DRUGS OF ABUSE

TOXICOLOGY OF DRUGS OF ABUSE

Assessment of drug abuse is of medical interest for many reasons. In drug

overdose, it is essential to identify the responsible agent to ensure appropriate and
timely treatment. In a similar manner, identification of drug abuse in non-overdose
situations provides a rationale for the treatment of addiction. For these reasons,
testing for drugs of abuse is commonly performed. This typically involves screening a
single urine specimen for many substances by qualitative test procedures. In most
instances, this procedure only detects recent drug use; therefore, with abstinence of
relatively short duration, many abusing patients can avoid detection. In addition, a
positive drug screen cannot discriminate between single casual use and chronic
abuse. Identification of chronic abuse usually involves several positive test results in
conjunction with clinical evaluation. In a similar manner, a positive drug screen does
not determine the time frame or dose of the drug taken. Drug abuse or overdose can
occur with prescription, over- the counter, or illicit drugs. The focus of this discussion
is on substances with addictive potential. The use of drugs for recreational or
performance enhancement purposes is relatively common. The National Institute on
Drug Abuse (NIDA) reports that approximately 30% of the adult population (older than
high-school age) have used an illicit drug. Drug abuse testing has become
commonplace in professional, industrial, and athletic settings. The potential punitive
measures associated with this testing may involve or result in civil or criminal litigation.

Therefore, the laboratory must ensure that all results are accurate and all
procedures have been properly documented as these results may be used in court as
evidence. This requires the use of analytical methods that have been validated as
accurate and precise. It also requires scrupulous documentation of specimen security.
Protocols and procedures must be established to prevent and detect specimen
adulteration. Measurement of urinary temperature, pH, specific gravity, and creatinine
is commonly performed to ensure that specimens have not been diluted or treated
with substances that may interfere with testing. Specimen collection should be
monitored and a chain of custody established to guard against specimen exchange.

Amphetamines

Amphetamine and methamphetamine are therapeutic drugs used for narcolepsy and
attention deficit disorder. These drugs are stimulants with a high abuse potential as
they produce an initial sense of increased mental and physical capacity along with a
perception of well-being. These initial effects are followed by restlessness, irritability,
and possibly psychosis. Abatement of these late effects is often countered with
repeated use; drug tolerance and psychological dependence develop with chronic
use.
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Methylenedioxymethamphetamine

Methylenedioxymethamphetamine (MDMA) is an illicit amphetamine derivative

commonly referred to as “ecstasy.” 7,8 Although it was strongly associated with club
culture in the 1990s, its use has continued to grow. There are as many as 200
“designer” analogues that have been developed to produce effects comparable to
those of MDMA. MDMA and its analogues are primarily administered orally in tablets
of 50 to 150 mg. Other, less-frequent routes of administration are inhalation, injection,
or smoking. MDMA has a circulating half-life of approximately 8 to 9 hours. The
majority of the drug is eliminated by hepatic metabolism, although 20% is eliminated
unchanged in the urine.

Anabolic Steroids

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Anabolic steroids are a group of compounds that are chemically related to the male
sex hormone testosterone. These artificial substances were developed in the 1930s
as a therapy for male hypogonadism though it was soon discovered that the use of
these compounds in healthy subjects increases muscle mass. In many instances, this
results in an improvement in athletic performance. Recent studies have reported that
6.5% of adolescent boys and 1.9% of adolescent girls reported the use of steroids
without a prescription.

Cannabinoids

Cannabinoids are a group of psychoactive compounds found in marijuana. Of these,

THC is the most potent and abundant. Marijuana, or its processed product, hashish,
can be smoked or ingested. A sense of well-being and euphoria are the subjective
effect of exposure. It is also associated with an impairment of short term memory and
intellectual function. Effects of chronic use have not been well established though
tolerance, and a mild dependence may develop over time. THC overdose has not
been associated with any specific adverse effects. THC is a lipophilic substance,
which is rapidly removed from circulation by passive distribution into hydrophobic
compartments, such as the brain and fat. This results in slow elimination as a result of
redistribution back into circulation and subsequent hepatic metabolism.

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Cocaine

Cocaine is an effective local anesthetic with few adverse effects at therapeutic

concentrations. At higher circulating concentrations, it is a potent CNS stimulator that
elicits a sense of excitement and euphoria. Cocaine is an alkaloid salt that can be
administered directly (e.g., by insufflation or intravenous injection) or inhaled as a
vapor when smoked in the free base form known as crack. The half-life of circulating
cocaine is brief; approximately 30 minutes to 1 hour. Acute cocaine toxicity is
associated with hypertension, arrhythmia, seizure, and myocardial infarction.

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Opiates

Opiates are a class of substances capable of analgesia, sedation, and anesthesia. All
are derived from or chemically related to substances derived from the opium poppy.
The naturally occurring substances include opium, morphine, and codeine. Heroin,
hydromorphone (Dilaudid), and oxycodone (Percodan) are chemically modified forms
of the naturally occurring opiates. Meperidine (Demerol), methadone (Dolophine),
propoxyphene (Darvon), pentazocine (Talwin), and fentanyl (Sublimaze) are the
common synthetic opiates. Opiates have a high abuse potential, and chronic use
leads to tolerance with physical and psychological dependence. Acute overdose
presents with respiratory acidosis due to depression of respiratory centers,
myoglobinuria, and possibly an increase in serum indicators of cardiac damage (e.g.,
CKMB, troponin). High-level opiate overdose may lead to death caused by
cardiopulmonary failure.

Treatment of overdose includes the use of the antagonist naloxone

Phencyclidine

Phencyclidine (PCP) is an illicit drug with stimulant, depressant, anesthetic, and

hallucinogenic properties. Adverse effects are commonly noted at doses that produce
the desired subjective effects, such as agitation, hostility, and paranoia. Overdose is
generally associated with stupor and coma. PCP can be ingested or inhaled by

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smoking PCP-laced tobacco or marijuana. It is a lipophilic drug that rapidly distributes
into fat and brain tissue. Elimination is slow as a result of redistribution into circulation
and hepatic metabolism.

Approximately 10% to 15% of an administered dose is eliminated and unchanged in

urine, which allows for identification of the parent drug in urine. In chronic, heavy
users, PCP can be detected up to 30 days after abstinence. Immunoassay is used as
the screening procedure with GC–MS as the confirmatory method.

Sedatives–Hypnotics

Many therapeutic drugs can be classified as sedatives–hypnotics or

tranquilizers, and all members of this class are CNS depressants. They have a
wide range of approved therapeutic roles, but they also have high abuse
potential, ranging from high to low. These drugs often become available for
illegal use through diversion from approved sources. Barbiturates and
benzodiazepines are the most common types of sedative–hypnotics abused.
Although barbiturates have a higher abuse potential, benzodiazepines are
more commonly found in abuse and overdose situations. This appears to be a
result of availability. There are many individual drugs within the barbiturate and
benzodiazepine classification. Secobarbital, pentobarbital, and phenobarbital
are the more commonly abused barbiturates. Diazepam (Valium),
chlordiazepoxide (Librium), and lorazepam (Ativan) are the most commonly
abused benzodiazepines. Overdose with sedatives–hypnotics initially presents
with lethargy and slurred speech, which can rapidly progress to coma.
Respiratory depression is the most serious toxic effect of most of these agents
though hypotension can occur with barbiturates as well. The toxicity of many of
these agents is potentiated by ethanol use.