Opioids 1: Opiates - College of American Pathologists

Chapter 17 

Opioids 1: Opiates 

Michael G. Bissell, MD, PhD, MPH 

Michael A. Peat, PhD 

Descriptive Chemistry 1,2 

Opioids are a diverse group of substances defined by 

having morphine-like pharmacological activity, either 

agonistic or antagonistic, in binding to one or more of 

the opioid receptors (m, k, and d), which are primarily 

located in the central nervous system (CNS) and gastrointestinal 

tract. 1 The opioids may be usefully classified 

into three categories* as follows: 

v Opiates are alkaloids either extracted from the 

resin of the opium poppy (Papaver somniferum) 

native to Asia Minor but now more widely cultivated 

(the natural opiates), or are simple chemical 

derivatives of these, (known as the semi-synthetic 

opiates). 

v Synthetic opioids are structurally distinct chemical 

agents synthesized to bind to opioid receptors. 

v Endogenous opioids are peptide opioid agonists 

produced naturally in the body including the enkephalins, 

b-endorphin, and the dynorphins. 

The opium poppy produces many different compounds, 

among which are a variety of alkaloids, including 

papaverine and noscapine, in addition to the natural 

opiates, morphine, codeine, and thebaine. Of these, 

morphine accounts for around 10% of the weight of 

dried opium and is responsible for most of the characteristic 

opiate psychotropic activity. 2 

Morphine 3,4 

Synonyms: morphia; (5a,6a)-7,8-Didehydro-4,5epoxy-17-methylmorphinan-3,6-diol 

monohydrate 

* Note that this chapter will cover compounds in the first of these 

categories (the opiates), while the second category (the synthetic 

opioids) will be dealt with in the next two chapters. The third category 

(the endorphins) is beyond the scope of this book, since these 

compounds are considered neurohormones rather than drugs and 

are therefore not included in the testing menus of clinical toxicology 

laboratories. 

140 

Trade names: DepoDur, Duramorph, MS Contin, etc 

Formula: C H NO 17 19 3 

Molecular mass = 285.3377 Daltons 

CAS-57-27-2 (anhydrous); 6008-81-0 (monohydrate) 

Structure: 

Codeine 

Synonyms: codeinum, methylmorphine, metilmorfina, 

morphine methyl ether; (5a,6a)-7,8-Didehydro-4,5epoxy-3-methoxy-17-methylmorphinan-6-olmonohydrate 



CAS-76-57-3 (anhydrous); 6059-47-8 (monohydrate) 

Structure:

Thebaine 

Synonyms: paramorphine; (5a)-6,7,8-Tetradehydro-4,5-epoxy-3-methoxy-17-methylmorphinan 



CAS-115-37-7 

Structure: 

The semi-synthetic opiates, including heroin, hydromorphone, 

hydrocodone, oxymorphone, and oxycodone, 

are simple chemical modifications of morphine 

or thebaine. 

Heroin 

Synonyms: acetomorphine, diacetylmorphine, diamorphine;(5a,6a)-7,8-Didehydro-4,5-epoxy-17-methylmorphinan-3,6-d 

diacetate (ester) 



CAS-561-27-3 

Structure: 

Hydromorphone 

Synonyms: dihydromorphinone, dimorphone; 4,5-epoxy-3-hydroxy-17-methylmorphinan-6-one 

Trade names: Dilaudid, Palladone 



CAS-466-99-9 

Structure: 

Opioids 1: Opiates | 17 

Hydrocodone 

Synonyms: dihydrocodeinone; 4,5-epoxy-3-methoxy- 

17-methylmorphinan-6-one 

Trade names: Vicodin, Panacet, etc 



CAS-125-29-1 

Structure: 

Oxymorphone 

Synonyms: 7,8-Dihydro-14-hydroxymorphinone; 

oximorphone; oxydimorphone; (5a)-4,5-epoxy-3,14dihydroxy-17-methylmorphinan-6-one 

