New approaches to addiction treatment

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

We are analyzing data from a project we ran in collaboration with a small pharmaceutical company: a human laboratory study to test the safety and efficacy of a selective (sometimes called “biased”) mu agonist for prevention and relief of opioid withdrawal in people with OUD. This was initial proof of concept for what we hope will be an addition to the choices now available for opioid maintenance treatment of OUD. The niche for a biased agonist is that it could have the easy induction and no-ceiling effectiveness of methadone while also being comparatively free of side effects such as constipation, sedation, and respiratory suppression. When we completed the pilot phase, we decided not to continue to the main arm of the study, because the pharmaceutical company is currently unable to continue the development of the medication, meaning that we do not have an orally active form with a long enough duration of action for outpatient use. Because we are committed to studies with the most direct possible real-world relevance, we will not invest more resources in this medication at this point. However, our pilot data will provide initial evidence for the feasibility of the mechanism. Another major project is to develop Just-in-Time Adaptive Interventions (JITAIs) for treatment of substance-use disorders. This aspect of our treatment research is related to our work with real-time, field-based assessment (ZIA DA000499-16, Quantifying Exposure to Illicit Drugs & Psychosocial Stress in Real Time, or Real-Time Assessment of Drug Use, Mental States, and Environments That Confer Risk or Protection), the difference being that real-time assessment is not inherently therapeutic. For JITAIs, one major component is predictive analytics, so that momentary interventions can be "pushed" when and where the patient needs them. To that end, we are actively revamping and relaunching a project that included on-site assessment of physiological measures via wearable devices, followed by collection of field data in the same participants. The goal was to make accurate inferences about mental states such as stress, using data that could be collected passively and continuously. We had previously collected such data in collaboration with a small technology company, as described in a prior annual report. We were not satisfied with the accuracy of the stress inferencing, so we have decided to move to different wearable devices, with inferencing of mental states to be done in collaboration with a new third-party vendor. We intend to focus on a psychological state that is often cited as a risk factor for drug craving and lapse, but rarely made the focus of scientific attention: boredom. In other fields of psychological science (separate from addiction research), investigators have made considerable recent strides in the physiological characterization of boredom (it can be either a low-arousal or high-arousal state) and in the study of its triggers, its subtypes, its purposes, and its remedies. In our own prior EMA research on addiction, we have noted that boredom may be a unique risk factor for lapses to drug use, bypassing more commonly studied mental states such as stress or craving. Some types of boredom, such as leisure boredom, are especially promising as targets for the pushing of JITAI content, because they represent moments of maximal receptivity to what the JITAI might offer. We have also published treatment-relevant data from our set of projects on the legal drug kratom, such as a set of guidelines for assessment and treatment of kratom use disorder. As we shift our focus to cannabis, we have published a commentary on the need for better outcome measures in randomized trials of cannabis and cannabinoids for pain. During this reporting period, we completed two large nationwide surveys on two different aspects of treatment for opioid use disorder. One of the surveys was not just a survey, but a randomized experiment, evaluating how differing presentations of information could increase prospective patients’ willingness to try new forms of treatment. Both surveys have direct relevance for optimization of treatment and prevention of opioid overdose. To make the most efficient use of our resources, we have decided to postpone the relaunching of an on-site study of alcohol craving. Our on-site research, which is more staff and resource intensive than online research, will focus on the biosensor work described above, and on an opioid-related project described immediately below. Surprising though it may seem, assessment of opioid use in people entering a research study has not kept up with changes in the market for illicit opioids. The gold standard for quantification of recent use (and, crucially, changes in use during an experimental intervention or across any assessment period) is the timeline followback (TLFB) interview, which may be accompanied by drug testing in biospecimens, but which provides details that biospecimens cannot. Available TLFBs date largely from the era of heroin and diverted prescription opioids. We are starting a protocol to develop an opioid-specific TLFB that accounts for current market conditions, in which interviewees know only the street names, physical appearances, and effects of what they were sold—not the contents. Although this was always true to some degree for heroin, there has been a drastic increase in variability and uncertainty, and researchers are often stymied by even such basic questions as what units to use for amounts of opioid use. Our interview study, to be accompanied by comprehensive toxicological testing of interviewees’ urine for upwards of 1,200 drugs, drug metabolites, and contaminants/adulterants, will bring clinical research much more fully in step with the times, and will increase the power and sensitivity of future treatment studies for opioid addiction.