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Two medications typically used to treat opioid addiction, nalmefene and naltrexone, have shown promise in treating compulsive gambling. This suggests that there may be similar brain circuits involved in behavioral addictions as those involved in drug addiction. While talking therapy is the usual treatment for gambling addiction, it does not work for everyone. Randomized trials have found that nalmefene and naltrexone were the most effective medications for gambling addiction, although side effects may cause some individuals to stop taking them. Further large-scale clinical trials are needed to explore treatment options for gambling disorder. [Extracted from the article]

The article focuses on the presence of endogenous psychedelics in the human brain and gut, which are produced with the help of symbiotic gut microbes. Researchers are exploring the roles of these compounds in neurotransmission, neuron protection and mental health, shedding light on the connections between human physiology and the natural world.

This month, the U.S. Food and Drug Administration (FDA) approved Zurnia, the first nalmefene hydrochloride auto‐injector for the emergency treatment of known or suspected opioid overdose in adults and pediatric patients ages 12 and older. The agency approved the first nasal spray formulation of nalmefene in May 2023 (see ADAWhttps://onlinelibrary.wiley.com/doi/10.1002/adaw.34062). [ABSTRACT FROM AUTHOR]

The article discusses a study conducted by Cara Therapeutics Inc. on the impact of renal impairment on the pharmacokinetic profile of intravenous difelikefalin, a kappa opioid receptor agonist used to treat pruritus in patients with chronic kidney disease. The research found that difelikefalin was well tolerated, with similar exposure in subjects with mild renal impairment compared to healthy subjects, while those with moderate or severe impairment had reduced clearance and higher exposure. The study also demonstrated dose proportionality in subjects with end-stage renal disease undergoing hemodialysis. The findings were published in BMC Nephrology and can be accessed for further information. [Extracted from the article]

Researchers from the Uniformed Services University of the Health Sciences conducted a study on the effects of Kappa opioid receptor (KOR) activation and antagonism on motivation in male and female rats. The study found that KOR activation reduced animals' performance in obtaining rewards, while KOR antagonism blocked these deficits. The research contributes to understanding how KORs modulate motivation and may inform future studies on alleviating anhedonic behaviors associated with stress. The study was supported by the United States Public Health Service and published in Pharmacology Biochemistry and Behavior. [Extracted from the article]

A clinical trial, NCT06637709, aims to analyze the role of Mu-Lympho Marker (MLM) in measuring pain progression in Osteoarthritis patients and its association with specific rehabilitation programs. The study will explore the relationship between Mu+ B and NK cells percentage and pain progression in OA patients, as well as investigate the potential confounding effect of biological and psychological elements. Participants will undergo blood sample collections at specific time points to evaluate MLM stability and its modulation according to interventions. The trial is recruiting participants in Italy and is expected to be completed by April 28, 2026. [Extracted from the article]

A patent has been issued to Nippon Chemiphar Co. Ltd. for the use of morphinan derivatives in treating opioid delta receptor agonist-related diseases, such as headaches. The patent, filed in December 2022 and published in October 2024, outlines the pharmaceutical composition and compounds involved in the treatment. The inventors aim to provide a medicament for therapeutic or prophylactic treatment of opioid delta receptor-related diseases, focusing on pain-associated anxiety or depression in mammalian subjects. [Extracted from the article]

A recent report from Alma Mater Studiorum - University of Bologna discusses the use of opioids in managing chronic pain, a condition that affects approximately 30% of the population. While opioids are commonly used to treat moderate-to-severe pain in both cancer and non-cancer patients, their chronic use can lead to various side effects. The report highlights the importance of understanding the molecular mechanisms behind the analgesic effects and adverse events of opioids to improve chronic pain treatment. For more information, the full article can be accessed for free at https://doi.org/10.1186/s44158-024-00201-2. [Extracted from the article]

The article discusses the development of a small-molecule antagonist radiotracer for positron emission tomography imaging of the mu opioid receptor. The study aimed to design ligands with high binding affinity for the mu opioid receptor while demonstrating selectivity over other opioid receptors to avoid respiratory depression. The results suggest that the developed radiotracer, [11C]1A, shows promise for safer interrogation of the endogenous opioid system. The preprint has not yet undergone peer review, and more information can be found on biorxiv.org. [Extracted from the article]

