The intoxication of pets with recreational or illicit drugs has been on the rise over the past decade, posing a growing concern. Exposure to these substances can occur accidentally, intentionally, or even maliciously.
Dogs, in particular, are more vulnerable due to their inquisitive nature and indiscriminate eating habits, making them susceptible to various forms of poisoning, including exposure to illicit drugs (Gupta, 2019).
The surge in illicit drug use among humans is a significant contributing factor to the increased incidence of pets being exposed to these substances. When pet owners have illicit drugs in their homes, their pets may inadvertently gain access to them.
According to the European Drug Report (2022) published by the European Monitoring Centre for Drug Addiction (EMCDDA), approximately 29% of adults in the European Union, aged 15 to 64, have used illicit drugs at some point, with substances like cocaine, MDMA, and amphetamines being among the most frequently consumed.
An example of the escalating exposure due to increased drug availability is the rise in cannabis-related calls to the American Animal Poison Control center, which increased from 0.84% to 1.53% of all toxicant calls between 2009 and 2014, especially in areas with less stringent cannabis legislation (Howard-Azzeh et al., 2021).
Furthermore, police dogs are at risk due to their frequent contact with large quantities of high-purity chemicals during training and search operations (Dumonceaux & Beasley, 1990; Kisseberth & Trammel, 1990). In cases of ingestion of entire drug packages, surgical or endoscopic removal is often necessary, with great care taken not to rupture the packaging.
Diagnosing drug intoxication in pets is challenging, primarily due to the illegal nature of illicit drugs. However, veterinarians are becoming more adept at recognizing these intoxications, as illicit drugs are gaining attention within the veterinary community. Pet owners, on the other hand, are often reluctant to admit to the use of illegal substances, leading to inaccurate or deceptive information about the exposure.
This results in a higher likelihood of veterinarians contacting poison control centers regarding opioid poisoning due to concerns about potential legal repercussions (Howard-Azzeh et al., 2020). Moreover, illicit drugs are frequently adulterated with other substances, making diagnosis even more complicated. Some of these adulterants, often found as impurities, can be more toxic to pets than to humans, such as caffeine and xylitol.
Private and public forensic laboratories have developed methods for detecting illicit drugs in the body fluids and tissues of humans. Some of these methods have also been validated for veterinary patients, but they are often expensive and time-consuming.
Over-the-counter urine test kits have been designed for human analysis. One study assessed the accuracy of these urine test kits for detecting drug intoxications in dogs, cross-referencing the results with gas chromatography/mass spectrophotometry. The kits correctly identified the presence of barbiturates, some opioids, benzodiazepines, and amphetamines/methamphetamine in the urine, although they did not detect phencyclidine or cocaine intoxication.
Nonetheless, over-the-counter urine test kits are both rapid and affordable. Table 1 provides information on false positives with urine test kits based on data for humans, as supplied by the American Society for the Prevention of Cruelty to Animals.
There is a limited number of published papers on pet intoxication with illicit drugs, primarily due to difficulties in diagnosis (leading to potential misdiagnosis) and ethical concerns surrounding animal toxicology studies. Most of the literature on toxicokinetics and toxicodynamics is from the 20th century.
To assist veterinary clinicians, we have gathered extensive data on the intoxication of dogs and cats with stimulating, hallucinogenic, and dissociative illicit drugs, including some case reports.
Methodology We primarily utilized electronic databases of published scientific literature for this review, including PubMed, Scopus, and Google Scholar. Additional relevant articles were identified through cross-referencing the initial literature. Our primary search terms included “illicit drugs,” “recreational drugs,” “toxicology,” “cats,” and “dogs,” yielding 403 search results.
We excluded papers not related to stimulating, hallucinogenic, or dissociative drugs, intoxication in dogs and cats, or the mechanisms of toxic actions, ultimately selecting 47 papers that met our inclusion criteria. We only considered papers published in English.
Amphetamines and Methamphetamine Amphetamines typically refer to a class of psychotropic drugs initially used in humans for treating attention deficit hyperactivity disorder (ADHD) and narcolepsy. Amphetamine, in particular, refers to α-methylphenethylamine (Heal et al., 2013). In contrast to amphetamines, which have clinical applications and specified usage, methamphetamine is a highly addictive psychostimulant and the second most frequently abused drug worldwide (Buchweitz et al., 2022).
The widespread availability of methamphetamine is due to its low cost, ease of synthesis, and strong addictive qualities. In some rare cases and regions, methamphetamine is still employed for the same clinical conditions as amphetamine (Pei & Zhang, 2014). Amphetamines are often abused for their stimulating, euphoric, anorectic, and empathogenic properties (Carvalho et al., 2012).
Between 2005 and 2014, methamphetamine accounted for 0.10% of all reported dog exposures and 0.07% of all cat exposures to the American Association of Poison Control Centers (Swirski et al., 2020).
Toxicity Given the increased use of amphetamines and methamphetamine, cases of accidental pet intoxication are becoming more common (Stern & Schell, 2018). The median lethal dose for oral consumption in dogs ranges from 9 to 27 mg/kg (Harris et al., 2022). For methamphetamine, the oral LD50 in dogs is 10 mg/kg (Buchweitz et al., 2022; Zalis et al., 1967).
