Exposures to illicit or abused drugs in pet animals can be
accidental, intentional, or malicious. Occasionally, drug-sniffing dogs also ingest
these substances. Because of the illegal nature of illicit or abused drugs, owners
may provide inaccurate, incomplete, or misleading exposure histories. Illicit drugs
are often adulterated with other pharmacologically active substances, making the
diagnosis even more difficult.
In suspected cases of exposure to illicit or abused drugs, an
attempt should be made to gather information about the animal's environment; amount
of exposure; and time of onset of clinical signs and their type, severity, and
duration. These questions will help include or exclude possible exposure to an
illicit or abused drug. Illicit and abused drugs are often known by street names
that vary from area to area. A call to a local police station, or animal or human
poison control center, may help identify the illicit substance if its street name is
known. Most human hospitals, emergency clinics, and some veterinary diagnostic
laboratories have illicit drug screens available and can check for the presence of
illicit drugs or their metabolites in different body fluids. The presence of a
parent drug or its metabolites in blood or urine may help confirm exposure in
suspect cases. The laboratories should be contacted for information on the types of
samples needed and time required to complete the screens or tests.
Commonly available over-the-counter drug test kits may help
exclude a suspected case of illicit drug toxicosis. They are designed to detect drug
metabolites in the urine and can detect most commonly available illicit or
recreational drugs such as amphetamines, cocaine, marijuana, opiates, and
barbiturates. The sensitivities and specificities of these test kits may vary. The
kits are inexpensive, efficient, and easy to use, but the instructions provided with
each kit should be followed carefully for best results.
Amphetamines and Related
Amphetamines and their derivatives are CNS and
cardiovascular system stimulants commonly used in people for suppression of
appetite, narcolepsy, attention deficit disorder, parkinsonism, and some
behavior disorders. Some commonly encountered amphetamines or related drugs are
methylphenidate, phentermine, diethylpropion,
and phenmetrazine. Amphetamines sold on
the street have common names such as speed, bennies, or uppers. Commonly used
adulterants are caffeine, ephedrine, or phenylpropanolamine.
Pharmacokinetics and Toxicity
Amphetamines are rapidly absorbed in the GI tract,
reaching peak plasma concentrations in 1–2 hr. Sustained-release
formulations have a delayed absorption and relatively longer half-life. The
plasma half-life of amphetamines depends on the urinary pH. With an alkaline
pH, the half-life is 15–30 hr; with an acidic pH, the half-life is 8–10 hr.
The acute oral LD50 of amphetamine in rats and mice
is 10–30 mg/kg. In people, deaths have been reported after ingestion of
methamphetamine at 1.3 mg/kg.
Amphetamine stimulates the release of norepinephrine,
affecting both α- and β-adrenergic receptor sites. Amphetamine also
stimulates catecholamine release centrally in the cerebral cortex, medullary
respiratory center, and reticular activating system. It increases the amount
of catecholamine at nerve endings by increasing release and inhibiting
reuptake and metabolism. The neurotransmitters affected in the CNS are
norepinephrine, dopamine, and serotonin.
Clinical Findings and Diagnosis
Clinical signs of amphetamine and cocaine toxicosis
are similar and difficult to differentiate clinically. The only difference
may be the longer duration of clinical signs of amphetamine toxicosis
because the half-life of amphetamine is longer than that of cocaine. The
most commonly reported signs are hyperactivity, aggression, hyperthermia,
tremors, ataxia, tachycardia, hypertension, mydriasis, circling, head
bobbing, and death.
Diagnosis is as for cocaine (see Clinical Findings and Diagnosis for cocaine) and relies mostly on owner knowledge of
exposure. Most amphetamines and related drugs or their metabolites are
detectable in the stomach contents and urine. They are difficult to detect
in plasma unless large amounts have been ingested.
Phenothiazines are preferred to control CNS signs in
amphetamine toxicosis (see Treatment of cocaine
toxicosis). Other anticonvulsants, such as diazepam, barbiturates, or
isoflurane, may be used if needed. Acidifying the urine with ammonium
chloride (25–50 mg/kg/day, PO, qid) or ascorbic acid (20–30 mg/kg, PO, SC,
IM, or IV) may enhance amphetamine elimination in the urine. However, this
should be done only if acid-base status can be monitored. Cyproheptadine
(1.1 mg/kg, PO or per rectum) may also be given once or twice (6–8 hr apart)
for serotonin syndrome (disorientation, muscle stiffness, agitation). Heart
rate and rhythm (see Treatment for using β
blockers to treat tachycardia), body temperature, and electrolytes should be
monitored and treated as needed.
