2020-500: Separation of the Analgesic and Addictive Consequences of Opiate Administration

SUMMARY:
UCLA researchers in the Department of Psychiatry have discovered a novel approach that decreases the additive response of patients to opiates, but maintains their potent pain relief property. 
 

BACKGROUND: 
Prescription opioids are commonly prescribed by medical doctors to treat symptoms of severe pain. Opioids function by binding and activating receptors throughout the central nervous system and other organs. Once the opioid binds to the receptors, they block pain signals from being sent to the brain and can release dopamine in the body. Although patients receive pain relief, the Center for Disease Control (CDC) and Prevention have issued a caution about their use in the medical field due to their addictive qualities, and the damage caused by these drugs in the ongoing opioid epidemic. The CDC estimates that 841,000 people have died from a drug overdose since 1999 in the United States, of those drug overdose deaths, over 70% of them were caused by opioids. Current efforts to combat the opioid epidemic with consideration for the medical value of opioids in the clinic are limited to educating healthcare providers with tools and guidance to enhance decision making when potentially prescribing opioids to patients. The guidance and resources offered to doctors is often ambiguous and unclear, leading to unfortunate consequences for patients in need of severe pain management. The addictive characteristics of opioids must be overcome to fully leverage their pain-relieving potential in a safe and effective manner.
 

INNOVATION: 
UCLA researchers led by  Dr. Jerome Siegel have shown that it is possible to provide patients with the potent pain relief provided by opiates, while reducing the risk of addiction through co-administration of another FDA approved molecule. Leveraging previous research from the same group that showed that human heroin addicted brains have cell morphology changes in their neurons that can remain for up to a three years after opioid drug treatment, the researchers have now made significant progress in identifying addiction-associated changes in neurons and how they can be prevented. The researchers identified that co-administration of this molecule, which is FDA approved and widely used in the clinic, with opioids completely prevents these physiological changes in neurons, without affecting the analgesic properties of opioid administration. This technology can serve to revolutionize how prescription opioids are administered to prevent addictive consequences. 
 

POTENTIAL APPLICATIONS:
•    Management of severe pain for individuals at risk of addiction
•    Combating opioid epidemic by reducing total volume of opioid drugs produced.
 

ADVANTAGES:
•    Reduced risk of addiction.
•    Maintains analgesic properties of opioids.
 

DEVELOPMENT-TO-DATE: 
Researchers have data that shows that the addiction-associated changes in specific neurons produced by morphine treatment of mice, is completely prevented through co-administration of an FDA approved drug.
 

Related Papers (from the inventors only):

McGregor, R., Ming-Fung, W., Holmes, B., Lam, H.A., Maidment, N. T., Gera, J., Yamanaka, A., Siegel, J. M. Hypocretin/Orexin Interactions with Norepinephrine Contribute to the Opiate Withdrawal Syndrome: The Journal of Neuroscience. 2022.

Thannickal,T.C., John, J., Shan, L., Swaab, D.F., Wu, M.F., Ramanathan, L., McGregor, R., Chew, K.T., Cornford, M., Yamanaka, A., Unutsuka, A., Fronczek, R., Lammers, G.J., Worley, P.F., Siegel, J.M.Opiates Increase the Number of Hypocretin-Producing Cells in Human and Mouse Brain and Reverse Cataplexy in a Mouse Model of Narcolepsy: Science Translational Medicine. 2018.
 

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Patent Information:
For More Information:
Thibault Renac
Business Development Officer
Thibault.Renac@tdg.ucla.edu
Inventors:
Jerome Siegel
Ronald McGregor
Frank Wu