A recent study conducted at the University of Arizona focused on the relationship between negative affect, sleep disruption, and opioid receptors in the brain. The research found that increased signaling at the kappa opioid receptor in the anterior cingulate cortex could lead to aversiveness and sleep disruption. Inhibiting this signaling pathway may offer therapeutic benefits for conditions associated with negative affect and sleep disturbances. The study highlights the potential of KOR antagonists in treating diseases linked to these symptoms. [Extracted from the article]

Researchers at Sun Yat-sen University have conducted a study on opioids, specifically focusing on the delta opioid receptor (dOR). The dOR is an attractive target for drug discovery due to its low risk of drug dependence compared to the Mu opioid receptor. However, the pharmacological properties and signaling pathways of the dOR are not well understood. In this study, the researchers used cryo-electron microscopy to determine the structure of the dOR-Gi complex when bound to a small-molecule agonist. They also identified a region involved in signaling bias and discovered a potential link between dOR activation and reduced gastrointestinal motility. These findings contribute to our understanding of the dOR's structure, signaling pathways, and biological functions, which could aid in the development of structure-based drug discovery. [Extracted from the article]

A recent report from researchers at the University of California Davis discusses the use of opioids and the potential for reducing drug-seeking behavior. The study focused on the role of arrestin-3, a protein involved in opioid receptor activation, and its impact on compulsive drug-seeking. The researchers found that mice lacking arrestin-3 did not show reduced drug-seeking behavior, suggesting that its absence does not protect against the abuse liability of opioids. The study suggests that opioids that engage both G protein and arrestin-3 may reduce abuse liability. [Extracted from the article]

A recent report from Tulane University in New Orleans, Louisiana, discusses the challenges of using mu-opioid receptor agonists for chronic pain management due to their significant side effects and the development of tolerance. The researchers investigated the effects of a specific mu-opioid receptor agonist called ZH853 on neuropathic pain in rats. They found that chronic ZH853 treatment led to decreased tolerance and reduced glial activation compared to chronic morphine treatment. This study suggests that ZH853 may be a more effective and potentially safer alternative for managing neuropathic pain. [Extracted from the article]

A recent study conducted by the University of Tsukuba in Japan explored the role of kappa opioid receptors in regulating feeding behavior and plasma glucose levels. The researchers found that the administration of nalfurafine, a kappa opioid receptor agonist, increased food intake in mice. This effect was observed when nalfurafine was injected into the nucleus accumbens, a region of the brain associated with reward and motivation. The study also investigated the potential of nalfurafine to alleviate anorexia induced by the anti-cancer agent 5-fluorouracil. The findings suggest that nalfurafine may be a potential candidate for reducing anorexia in cancer patients. [Extracted from the article]

A recent report from the University of Pittsburgh discusses research findings on opioids and their effects on itch. The study used two-photon Ca 2+ imaging to identify spinal interneurons that are activated by itch-inducing agents. The researchers found that itch is conveyed to the brain through spinal output neurons that target the lateral parabrachial nuclei. They also discovered that the kappa opioid receptor agonist nalfurafine can relieve itch by selectively inhibiting these neurons. This research provides valuable insights into the neural basis of itch and the potential for using opioids to suppress it. [Extracted from the article]

A study conducted by researchers at the University of Michigan explores the cellular adaptations that lead to opioid analgesic tolerance, specifically focusing on chronic morphine treatment. The study investigates the effects of chronic morphine exposure on mu-opioid receptor signaling in a thalamo-cortical circuit relevant to pain and opioid analgesia. The findings suggest that chronic morphine treatment induces cellular tolerance in a sex-specific and phosphorylation-dependent manner. This research contributes to a better understanding of how chronic opioid exposure alters cellular signaling and may contribute to opioid analgesic tolerance. [Extracted from the article]