Trade names: Numorphan, Opana 



CAS-76-41-5 

Structure: 

141

III A | The Toxicology Laboratory’s Test Menu: Abused Substances 

Oxycodone 

Synonyms: 7,8-Dihydro-14-hydroxycodeinone; dihydrone; 

oxycone; (5a)- 4,5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one 

Trade names: Oxycontin, Percocet, Percodan, etc 


Molecular mass = 315.3636 

CAS-76-42-6 

Structure: 

Origin 1,2,5 

Opium, the viscous fluid within the unripe capsule of 

the flowering head of the opium poppy, is the source 

of the naturally occurring opiates. Opium was originally 

administered by smoking—and still is in southeast 

Asian communities around the world. Tincture of 

opium and paregoric are traditional oral pharmaceutical 

preparations of opium. Morphine and codeine, the 

natural opiates in use as drugs today, are obtained, legally 

or illegally, in commercially purified oral or IV 

pharmaceutical preparations. This is also true of the 

semi-synthetic opiates, the morphine derivatives hydromorphone 

(Dilaudid) and hydrocodone (Vicodin, 

etc), and the thebaine derivatives oxycodone (Oxycontin, 

etc) and oxymorphone (Numorphan, Opana), all of 

which have legitimate places in the pharmacopeia. The 

exception among this class of drugs is heroin, which, 

although available legally for treatment of terminal 

cancer pain in other parts of the world (“Brompton 

cocktail”), is a Schedule I substance (ie, available only 

illicitly) in the US. 

Heroin is made by extracting morphine from opium 

and acetylating it at the two phenolic groups. Supplied 

in varying degrees of purity (2% to 6%) on the street 

as a white to brownish powder, heroin is nearly always 

“cut” with other substances as it works its way through 

the chain of distribution, being commonly adulterated 

with other depressant drugs like benzodiazepines or 

other opioids, 2 diluted with neutral powders like sugar, 

and sold in packets containing 3 to 16 mg heroin each. 

The chemical form of the heroin itself depends to some 

142 

extent on where the opium was originally harvested 

and processed, the two main opium-growing regions 

being in central Asia (Afghanistan, Pakistan, Iran), 

known as the “Golden Crescent,” and in southeast Asia 

(Laos, Myanmar, Thailand), known as the “Golden Triangle.” 

Heroin from the former region is most typically 

supplied as the hydrochloride salt, which is soluble in 

cold water, whereas that from the latter region may be 

in the form of the free base, which must be heated in 

an acidic solution before injection. Known by a number 

of slang synonyms such as “H,” “smack,” “junk,” “horse,” 

and “skag,” heroin is among the most widely abused 

opioids because of its combination of being lipophilic 

and water soluble, making it bioavailable and potent, 

facilitating rapid achievement of psychoactive concentrations 

in the brain. Although the powder can be administered 

by inhalation of the vapor (“skagging”), by 

nasal insufflation (“snorting”), or by smoking in “reefers,” 

it is most commonly injected intravenously or subcutaneously 

in doses of up to 200 mg per day. 

Pharmacology 

Type of Agent 1,6 

The opioids in general are classified as narcotic analgesics 

and CNS depressants, although they have a variety 

of therapeutic effects including analgesia, antitussive 

effects, and decreasing gastrointestinal motility, as well 

as side-effects on respiration. The term “narcotic” was 

derived from the Greek word for stupor and has been 

associated with strong opiate analgesics, but now has 

connotations that are more legal than pharmacological. 

In 1977, Martin and Sloan 6 proposed the existence of 

multiple opioid receptors, and this has been confirmed 

by numerous studies since then. Shortly after the existence 

of these receptors had been confirmed, three 

classes of endogenous opioid peptides were identified. 

They are encoded by different genes, are expressed in 

different neuronal pathways, and have different selectivities. 

