Page 435 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

402 SECTION | IV Drugs of Use and Abuse

VetBooks.ir activity and emotion/consciousness, sometimes producing approximately 1/10th as potent as LSD, at a concentration
of 0.02% dry matter (Halpern, 2004). Ingestion of
a cataleptic-type state (Branson, 2001). Affected indivi-
150 300 seeds causes clinical effects in humans (Frohne
duals become disconnected from their environment, and
there is an absence of response to nociceptive stimuli. and Pfa ¨nder, 2004; Halpern, 2004; Volmer, 2005). The
The synthetic drug phencyclidine is an example of a dis- seed coat is protective, thus seeds must be crushed, germi-
sociative agent. Ketamine, a familiar therapeutic drug to nated, or soaked in water for ingestion to be effective.
most veterinarians, is a dissociative anesthetic and popu- A word of caution to the adventurous: emetics are some-
lar as a “club drug.” times added to commercial morning glory seeds. Other
Several naturally occurring substances other than sources of LSA include seeds of the Hawaiian baby woo-
those mentioned above have been used to produce drose, Argyreia nervosa, at a concentration of 0.14% dry
hallucinogenic effects by various mechanisms. Certain matter, and endophyte-infected sleepy grass, Stipa
species of mushrooms in the genus Amanita, specifically robusta. S. robusta, is present in the southwestern United
A. muscaria and A. pantherina, are sometimes inten- States.
tionally ingested. These mushrooms contain ibotenic acid
and muscimol, which bind glutamate receptors. Various Toxicity
plants containing atropine and scopolamine, including
The effective dose of LSD for humans is between 0.05
Datura stramonium, Atropa belladonna, Mandragora
and 0.20 mg. Products sold currently usually contain
officinarum and Hyoscyamus niger, are routinely smoked
0.04 0.06 mg and are less likely to cause an adverse
or ingested as recreational drugs (Halpern, 2004). The
reaction than the pills sold in the 1960s, which could con-
drug dextromethorphan has been used recreationally for
tain up to 0.25 mg LSD. Increasing the dose produces
its dissociative effects.
both quantitative and qualitative differences in the
response (Nichols, 2004). Some cats given intraperitoneal
LSD and LSA (IP) injections of 2.5 μg LSD/kg body weight showed
mild clinical signs, and a dose of 50 μg/kg produced sig-
LSD is the most powerful known hallucinogen (Nichols,
nificant clinical signs in all cats tested (Jacobs et al.,
2004; O’Shea and Fagan, 2006). The D-isomer of LSD is
1977). The IV LD 50 for rats is 16 mg/kg (Volmer, 2005).
responsible for the molecule’s effect on the CNS. The
story of Albert Hoffman’s synthesis and subsequent expo- Toxicokinetics
sure to LSD is well documented elsewhere. LSD was
LSD is rapidly absorbed after ingestion in humans
marketed under the trade name Delysid and used in psy-
(Riordan et al., 2002; Volmer, 2005). Peak plasma con-
chotherapy and for experimental purposes. Though there
centrations occur within 6 h and LSD is approximately
are no currently accepted medical uses for this drug, it
80% protein bound. Metabolism occurs primarily in the
has shown some promise for use in the treatment of alco-
liver by hydroxylation and glucuronide conjugation to an
holism, drug addiction, and obsessive-compulsive disor-
inactive metabolite. A dose of LSD is 89% excreted in
der. After becoming a popular recreational drug, LSD use
the feces, and the elimination half-life is between 2 and
was banned by the US government in 1966, and it is cur-
5 h. Clinical effects can persist for 12 h (Nichols, 2004).
rently a Schedule I drug (Nichols, 2004; Volmer, 2005).
LSD is a colorless, odorless, and flavorless white pow-
Mechanism of Action
der that is usually dissolved in water and then applied to
other substances such as blotter paper, microdots, tiny Like many “recreational” hallucinogens, LSD acts primar-
tablets, gelatin squares (termed “window pane” or “win- ily as an antagonist at serotonin receptors (Volmer, 2005;
dow glass”), stamps, gummy bears and other candies, and O’Shea and Fagan, 2006). LSD is structurally similar to
sugar cubes (Rimsza and Moses, 2005; Volmer, 2005; serotonin. Actions at the 5-HT 2A receptor are believed to
O’Shea and Fagan, 2006; Anonymous, 2011). Street be responsible for the hallucinogenic effects, though the
names for LSD reflect these applications and include signaling pathways involved have not been completely
“acid,” as in “spiked with acid,” “blotter” or “blotter elucidated. The 5-HT 2A receptors are located in the pyra-
acid,” “cubes,” “dots” or “microdot,” “L,” “sugar” or midal cells of the prefrontal cortex, the reticular nucleus
“sugar cubes,” “trip,” or “wedding bells.” Use of LSD is of the thalamus, and possibly the locus coeruleus, where
declining in the United States (Banken, 2004; Nichols, they are involved in sensory processing. LSD and some
2004). Still, a survey found that 3% of US high-school other hallucinogens also have a strong affinity for the
seniors had used LSD over a period of 12 months 5-HT 1A , 5-HT 2C and other serotonin receptors, but the
(Latimer and Zur, 2011). significance of this is not understood (Nichols, 2004). LSD
The seeds of Ipomoea violacea, the morning glory, causes increased release of glutamate in the prefrontal
contain lysergic acid amide (LSA), which is cortex, has a high affinity for dopamine receptors D 1 and