A recent study conducted at Tulane University in New Orleans, Louisiana has provided new information about pain and the central nervous system. The researchers developed cyclic glycopeptide endomorphin analogs as potential drug candidates for pain relief. These analogs showed promising results in receptor binding and functional assays, as well as in blood-brain barrier penetration tests. The study concluded that further research is needed to explore the potential clinical applications of these glycopeptide analogs. This research was supported by grants from the NIDA and the US Department of Veterans Affairs. [Extracted from the article]

A patent has been issued to Allergan Holdings Unlimited Company for opioid receptor modulator dosage formulations. The patent describes solid oral pharmaceutical formulations of a specific active ingredient with improved stability and unique physico-chemical features that may deter or limit abuse. The formulations consist of the active ingredient and inert ingredients such as silicified microcrystalline cellulose, colloidal silicon dioxide, crospovidone, mannitol, and magnesium stearate. The patent also includes methods of reducing abdominal pain and diarrhea in patients with irritable bowel syndrome with diarrhea by orally administering the formulation. [Extracted from the article]

A recent study conducted by researchers at the University of Massachusetts focused on the perioperative management of buprenorphine, a medication used to treat opioid use disorder, in surgical patients. The study found that patients who continued taking buprenorphine after surgery required half the dose of nonbuprenorphine opioids compared to those who had buprenorphine discontinued. Both groups experienced similar levels of pain relief and adverse events. The findings suggest that continuing buprenorphine perioperatively may lead to lower opioid requirements without compromising analgesia. This research has been peer-reviewed and published in the Journal of Surgical Research. [Extracted from the article]

A patent application has been submitted by researchers from the University of Florida Research Foundation Inc. for the use of compounds with sigma receptor binding affinity in the treatment and prevention of SARS-CoV-2 infection. The compounds mentioned in the application include 4-PPBP, SA 4503, ditolylguanidine, dimethyltryptamine, siramesine, AZ 66, CM304, CM398, and diphenhydramine. The application also mentions the use of these compounds in treating respiratory, pulmonary, cardiovascular, and metabolic dysfunction associated with SARS-CoV-2 infection. The patent application provides detailed information on the methods and compositions for using these compounds. [Extracted from the article]

A recent preprint abstract discusses the transcriptomic characterization of human lateral septum neurons, a subcortical structure that plays a role in regulating social behaviors. The study used single nucleus RNA-sequencing to analyze postmortem human brain tissue samples and identified five distinct neuronal cell types within the lateral septum. The researchers found that certain genes, such as TRPC4, were highly conserved between humans and mice, while others, like FREM2, were specific to the human lateral septum. This research provides valuable insights into the molecular profiling of the human lateral septum and identifies potential marker genes for further study. [Extracted from the article]

A recent report from the University of Southern Florida discusses the neurological underpinnings of alcohol use disorder (AUD) and the limited treatment options available. The study focuses on the role of the kappa-opioid receptor (KOR) system in the nucleus accumbens shell (AcbSh) in AUD. The researchers found that KOR antagonism in the AcbSh reduced escalated alcohol intake and negative affective-like states in alcohol-dependent rats. This research highlights the potential of targeting the KOR/DYN system as a therapeutic approach for AUD. [Extracted from the article]

A recent study conducted at the University of North Carolina has explored the potential of kappa opioid receptor (KOR) agonists as a promising alternative to traditional opioids for pain relief. These agonists have shown analgesic properties with lower abuse potential than mu opioid receptor agonists. However, they often produce sedation and dysphoria. The researchers focused on developing G protein signaling-biased KOR agonists that could separate the desired analgesic effects from the unwanted side effects. The study describes the synthesis and evaluation of a new series of these agonists, which displayed enhanced potency and maintained G protein-signaling bias. This research has been peer-reviewed and provides valuable insights into the development of more effective pain medications. [Extracted from the article]