Cocaine (benzoyl-methylecgonine) alkaloid is obtained from
the leaves of the coca plant, Erythroxylon coca and
monogymnum. Some common street names for cocaine are coke, gold
dust, stardust, snow, C, white girl, white lady, baseball, and speedball
(cocaine and heroin). Cocaine alkaloid from coca leaves is processed into
cocaine hydrochloride salt, then reprocessed to form cocaine alkaloid or free
base (a process called free-basing or base balling), which is colorless,
odorless, transparent, and more heat stable. Free-base cocaine is also called
crack, rock, or flake. Cocaine is cut (diluted) several times before it reaches
the user. Xanthine alkaloids, local anesthetics, and decongestants are some of
the most common adulterants.
Cocaine is a schedule II drug approved for human use. Its
medical uses are restricted to topical administration as a local anesthetic on
mucous membranes of the oral, laryngeal, and nasal cavities. However, it is
mostly used as a recreational drug.
Pharmacokinetics and Toxicity
Cocaine is absorbed from most routes. Orally, it is
better absorbed in an alkaline medium (ie, intestine). In people, ~20% of an
oral dose is absorbed. The reported plasma half-life is 0.9–2.8 hr. Cocaine
is extensively metabolized by liver and plasma cholinesterases to several
inactive metabolites that are primarily excreted in the urine. The acute
LD50 of cocaine hydrochloride administered IV in
dogs is 13 mg/kg; the LD100 is 12 mg/kg in dogs and
15 mg/kg in cats. The oral LD50 in dogs is believed
to be 2–4 times more than the IV dose.
Cocaine acts on the sympathetic division of the
autonomic nervous system. It blocks the reuptake of dopamine and
norepinephrine in the CNS, leading to feelings of euphoria, restlessness,
and increased motor activity. Cocaine can also decrease concentrations of
serotonin or its metabolites. Topical use of cocaine causes vasoconstriction
of small vessels. Hyperthermia in cocaine toxicosis may develop either due
to increased heat production from muscular activity or due to decreased heat
loss from vasoconstriction.
Clinical Findings and Diagnosis
CNS excitation, hyperactivity, shaking, ataxia,
panting, agitation, mydriasis, nervousness, seizures, tachycardia,
hypertension, acidosis, or hyperthermia characterize cocaine toxicosis. CNS
depression and coma may follow CNS excitation. Death may be due to
hyperthermia, cardiac arrest, or respiratory arrest. Some nonspecific
chemistry changes may include hyperglycemia and increased CK and
Diagnosis is based on a history of exposure and the
presence of characteristic clinical signs. Identification of cocaine in
plasma, stomach contents, or urine can confirm exposure. Differential
diagnoses include amphetamines, pseudoephedrine, ephedrine, caffeine,
chocolate, metaldehyde, strychnine, tremorgenic mycotoxins, lead, nicotine,
permethrin (cats) and other pesticides, and encephalitis.
The objectives of treatment are GI decontamination,
stabilization of CNS and cardiovascular effects, thermoregulation, and
supportive care. Animals with clinical signs should be stabilized first
before attempting decontamination. Emesis can be induced in a recent
exposure if the animal is asymptomatic and has the ability to guard its
airway via a gag reflex. This should be followed by administration of
activated charcoal with a cathartic. If the animal's condition
contraindicates induction of emesis (eg, presence of CNS signs or extreme
tachycardia), a gastric lavage with a cuffed endotracheal tube to reduce the
risk of aspiration should be performed. A dose of activated charcoal with a
cathartic should be left in the stomach after the lavage.
Controlling the CNS signs may require use of more than
one anticonvulsant. Clinical signs of CNS excitation can be controlled with
diazepam; however, the effects of diazepam are short-lived, and repeated
administration may be needed. Phenothiazine tranquilizers such as
acepromazine (0.05–1 mg/kg, IV, IM, or SC, repeated as needed) or
chlorpromazine (0.5–1 mg/kg, IV or IM) also usually work well to control the
CNS effects. However, phenothiazines should be used cautiously, because they
may lower the seizure threshold. If phenothiazines are ineffective,
phenobarbital at 3–4 mg/kg, IV, or pentobarbital, IV to effect, could be
used. If CNS signs are uncontrolled by the preceding measures, a gas
anesthetic such as isoflurane may be useful.
Blood pressure, heart rate and rhythm, ECG, and body
temperature should be monitored frequently and treated as needed.
Propranolol at 0.02–0.06 mg/kg, IV, tid-qid or other β-blocking agents such
as esmolol (0.2–0.5 mg/kg, slow IV over 1 min, or 25–200 mcg/kg/min as a
constant-rate infusion) can be used to control tachycardia. After CNS and
cardiovascular effects have been stabilized, IV fluids should be
administered, and electrolyte changes and acid-base status monitored and
corrected as needed. Treatment and monitoring should continue until all
clinical signs have resolved.
