Page 422 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

Toxicity of Drugs of Abuse Chapter | 22 389

VetBooks.ir distributed to the brain and other tissues. Within the brain, Clinical Signs
THC accumulates in the neocortical, limbic, sensory, and
Clinical signs of marijuana intoxication reported in dogs
motor areas. Distribution is blood flow dependent, and
peak accumulation in adipose tissue occurs in 4 or 5 days are similar to those in humans (Dumonceaux and Beasley,
are
Symptoms
1995).
Dumonceaux,
1990;
evident
in humans (Ashton, 2001). The plasma half-life of THC is
30 60 min after ingestion and attributable to the CNS
short because of the rapid tissue distribution.
effects: depression, ataxia, mydriasis, disorientation, behav-
THC is rapidly metabolized by the mixed-function
ioral disturbances, hyperesthesia, recumbence, tachycardia,
oxidase system of the liver (Burrows and Tyrl, 2001). The
hypotension, or less commonly, stupor, tremors, or seizures.
significant first-pass effect likely accounts for the lower
Urinary incontinence is reported in exposed dogs about half
blood concentrations associated with ingestion versus
the time. Ingestion exposures can also cause mild gastroin-
inhalation (Ashton, 2001; Janczyk et al., 2004). 11- testinal irritation and vomiting. Other symptoms that have
9
Hydroxy-Δ -THC is the physiologically active major
been reported include hypothermia, or less commonly,
metabolite of THC (Volmer, 2005). There are more than
hyperthermia as well as bradycardia, vocalization, and
20 other known metabolites (Ashton, 2001).
compulsive eating. Severe clinical signs described in a fer-
Between 65% and 90% of a dose of THC is excreted
ret included ataxia with rapid onset of coma, muscle twitch-
as the parent compound or conjugated metabolites
ing, hypotension, and hypothermia (Smith, 1988). A case of
through the feces, and there can be significant enterohepa-
atopic dermatitis was reported in a dog living in a home
tic cycling (Kisseberth and Trammel, 1990; Ashton, 2001;
where C. sativa had been cultivated (Evans, 1989).
Volmer, 2005). Ten to twenty-five percent of THC is
Synthetic cannabinoids can have a higher potency than
excreted as the parent compound, metabolites, and conju-
THC, and clinical signs of anxiety, hallucinations, seizures,
gates in the urine in humans, and renal excretion is psychosis, and tachycardia are reported in people and most
unlikely to be a major elimination pathway in dogs. recover within several hours (Rech et al., 2015). One case
report describes a dog and its owner. The dog presented
with anxiety and hyper responsiveness; the owner had a
Mechanism of Action tonic-clonic seizure while the dog was being examined,
which progressed until the owner was unresponsive. The
CB1 and CB2 are the cannabinoid receptors that have been
dog was placed in a low-stimulus environment and treated
identified in rats, guinea pigs, dogs, monkeys, pigs, and
with supportive care. Dog and owner recovered, though the
humans (Ashton, 2005). CB1 is widely distributed in cer-
dog remained agitated at the time of discharge.
tain areas of the brain: receptors in the cerebral cortex reg-
Onset of clinical signs in cattle began 20 h after
ulate cognitive function; receptors in the hippocampus and
ingesting dried plant material and included muscle tre-
amygdala are important in emotional status; cerebellar
mors, hypersalivation, and mydriasis. Animals were reluc-
receptors influence dopaminergic signaling, movement and
tant to move and lacked coordination. Four of the five
postural reflexes; and receptors in the basal ganglia, brain-
exposed animals died within 3 days; one recovered with
stem and autonomic nervous system (ANS) regulate pain
no treatment. These cattle were already debilitated at the
perception and cardiovascular and gastrointestinal function
time of exposure (Driemeier, 1997). Rapid onset of clini-
(Ashton, 2005; Di Marzo and De Petrocellis, 2006). CB1
cal signs was described in eight horses and seven mules
receptors are located within lipid membranes of presynap-
ingesting fresh plant material, including dyspnea, tremors,
tic neurons and coupled to G-proteins. They inhibit cAMP
hypothermia, hypersalivation, sweating, recumbence, and
and stimulate mitogen-activated protein kinases to modu-
death within 30 min (Cardassis, 1951).
late control of ion channels, particularly voltage-activated
calcium ion channels and potassium channels (Ashton,
2005; Di Marzo and De Petrocellis, 2006; Janczyk et al., Treatment
2004). The end result is inhibition of neurotransmitter The prognosis for full recovery in small animals exposed
release, both excitatory and inhibitory. CB1 receptors also to marijuana is usually excellent with proper treatment.
activate phospholipase C and PI-3-kinase. The endogenous Janczyk et al. (2004) describe 213 cases with 100% sur-
ligand for cannabinoid receptors, known as endocannabi- vival. Rate of recovery is dependent on dose and route of
noids, are derived from arachidonic acids and closely exposure. Most animals exposed to second-hand smoke
related to prostaglandins. CB2 receptors are absent in the recover within a few hours. Dogs who ingest a small dose
CNS but found in the peripheral nervous system (PNS) and of plant material usually recover within 24 h, but those
immune system where they play a part in inflammation ingesting large doses can have clinical signs for several
and pain regulation (Di Marzo and De Petrocellis, 2005; days (Kisseberth and Trammel, 1990; Dumonceaux,
Volmer, 2005). CB2 receptors regulate ceramide biosyn- 1995; Burrows and Tyrl, 2001; Volmer, 2005). More
thesis (Di Marzo and De Petrocellis, 2006). severe clinical effects have been recently reported and