A recent preprint abstract discusses the challenges of reversing fentanyl-induced respiratory depression, which contributes to the high rates of overdose deaths among Americans with Opioid Use Disorders (OUD). The study examines the role of central and peripheral mu opioid receptors (MORs) in mediating fentanyl's effects. The researchers found that a peripherally-restricted MOR antagonist called naloxone methiodide (NLXM) was able to prevent and reverse opioid-induced respiratory depression without producing aversive behaviors. These findings suggest that selective peripheral MOR antagonism could be a promising therapeutic strategy for managing opioid-induced respiratory depression. However, it is important to note that this preprint has not yet undergone peer review. [Extracted from the article]

Researchers from the University of Arizona have conducted a study on the effects of sub-anesthetic ketamine treatment in preclinical models of Parkinson's disease (PD). They found that ketamine produced acute antiparkinsonian and anti-dyskinetic effects. The researchers also explored the role of the opioid system in these effects and found that while opioid receptor activation is not necessary for the anti-dyskinetic effects of ketamine, it does have a modulatory effect. This study provides new insights into the potential repurposing of ketamine for individuals with Parkinson's disease. [Extracted from the article]

A preprint abstract from biorxiv.org discusses the impact of chronic infection with the parasite Toxoplasma gondii on visceral nociception, or the perception of pain in the internal organs. The study, conducted on mice, found that T. gondii infection decreased visceral nociceptive responses through opioid signaling. Despite the presence of immune cells in the colon of infected mice, the involvement of T cell-derived enkephalins in hypoalgesia was ruled out. These findings suggest that T. gondii infection may be negatively associated with abdominal pain. However, it is important to note that this preprint has not yet undergone peer review. [Extracted from the article]

Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have identified a drug called SNC80 that can slow down metabolic and physiological processes in organs, making it potentially valuable for organ preservation. The drug was found to preserve cell and tissue viability in Xenopus, microfluidic human organs-on-chips, and explanted porcine hearts and limbs. This research suggests that pharmacological induction of physiological slowing, combined with organ perfusion transport systems, could be a new therapeutic approach for organ preservation in transplantation, trauma management, and remote locations. [Extracted from the article]

New research from the University of Nebraska at Omaha explores the potential of the psychedelic drug 2,5-dimethoxy-4-iodoamphetamine (DOI) to reduce the demand for fentanyl, an opioid. The study found that the efficacy of DOI in mitigating fentanyl demand is influenced by biological sex, with different effects observed in male and female rats. While DOI decreased fentanyl intake in female rats, it increased intake in male rats. These findings highlight the importance of considering biological sex in the development of therapeutics for opioid use disorder. The research has been peer-reviewed and published in Drug and Alcohol Dependence. [Extracted from the article]

A recent study conducted by researchers at Columbia University has found that a class of iboga alkaloids called oxa-iboga lack the cardiac risks associated with other compounds like ibogaine and noribogaine. These oxa-iboga compounds have shown superior efficacy in animal models of opioid use disorder and act as potent kappa opioid receptor agonists. They have also demonstrated atypical behavioral features compared to standard kappa opioid agonists. The study suggests that oxa-iboga compounds have therapeutic potential and represent mechanistically distinct iboga analogs. [Extracted from the article]

A recent study conducted at Lanzhou University in China has discovered a new opioid, MCRT, that demonstrates potent pain-relieving effects with limited side effects. The researchers used various pain and opioid side effect models to evaluate the effectiveness and safety of MCRT at the spinal level. They found that MCRT acts on multiple targets, including the mu opioid receptor (MOR), mu-S heterodimer (MDOR), and neuropeptide FF receptor 2 (NPFFR2), and produces more effective pain relief in chronic inflammatory pain models. Importantly, MCRT did not develop tolerance, opioid-induced hyperalgesia, addictive properties, gastrointestinal inhibition, or effects on motor coordination. The researchers suggest that MDOR could be a promising target for managing chronic inflammatory pain and addressing the opioid crisis. [Extracted from the article]

A recent study conducted by researchers at Shaanxi Normal University in China has revealed new findings on opioids and their role in the modulation of stress-induced analgesia (SIA). The study focused on the mu opioid receptors (MORs) expressed in the medial prefrontal cortex (mPFC) and their contribution to SIA in male mice. The results showed that MORs expressed on GABAergic neurons in the mPFC played a major role in modulating the effects of SIA, while MORs expressed on glutamatergic neurons seemed to be unrelated to the process. Additionally, the study found that the activation of mPFC-PAG projections mediated by MORs on GABAergic neurons produced analgesic effects. These findings provide a potential theoretical basis for pain treatment or drug screening targeting the mPFC. [Extracted from the article]

