Methadone Pills, Diskettes or Death HA-7-12-07

Food and Drug Administration v. Center for Substance Abuse Treatment

Socrates now passes abruptly to claim for justice those rewards, in this life and after death.

                                                                                                                   Republic of Plato

1. The issue that this essay treats upon is that the rate of drug users who fatally overdose on methadone - a prescription that curbs heroin 

addiction and is also used in pain relief - is reported by a new Department of Justice study to be skyrocketing - methadone-related deaths 

rose nationwide from 786 in 1999 to 3,849 in 2004 - a 390 percent increase. By comparison, people who died from cocaine overdoses 

rose by 43 percent, from 3,822 to 5,461 over the five-year period, which reflects the latest statistics available.  Statistics on illicit drug 

overdoses are almost impossible to find. As a rule from the last century overdoses from all illicit drugs are around 3,000 per year in the 

United States and over 100,000 die from adverse drug reactions to prescription drugs.  About 20% of the estimated 810,000 heroin addicts 

in the United States receive methadone.  Every day some 115,000 Americans take the prescribed drug methadone, a synthetic opiate, used 

as maintenance treatment for heroin addiction.  Heroin is one of the hardest addictive drugs to "kick" for good it is reported to be almost as 

difficult to quit heroin as tobacco.  

2. Dolophine®Hydrochloride (Methadone Hydrochloride Tablets, USP) for oral administration, each contain 5mg or 10 mg of methadone 

hydrochloride.  Methadone hydochloride is a white, crystalline material that is water-soluble.  Methadone hydrochloride is a white, 

crystalline material that is water-soluble.  Methadone hydrochloride is chemically described as 6-(dimethulamino)-4,4-diphenyl-3-

hepatanone hydrochlorid.  Its molecular formula is C21H27NO-HCI and it has a molecular weight of 345.91. Methadone hydrochloride 

has a melting point of 235 C and a pKa of 8.25 in water at 20 C.  Its octanol/water partition coefficient at pH 7.4 is 117.  A solution 

(1:100) in water has a pH between 4.5 and 6.5.  

3. While methadone’s duration of analgesic action (typically 4 to 8 hours) in the setting of single-dose studies approximates that of 

morphine, methadone’s plasma elimination half-life is substantially longer than that of morphine, typically 8 to 59 hours vs. 1 to 5 

hours.  Methadone’s peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects.  

Complexities involved in methadone dosing can result in iatrogenic overdose.  A high degree of opiod tolerance does not eliminate 

the possibility of methadone overdose.  Serious overdosage on methadone is characterized by respiratory depression, a decrease in 

repiratory rate and/or volume, Cheynes-Stokes respiration, cyanosis, extreme somnolence progressing into stupor or coma, 

maximally constricted pupils, skeletal-muscle flexibility, cold and clammy skin, and sometimes bradycardia and hypotension.  

In severe overdosage, particularly in the intravenous route, apnea, circulatory collapse, caridiac arrest, and death may occurr.  

The risk of suffering serious or life threatening side-effects are greatest when first starting to take methadone.

4. For 30 years the Food and Drug Administration, the federal agency that monitors the production of food and drugs primarily for 

purity regulated methadone treatment.  The regulations focused on safety of the medication and preventing diversion. There was little 

attention to the nature of methadone as a drug treatment, the needs of the patients, or even the needs of the staff providing the treatment. 

Methadone was dispensed only in special clinics, under a thick load of regulations.  One year of methadone treatment costs an estimated 

$5,000, per patient. There are approximately 737 active methadone clinic programs in the U.S., according to the FDA.  Many states don't 

allow methadone clinics, forcing some patients to drive hundreds of miles each day to get their required daily dosage. Idaho, Mississippi, 

Montana, North Dakota, South Dakota, West Virginia, Vermont, and New Hampshire don't allow methadone clinics. Clinics in states that 

do allow methadone often have strict morning hours that make it difficult for patients to stick to the regimen.

5. Scientific information about the neurobiology of addictive behaviors provides an increasingly important rationale to support opioid

agonist pharmacotherapy, primarily methadone maintenance treatment, for long-term heroin addiction. The underlying hypothesis is

that heroin addiction is a disease. Both clinical research as well as laboratory-based research, using a variety of appropriate animal models

as well as in vitro techniques, has shown that drugs of abuse in general, and specifically the short-acting opiates, such as heroin, may

profoundly alter molecular and neuro-chemical indices, and thus physiologic functions. Also, research has shown that after chronic

exposure to a short-acting opiate, these alterations may be persistent, or even permanent, and may contribute directly to the

perpetuation of self- administration of opiates, and even the return to opiate use after achieving a drug-free and medication-free state.

6. There is no question that the sociological, economic, and psychological factors leading to inappropriate use of mood-altering drugs

are exceptionally important. However, recent evidence unequivocally establishes the existence of neurobiological determinants of both

initial and especially continuing drug use. The initiation of drug use is a voluntary, self-willed action.  Nonetheless, once this use

continues, depending on the specific drug, considerable change occurs in the brain that, unless understood and addressed, makes it quite

difficult, though obviously not impossible, to provide effective treatment. As noted by Gardner, with the exception of hallucinogens,

laboratory animals will voluntarily self-administer mood-altering substances commonly used inappropriately by humans. In addition,

with respect to such drugs as cocaine, animals will continue to administer these substances, often choosing them over food and water. 

