Researchers
from The University of Texas Medical Branch at Galveston
have confirmed that a prescription weight-loss pill decreases the urge to use
opiates such as oxycodone.
In a
study published in ACS Chemical Neuroscience, the researchers led by UTMB scientist
Kathryn Cunningham found that the drug, lorcaserin, reduced the use and craving
for the opioid oxycodone in preclinical studies. Cunningham is director of
UTMB’s Center for Addiction Research and a professor in the department of
Pharmacology and Toxicology.
Opiate
abuse is a major public health problem and according to the U.S. Centers for
Disease Control and Prevention, the number of deaths from prescription opiate
overdose in America has quadrupled since 1999. High relapse rates and too few
people remaining in treatment programs long enough for it to really benefit
them continues to pose major challenges in treatment for the misuse of
prescription opiates such as oxycodone and illegal opiates such as heroin.
Most of
the treatments available to reduce opiate misuse work by occupying opioid
receptors in the brain. If someone were to take an opiate while on these
treatments, they would not feel the signature euphoria as strongly. However, a
person’s drug-taking environment is a powerful cue that can condition someone
to anticipate the experience of taking of the drug; this is called cue
reactivity. People who have tried the currently available medications often
relapse when they are around the people, places or paraphernalia that they
associate with opiate use.
Lorcaserin,
prescribed for weight loss, alters the serotonin system by changing
chemical signals that affect satiety, the sensation of fullness. Serotonin
regulates the brain circuitry involved in drug reward and cue reactivity, Cunningham
particularly though activating serotonin 2C receptors. Previous work by and her
team have shown that lorcaserin decreases how many times rats will complete a
simple task to earn a dose of cocaine.
However, much less is known about the involvement of the serotonin 2C
receptors in altering how opiates feel rewarding for the user.
The
researchers trained rats to self-administer oxycodone while exposed to specific
lights and sounds that create a drug-taking environment. Once the rats were
used to regularly consuming oxycodone, they went through a period where no
oxycodone was available to them. The researchers then gave lorcaserin to some
of the rats while others were given a placebo and placed them in the
drug-associated environment. At this point, oxycodone was again made available
to the rats. The lorcaserin rats self-administered less oxycodone and reacted
less strongly to cues associated with taking the drug. In order to show that
this effect was attributed to the lorcaserin, a group of rats was given lorcaserin
as well as a drug that blocks the serotonin 2C receptors – thus cancelling out
the effect of the lorcaserin – those rats tried very hard to get oxycodone.
“The
effectiveness of lorcaserin in reducing oxycodone seeking and craving
highlights the therapeutic potential for lorcaserin in the treatment of opioid
use disorder,” said Cunningham. “We plan more studies to better understand how
drugs like lorcaserin can help us stem the tide of addiction in America.”