Researchers at Oregon Health & Science University (OHSU) have conducted a study on benzimidazole opioids, specifically substituted nitazenes, which are highly potent mu opioid receptor (MOR) agonists. These compounds have been associated with hospitalizations and fatal overdoses. The researchers characterized the pharmacology and structure-activity relationships of 19 nitazenes and found that many of them have higher affinities and potencies than fentanyl, suggesting a high potential for toxicity and overdose at low doses. The study highlights the growing public health threat posed by substituted nitazenes. [Extracted from the article]

A recent study conducted at Stony Brook University in New York examined the relationship between the kappa opioid receptor (KOR) and symptoms of anhedonia in schizophrenia. The researchers used positron emission tomography (PET) to measure KOR expression in unmedicated patients with schizophrenia and matched controls. They also assessed neuromelanin accumulation and symptoms of anhedonia. The study found a strong positive association between KOR expression and symptoms of anhedonia in patients with schizophrenia. This finding aligns with previous research on kappa antagonism as a potential therapy for anhedonia in depression. [Extracted from the article]

A preprint abstract discusses a study that explores the role of beta-endorphins, neuropeptides released during pleasurable experiences, in mediating attentional broadening after receiving a reward. The study used a placebo-controlled cross-over design with forty volunteers and found that attentional broadening observed after reward receipt was eliminated when opioid receptors were blocked. The study suggests that endogenous opioids play a specific role in attentional breadth and may enhance cognitive flexibility and resilience through natural positive experiences. The hypotheses, methods, and analyses were preregistered, and all data and analysis scripts are publicly available. However, it is important to note that this preprint has not been peer-reviewed. [Extracted from the article]

New research from the CSIR - Central Institute of Medicinal and Aromatic Plants in Lucknow, India, explores the potential therapeutic applications of the medicinal plant Oroxylum indicum (L.) Kurtz in neurological conditions. The study isolated the compound baicalein from the plant and found that it exhibited potent and competitive antagonistic activity at opioid receptors. In vivo experiments showed that baicalein blocked morphine-induced antinociception. In silico studies also supported the findings, indicating that baicalein binds with mu-opioid and kappa-opioid receptors. This research provides new insights into the potential of baicalein as an opioid receptor antagonist. [Extracted from the article]

A preprint abstract discusses the genetic factors underlying sensitivity to oxycodone-induced locomotor activation and withdrawal-induced anxiety-like behaviors in C57BL/6 mouse substrains. The study found that C57BL/6NJ mice were less sensitive to oxycodone-induced locomotor activation compared to C57BL/6J mice. Quantitative trait locus (QTL) mapping identified two QTLs on chromosomes 1 and 5 that explained a significant portion of the variance in oxycodone locomotion and withdrawal behavior. Further analysis identified two candidate genes, KCNJ9 and ATP1A2, which are involved in neuronal signaling and regulation of excitability. These findings have implications for both preclinical research and human genetic studies of opioid use disorder. [Extracted from the article]

A patent has been issued for a medication disposal apparatus and methods of manufacture and use. The invention aims to address the problem of unused medications, including opioids, which can lead to addiction and fatal overdoses. The apparatus includes a collection chamber with a converter and a reservoir with a second converter to safely dispose of medication. The invention provides multiple stages of conversion and deactivation to ensure the medication is fully destroyed and cannot be accessed again. The patent was filed by Surgical Device Innovations LLC and published in September 2024. [Extracted from the article]

A recent study conducted at Temple University in Philadelphia, Pennsylvania has provided new insights into opioids. The study focused on a compound called NCP, which acts as a dual kappa and mu opioid receptor agonist. The researchers found that NCP displayed potent analgesic effects against inflammatory pain without producing reinforcing or aversive properties. The compound did not cause addiction, respiratory depression, sedation, or other side effects commonly associated with opioids. These findings suggest that dual kappa and mu opioid receptor agonists like NCP could be promising nonaddictive analgesics for inflammatory pain. [Extracted from the article]

