18-Month efficacy and safety analysis of monthly subcutaneous buprenorphine injection for opioid use disorder: Integrated analysis of phase 3 studies.

Background: Few studies investigate the natural history of patients on long-term treatment for opioid use disorder (OUD). We evaluated the long-term efficacy, safety, and tolerability experience of monthly extended-release buprenorphine (BUP-XR) in participants seeking treatment for OUD, via integrated analysis of phase 3 studies.

Methods: Study 1 was a 24-week randomized, double-blind, placebo-controlled trial of participants receiving monthly injections of BUP-XR (300 mg × 2, 100 mg × 4 [n = 203] or 300 mg × 6 [n = 201]) or placebo (n = 100).

Continued Posttrial Benefits of Buprenorphine Extended Release: RECOVER Study Findings.

Background: This analysis describes participants' opioid use disorder (OUD) outcomes for 18 months after discontinuing extended-release buprenorphine injection (BUP-XR, SUBLOCADE).

Methods: The RECOVER (Remission From Chronic Opioid Use: Studying Environmental and Socioeconomic Factors on Recovery) study recruited participants from BUP-XR clinical trials (NCT02357901, NCT025100142, and NCT02896296) to assess whether there were sustained benefits after leaving the trial. Abstinence from opioids and from all illicit substances (excluding medical cannabis), health-related quality of life, depression, and employment were measured after BUP-XR discontinuation and change in outcomes assessed at 6, 12, and 18 months.

Open-label, rapid initiation pilot study for extended-release buprenorphine subcutaneous injection.

For patients with opioid use disorder, buprenorphine extended-release injection (BUP-XR) achieves sustained therapeutic plasma concentrations, controls craving and withdrawal symptoms, and improves patient outcomes. Given retention challenges during transmucosal buprenorphine (BUP-TM) induction, assessing methods to quickly achieve sustained buprenorphine concentrations is important. This open-label, single-group, single-center pilot study (NCT03993392) evaluated safety and tolerability of initiating BUP-XR following a single BUP-TM 4 mg dose.

Assessment of craving in opioid use disorder: Psychometric evaluation and predictive validity of the opioid craving VAS.

Background: This work evaluated the psychometric properties of the single-item Opioid Craving Visual Analog Scale (OC-VAS) for opioid use disorder (OUD).

Methods: Psychometric evaluation of the OC-VAS (range: 0-100 mm) was supported by Subjective Opiate Withdrawal Scale (SOWS) item 16 and total score, Clinical Opiate Withdrawal Scale (COWS) scores, and the 36-Item Short-Form Health Survey, using data from phase 3 study (NCT02357901; N = 487) participants who received randomized treatment and completed the OC-VAS at screening. Descriptive properties, test-retest reliability, construct validity, known-groups validity, and responsiveness were assessed.

Cannabis-Induced Hypodopaminergic Anhedonia and Cognitive Decline in Humans: Embracing Putative Induction of Dopamine Homeostasis.

Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults.

In Search of Reward Deficiency Syndrome (RDS)-free Controls: The "Holy Grail" in Genetic Addiction Risk Testing.

Background: The search for an accurate, gene-based test to identify heritable risk factors for Reward Deficiency Syndrome (RDS) was conducted based on hundreds of published studies about the role of dopamine in addictive behaviors, including risk for drug dependence and compulsive/impulsive behavior disorders. The term RDS was first coined by Blum's group in 1995 to identify a group of behaviors with a common neurobiological mechanism associated with a polymorphic allelic propensity for hypodopaminergia.

Objectives: To outline the process used to select risk alleles of reward genes for the Genetic Addiction Risk Score (GARS) test.

Transmodulation of Dopaminergic Signaling to Mitigate Hypodopminergia and Pharmaceutical Opioid-Induced Hyperalgesia.

Neuroscientists and psychiatrists working in the areas of "pain and addiction" are asked in this perspective article to reconsider the current use of dopaminergic blockade (like chronic opioid agonist therapy), and instead to consider induction of dopamine homeostasis by putative pro-dopamine regulation. Pro-dopamine regulation could help pharmaceutical opioid analgesic agents to mitigate hypodopaminergia-induced hyperalgesia by inducing transmodulation of dopaminergic signaling. An optimistic view is that early predisposition to diagnosis based on genetic testing, (pharmacogenetic/pharmacogenomic monitoring), combined with appropriate urine drug screening, and treatment with pro-dopamine regulators, could conceivably reduce stress, craving, and relapse, enhance well-being and attenuate unwanted hyperalgesia.

Death by Opioids: Are there non-addictive scientific solutions?

In the face of the current Opioid crisis in America killing close to 800,000 people since 2004, we are proposing a novel approach to assist in at least attenuating these unwanted premature deaths. While we applaud the wonderful efforts of our governmental institutes and professional societies (NIDA, NIAAA, ASAM, ABAM ) in their extraordinary efforts in combating this continued dilemma, the current approach is failing, and other alternative approaches should at least be tested. These truths present a serious ethical dilemma to scientists, clinicians and counselors in the Reward Deficiency Syndrome (RDS) treatment community.

Hypodopaminergia and "Precision Behavioral Management" (PBM): It is a Generational Family Affair.

Background/aims: This case series presents the novel Genetic Addiction Risk Score (GARS®) coupled with a customized pro-dopamine regulator matched to polymorphic reward genes having a hypodopaminergic risk.

Methods: The proband is a female with a history of drug abuse and alcoholism. She experienced a car accident under the influence and voluntarily entered treatment.

The Individualized Treatment of Opioid Use Disorder.

No outside funding supported the writing of this commentary. Boyett is Chief Medical Officer and founder of the medical division of Pathway Healthcare, which provides treatment for opioid and other drug addictions.