However, the drug is now often sold at a much higher purity level compared to earlier forms, with purity levels as high as 40%, making the new forms significantly more toxic (Chomchai & Chomchai, 2015). While there is no official data on the incidence of methamphetamine intoxication in pets, individual cases of methamphetamine poisonings have been reported, including two cases with three patients each that resulted in successful outcomes and one death in both case reports (Buchweitz et al., 2022).
Toxicokinetics In humans, amphetamines exhibit high oral bioavailability, a high volume of distribution (approximately 4 L/kg), and a low affinity for binding to plasma proteins (below 20%). Their half-life ranges from 6 to 12 hours, with most of them being metabolized in the liver, and a high percentage is excreted unchanged (Carvalho et al., 2012; Kraemer & Maurer, 2002).
Peak concentration is typically reached 1 to 3 hours after ingestion (Bischoff, 2018). The oral bioavailability of methamphetamine in dogs is around 67%, and it distributes throughout most body tissues.
In one case report, the ratio of metabolites to the parent compound was considerably higher in dogs than the reported ratio in humans, possibly due to interspecies differences in cytochrome P450 enzymes, causing the drug to be metabolized more rapidly (Buchweitz et al., 2022).
Amphetamines can penetrate the blood-brain barrier, and methamphetamine tends to reach the highest concentration in the brain, more so than other related drugs (Bischoff, 2018).
Mechanism of Toxic Action Amphetamines exhibit affinity for both α- and β-adrenergic receptors, leading to the release of noradrenaline. This stimulation of adrenergic receptors results in the stimulation of the cerebral cortex, reticular activating system, and the medullar respiratory center.
Amphetamines also inhibit the reuptake and metabolism of catecholamines (Gupta, 2019). Both methamphetamine and amphetamines cause the release of dopamine in the central nervous system, display serotonergic and glutamatergic activity, and overall stimulate the sympathetic nervous system (Pei & Zhang, 2014).
Clinical Signs and Symptoms In humans, following oral ingestion, the effects typically begin within 30 minutes and can last for several hours (United Nations Office on Drugs & Crime, 2003). The clinical signs of amphetamine and methamphetamine intoxication closely resemble those of cocaine intoxication and are challenging to differentiate (Gupta, 2019).
Clinical signs of poisoning in both animals and humans may include hyperactivity, aggression, hyperthermia, tremors, ataxia, tachycardia, hypertension, mydriasis, circling, rhabdomyolysis, heart, kidney, and liver dysfunction, ischemia, seizures, head bobbing, and even death (Gupta, 2019; Pei & Zhang, 2014). Lesions observed in experimental dog models include subendocardial and epicardial hemorrhages, as well as myocardial necrosis (Bischoff, 2018).
Ecstasy (MDMA, 3,4-methylenedioxy-methamphetamine) MDMA, also known as Ecstasy or Molly, belongs to the amphetamine class of drugs. Because its properties are similar to those of amphetamines, we will focus on the differences here. MDMA, like methamphetamine, has psychedelic and hallucinogenic effects, making it a popular choice as a party drug.
Toxicity One of the major concerns with party drugs like MDMA is that they are often adulterated with substances such as cocaine, methamphetamine, ketamine, cathinones (commonly known as “bath salts”), and caffeine, which can exacerbate the clinical signs of intoxication.
Caffeine is particularly significant in veterinary medicine as dogs and cats are more sensitive to it than humans. Additionally, cathinones can induce aggression and epileptic seizures (Baumann et al., 2013).
Mechanism of Toxic Action MDMA has a more pronounced effect on the release of serotonin, while methamphetamine is a stronger releaser of dopamine and noradrenaline (Rothman et al., 2001). The increased release of serotonin is observed for up to 5 hours after intravenous injection (Nishisawa et al., 1999).
A study conducted by Kirkpatrick et al. in 2012 compared the behavioral and physiological effects of methamphetamine and MDMA on eleven adult volunteers. They found that methamphetamine improved cognitive and psychomotor performance, whereas MDMA had a negative impact on these functions.
Clinical Signs and Symptoms In pets, clinical signs typically appear within 30 minutes to 2 hours after ingestion (Hooser & Khan, 2012). MDMA can lead to a potentially life-threatening condition called serotonin syndrome.
Mild signs of serotonin syndrome include mydriasis, shivering, sweating, and mild tachycardia. Moderate serotonin syndrome is characterized by altered mental status (agitation, disorientation, excitement), autonomic hyperactivity (rigidity, tachycardia, hyperthermia), and neuromuscular abnormalities.
If left untreated, clinical signs progress to delirium, hypertension with tachycardia, life-threatening hyperthermia, and muscle rigidity (Mohammad-Zadeh et al., 2008). In dogs, MDMA has been shown to cause circling, depression, dilated pupils, hyperactivity, rapid breathing, and salivation (Frith et al., 1987). Table 2 outlines the clinical symptoms of serotonin syndrome based on the severity of the symptoms.