Lucemyra (lofexidine) / US WorldMeds, Stada - LARVOL DELTA

Fixed-proportion mixtures with the α2-adrenergic agonist clonidine or lofexidine do not alter fentanyl self-administration in non-opioid-dependent male and female rats. (PubMed, J Pharmacol Exp Ther) - "The present results demonstrate that clonidine and lofexidine neither enhance nor attenuate fentanyl self-administration under either behavioral economic demand or drug-choice procedures. These results suggest other factors than reinforcement modulation should be examined regarding the premise for α-2 agonist adulteration of illicitly manufactured fentanyl."

Journal • Preclinical • Addiction (Opioid and Alcohol) • Anesthesia

Assessing a Clinically-meaningful Opioid Withdrawal Phenotype (clinicaltrials.gov) - P2 | N=60 | Recruiting | Sponsor: University of Maryland, Baltimore | Trial completion date: Feb 2026 ➔ Feb 2027 | Trial primary completion date: Nov 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Substance Abuse

Sublingual Dexmedetomidine for Treating Opioid Withdrawal (clinicaltrials.gov) - P1/2 | N=160 | Active, not recruiting | Sponsor: New York State Psychiatric Institute | Recruiting ➔ Active, not recruiting | Trial completion date: Jul 2025 ➔ Nov 2025

Enrollment closed • Trial completion date • Substance Abuse

Bridge: An Innovative Intervention for OUD Treatment (clinicaltrials.gov) - P2/3 | N=75 | Recruiting | Sponsor: Johns Hopkins University | Trial primary completion date: Oct 2025 ➔ Apr 2025

Trial primary completion date • Addiction (Opioid and Alcohol) • CNS Disorders • Psychiatry • Substance Abuse

USWM-LX1-1014: A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: USWM, LLC (dba US WorldMeds) | N=16 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Substance Abuse

Effects of Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD), and THC:CBD mixtures on behavioral and physiological signs of morphine withdrawal in rhesus monkeys. (PubMed, J Pharmacol Exp Ther) - "The mu-opioid receptor agonists methadone and buprenorphine are effective for treating opioid use disorder (OUD); however, both drugs are diverted and misused and withdrawal signs can emerge when treatment is tapered or discontinued. SIGNIFICANCE STATEMENT: Δ9-Tetrahydrocannabinol (THC) alone, but not cannabidiol either alone or in combination with THC, decreased some behavioral and physiological signs of opioid withdrawal in monkeys. However, those effects of THC were not greater than the effects of the currently available nonopioid medication lofexidine."

Journal • Substance Abuse

Dexmedetomidine potently and reversibly regulates stress-mediated behaviors. (PubMed, Front Pharmacol) - "Dexmedetomidine is both more potent (<10 nM EC50) and has higher intrinsic activity than other α2-AR agonists (clonidine, lofexidine or guanfacine). Dexmedetomidine may be a suitable drug for a chronic dosing for a wide range of stress-mediated symptoms, not limited to the acute treatment of agitation. Brain levels are highly predictable based on plasma exposures and are consistent with the known affinity for α2-ARs."

Journal • Mood Disorders • Psychiatry • Sleep Disorder

Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids (clinicaltrials.gov) - P2 | N=24 | Active, not recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Recruiting ➔ Active, not recruiting

Enrollment closed

Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance | Trial completion date: Sep 2025 ➔ Dec 2025 | Trial primary completion date: Jun 2025 ➔ Dec 2025

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Substance Abuse

From Bench to Bedside: The Development of A Novel Clinical-Stage Therapeutic, KNX100, for the Treatment of Opioid Use Disorder (CPDD 2025) - "KNX100 outperformed lofexidine in reducing withdrawal related negative affective symptoms and withdrawal-induced aversion in a conditioned place aversion model. Given strong preclinical evidence, Kinoxis is advancing KNX100 into a placebo-controlled, randomized, crossover, in-patient Proof of Concept study in ~45 patients with moderate-to-severe OUD. The study will evaluate KNX100’s effect on cue-induced craving and reactivity in non-treatment-seeking patients. The primary outcome is craving reduction, with secondary outcomes assessing cue reactivity, withdrawal, safety, and tolerability."

Clinical • Addiction (Opioid and Alcohol) • Substance Abuse • DRD2

Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Trial primary completion date: Dec 2024 ➔ May 2025

Trial primary completion date

USWM-LX1-1014: A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Initiation date: Jan 2025 ➔ Jun 2025

Trial initiation date • Substance Abuse

RESTORE: Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (clinicaltrials.gov) - P=N/A | N=108 | Completed | Sponsor: Spark Biomedical, Inc. | Active, not recruiting ➔ Completed | N=168 ➔ 108 | Trial completion date: Jul 2025 ➔ Apr 2025

Enrollment change • Trial completion • Trial completion date • Substance Abuse

RESTORE: Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (clinicaltrials.gov) - P=N/A | N=168 | Active, not recruiting | Sponsor: Spark Biomedical, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: May 2025 ➔ Jul 2025

Enrollment closed • Trial completion date • Substance Abuse

Microfluidic Blood-Milk Barrier and Physiologically Based Pharmacokinetic Model to Predict Lofexidine Secretion into Breast Milk. (PubMed, J Pharm Sci) - "This study introduces comprehensive and novel approaches to predict lofexidine secretion into breast milk. Most predictions suggest higher lofexidine concentration in milk than in plasma, raising potential safety concerns for opioid withdrawal management. Further pharmacokinetic clinical lactation studies are needed to validate these predictions."