There are three major classes of receptors in the 

central nervous system: m, k, and d receptors. There are 

a number of subtypes within each class. Receptor studies 

have revealed differing selectivity profiles for each 

class, and functional studies have also shown differing 

functional profiles. Most of the clinically used opioids 

are relatively selective for m receptors, but they will interact 

with other receptors at higher doses. This is especially 

true as doses are increased to overcome tolerance. 

Some drugs, particularly mixed agonists/antagonists, 

interact with more than one receptor class at usual doses. 

When morphine is given systemically, it produces

analgesia through supraspinal m1 receptors. Respiratory 

depression and inhibition of gastrointestinal motility 

are thought to be mediated through m2 receptors. 1 

Context of Human Use 1,2 

Opium has been used and abused for millennia, the 

first undisputed reference to the medicinal use of poppy 

juice being in the writings of Theophrastus in the 

third century bce. The word “opium” is derived from 

the Greek word for “juice.” Opium smoking in a pipe 

probably originated in seventeenth century China, and 

its abuse became extremely widespread, a problem exacerbated 

by the British opium trade and giving rise 

to the two nineteenth century Opium Wars. Similarly, 

in nineteenth century Europe and America, wide-scale 

availability of opium and opium derivative medicines, 

sold legally over-the-counter for a variety of ailments, 

led to major problems with addiction and ultimately 

to declaring opium an illicit substance. However, the 

problem of opioid abuse has remained ever since, in 

one form or another. 

There are more than 20 distinct alkaloids in opium. 

In 1806, Serturner isolated morphine from opium, 

naming it after Morpheus, the Greek god of dreams. 

During the nineteenth century, other alkaloids, for 

example codeine and papaverine, were isolated. This 

resulted in the use of the pure alkaloids and their derivatives, 

rather than opium. One of these derivatives 

was diacetylmorphine, originally marketed in 1898 as 

a cough medicine and called “Heroin” (from the Greek 

word “hero”)—actually felt at the time to be a less addictive 

alternative to opium. 

The need for effective analgesia grew steadily in 

medicine, while at the same time the abuse potential 

of morphine and derivatives was increasingly being 

recognized. These trends during the nineteenth and 

early twentieth century led to the search for potent 

analgesics free of this addictive potential. This resulted 

in the introduction of the synthetic compounds, such 

as meperidine and methadone, around the time of 

World War II. Unfortunately, the problem of opioid 

abuse has continued unabated, now also involving the 

abuse of these synthetic compounds, typically obtained 

by diversion from legitimate prescription use. Today, 

larger numbers of individuals than ever before are being 

treated for opioid abuse. The first compound with 

opioid antagonistic properties was nalorphine, which 

was first used in the 1950s to reverse the effects of morphine 

poisoning. Nalorphine use led to the introduction 

of purer antagonists, for example naloxone, and 

mixed agonists/antagonists, such as pentazocine and 

buprenorphine. 


Abuse Potential and Characteristics 1,7-9 

The high abuse potential of opioids is initially accountable 

in terms of the “high,” consisting of euphoria, followed 

by a pleasant warmth, relaxation, and happiness, 

without accompanying ataxia. Larger doses produce 

dream-like torpor and somnolence. Regular use leads 

to definite dependence that is dose and frequency related. 

Tolerance to the “high” develops rapidly, and dose 

escalation in quest of the lost euphoria follows, until a 

maximum is reached, often dictated by practical difficulties 

in obtaining increasing quantities of the drug. 

At this point, tolerance to the positive drug effects becomes 

permanent, and the motivation for further drugseeking 

shifts from positive to negative reinforcement, 

that is, the desire to avoid a withdrawal reaction becomes 

primary. Since all opioids share cross-tolerance, 

drug substitution (eg, over-the-counter opioids for 

heroin) frequently occurs at this point. 

