The novel uncompetitive NMDA receptor antagonist esmethadone (REL-1017) has no meaningful abuse potential in recreational drug users.

Esmethadone (REL-1017) is the opioid-inactive dextro-isomer of methadone and a low-affinity, low-potency uncompetitive NMDA receptor antagonist. In a Phase 2, randomized, double-blind, placebo-controlled trial, esmethadone showed rapid, robust, and sustained antidepressant effects. Two studies were conducted to evaluate the abuse potential of esmethadone. Each study utilized a randomized, double-blind, active-, and placebo-controlled crossover design to assess esmethadone compared with oxycodone (Oxycodone Study) or ketamine (Ketamine Study) in healthy recreational drug users. Esmethadone 25 mg (proposed therapeutic daily dose), 75 mg (loading dose), and 150 mg (Maximum Tolerated Dose) were evaluated in each study. Positive controls were oral oxycodone 40 mg and intravenous ketamine 0.5 mg/kg infused over 40 min. The Ketamine study included oral dextromethorphan 300 mg as an exploratory comparator. The primary endpoint was maximum effect (Emax) for Drug Liking, assessed using a bipolar 100-point visual analog scale (VAS). A total of 47 and 51 participants completed the Oxycodone Study and the Ketamine Study, respectively (Completer Population). In both studies, esmethadone doses ranging from therapeutic (25 mg) to 6 times therapeutic (150 mg) had a meaningful and statistically significantly (p < 0.001) lower Drug Liking VAS Emax compared with the positive control. Results were consistent for all secondary endpoints in both studies. In both studies, all doses of esmethadone were statistically equivalent to placebo on Drug Liking VAS Emax (p < 0.05). In the Ketamine Study, Drug Liking VAS Emax scores for esmethadone at all tested doses were significantly lower vs. dextromethorphan (p < 0.05) (exploratory endpoint). These studies indicate no meaningful abuse potential for esmethadone at all tested doses.

The Dangerous Specter of Addiction A Cautionary Tale.

The literature is equivocal: dentists are either as susceptible to substance abuse or somewhat more susceptible than the general public. Most of us have suspected at one time that a colleague was troubled by excessive alcohol consumption or prescription pain medications. We often sit on the sidelines, waiting for an ideal opportunity to help, wary about offering unsolicited advice or invading the privacy of a colleague. When the problem is confronted and intervention begins, we hold our breath, yearning for a healthy outcome but dreading the worst. This brief memoir describes the first author's real-life attempts to support a colleague (with the help of a psychologist, the second author) at various intersections of treatment. The moral challenge of professional confrontation is explored. Suggestions on how to intervene with friends, colleagues, and loved ones are offered.

Sharing early preventive oral health with medical colleagues: a dental pain prevention strategy.

An alarming number of children suffer from preventable dental pain and infections. Untreated caries may cause severe discomfort and grave systemic problems. Using this article as a curriculum of fundamentals, all dental professionals are encouraged to share current best practice oral health prevention strategies with their local community medical providers. Subject matter includes rudimentary pathophysiology, very early oral health risk assessment, anticipatory guidance, fluoride varnish, and establishing a dental home by age 1.