Journal • PK/PD data • Addiction (Opioid and Alcohol)

Sublingual Dexmedetomidine for Treating Opioid Withdrawal (clinicaltrials.gov) - P1/2 | N=160 | Recruiting | Sponsor: New York State Psychiatric Institute | Trial completion date: Apr 2025 ➔ Jul 2025 | Trial primary completion date: Jan 2025 ➔ Apr 2025

Trial completion date • Trial primary completion date • Substance Abuse

Nonopioid medications for managing opioid withdrawal in acute care settings: A scoping review. (PubMed, Am J Health Syst Pharm) - "For the nonopioid alternative agents that have been studied for acute opioid withdrawal, there is more evidence supporting the efficacy of α-adrenergic receptor agonists as opposed to NMDA antagonists, GABA modulators, or sertonergic agents; however, more research is needed regarding the efficacy and safety of nonopioid alternatives for acute opioid withdrawal in order to better guide clinical decision-making."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Substance Abuse

A Pharmacokinetic, Safety, and Tolerability Study of LUCEMYRA in the Treatment of Opioid Withdrawal Management in Adolescent Subjects (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: USWM, LLC (dba US WorldMeds)

New P1 trial • Substance Abuse

Comparison Study of Mutations in Drug-Resistant M. tuberculosi s Isolates with Rifampicin, Bedaquiline, Delamanid, Pretomanid, and Linezolid MICs in Korea Using WGS and the 2023 WHO Mutation Catalogue (AMP 2024) - "Minimum inhibitory concentration (MIC) for rifampicin (RIF), pretomanid (PA), delamanid (DLM), linezolid (LZD), and bedaquiline (BDQ), as well as isoniazid, rifampicin streptomycin, kanamycin, moxifloxacin, lofexidine, and ethionamide, was determined using the 7H9 microbroth dilution method and absolute concentration method. Our findings demonstrate consistent mutation associations with RIF resistance across all cases. In 1 case of a DLM-susceptible isolate, mutations in fbiC and a deletion were detected. Further studies are needed to explore mutations associated with resistance in PA, BDQ, LZD, and DLM isolates."

Infectious Disease • Respiratory Diseases • Tuberculosis

Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance | Trial completion date: Feb 2025 ➔ Sep 2025 | Trial primary completion date: Nov 2024 ➔ Jun 2025

Trial completion date • Trial primary completion date • CNS Disorders • Mood Disorders • Post-traumatic Stress Disorder • Substance Abuse

Randomized, Double-Blind, Placebo-Controlled Pilot Study on the Safety and Effectiveness of LUCEMYRA During an Opioid Taper in Treatment of Withdrawal (clinicaltrials.gov) - P2 | N=4 | Terminated | Sponsor: USWM, LLC (dba US WorldMeds) | N=60 ➔ 4 | Suspended ➔ Terminated; COVID pandemic and enrollment issues necessitating an adjustment to the study design.

Enrollment change • Trial termination • Oncology • Pain

RESTORE: Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (clinicaltrials.gov) - P=N/A | N=168 | Recruiting | Sponsor: Spark Biomedical, Inc. | Trial primary completion date: Jan 2025 ➔ May 2025

Trial primary completion date • Substance Abuse

Pharmacokinetic and Safety Study of Oral Lofexidine in Neonates Experiencing Opioid Withdrawal Due to Intrauterine Exposure to Opioids (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: USWM, LLC (dba US WorldMeds) | Trial completion date: May 2026 ➔ Dec 2026 | Trial primary completion date: May 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date

Efficacy and Safety of Alpha-2 Agonists in Autism Spectrum Disorder: A Systematic Review. (PubMed, Adv Ther) - "The present investigation encourages physicians to consider treatment outcomes of clonidine, guanfacine, and lofexidine to determine the most effective management of ASD-related symptoms and to minimize adverse effects. However, our review cannot provide definitive treatment protocols related to various study limitations."

Journal • Review • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Psychiatry

The Mitragyna speciosa (kratom) alkaloid mitragynine: analysis of adrenergic α2 receptor activity in vitro and in vivo. (PubMed, Eur J Pharmacol) - "Mitragynine displaced a radiolabeled Aα2R antagonist ([3H]RX821002) from human Aα2ARs in vitro with lower affinity (Ki=1,260 nM) than the agonists (-)-epinephrine (Ki=263 nM) or lofexidine (Ki=7.42 nM)...Both α2R antagonists (atipamezole and yohimbine) and MOR antagonists (naloxone and naltrexone) produced rightward shifts in mitragynine discrimination dose-effect function and Aα2R agonists lofexidine and clonidine produced leftward shifts. In the mitragynine trained rats, Aα2R agonists also produced leftward shifts in discrimination dose-effect functions for morphine and fentanyl...Mitragynine did not produce hypothermia. Together, these data demonstrate that mitragynine acts in vivo like an Aα2R agonist, although its failure to induce hypothermia or stimulate [35S]GTPγS binding in vitro, suggests that mitragynine maybe a low efficacy Aα2R agonist."

Journal • Preclinical