Opioid withdrawal includes a range of nonfatal but 

notoriously unpleasant symptoms generally understandable 

in terms of a subjective reversal of CNS level 

of arousal from depression to hyperactivity. These may 

include initial tearing, runny nose, perspiration, sneezing, 

coughing, increased respiratory rate, inability to 

sleep, restlessness, and anxiety, followed by chills, goose 

bumps, hot flashes, abdominal pain, muscle twitching, 

flu-like aching of muscles and joints, tremors, sweating, 

and headaches. In severe cases, subjects may show fever, 

dehydration, elevated blood pressure, rapid heart rate, 

and extreme agitation. These symptoms are accompanied 

by progressive drug craving, and voluntary efforts 

at drug withdrawal frequently result in relapse. Such 

attempts, when abruptly undertaken without medical 

support, are known as “going cold turkey” (doubtlessly 

named for the characteristic piloerection, or “gooseflesh,” 

during withdrawal), which typically begins 6 

to 12 hours after ceasing heroin, peaking at 36 to 72 

hours, and persisting 5 to 10 days, followed by a period 

of chronic symptoms of malaise, fatigue, anxiety, 

emotional lability, and depression that may persist for 

months. It has been postulated that anti-opioid peptides 

may be produced by the brain, which accounts for 

the development of tolerance in the presence of high 

levels of exogenous opioids. 9 The actions of these antiopioids, 

unopposed by drug during abstinence, may account 

for the symptoms of withdrawal. 9 

Overdose and Toxicity 10-12 

Opiate intoxication and milder degrees of overdose 

are accompanied by characteristic pupillary constriction 

(“pinpoint pupils”), hypotension, bradycardia, hypothermia, 

decreased bowel sounds, slowed mentation 

143


Table 17-1. Toxic Dose 3,10 

Drug Estimated Minimum 

Lethal Dose (g) 

(including slurring of speech, confusion, loss of alertness, 

apathy, and depression), drooping eyelids, and loss 

of muscle tone, including difficulty maintaining the 

head erect (so-called “nodding off ”). There may also be 

a degree of dose-dependent motor stimulation, but seizures 

are rare (more common with synthetic opioids). 

More severe overdose leads to coma with respiratory 

depression, which may be accompanied by noncardiogenic 

pulmonary edema, and which can progress to 

sudden death by apnea or gastric aspiration. 

Adverse Effects and Complications13,14 Chronic IV heroin use is associated with all the risks of 

self-injection, including peripheral nerve trauma, pulmonary 

hypertension, and bloodborne infections when 

needle-sharing is practiced. 

Chronic opiate abuse more generally is associated 

with the following: 

Cardiovascular 

Opiates are associated with hypotension but do not exacerbate 

existing hypertension, although some patients 

may develop a blood pressure increase during withdrawal. 

Respiratory 

Since opiates have respiratory depression as a major 

side effect, these drugs should be used with care in patients 

with any degree of respiratory compromise. Heroin 

is sometimes smoked or vaporized, with resulting 

respiratory symptoms. 

Renal 

Rhabdomyolysis may be precipitated by intra-arterial 

opiates or prolonged unconsciousness during intoxication, 

and in turn may precipitate acute renal failure, as 

can hypotension associated with IV heroin overdose. 

144 

Fatal Plasma Concentrations 

(µg/mL) 

Morphine 120 – 200 mg 0.2 – 2.3 Yes 

Codeine 0.5 – 1.0 g 1.0 – 8.8 Yes 

Heroin Not reported 0.05 – 3.0 (as free morphine) N/A 

Hydromorphone Not reported 0.02 – 1.2 Yes 

Hydrocodone 100 mg 0.12 – 1.6 Yes 

Oxycodone Not reported 5.0 Yes 

Subject to Postmortem 

Redistribution 

Metabolic 

Diabetics’ self-monitoring of blood glucose and hypoglycemic 

dose adjustment may be disrupted by apathy 

and also by vomiting, a recognized side-effect of opiates. 

Opiate intoxication may be confused with a hypoglycemic 

episode by the patient or others. 

Immune 

There is some evidence that immunoregulatory effects 

of the endogenous opioids may be disrupted by administration 

of exogenous opiates. 

