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Simple Summary: Cancer is a major disease and a leading cause of death worldwide. Improving treatment and management strategies for cancer is critical. This article explores cannabis and its pharmacological properties as a promising tool in cancer care, especially in easing symptoms like appetite loss, pain, nausea, vomiting, and insomnia. Moreover, it examines the anti-tumor properties of cannabis, highlighting that, although some evidence suggests benefits, more research is necessary to confirm these effects. The article addresses the evidence concerning the clinical challenges of using cannabis, such as its psychoactive effects, and potential side effects. The article aims to clarify the current understanding of cannabis use in cancer care, helping healthcare professionals and patients make better-informed decisions and improve treatment outcomes. As the legalization of medical cannabis expands across several countries, interest in its potential advantages among cancer patients and caregivers is burgeoning. However, patients seeking to integrate cannabis into their treatment often encounter frustration when their oncologists lack adequate information to offer guidance. This knowledge gap is exacerbated by the scarcity of published literature on the benefits of medical cannabis, leaving oncologists reliant on evidence-based data disheartened. This comprehensive narrative article, tailored for both clinicians and patients, endeavors to bridge these informational voids. It synthesizes cannabis history, pharmacology, and physiology and focuses on addressing various symptoms prevalent in cancer care, including insomnia, nausea and vomiting, appetite issues, pain management, and potential anti-cancer effects. Furthermore, by delving into the potential mechanisms of action and exploring their relevance in cancer treatment, this article aims to shed light on the potential benefits and effects of cannabis in oncology. [ABSTRACT FROM AUTHOR]

Examines the effectiveness and safety of topical non-steroidal anti-inflammatory drugs in acute and chronic pain conditions. Methodology used in the study; Comparison of topical non-steroidals to placebo preparations; Findings on the side effects of non-steroidals.

Simple Summary: Cannabinoids have been widely used for pain, nausea, and appetite stimulation, and have also shown anti-tumor activity in preclinical studies of prostate cancer. Epidiolex is an oral cannabidiol solution that is FDA approved for the treatment of certain types of seizures in patients one year of age and older. We studied phase I Epidiolex dose escalation followed by dose expansion in patients with biochemically recurrent prostate cancer. A total of 21 patients were enrolled. No dose-limiting toxicities were observed at any dose level. The recommended phase 2 dose was 800 mg daily. An additional 14 patients were enrolled in the dose expansion. The most common adverse events were 55% diarrhea (grade 1–2), 25% nausea (grade 1–2), and 20% fatigue (grade 1–2). Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer, supporting a safe dose for future studies. Purpose: Cannabinoids (CBD) have anti-tumor activity against prostate cancer (PCa). Preclinical studies have demonstrated a significant decrease in prostate specific antigen (PSA) protein expression and reduced tumor growth in xenografts of LNCaP and DU-145 cells in athymic mice when treated with CBD. Over-the-counter CBD products may vary in activity without clear standardization, and Epidiolex is a standardized FDA-approved oral CBD solution for treatment of certain types of seizures. We aimed to assess the safety and preliminary anti-tumor activity of Epidiolex in patients with biochemically recurrent (BCR) PCa. Experimental design: This was an open-label, single center, phase I dose escalation study followed by a dose expansion in BCR patients after primary definitive local therapy (prostatectomy +/− salvage radiotherapy or primary definitive radiotherapy). Eligible patients were screened for urine tetrahydrocannabinol prior to enrollment. The starting dose level of Epidiolex was 600 mg by mouth once daily and escalated to 800 mg daily with the use of a Bayesian optimal interval design. All patients were treated for 90 days followed by a 10-day taper. The primary endpoints were safety and tolerability. Changes in PSA, testosterone levels, and patient-reported health-related quality of life were studied as secondary endpoints. Results: Seven patients were enrolled into the dose escalation cohort. There were no dose-limiting toxicities at the first two dose levels (600 mg and 800 mg). An additional 14 patients were enrolled at the 800 mg dose level into the dose expansion cohort. The most common adverse events were 55% diarrhea (grade 1–2), 25% nausea (grade 1–2), and 20% fatigue (grade 1–2). The mean PSA at baseline was 2.9 ng/mL. At the 12-week landmark time-point, 16 out of 18 (88%) had stable biochemical disease, one (5%) had partial biochemical response with the greatest measurable decline being 41%, and one (5%) had PSA progression. No statistically significant changes were observed in patient-reported outcomes (PROs), but PROs changed in the direction of supporting the tolerability of Epidiolex (e.g., emotional functioning improved). Conclusion: Epidiolex at a dose of 800 mg daily appears to be safe and tolerable in patients with BCR prostate cancer supporting a safe dose for future studies. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 80% hepatocellular carcinoma (HCC) patients are in intermediate or advanced stages at diagnosis and have lost the chance of curative surgery, resulting in poor prognosis. Lenvatinib was approved in 2018 as a first-line treatment for unresectable HCC. The aim of this study was to evaluate the efficacy and safety of lenvatinib as a first-line treatment for unresectable HCC by reviewing the currently available data and comparing lenvatinib with sorafenib. An overview of 24 studies indicates that lenvatinib can provide better tumor responses and survival benefits as compared with sorafenib for unresectable HCC patients, with a comparable incidence of adverse events. Lenvatinib was approved in 2018 as a first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). This systematic review and meta-analysis aimed to provide the most updated evidence about the efficacy and safety of lenvatinib as a first-line treatment for unresectable HCC. An electronic search of the PubMed database, Web of Science, Embase, and Cochrane Library was undertaken to identify all relevant studies up to May 2022. The pooled effect sizes were calculated based on the random-effects model. One phase III randomized controlled trial and 23 retrospective studies of 2438 patients were eligible for analysis. For patients treated with lenvatinib as first-line treatment, the pooled median overall survival (OS), median progression-free survival (PFS), 1-year OS rate, 1-year PFS rate, objective response rate (ORR), and disease control rate (DCR) were 11.36 months, 6.68 months, 56.0%, 27.0%, 36.0% and 75.0%, respectively. Lenvatinib showed a significantly superior efficacy compared with sorafenib (HR for OS, 0.85 and HR for PFS, 0.72; OR for ORR, 4.25 and OR for DCR, 2.23). The current study demonstrates that lenvatinib can provide better tumor responses and survival benefits than sorafenib as a first-line treatment for unresectable HCC, with a comparable incidence of adverse events. [ABSTRACT FROM AUTHOR]

