We previously reported that both cannabidiol (CBD) and low‑dose naltrexone (LDN) exhibit complex effects on G‑protein coupled receptors, which can impact the expression and function of other members of this superfamily. These receptors feed into and interact with central signalling cascades that determine the ease by which cells engage in apoptosis, and can be used as a way to prime cancer cells to other treatments. The present study was designed to investigate the effect of combining these two agents on cancer cell lines and in a mouse model, and focused on how the sequence of administration may affect the overall action. The results showed both agents had minimal effect on cell numbers when used simultaneously; however, the combination of LDN and CBD, delivered in this specific sequence, significantly reduced the number of cells, and was superior to the regimen where the order of the agents was reversed. For example, there was a 35% reduction in cell numbers when using LDN before CBD compared to a 22% reduction when using CBD before LDN. The two agents also sensitised cells to chemotherapy as significant decreases in cell viability were observed when they were used before chemotherapy. In mouse models, the use of both agents enhanced the effect of gemcitabine, and crucially, their use resulted in no significant toxicity in the mice, which actually gained more weight compared to those without this pre‑treatment (+6.5 vs. 0%). Overall, the results highlight the importance of drug sequence when using these drugs. There is also a need to translate these observations into standard chemotherapy regimens, especially for common tumour types where treatment is often not completed due to toxicities.
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http://dx.doi.org/10.3892/or.2022.8287 | DOI Listing |
Pharmaceutics
December 2024
Pharmathen SA, 31 Spartis Str., 14452 Metamorfosi Attica, Greece.
Regulatory authorities typically require bioequivalence to be demonstrated by comparing pharmacokinetic parameters like area under the plasma concentration-time curve (AUC) and maximum plasma concentration (C). Because in certain cases, AUC and C alone may not be adequate to identify formulation differences in early and/or late segments of the dosing interval, partial AUCs (pAUCs) have been proposed as additional metrics to evaluate bioequivalence. Even though cut-off points for pAUCs are usually decided based on clinical relevance, the identification of the correct cut-off range remains elusive in many other cases and tends to contribute to increased pAUC estimate variabilities.
View Article and Find Full Text PDFPsychopharmacology (Berl)
January 2025
Edith Collins Centre for Translational Research in Alcohol, Drugs and Toxicology, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, NSW, Australia.
Rationale: Both topiramate and naltrexone have been shown to affect neural alcohol cue reactivity in alcohol use disorder (AUD). However, their comparative effects on alcohol cue reactivity are unknown. Moreover, while naltrexone has been found to normalize hyperactive localized network connectivity implicated in AUD, no studies have examined the effect of topiramate on intrinsic functional connectivity or compared functional connectivity between these two widely used medications.
View Article and Find Full Text PDFDrug Alcohol Depend Rep
March 2025
Center to Improve Veteran Involvement in Care, VA Portland Health Care System, 3710 SW US Veterans Hospital Rd, Portland, OR 97239, United States.
Aim: We examined differences in medications for opioid use disorder (MOUD) receipt between rural and urban veteran patients following initiatives within the US Department of Veterans Affairs (VA) to expand access to MOUD.
Methods: Data for this retrospective cohort study were obtained from the VA Corporate Data Warehouse, which contains national electronic health record data for all VA patients. The analytic sample included all patients diagnosed with OUD from 10/1/2018-9/30/20.
BMC Neurosci
January 2025
National Brain Research Centre, Manesar, Gurugram, 122052, Haryana, India.
Delta-opioid receptors (δ-ORs) are known to be involved in associative learning and modulating motivational states. We wanted to study if they were also involved in naturally-occurring reinforcement learning behaviors such as vocal learning, using the zebra finch model system. Zebra finches learn to vocalize early in development and song learning in males is affected by factors such as the social environment and internal reward, both of which are modulated by endogenous opioids.
View Article and Find Full Text PDFClin Ther
January 2025
Department of Pharmacology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia. Electronic address:
Purpose: This systematic review was conducted to determine which type of oral medication for obesity provides the best weight loss effect.
Methods: This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guideline. For this systematic review, we used 3 databases for journal searches: PubMed, ScienceDirect, and Scopus.
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