Reproductive 

Opiates are not considered to be teratogenic, and although 

various perinatal complications have been observed 

to be more frequent in heroin-addicted mothers, 

it is unclear whether these are attributable specifically 

to heroin exposure or to the generally poor health of 

such mothers. Characteristic opiate withdrawal reactions 

resembling those in adults may be seen for up to 

a week after birth in infants born after third-trimester 

opiate exposure. The opiates are expressed in breast 

milk, but the resulting levels are insignificant clinically. 

Cognitive and behavioral problems have been noted in 

preschool-aged children exposed in utero to opiates. 

The degree to which these symptoms can be attributed 

to drug exposure is unclear. 

Toxic Dose 

Known toxic dose and concentration range information 

is summarized in Table 17-1. 

Pharmacokinetics, Metabolism, 

and Excretion 

Pharmacokinetics 

Pharmacokinetic parameters (volume of distribution 

[Vd] and half-life [t½]) are summarized in Table 17-2. 

Drug abusers typically inject heroin or morphine

Table 17-2. Volume of Distribution (Vd) 

and Half-Life (t ½) 3,10 

Drug Vd (L/kg) Plasma t ½ (h) 

Morphine 2.0 – 5.0 1.3 – 6.7 

Codeine 2.5 – 3.5 1.2 – 4.0 

Heroin 25.0 2.0 – 6.0 

6.0 – 25.0 (6-MAM) 

Hydromorphone 2.0 – 4.0 2.5 – 9.0 

Hydrocodone 3.3 – 4.7 3.4 – 8.8 

Oxymorphone 2.0 – 4.0 4.0 – 12.0 

Oxycodone 1.8 – 3.7 2.0 – 6.0 

but take other opiates orally; however, sometimes tablets 

or time-release capsules can be crushed and heated 

into inhalable or injectable forms. Opiates are generally 

well absorbed whether taken orally or injected. Injected 

opiates result in effects within minutes, whereas after 

an oral dose, peak effects typically occur within 2 to 

3 hours; however, some slowing of absorption of oral 

opiates may occur due to drug effects on gastrointestinal 

tract receptors. Also, the dose form (extended release, 

etc) may affect the rate of absorption. 

Metabolism 1,10,15 

The opiates are generally metabolized in the liver by 

the cytochrome P450 systems and then conjugated. 

Since several of the opiates are 

metabolized into each other, 

the pattern of metabolite excretion 

requires interpretation 

as a whole to determine the 

parent drug or drugs involved 

in a given case of opiate exposure. 

The individual drugs are 

metabolized as follows 10 : 

Heroin is rapidly de-acetylated 

to 6-monoactetylmorphine 

(6-AM), which in turn 

is rapidly hydrolyzed to morphine. 

Heroin itself has little 

psychoactive potency and can 

be regarded as a pro-drug delivering 

6-AM and morphine 

to the brain. 

Morphine is principally excreted 

directly and as the gluc- 

Poppy 

seeds 

Parent drug and/or 

metabolite 

Figure 17-1. Principal opiate metabolic pathways. 

Figure courtesy of Dr. Tai Kwong. 


uronide but, in high dose or chronic abuse situations, 

may be converted to hydromorphone and normorphine 

to a minor degree. 

Codeine is principally demethylated by the cytochrome 

P450 2D6 (CYP2D6) to morphine and norcodeine, 

and to a minor degree converted to hydrocodone. 

All four compounds are excreted as both free 

drugs and conjugates. Metabolism of codeine is subject 

to significant genetic variation of CYP2D6 polymorphisms 

among poor and rapid metabolizers, the incidence 

of which varies between ethnic groups, with, for 

example, poor metabolizers representing an estimated 

7% of Caucasians but up to 50% of Chinese. 15 

Hydrocodone is principally metabolized to hydromorphone, 

norhydrocodone, and dihydrocodeine, and 

to a minor degree to 6-hydromorphol. 

Hydromorphone is principally excreted as the conjugate 

and minorly as 6-hydromorphol. 