The study aims to evaluate whether the analgesic effect of intra-articular (IA) route of xylazine administered to horses following arthroscopic surgery is due to a local or a systemic action. Two connected studies were performed. In the first, 1 mg/kg b.w. of xylazine was injected IA, and blood samples were taken to assess drug systemic absorption. In addition, systemic effects of the drug (sedation, ataxia or reduction of respiratory and cardiac rate) were registered. Control horses injected with saline IA were included in the study to exclude the influence of anaesthesia in the occurrence of these manifestations. In the second study, 1 mg/kg b.w. of xylazine was administered intravenously (i.v.) in healthy horses. Blood samples were collected to determine the concentrations of xylazine, and the same signs of systemic effects of the drug were recorded. By correlating these parameters, a systemic 'no effect' concentration was defined. Pharmacokinetic data after IA administration resulted in some xylazine absorption (bioavailability equal to 58.12%) with values above the systemic 'no effect' concentration. The occurrence of some signs related to systemic effects in horses receiving IA xylazine was significant compared with horses receiving saline. In conclusion, a systemic action of the drug after IA administration cannot be excluded. [ABSTRACT FROM AUTHOR]

This paper proposes the design of combination opioid–adrenergic tethered compounds to enhance efficacy and specificity, lower dosage, increase duration of activity, decrease side effects, and reduce risk of developing tolerance and/or addiction. Combinations of adrenergic and opioid drugs are sometimes used to improve analgesia, decrease opioid doses required to achieve analgesia, and to prolong the duration of analgesia. Recent mechanistic research suggests that these enhanced functions result from an allosteric adrenergic binding site on opioid receptors and, conversely, an allosteric opioid binding site on adrenergic receptors. Dual occupancy of the receptors maintains the receptors in their high affinity, most active states; drops the concentration of ligand required for full activity; and prevents downregulation and internalization of the receptors, thus inhibiting tolerance to the drugs. Activation of both opioid and adrenergic receptors also enhances heterodimerization of the receptors, additionally improving each drug's efficacy. Tethering adrenergic drugs to opioids could produce new drug candidates with highly desirable features. Constraints—such as the locations of the opioid binding sites on adrenergic receptors and adrenergic binding sites on opioid receptors, length of tethers that must govern the design of such novel compounds, and types of tethers—are described and examples of possible structures provided. [ABSTRACT FROM AUTHOR]