Ecstasy (MDMA or
Ecstasy is a semisynthetic psychoactive designer drug
(developed by street chemists with minor structural changes in parent compounds)
with hallucinogenic and amphetamine-like properties. Street names include Adam,
XTC, E, Roll, X, or Love Drug. A typical dose may be 75–150 mg. MDMA is believed
to cause excessive release of serotonin. It also binds to serotonin transporter
(a protein), which is responsible for removing serotonin from the synapse. The
overall effect is increased serotonin and serotonergic effects. MDMA also
affects dopamine and norepinephrine. Studies in rodents indicate that use of
MDMA can lead to permanent serotonergic neuronal injury.
In pets, MDMA toxicosis is not common. It is usually acute
and occurs from accidental ingestion (powder, pills, or capsules). Clinical
signs develop within 30 min to 2 hr after ingestion and may consist of
sympathomimetic effects (CNS excitation, agitation, hyperactivity, pacing,
hyperthermia, tachycardia, hypertension, seizures [just like amphetamines]),
sedation, or signs thought to be related to hallucination (vocalization,
disorientation, muscle rigidity). The half-life in people is 7.6–8.7 hr.
Treatment is similar to that for amphetamine toxicosis (see Treatment). For serotonergic effects (agitation, muscle rigidity,
nervousness), antiserotonergic drugs such as cyproheptadine can be tried (1.1
mg/kg, PO, repeated once in 6–8 hr).
Marijuana refers to a mixture of cut, dried, and ground
flowers, leaves, and stems of the leafy green hemp plant Cannabis sativa.
Several cannabinoids are present in the plant resin, but
delta-9-tetrahydrocannabinol (THC) is considered the most active and main
psychoactive agent. The concentration of THC in marijuana varies between 1%–8%.
Hashish is the resin extracted from
the top of the flowering plant and is higher in THC concentration than
marijuana. Street names for marijuana include pot, Mary Jane, hashish, weed,
grass, THC, ganja, bhang, and charas. Pure THC is available by prescription
under the generic name
dronabinol. A synthetic
cannabinoid, nabilone, is also available. Marijuana or hashish sold on the
streets may be contaminated with phencyclidine, LSD, or other drugs.
Marijuana is a schedule I controlled substance mostly used
by people as a recreational drug. It is also used as an antiemetic for
chemotherapy patients and to decrease intraocular pressure in glaucoma patients.
Some clinicians advocate the use of dronabinol as an appetite stimulant, but the
dysphoric effects of this drug outweigh any benefit of appetite
Synthetic marijuana is a designer drug in which different herbs or
incense or other leafy materials are sprayed with laboratory-synthesized
chemicals. The use of synthetic marijuana produces psychoactive effects similar
to those of THC. It is often claimed to be natural, safe, and legal. Spice, K-2
, Skunk, and Moon Rocks are some of the common street names. Clinical signs of
toxicosis from ingestion of synthetic marijuana in dogs can be more severe and
last longer than those of THC.
Pharmacokinetics and Toxicity
The most common route of exposure is oral. After
ingestion, THC goes through a substantial first-pass effect. It is
metabolized by liver microsomal hydroxylation and nonmicrosomal oxidation.
In dogs, clinical signs begin within 30–90 min and can last up to 72 hr. THC
is highly lipophilic and readily distributes to the brain and other fatty
tissues after absorption. The oral LD50 of pure THC
is 666 mg/kg in rats and 482 mg/kg in mice. However, clinical effects of
marijuana are seen at much lower doses than this.
THC is believed to act on a unique receptor in the
brain that is selective for cannabinoids and is responsible for the CNS
effects. Cannabinoids can enhance the formation of norepinephrine, dopamine,
and serotonin. They can also stimulate release of dopamine and enhance
γ-aminobutyric acid turnover.
Clinical Findings and Diagnosis
The most common signs of marijuana toxicosis are
depression, ataxia, bradycardia, hypothermia, vocalization, hypersalivation,
vomiting, diarrhea, urinary incontinence, seizures, and coma.
Diagnosis is based on a history of exposure and
typical clinical signs. THC is difficult to detect in body fluids because of
the low levels found in the plasma. Urine testing at human hospitals or
using an over-the-counter marijuana drug test kit in the early course of
exposure may help confirm the diagnosis. Marijuana toxicosis can be confused
with ethylene glycol (antifreeze, see Ethylene Glycol Toxicity) or ivermectin toxicosis; hypoglycemia; benzodiazepine, barbiturate, or
opioid overdose; intervertebral disc problems; or head trauma.