Oxycodone is principally converted to noroxycodone, 

oxymorphone, and noroxymorphone, which are 

excreted free and as conjugates. Minor metabolites are 

free and conjugated a- and b-oxycodol, noroxycodol, 

and oxymorphol. 

Oxymorphone is principally excreted as the conjugate 

and to a lesser degree as free and conjugated 

6-oxymorphol. 

These relationships are summarized in Figure 17-1. 

Excretion 

The opiates and their metabolites are primarily excreted 

in the urine and feces, and glucuronated opi- 

Heroin 

6-AM Oxymorphone 

Oxycodone 

Morphine 

Hydromorphone 

Major 

pathway 

Codeine 

Hydrocodone 

Dihydrocodeine 

Minor 

pathway 

Manufacturing 

pathway 

145


Table 17-3. Opioid Metabolites and Types of Specimens in Which They Can Be Detected 

Drug Metabolites Present in * 

ates/metabolites are subject to enterohepatic recirculation. 

Plasma clearance of codeine is 10.0 to 15.0 mL/ 

min/kg, while that of morphine (and heroin) is 15.0 to 

20.0 mL/min/kg (dose-dependent). 

Analysis 1 

Specimen Types, Requirements, 

and Characteristics 1 

Specimen types, requirements, and characteristics are 

summarized in Table 17-3. 

Modes of Analysis 1 

The opiates are generally detected by immunoassay 

and/or chromatographic procedures, with confirmation 

by a mass spectrometric method. To some extent, 

the analysis of opioids is dependent on the specimen 

to be tested, the drug to be detected, and the circumstances 

surrounding the analysis. There are a number of 

commercial immunoassays available, including enzyme 

immunoassays, fluorescence immunoassays, and microparticle 

immunoassays. Some of these are available 

as point-of-collection tests as well. This latter group use 

morphine as the calibrator, and in addition to detecting 

morphine, they will cross-react to morphine-6-glucuronide, 

codeine, hydrocodone, hydromorphone, and 

146 

Blood Urine Hair Oral Fluids 

Morphine Morphine X X X X 

Morphine-6-glucuronide X X X ? 

Normorphine X X 

Hydromorphone X 

Codeine Codeine X X X X 

Norcodeine X X X X 

Morphine X X X X 

Morphine-6-glucuronide X X X 

Hydrocodone X 

Heroin Heroin X X X 

6-Monoacetylmorphine X X X X 

Morphine X X X X 

Morphine-6-glucuronide X X X ? 

* These are dependent upon dose, duration of use, analytical sensitivity, etc. 

other opioids of similar chemical structure. As with all 

point-of-collection tests, any positive result should be 

confirmed by mass spectrometry. 

Laboratory-based immunoassays are used to detect 

opioids in urine, blood (or plasma), oral fluid, 

and hair. Commercial kits are available for morphine 

and opioids related in chemical structure: methadone, 

propoxyphene, buprenorphine, oxycodone, and fentanyl. 

Enzyme immunoassays are used for urine, and 

enzyme-linked immunosorbent assays (ELISAs) are 

used for other specimens. Fluorescence and microparticle 

assays are recommended for urine testing only. 

Confirmation procedures are usually based on mass 

spectrometry and include gas chromatography/mass 

spectrometry (GC-MS), gas chromatography/tandem 

mass spectrometry (GC-MS/MS), and the corresponding 

liquid chromatography (LC) techniques, 

LC-MS and LC-MS/MS. 

There are also numerous reports of detection of opioids 

in hair and oral fluid. Table 17-3 lists some of the 

major metabolites of the most commonly used opioids 

and the specimens in which they can be detected. For 

some, data may not be available for their detection in 

hair or oral fluid; however, it would be expected that 

they would be found in these specimens. Examples 

would be meperidine and its metabolite, normeperi-

dine; as weak bases, they should both be found in these 

specimens. Another factor to consider is the dose of 

the opioid. Detection in hair is dependent on the dose, 

and a single dose may lead to insufficient drug being 

deposited in the hair shaft for detection. 