Background Inhibitors of p38 mitogen-activated protein kinase are undergoing evaluation as a novel class of anti-rheumatic drugs, by virtue of their ability to suppress the production of pro-inflammatory cytokines. Emerging data suggests that they may also attenuate peripheral or central sensitization in neuropathic pain. A double-blind, placebo-controlled study was undertaken to evaluate the analgesic efficacy of losmapimod ( GW856553), a novel p38α/β inhibitor, in subjects with neuropathic pain following traumatic peripheral nerve injury. Methods One hundred and sixty-eight subjects with pain of at least moderate intensity (average daily score ≥4 on an 11-point pain intensity numeric rating scale; PI-NRS) at baseline were randomized to receive oral losmapimod, 7.5 mg BID or placebo for 28 days. Efficacy and safety assessments were undertaken at weekly clinic visits. Results The mean treatment difference for the change in average daily pain score from baseline to week 4 of treatment based on the PI-NRS was −0.22 (95% CI −0.73, 0.28) in favour of losmapimod over placebo ( p = 0.39). There were no statistically significant or clinically meaningful differences between the treatment groups over the 4-week dosing period for either the primary or secondary efficacy variables. There were no unexpected safety or tolerability findings following dosing with losmapimod. Conclusions Losmapimod could not be differentiated from placebo in terms of a primary analgesia response in patients with pain following peripheral nerve injury. The lack of response could reflect inadequate exposure at central sites of action or differences between rodent and human with respect to the target or neuropathic pain mechanisms. [ABSTRACT FROM AUTHOR]

Compelling clinical evidence establishes that buprenorphine is similar to methadone in efficacy for opiate detoxification and maintenance but safer than methadone in an overdose situation. The Drug Abuse Treatment Act of 2000 (DATA 2000) enabled US physicians with additional training to prescribe buprenorphine to a limited number of opiate-dependent patients. The sublingual tablets Subutex® (buprenorphine alone) and Suboxone® (a combination of buprenorphine and naloxone) meet the specifications of DATA 2000. Suboxone is intended to discourage intravenously administration and has less abuse potential than buprenorphine alone. Suboxone is generally recommended for maintenance treatment except for women who are pregnant. Subutex is recommended in treatment of pregnant women. A buprenorphine opiate withdrawal syndrome can occur in newborns. Although intravenous buprenorphine abuse is a significant public health problem in some countries, buprenorphine alone or in combination with naloxone has less potential for abuse than heroin and some prescription opiates, such as oxycodone. Pharmacotherapy from physicians' offices makes buprenorphine treatment acceptable to some opiate-dependent patients who would not accept treatment in traditional opiate-maintenance clinics. For reasons not adequately understood, some patients find discontinuation of buprenorphine following long-term use difficult. This article reviews the pharmacology of buprenorphine, summarizes evidence supporting the safety and efficacy of buprenorphine and provides clinical guidelines for treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the antinociceptive effects of epidural buprenorphine (EB), epidural medetomidine (EM) or epidural buprenorphine–medetomidine (EBM). Eight cats were studied. Thermal thresholds (TT) were measured by increasing the temperature of a probe placed on the thorax. Mechanical thresholds (MT) were measured through inflation of a modified blood pressure bladder to the cat’s forelimb. After baseline measurements, EB (0.02 mg/kg), EM (0.01 mg/kg) or half of the doses of each drug (EBM) were administered. Data were analysed usinganova ( P < 0.05) and 95% confidence interval (CI). TT increased from 30 min to 1 h after EB and at 45 min after EM. MT increased from 45 min to 2 h after EB, from 15 min to 1 h after EM and at 30, 45 min and at 2 h after EBM. MT were significantly lower after EB than EM at 30 min. TT were above the upper 95%CI from 15 min to 24 h after EB, from 15 min to 4 h after EM and from 15 min to 8 h after EBM. MT were above the upper 95%CI from 15 min to 5 h, and at 8, 12 and 24 h after EB, from 15 min to 6 h after EM and from 15 min to 6 h and at 12 and 24 h after EBM. All treatments had similar onset. Overall, EB presented longer period of action than EBM and EM. The same magnitude of analgesia was achieved, but with fewer side effects when EBM was compared with EM. [ABSTRACT FROM AUTHOR]

Meta-analyses (MAs) of non-surgical chronic pain treatment studies were systematically reviewed to determine effectiveness. Twenty-four MAs were found relating to non-surgical, non-malignant, non-headache chronic pain treatment. Two natural groupings, pain facility treatment and specific pain treatments, were created. In addition, a number of the MAs examined the same treatments including pain facility treatments, manipulation, capsaicin, acupuncture, antidepressants, back school, physical therapy, and cognitive behavior treatments. MAs addressing the same treatments were reviewed for replicate variability or reliability of results, thereby allowing some conclusions about the consistency of this type of data. The following treatments were consistently effective demonstrating replicate non-variability or reliability: pain facility treatment, capsaicin, anti-depressants, physical therapy, topical NSAIDs, and cognitive behavioral treatments. Only one MA demonstrated the effectiveness of anticonvulsants and psychoeducational. Potential problems with the reviewed MAs and cost effectiveness of treatment are discussed. Finally, potential future initiatives in this area of research are presented. Although pain facility treatment and a number of specific pain treatments are consistently demonstrated to be effective, at the present time, it is impossible to isolate a set of 'effective treatments' within the pain facility treatment package. [ABSTRACT FROM AUTHOR]