A recent report discusses research findings on opioids, highlighting the historical use of opioids for medical and recreational purposes. The study focuses on the differences in opioid use disorder between men and women, with women being more susceptible to developing dependence quickly and experiencing the addictive nature of opioids. The research explores various factors such as opioid receptor mechanisms, pain modulation, hormonal influences, and the complexities of addiction and withdrawal. The study concludes that further research is needed to understand the sex-specific biological mechanisms of opioids and their impact on personalized opioid therapies. [Extracted from the article]

This article discusses a study on neonatal opioid withdrawal syndrome (NOWS) in mice. The researchers aimed to understand the behavioral and vocalization patterns, brainstem transcriptomic adaptations, and the role of kappa opioid receptors in USVs (ultrasonic vocalizations) during opioid withdrawal. The study found that there were increased USV emissions and altered USV syllables during withdrawal, with a specific increase in Complex 3 syllables in female mice. The researchers also identified the involvement of the kappa opioid receptor system in increased USVs associated with withdrawal severity. However, it is important to note that this study has not yet undergone peer review. [Extracted from the article]

A recent report from the University of Salerno in Italy discusses the emerging molecular mechanisms and clinical applications of opioids and cannabinoids in pain management. The researchers highlight the challenges of pain control, particularly in patients with chronic pain, and the potential for drug addiction and substance use disorders. The study explores the epigenetic modulation of opioid and cannabinoid receptors, as well as the potential benefits of cannabidiol (CBD) in pain management. The researchers suggest that CBD, a non-psychoactive cannabinoid found in marijuana, may have analgesic, anti-inflammatory, and antioxidant effects, making it a potential treatment option for conditions such as cancer, neurodegeneration, autoimmune diseases, and even in health and fitness contexts. [Extracted from the article]

Researchers from Cairo University have conducted a study on the medicinal properties of Juniperus leaves, which have been traditionally used in ancestral folk medicine for various ailments. The study aimed to assess the safety and effectiveness of three different Juniperus species in treating inflammation and pain. The results showed that the extracts from J. thurifera were particularly effective in reducing inflammation and pain, and the study identified several bioactive compounds responsible for these effects. The research suggests that Juniperus extracts and their metabolites have the potential to be developed into non-addictive painkillers. [Extracted from the article]

According to a preprint abstract, researchers have found that the locus coeruleus (LC) in the brain plays a complex role in chronic pain. While it is known to provide natural pain relief, it can also become a source of chronic pain after injury. The researchers used optogenetic inhibition to show that inhibiting LC activity can provide acute pain relief. They also found that endogenous LC mu opioid receptors (LC-MOR) play a critical role in modulating pain, bidirectionally regulating hyperalgesia. This research has not yet been peer-reviewed. [Extracted from the article]

The article highlights a survey showing that over 75 percent of Americans feel unprepared to handle an opioid overdose, despite the availability of life-saving medications like naloxone. Topics include public unpreparedness for overdose emergencies, the role of naloxone in reversing opioid overdoses, and the importance of community awareness and training.

A recent study conducted by researchers at the National Laboratory of Biomacromolecules in Beijing, China, has shed light on the mechanisms underlying morphine analgesic tolerance. Morphine, a commonly used pain medication, can lead to side effects such as addiction, analgesic tolerance, and hyperalgesia with long-term use. The study found that the down-regulation of S-nitrosoglutathione reductase (GSNOR) in the prefrontal cortex, caused by repeated administration of morphine, increased excessive total protein S-nitrosation and promoted the development of morphine analgesic tolerance. The deficiency of GSNOR enhanced S-nitrosation of cellular protein kinase alpha (PKCa), leading to the inhibition of PKCa kinase activity and the development of morphine analgesic tolerance. This research provides valuable insights into potential therapeutic targets for morphine tolerance. [Extracted from the article]