Page 1030 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

962 SECTION | XIV Poisonous Plants

VetBooks.ir at the GABA receptors, and they can potentiate CNS and or as psilocin glucuronide in urine and to some extent
unchanged via the bile (Hasler et al., 2002).
respiratory depression. Careful monitoring of the animal’s
oxygenation status is vital until the animal is fully awake
and alert. Supplemental oxygen can be used if necessary. Mechanism of Action
General supportive measures of unconscious animals
include maintaining hydration with i.v. fluids, maintaining Psilocin is the pharmacologically active metabolite of psi-
the airway free of respiratory secretions, and frequent locybin. Because of its structural similarity to serotonin,
position changes to prevent decubitus skin ulcerations. In psilocin stimulates serotonin receptors in the CNS
humans, the use of atropine is contraindicated because of (McKenna et al., 1990). Psilocin has affinity for 5-HT 1A ,
the atropine-like clinical presentation in poisonings. 5-HT 2A , and 5-HT 2C receptors (Halberstadt et al., 2010).
Activation of 5-HT 2A receptors leads to increased cortical
activity via glutamatergic excitatory postsynaptic poten-
PSILOCIN AND PSILOCYBIN tials (Aghajanian and Marek, 1997). Activation of 5-HT 1A
receptors results in the inhibition of pyramidal cell activ-
Mushrooms that contain psilocybin are commonly
ity (Puig et al., 2005). In addition, psilocin may have
referred to as hallucinogenic or magic mushrooms.
peripheral effects that involve serotonergic receptors. In
Psilocybe, Panaeolus, Conocybe, and Gymnopilus are the
humans, psilocin’s psychoactive effects are similar to
four genera in North America that contain psilocybin
those produced by LSD, are observed within 20 30 min
(Smolinske, 1994). Many of these mushrooms are copro-
of ingestion, and include visual hallucinations, intensified
philic and grow in fields and animal pastures, particularly
hearing, and incoordination. Other autonomic-mediated
in the northwestern and southeastern United States. The
effects include increased heart rate, increased blood pres-
majority of mushrooms contain only psilocybin, but
sure, mydriasis, tremors, and increased temperature. The
some, such as Psilocybe cyanescens, contain both psilocy-
effects can last up to 8 h, but hallucinogenic activity
bin and psilocin. The concentrations of psilocybin and
rarely exceeds 1 h. Clinical signs in dogs include ataxia,
psilocin are influenced by growth conditions, geographic
vocalization, overt aggression, nystagmus, and increased
location, storage conditions, and species. Species com-
body temperature (Kirwan, 1990). In contrast to the CNS
monly found in the Pacific Northwest contain between
effects after exposure to isoxazoles, there is no subsequent
1.2 and 16.8 mg/kg psilocybin on a dry weight basis. If
coma. Sedation may be necessary until behavioral signs
psilocin is present, concentrations may reach up to
resolve.
9.6 mg/kg on a dry weight basis (Smolinske, 1994).
Psilocin and psilocybin are sensitive to heat. Some mush-
rooms in this group also contain other pharmacologically Toxicity
active substances, such as serotonin and tryptophan.
In many countries (e.g., the United States, Great Britain,
There is only one published report of hallucinogenic
and Germany), psilocybin and psilocin are classified as
mushroom ingestion in a dog (Kirwan, 1990).
controlled substances. In humans, oral exposure to
10 20 mg of psilocybin can cause mood changes and hal-
lucinations. Information regarding lethal doses in animals
Pharmacokinetics/Toxicokinetics
is not found in the literature.
Psilocybin is a prodrug and is rapidly dephosphorylated to
psilocin. Dephosphorylation can take place in a variety of Treatment
tissues, but high activity has been identified in kidney and
liver of rodents (Horita and Weber, 1961) and in plasma The management of hallucinogenic mushroom poisonings
of humans (Grieshaber et al.,2001). However, the general is primarily supportive, and in most cases treatment is not
assumption is that complete conversion of psilocybin to necessary. Gastric emptying procedures have not proven
psilocin occurs prior to absorption into the systemic circu- beneficial and are not recommended. The effect of acti-
lation (Laatsch, 1996). In humans, the absolute bioavail- vated charcoal in poisonings is not known, but activated
ability of psilocin liberated from orally administered charcoal administration can be considered. If severe neu-
psilocybin was estimated to be 52.7% 6 20% (Hasler rologic signs such as seizures occur, diazepam is consid-
et al., 1997). Absorption is rapid with maximum concen- ered the first-line medication. Diazepam can be given to
trations reached in 1 1.5 h. In plasma, psilocin is further effect to dogs and cats at 0.5 1.0 mg/kg i.v. in incre-
metabolized to 4-hydroxytryptophole (4HT) and 4- ments of 5 10 mg. If diazepam is unsuccessful, subse-
hydroxyindole-3-acetic acid (4HIAA). Psilocin crosses quent seizures can be controlled with phenobarbital at
the blood brain barrier and concentrates in brain tissue 6 mg/kg to effect. In addition, control of body tempera-
(Horita and Weber, 1961). Psilocin is excreted unchanged ture is an important factor in symptomatic care.