Complementary and alternative medicines such as herbal medicines are not currently part of the conventional medical system. As the popularity of and global market for herbal medicine grows among all age groups, with supporting scientific data and clinical trials, specific alternative treatments such as herbal medicine can be reclassified as a practice of conventional medicine. One of the most common conditions for which adults use herbal medicine is pain. However, herbal medicines carry safety concerns and may impact the efficacy of conventional therapies. Unfortunately, mechanisms of action are poorly understood, and their use is unregulated and often underreported to medical professionals. This review aims to compile common and available herbal medicines which can be used as an alternative to or in combination with conventional pain management approaches. Efficacy and safety are assessed through clinical studies on pain relief. Ensuing herb–drug interactions such as cytochrome modulation, additive and synergistic effects, and contraindications are discussed. While self-management has been recognized as part of the overall treatment strategy for patients suffering from chronic pain, it is important for practitioners to be able to also optimize and integrate herbal medicine and, if warranted, other complementary and alternative medicines into their care. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is considered to be one of the most disabling diseases. The intra-articular opioid injection has been widely studied for its simplicity, safety, and efficacy in OA. In this study, however, we suggest a novel method of buprenorphine transdermal patch (BTDP) to painful knee joints of OA patients, instead of intra-articular opioid injection, and subsequently compared the knee application with conventional chest application. We retrospectively enrolled 213 patients with knee OA who did not respond to conventional therapy. The Numeric Rating Scale (NRS), adverse effects, and compliance were recorded before and after the application of the BTDP. All parameters were compared between the knee applied group and the chest applied group. After the BTDP application, the NRS score in the knee applied group was lower than that of the chest applied group (p = 0.007). NRS scores after buprenorphine patch decreased to 2.21 ± 0.77, and 2.55 ± 0.71 in the chest applied group and the knee applied group, respectively. The adverse effects were 19.32% in the knee applied group, and 64.00% in the chest applied group. The compliances were 82.95% and 37.60% in the knee applied group and chest applied group, respectively. This novel application of BTDP directly to the painful knee joint of knee OA patients led to a decrease in the NRS score, adverse effects, and an increase in compliance compared with the chest application method. [ABSTRACT FROM AUTHOR]

There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions. The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety. The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature of cannabinoids means that they are seen as suitable candidates for advanced nanosized drug delivery systems, which can be applied via a range of routes. Nanotechnology-based drug delivery strategies have flourished in several therapeutic fields in recent years and numerous drugs have reached the market. This review explores the most recent developments, from preclinical to advanced clinical trials, in the cannabinoid delivery field, and focuses particularly on pain and inflammation treatment. Likely future directions are also considered and reported. [ABSTRACT FROM AUTHOR]

Background Systemic administration of dexmedetomidine ( DEX; selective α2-adrenoceptor agonist) is found to inhibit diffuse noxious inhibitory control in rats, now referred to as conditioned pain modulation ( CPM) in humans. The present study was designed to investigate the effect of intravenous administration of DEX on CPM in humans. Methods There were two sequential sessions in this double blind, randomized study. The first session was the control with normal saline infusion ( N1st, L1st, H1st). During the second session, three types of agents were infused: normal saline ( N2nd); a low plasma concentration of DEX (0.04 ng/mL; L2nd); and a high plasma concentration of DEX (0.08 ng/mL; H2nd). The amplitude of somatosensory evoked potentials (amp SEP)s and the visual analogue scale of tooth pain ( VASt) induced by electrical tooth stimulation were evaluated with and without conditioning CO2 laser stimulation of the hand. The inhibition rate (% inhibition) was calculated [= (1-[amp SEP or VASt with conditioning stimuli]/[amp SEP or VASt without conditioning stimuli]) × 100] to compare the magnitude of the DEX effects on CPM. Results The inhibition rates of amp SEPs and VASt in Types N, L and H varied significantly, demonstrating a dose-dependent reduction of CPM effects of amp SEP and VASt during randomized DEX administration, consistent with results from animal studies. Conclusions The present study shows that systemic administration of an α2-adrenoceptor agonist ( DEX), less than the clinical dose, inhibited CPM in humans. These results may provide some mechanistic insight into why many chronic pain patients show impaired CPM. [ABSTRACT FROM AUTHOR]