Known Analytical Issues and Problems 1 

There are a large number of opioids that will not crossreact 

with any of these kits and will therefore require 

the use of chromatographic procedures. Because the 

concentrations are often low, mass spectrometry may 

be necessary for their detection. Examples include naltrexone, 

meperidine, pentazocine, alfentanil, and tramadol. 

Clinical Issues 

Clinical Interpretation 

of Analytical Findings 1 

As with a number of drugs, the interpretation of opioid 

concentrations in blood and other specimens should be 

approached with caution. There are a number of factors 

that need to be considered, including the development 

of tolerance, the pharmacodynamics in seriously ill and 

geriatric patients, and whether the patient is a fast or 

slow metabolizer (for example, methadone). In addition, 

one might expect postmortem distribution with a 

number of these drugs. 

Since the introduction of workplace drug testing, the 

interpretation of positive urine drug tests for morphine 

and codeine has caused concern for medical review officers 

(MROs). Testing for morphine and codeine is 

routine in these programs. Morphine is a metabolite 

of codeine and heroin, as well as being a constituent of 

poppy seeds. A morphine-positive result could result 

from the use of heroin, codeine, or morphine, or the 

ingestion of poppy seeds. Obviously if 6-monoacetylmorphine 

(6-AM) is detected with morphine, the donor 

has used heroin. Generally the confirmation cutoff 

used for both codeine and morphine is 2000 ng/mL 

(which reflects total codeine or total morphine), and 

10 ng/mL for 6-AM. Over the years, certain guidelines 

have been used for the interpretation of these results, 

as follows: 

After codeine use, the codeine concentration is 

greater than that of morphine. If the program uses a 

300-ng/mL cutoff, then late in the urinary excretion 

curve the morphine concentration may exceed that of 

codeine. 

After poppy seed ingestion, there is normally very 

small amounts of codeine present, which often does 

not exceed the cutoff and would not be reported to the 


MRO. There are a number of reports of urine morphine 

concentrations in the 100s of ng/mL after the 

ingestion of poppy seeds, and some where concentrations 

of 1000s of ng/mL were reported after repeated 

ingestion. In ethnic communities that cook with poppy 

seed paste, there are reports of much higher urine morphine 

concentrations. 

In regulated drug testing programs, the MRO and 

the laboratory use the following procedure: 

6-AM is screened for against a 10-ng/mL cutoff. In 

6-AM confirmed positives: 

v If the morphine is at or above 2000 ng/mL, proceed 

with MRO review. 

v If the morphine is less than 2000 ng/mL, the 

MRO must first confer with the laboratory to 

determine if morphine was confirmed below 

2000 ng/mL. 

v If morphine was not confirmed, the MRO and 

the laboratory must determine if further testing is 

necessary. 

v If the laboratory finds no detectable morphine at 

their assay’s limit of detection, they must report 

this to the program. 

Treatment and Rehabilitation 11,16 

Opiate overdose classically manifests as pinpoint pupils 

accompanied by respiratory and CNS depression 

and loss of consciousness from which patients awaken 

after naloxone injection. Needle track-marks and other 

signs of intravenous drug abuse may be evident. 

Specific drug concentrations are usually not utilized 

in the acute overdose situation, but qualitative urine 

screening may confirm recent opiate use, although 

synthetic opioids are often not detected by these tests. 

Laboratory tests that are of use include electrolytes, 

glucose, arterial blood gases or oximetry, chest x-ray, 

and, to cover for the possibility of combined ingestions, 

stat serum acetaminophen or salicylate levels. 

In the emergency situation, airway management 

and assisted ventilation may be necessary, along with 

supplemental oxygen. Noncardiogenic pulmonary 

edema and hypotension may require emergent treatment, 

as would seizures or coma. Activated charcoal, 

if instituted rapidly, need not be accompanied by gastric 

emptying, and attempting to enhance elimination 

is obviated by the opiates’ relatively large volumes of 

distribution and the availability of an effective antidote. 