There is therefore great potential for abuse, both by the user and by their supplier.

7. A practitioner of methadone treatment is certified now by the Center for Substance Abuse Treatment (CSAT), an agency of the 

Substance Abuse and Mental Health Services Administration (SAMHSA) which is part of the U.S. Department of Health and 

Human Services. CSATis also in charge of the national standards for drug treatment and a good complement. Clinics no longer 

simply need a license to operate. To get CSAT approval to stay in operation, they need to be accredited, like most other clinics 

and health-care facilities (i.e. hospitals). An accrediting agency will visit the clinic, see its procedures, talk to its staff and patients, 

give it "grades," and determine if it will be accredited. 

8. These conditions for take-home medication are: (1) no recent drug use, (2) attends clinics regularly, (3) no serious behavioral 

problems, (4) no criminal activity, (5) stable home environment and good social relationships, (6) length of time in treatment, (7)

assurance that take-home medication will be safely stored, and (8) judgment that the rehabilitative benefit to the patient will 

outweigh the risk of diversion under CRF42.8.12.i (2) (i-viii)). Programs do not to dispense liquid methadone under CRF 42.8.12.h 

(3) (I)) however for patients with 31 day take-home schedules a Program may request a special exemption under 66 FR 4085, 

January 17, 2001, for pills or diskettes.  The same federal requirement of eight random urine analyses per year remains 

CRF 42.8.12.f (6)). States often added their own regulations, which were stricter than the basic federal rules, and the clinics 

sometime set their own policies even more inflexible than the states required.  

9. There is obviously a serious problem in the regulation of the purity of methadone.  If the report of the Department of Justice 

is to be believed, federal and state regulated administrators of methadone are more dangerous than heroin dealers.  The cruel joke 

seems to be that fatal overdoses on heroin itself are something of a myth.  Acute overdoses on heroin are of course a common 

occurrence on the street.  Fatalities involving only heroin appear to form a minority of overdose occasions, the presence of other 

drugs (primarily central nervous system depressants such as alcohol and benzodiazepines) being commonly detected at autopsy.  

On the other hand it is well documented that heroin users are at substantially greater risk of premature mortality than their non-

heroin-using peers. Excess mortality rates among heroin users in these studies have been variously estimated to be between six 

and 20 times those expected among peers of the same age and gender. The causes of this excess mortality are manifold, including 

HIV/AIDS, the hepatitises and violence. Despite the HIV pandemic among injecting drug users, deaths attributed to overdose 

remain a major cause of mortality for heroin users, and in many countries is the leading cause of death amongst users.  

10. It is definitely a good idea to quit heroin.  Methadone is however far from safe.  A 390 percent increase in mortality, from 

786 in 1999 to 3,849 in 2004 is not something to ignore, even if it is reported anonymously by the Associated Press in reference 

to an unpublished study by the Department of Justice.  Further public health research is needed on methadone.  RxList reports 

that sex related studies have not yet been conducted, nor have studies on old age been conducted, for a lack of consumers.  Not 

mentioning the danger of bio-terrorism, that is very likely to be the leading cause of death, political researchers during the safer 

period of the nineties suggested repeatedly that the regulation of methadone be lessened.  The FDA is of course the lead researcher 

in regards to drug purity, across the nation, there is however enormous room for misconduct on the part of SAMHSA and state 

regulators, not to mention the judiciaries these people are in so much trouble with, in regards to drug purity and the delivery of 

toxins causing adverse reactions with methadone.  In conclusion, the liquid mixture may be too risky of a vehicle for corruptible 

administrators and the tablet and the pills and diskettes should come into common use.

Bibliography

1. AP. Methadone Related Death  Skyrocket. December 5, 2007

2. Boundy, Donna, "Profile: Methadone Maintenance: The Invisible' Success Story, Moyers on Addiction, New York, NY: Public 

Broadcasting Service, 1998

3. Darke, Shane and Zador, Deborah, Fatal Heroin Overdose: A Review." Addiction. 1996; 91(12): pp. 1765-1772

4. Firshein, Janet, "The Politics of Methadone," Moyers on Addiction, New York, NY: Public Broadcasting Service, 1998

5. Medline Plus. Methadone

6. National Alliance of Methadone Advocates (NAMA)

7. Office of National Drug Policy Information Clearinghouse. Methadone

8. RxList Methadone. Dolophine (Methadone)

9. Stimmel, Barry MD; Kreek, Mary Jeene MD. Neurobiology of Addictive Behaviors and Its Relationship to Methadone

10. Maintenance. Mount Sinai Journal of Medicine. Vol. 67 Nos. 5 & 6. November 2000

11. American Association for the Treatment of Opioid Dependence

12. Center for Substance Abuse Treatment (CSAT) Division of Pharmacologic Therapies