BIO 2020: Disruptive Thinking About Addiction Management

Addiction_Compressed

Novel treatments are desperately needed to treat substance abuse disorders (SAD), Kurt Rasmussen, director, division of therapeutics and medical consequences at the National Institute on Drug Abuse, said as he opened BIO 2020’s on-demand session, “Disruptive Thinking About Addiction Management.”

The session discussed three “out-of-the-box” innovations that apply to multiple types of addictions.

1. Mind Medicine has developed a non-hallucinogenic analog of the psychedelic drug ibogaine that targets opioid addiction and withdrawal without negative cardiac effects of the original compound. In proof of concept work, the drug appeared to confer a durable effect after a single dose. The drug, 18-MC, is in early trials. “We’re expecting the first patient clinical trials later this year in opioid abuse,” Stephen Hurst, co-founder, executive chairman and co-CEO, said.

“18-MC works by regulating dopamine in the reward/pleasure centers of the mid-brain,” he explained. Dopamine drives the cravings and changes associated with the neuroplasticity phenomenon in the brain, which drives the desire for the pleasurable substance a person has been using. Eventually, the dysregulation doesn’t reset itself and the patient needs help.”

The most common medical approaches to treating addition, in contrast, are substitution therapies, Hurst said, in which a substance with a low health liability is substituted for one with a greater liability. Replacing a nicotine patch for tobacco is an example.

“This mechanism is common to all kinds of addictive and repetitive behavior,” he continued. “We have data on opioids, nicotine, alcohol, stimulants such as cocaine and meth-amphetamine, and compulsive eating disorders.” In what Hurst calls the “fat rat model,” administration of 18-MC caused the rats to favor a normal diet rather than one high in sucrose or fat. This offers a new approach to eating disorders and other additions.

Mind Medicine’s other programs investigate psychedelic compounds that have anecdotal data regarding anti-addictive effects.

In addition to novel therapeutics exploiting new pathways, addiction counselors also need ways to identify drug-to drug interactions, especially as a growing segment of their patients with substance abuse disorders are elderly with co-morbidities.

2. The Human-on-a-Chip system developed by Hesperos, Inc. models an overdose in a multi-organ system, testing drug efficacy of drugs and off-target toxicity, and then recovery after naloxone is administered. “It also looks at the effects of repeated doses of naloxone and comorbidities, such as heart disease,” said James J. Hickman, chief scientist, Hesperos, Inc.

Hesperos creates pre-Bӧtzinger complex neurons and puts them in electrodes. “These are the neurons in the brain stem that control rhythmic breathing, and the main target that causes people to go into overdose,” Hickman explained. They establish a baseline and then simulate an overdose and a naloxone-generated recovery. “We can put in pain receptors and the addiction circuit from the brain. We can look at any neurons involved in the addition cycle, and can add drug-to-drug interactions.” The result, he said, is a predictive in silico model that can inform treatments for individuals

3. A smart phone-type app, dubbed HS, monitors SAD patients and helps them cope. David Gustafson, emeritus research professor, University of Wisconsin−Madison’s Center for Health Enhancement Systems Studies, said that with it, patients can:

  • Communicate anonymously with each other about their issues
  • Access mindfulness and relaxation programs
  • Improve and retain their motivation to stay clean and sober
  • Receive encouragement before they stray

“For alcoholics, we enter GPS data on the bars they frequented. If they are there for five minutes, they receive a recorded message they defined themselves. One patient had a recording saying ‘Daddy, please don’t do that. Come home,’” Gustafson said.

 The device also collects 10 different types of information.

The next step is to incorporate natural language and machine learning. So far, he’s learned that the more people swear (above their baseline), the more likely they are to relapse.

“It explains about 40% of the variants, so we look at the words the patients are using to help us determine what’s happening,” Gustafson explained.

Tests of 200 women in Appalachia found that the half using the HS system continued to receive almost double the number of services as those without the HS. The system currently serves more than 10,000 patients.

The face of substance abuse disease has changed dramatically, and is one of the reasons novel treatments are needed, said Anna Lembke, associate professor of psychiatry and behavioral sciences at Stanford University Medical Center. Rather than the 5:1 male/female ratio, it has shifted to 1:1, and SAD patients are, increasingly, elderly. Her practice also is seeing more low-level addictions (like video games or gambling) and people who want to gain repetitive control so they can, for example, drink in moderation.

With approximately 40 million Americans suffering from SAD, we have perhaps 8 drugs to treat them all,” Lembke said. Drugs that target a variety of pathways, therefore, are needed. “Anything to provide more objective data points is super helpful, along with something to track the harbingers of relapse.”

Innovators are well on their way. As Hurst predicted, “In 20 years, the methods used today to treat addition will be considered primitive. This will be the century of neurosciences.”

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