Whole bowel irrigation may be appropriate for body 

packers and stuffers, and surgical removal may even be 

necessary in instances of intestinal perforation or obstruction 

in such cases. 

147


As an antidote, naloxone, an opioid antagonist without 

any agonist properties, may usually be given safely 

in doses up to 10 to 20 mg, but with the relatively short 

1- to 2-hour duration of naloxone effects, it is generally 

recommended that, after awakening, opiate coma patients 

should be held and/or admitted for observation 

for at least 6 to 12 hours. 17 Nalmefene is a newer opioid 

antagonist with a somewhat longer duration of effect. 

Complications of opiate overdose may include aspiration, 

rhabdomyolysis, anoxic brain injury, as well as 

adulterant and coingestant effects. 

References 

1. Peat MA. The Opiates [educational module]. Northfield, 

IL: College of American Pathologists; 2006. 

2. Wills S. Drugs of Abuse. 2nd ed. London, UK: Pharmaceutical 

Press; 2005:35-42. 

3. Moffat AC, Osselton MD, Widdop B, eds. Clarke’s 

Analysis of Drugs and Poisons. 3rd ed. London, UK: Pharmaceutical 

Press; 2004:845-847, 894-896, 1110-1111, 

1113-1114, 1302-1305, 1380-1382, 1383-1384. 

4. Wu AR. Personal communication, 2010 [on measured 

molecular masses]. 

5. Baselt RC. Disposition of Toxic Drugs and Chemicals in 

Man. 8th ed. Foster City, CA: Biomedical Publications; 

2008:730. 

6. Martin WR, Sloan JW. Neuropharmacology and neurochemistry 

of subjective effects, analgesia, tolerance and 

dependence produced by narcotic analgesics. In: Martin 

WR, ed. Handbook of Experimental Pharmacology. Vol 45/1, 

Drug Addiction I: Morphine Sedative/Hypnotic and Alcohol 

Dependence. Berlin: Springer-Verlag; 1977:43-158. 

148 


Press; 2005:38. 

8. Shults TF. Medical Review Officer Handbook. 9th ed. Research 

Triangle Park, NC: Quadrangle Research, LLC; 

2009;259. 

9. Rothman R B. A review of the role of anti-opioid peptides 

in morphine tolerance and dependence. Synapse. 

1992;12:129-138. 

10. Baselt RC. Disposition of Toxic Drugs and Chemicals in 

Man. 8th ed. Foster City, CA: Biomedical Publications; 

2008:355-360, 730-735, 745-747, 750-752, 1057-1061, 

1166-1172. 

11. Olson KR, ed. Poisoning and Drug Overdose. 4th ed. New 

York, NY: McGraw-Hill; 2004;286-291. 

12. Ling LJ, Clark RF, Erickson TB, Trestrail JH. Toxicology 

Secrets. Philadelphia, PA: Hanley and Belfus; 2001:105- 

108. 


Press; 2005:55-59. 

14. Friedman JM, Polifka JE. The Effects of Drugs on the Fetus 

and Nursing Infant. Baltimore, MD: Johns Hopkins 

University Press; 1996:176-179, 297-301, 417-421, 454- 

455. 

15. Stout PR. Opioids. In: Ropero-Miller JD, Goldberger 

BA, eds. Handbook of Workplace Drug Testing. 2nd ed. 

Washington DC: AACC Press; 2009:289-316. 

16. Linden CH, Rippe JM, Irwin RS. Manual of Overdoses 

and Poisonings. Philadelphia, PA: Lippincott, Williams 

and Wilkins; 2006:161-164. 

17. Goldfrank K, Weisman RS, Errick JK, et al. A dosing 

nomogram for continuous infusion intravenous naloxone. 

Ann Emerg Med. 1986;15:566-570.

Opioids 1: Opiates - College of American Pathologists

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