Pregnancy Category C

Uses. LAAM has pain-relieving qualities, but its main medical use is for treatment of opiate/opioid addiction, typically switching addicts from illegal heroin to the legal substance LAAM.

Drawbacks. LAAM can produce heartbeat irregularity, and although this unwanted action has not been known to harm users, it is a factor in deciding between LAAM or methadone for drug addiction treatment. When used for addiction therapy LAAM is generally considered to produce no significant reduction in alertness, but persons new to the drug or who take high doses are told to be careful about engaging in dangerous activity such as driving a car. One study involving over 600 users found weariness to be a frequent undesired LAAM effect, also constipation, abdominal discomfort, anxiety, perspiration, and decreased male sexual ability. In one study scientists found that testosterone measurements in males declined to levels below normal when those persons used LAAM, but another study showed no change. In one study euphoria was an unusual effect, but another study typically found LAAM users to be "slightly euphoric" in comparison to methadone users. Researchers have noted aggressiveness in monkeys taking LAAM, but that effect is unconfirmed in humans. Rodent experiments measuring food intake have produced conflicting results showing increased, unchanged, and decreased appetite. One human study reported no appetite change in LAAM users.

Because oral LAAM's long-lasting effects are slow to start, some illicit users have taken more and more of the drug in order to feel expected effects and then died from a cumulative fatal overdose when LAAM's full actions finally kicked in.

Abuse factors. In drug abuse treatment programs, some addicts prefer

LAAM, and some prefer methadone. LAAM is related to methadone and is generally considered weaker, but some research has found LAAM stronger in certain ways. A dose of LAAM can last three times as long as one from methadone, making LAAM more convenient for addicts in a treatment program, as they can come less often to the clinic to receive LAAM than if they were receiving methadone. Convenience can influence an addict's decision on whether to continue with a program. Another LAAM advantage is that the long-lasting nature of a dose means that effects may be steadier over a given amount of time than those from methadone, allowing more consistent job performance by addicted employees. A case report mentions addicts who preferred LAAM over methadone because LAAM's steadiness reduced mood swings that occurred with methadone. One experiment, however, discovered that LAAM users are far more physically active on days when they receive the drug than on days when they don't—a finding that questions whether LAAM effects are as steady as commonly believed. Scientists know less about actions of LAAM than about those of methadone, so sometimes addicts with complicated medical conditions are given methadone instead of LAAM because methadone's influence on those conditions is better understood.

Experimentation with rhesus monkeys revealed that LAAM does not necessarily have uniform cross-tolerance with other opioids. Thus switching someone to LAAM from another opioid can be tricky; LAAM may closely match the other drug in some ways but not in others. For example, the same level of pain relief may be achieved by particular doses of LAAM or some other opioid, but those same doses will not necessarily affect breathing to the same extent.

LAAM is supposed to provide no drug high to persons on maintenance doses, but by definition a "maintenance" dose is only enough to hold off withdrawal symptoms and not enough to produce effects desired by drug misusers. So the lack of a high may be related to size of dose rather than to chemistry of the drug.

Dependence can develop.

Drug interactions. Because of oral LAAM's slow onset of effects, judging safe amounts to take with other depressants can be perilous. Alcohol is considered especially risky to use with LAAM. Phénobarbital is suspected of altering the effectiveness of an LAAM dose, and the same suspicion holds for the epilepsy drugs carbamazepine and phenytoin, the tuberculosis medicine rifampin, and the antacid-ulcer drug cimetidine.

Cancer. LAAM's potential for causing cancer is unknown. Data from laboratory tests are inconclusive. One two-year test of the drug on rats and mice produced no evidence of cancer, but another two-year test yielded some evidence of liver cancer in rats. A human LAAM study looking for chromosome mutations, which can lead to cancer, found none. Another human study found no evidence of tumor development.

Pregnancy. LAAM's impact on fetal development is unknown, but concern is high enough that women of childbearing age are supposed to have monthly pregnancy tests while on LAAM and to switch to methadone if pregnancy occurs. Upon examining results from chicken and rat experiments, however, some researchers suspect that more fetal damage may occur by stopping ex posure to LAAM than by continuing it, and there has been speculation about whether the same applies to humans. Abnormal breathing is seen in puppies that had lengthy fetal exposure to LAAM. Rat experiments have attributed no physical birth defects to LAAM, but some researchers suspect that fetal exposure to the drug affects offspring behavior. Animal experiments also indicate that even if LAAM causes no birth defects, risk of miscarriage may increase. If pregnant rats routinely receive LAAM, their offspring quickly show withdrawal symptoms upon birth (an event that stops exposure to the drug) even though the drug is long-lasting in adults and would not produce withdrawal symptoms in adults for quite some time after the last dose.

Additional information. Scientific literature often refers to LAAM as meth-adyl acetate, short for levo-alpha-acetylmethadol. "Methadyl acetate," however, is also the name of a Schedule I substance occasionally called acetylmethadol, and some scientific literature uses acetylmethadol as a synonym for LAAM. Even the CAS Registry Numbers of these substances get mixed up, with articles sometimes assigning CAS RN 509-74-0 to LAAM. Adding even more confusion, LAAM and the Schedule I substances acetylmetha-dol, alphacetylmethadol, and betacetylmethadol all have the same molecular formula (and Orlaam is similar but with the addition of hydrochloride). Persons using this book as a starting point for more research about LAAM should look carefully at other information sources to be sure which drug is being discussed.

Additional scientific information may be found in:

Finn, P., and K. Wilcock. "Levo-Alpha Acetyl Methadol (LAAM). Its Advantages and

Drawbacks." Journal of Substance Abuse Treatment 14 (1997): 559-64. Prendergast, M.L., et al. "Levo-Alpha-Acetylmethadol (LAAM): Clinical, Research, and Policy Issues of a New Pharmacotherapy for Opioid Addiction." Journal of Psychoactive Drugs 27 (1995): 239-47. Rawson, R.A., et al. "A 3-Year Progress Report on the Implementation of LAAM in the United States." Addiction 93 (1998): 533-40. Sorensen, J.L., W.A. Hargreaves, and J.A. Weinberg. "Heroin Addict Responses to Six Weeks of Detoxification with LAAM." Drug and Alcohol Dependence 9 (1982): 79-87.

Tennant, F.S., Jr., et al. "Clinical Experiences with 959 Opioid-Dependent Patients Treated with Levo-Alpha-Acetylmethadol (LAAM)." Journal of Substance Abuse Treatment 3 (1986): 195-202.

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