National Clearinghouse for Drug Abuse Information recognizes the need for clarifying some of the more complex issues in drug abuse oy gathering the significant research findings on each subject and developing fact sheets on the problem. These fact sheets. which are partof the Clearinghouse Report Series. present information about treatment modalities. the pharmacology and chemistry of the various drugs of abuse. and opinions and practicesof recognized authorities in the field. This' publication was researched and written by James R.Gamage and E. Lief Zerkin of the Student Association for the Study of Hallucinogens (STASH). Beloit. Wisconsin. under ContractNo. HSM-42-72-281. METHADONE. THE DRUG AND ITS THERAPEUTIC USES IN THE TREATMENT OF ADDICTION Methadone, chemically known as di-4,4-diphenyl-6-dimethylamino-3-heptanone hydrochloride, was first symnesized by the Germans during World War II. The drug was uncovered by an intelligence team of the U.S. Department of Commerce during the course of an investigation of the German pharmaceutical industry shortly after the war. Methadone has been referred to by a variety of other names. in- cluding dokohine, adanone, arnidone, physeptone, miadone, butalgin,diadone, polamidone, and 10820.In 1947, the Council on Drugs of the American Medical Association established "methadone" as the generic term for this compound. Early clinical trials established methadone as a potent analgesic which possessed many of the pharmacologic actions of morphine. In 1949, studies byIsbell and Vogel revealed that methadone had a marked addiction liability. They noted that the drug "In sufficient doses produces a type of euphoria which is even more pleasant to some c morphine addicts than is the euphoria produced by morphine.* Despite this early clinical evidence, however, notices in the American lay press soon heralded the discovery of methadone as a breakthrough inaddiction treatment. A story published on October 19, 1947, for example, claimed that methadone 'does not produce the euphoria, the feeling of exaltation which comes tothe addict from cocaine or other (sic) narcotics" and, further, that wit is thesafest narcotic drug yet produced. i . Fot turette:y, physielans were t1 1hto heed the warnings of Isbell and his colleagues, and the- widespread t.tef moth:alone in the indiyeriminate treatment of narcotic rddiction Wfifi avoided. as %ere thousands of potential medical addicts that might hove btt ereated clitiana prescribed the drug in the belief that it was a nettaddicting analgesic. Interest in the clinicat apptioations ot methadone did not develop rapidly.In 1952. Davis et al. reported their results in 2.O00 deliveries at Chicago's Lying-1n Hospital after airying doses of metiladore for t.sttra! analgesia. In doses which produced effective pain relief. however. methadone ft 'Mid to abnormally depress respi- ration in the newborn. 1 hi:; study :unirtoed earlier impressions of Lund (1948). ho abandoned methation in .tistetri aftera very short trial. Early interest also developed with ..eglitl to the drog's atititussive cough suppressing possibilities. lb:et:cr. tiVeilt4tilt' addletiMi itAliity of methadone eventually came to be regarded as far Ixe,s of that of code'in'e. the hater drug remained preferable in treating eota.41. h. relief of pain, in situations where subcutaneous or other injection routes aretOntrs !fidit*.itdPc4101:itilins 1)ecarno the analgesic of choice largely because it is rreal fftive in oval preparations than is morphine and other narcotics. At the present titer the approved use' of methadone are limited to analgesia in severe pain, ;eat detexification and maintenance treatment for narcotic addiction. Because of the initior,ce- of illicit use and terrine' of methadone in recent years. the .F(101.4. and Drug Administration has placed tighter restrictions on its use By far the greatest interest in teeth:alone, however. has centered around its use in the iamothrpy of nereetE: addition. In this regard. methadone is viewedas potentially a tii.e.1 beneficial tool for detoxification and long-term maintenance of individuals addicted to heroin and other opiates. The therapeutic potential of metha- (tale will 1w addreased in the second half of this review,following a short survey of the drug'' pharnsieology.physiological and psychological effects, patterns of use. 'dyers' effects and toxicity. Pharm924212gy_ "Ile! main phatar.acological properties of methadone are qualitatively similar to those ..f we:Thine. Methadone's most valuable action is its production of analgesia, or inser,sifivity to pain. As k the case with must other narcotics, analgesic activity is ic.,.01..panied by ailation.depression of respiration and central nervous system activity 1cl:ix:diem of smoeth muscle. When atIlltihi-tf.r.-.41 !larmtPrhily7.3 to 10 milligrams (mg.) of methadone produces (!eee of anale:sia equivalent to that seen after In tug. of morphine. Methadone, in quiatedgese doses, has less of a hypnotic action hum does morphine. but this diff..no Itignn.:4 1s:-: marked after chronic administration. Like morphine, metha- dem. produce.; hyperglycemia (high blood glucose concentrations). hypo- thermia (less than normal body temperature). and the release of antidiuretic hormone. MST COPY NOME Methadone is rapidly absorbed after oral or subcutaneous administration: signifi cant concentrations.of the drug can be found in frlasma within 10 minutes of injeetion. Like most other narcotic analgesies, methadone ctuiekly leaves the blood and localizes in the lung, liver. kidney. ar:d spleen. Only a small fraction of the administered dose passes the Moo& brain :carrier. thehighest levels of mnentration in the brain oec' r about 1 or 2 hours after administration. Methadone undergoes extensive biotransformation. chiefly in the liver: only 10 per- cent of the administered dose is recovered unchanged in the urine and feces. As early as 1950. Fisenhrandt and his colleagues established that methadone. readily crosses the placental barrier and enters into fetal circulation. In this regard. it has been 'mom or some time that infants of mothers who have been maintained on methadone duriier pregnancy may display narcotic withdrawal symptoms after birth. Tolerance. to the analge sic. nauseant. anoreetic, miatic, sedative, respiratory depressant and cardiovascular effects of methadone develops markedly. but at a slower pace than with morphine: however, tolerance to methadone's constipating actions does not readily develop. .Individuals tolerant to methadone will also be tolerant to the actions of other narcotic drugs (a phenomenon termed "cross- tolerance" ) .As such, a patient receiving a high dose of methadone (80 to 120 mg.) per day will typically have little or no subjective or physiological reaction to a shot of illicit heroin. considering the low percentage available on the street. Isbell and Vogel (1949) have established that physical dependence upon methadone can develop in individuals who receive the drug for as little as 56 days: verylittle evidence of an abstinence syndrome was observed in three trial subjects who had received methadone for only 28 dcys. The abstinence syndrome which developed following abrupt withdrawal of methadone was slower in onset. milder, but more pro- longed than abstinence from morphirc. In general. Jaffe (1965) has noted that the "character and severity of the withdr; wal symptoms that appear when a narcotic is discontinued depend upon many factors. including the particular drug. the total daily dose used. the interval between doses. the duration of use. and the health and person- ality of the addict ." The symptoms of methadone withdrawal generally take longer to appear (8 to 24 hours after the last dose) than those