Treatment consists of supportive care. If the exposure
is recent and there are no contraindications, emesis should be induced and
activated charcoal administered. Comatose animals should be monitored for
aspiration pneumonia, given IV fluids, treated for hypothermia, and rotated
frequently to prevent dependent edema or decubital ulceration. Diazepam can
be given for sedation or to control seizures. Treatment and monitoring
should continue until all clinical signs have resolved (up to 72 hr in
dogs). For cases of synthetic marijuana toxicosis, in addition to the
preceding treatment options, use of IV lipid emulsion solution may be
The term opiate initially referred to all naturally
occurring alkaloids obtained from the sap of the opium poppy
somniferum). Opium sap contains morphine, codeine, and several
other alkaloids. Currently, opioid refers to all drugs, natural or synthetic,
that have morphine-like actions or actions mediated through opioid receptors.
Structurally, opioids can be divided into five classes. Some of the common
agents within each class are 1) phenanthrenes—morphine, heroin, hydromorphone, oxymorphone, hydrocodone, codeine, and oxycodone; 2)
diphenylheptanes—methadone and propoxyphene; 4)
phenylpiperidines—meperidine, diphenoxylate, fentanyl, loperamide, and
profadol; and 5)
of the widely used opioids in veterinary medicine include tramadol,
buprenorphine, fentanyl, loperamide (antidiarrheal), and hydromorphone. The use
of meperidine is not common anymore.
Opioids are used primarily for analgesia. In addition,
they are used as cough suppressants and to treat diarrhea. Occasionally, opioids
are used for sedation before surgery and as a supplement to anesthesia.
Pharmacokinetics and Toxicity
Opioids are generally well absorbed after oral,
rectal, or parenteral administration. Some more lipophilic opioids are also
absorbed through nasal, buccal, respiratory (heroin, fentanyl,
buprenorphine), or transdermal (fentanyl) routes. For some opioids, there is
variable reduction in bioavailability because of a first-pass effect when
given orally. Opioids generally undergo hepatic metabolism with some form of
conjugation, hydrolysis, oxidation, dealkylation, or glucuronidation.
Because cats are deficient in glucuronidase, the half-life of some opioids
in cats may be prolonged. After absorption, opioids are rapidly cleared from
blood and stored in kidney, liver, brain, lung, spleen, skeletal muscle, and
placental tissue. Most of the opioid metabolites are excreted through the
Toxicity of opioids in animals is highly variable. In
dogs, morphine administered at 100–200 mg/kg, SC or IV, is considered
lethal. The estimated lethal dose of codeine in human adults is 7–14 mg/kg;
in infants, 2.5 mg of hydrocodone has been lethal.
The effects of opioids are due to their interaction
with opiate receptors (μ, κ, δ, σ, and ε) found in the limbic system, spinal
cord, thalamus, hypothalamus, striatum, and midbrain. Opioids may be
agonists, mixed agonist-antagonists, or antagonists at these receptors.
Agonists bind and activate a receptor, whereas antagonists bind without
The primary effects of opioids are on the CNS,
respiratory, cardiovascular, and GI systems. Commonly reported clinical
signs of toxicosis include CNS depression, drowsiness, ataxia, vomiting,
seizures, miosis, coma, respiratory depression, hypotension,
constipation/defecation, and death. Some animals—especially cats, horses,
cattle, and swine—can show CNS excitation instead of CNS depression.
Diagnosis of opioid toxicosis is based on history of
exposure and the types of clinical signs (CNS and respiratory depression)
present. Plasma opioid levels are usually not clinically useful. Urine may
be used to determine exposure to opioids using some of the over-the-counter
illicit drug kits (manufacturer's instructions should be followed). Opioid
toxicosis should be differentiated from ethylene glycol, ivermectin,
benzodiazepine, barbiturate, and marijuana toxicosis, as well as
Clinical signs can be reversed with the opiate
antagonist naloxone. The dosages in different species are dog and cat,
0.04–0.16 mg/kg, IV, IM, or SC; rabbit and rodent, 0.01–0.1 mg/kg, SC or IP;
horse, 0.01–0.02 mg/kg, IV. Administration of naloxone should be repeated as
needed (hourly), because its duration of action may be shorter than that of
the opioid toxicity being treated. Animals should be closely monitored for
respiratory depression and ventilatory support provided if needed. Other
signs should be treated symptomatically. Dysphoric reactions (vocalization,
agitation, restlessness, and excitation) can be treated with diazepam or
other benzodiazepines. For serotonin-like syndrome (disorientation, muscle
rigidity, agitation) induced by some opioids, cyproheptadine (1.1 mg/kg, PO
or per rectum) once or twice (6–8 hr apart) can be tried.
Last full review/revision August 2014 by Safdar A. Khan, DVM, MS, PhD, DABVT