Eye reactions under the influence of drugs of abuse as measured by smartphones: a controlled clinical study in healthy volunteers.

Background: It is known that illicit and prescribed drugs impact pupil size, eye movement and function. Still, comprehensive quantitative evaluations under known ambient light conditions are lacking, when smartphones are used for monitoring.

Methods: In this clinical study (NCT05731999), four medicinal products with addiction risks were administered to 48 subjects (18-70 years old, all with informed consent, 12 subjects per drug).

In clinical hand osteoarthritis research, self-reported pain questionnaires do not reflect the patient experience.

Objective: Pain in hand osteoarthritis (OA) is evaluated with repeated pain questionnaires. It is unclear whether these questionnaires adequately capture changes in pain recalled by patients. This study investigated whether changes on pain questionnaires (real-time evaluation) correspond to recalled pain.

Cannabis combined with oxycodone for pain relief in fibromyalgia pain: a randomized clinical self-titration trial with focus on adverse events.

Objectives: We determined whether adding cannabis to oxycodone for chronic non-cancer pain management could reduce treatment-related adverse effects (AEs) while maintaining effective analgesia.

Methods: In this open-label study, fibromyalgia patients aged ≥18 years were randomized to receive 5 mg oxycodone tablets (max. four times/day), 150 mg of inhaled cannabis containing 6.

Acute effects of esketamine on hypoxic ventilatory response, haemodynamics, and brain function in healthy volunteers.

Background: The acute hypoxic ventilatory response is a critical chemoreflex originating at the carotid bodies. This study investigates the impact of low-dose i.v.

Intravenous Lidocaine for Refractory Pain in Patients With Pancreatic Ductal Adenocarcinoma and Chronic Pancreatitis: A Multicenter Prospective Nonrandomized Pilot Study.

Introduction: Refractory pain is a major clinical problem in patients with pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP). New, effective therapies to reduce pain are urgently needed. Intravenous lidocaine is used in clinical practice in patients with PDAC and CP, but its efficacy has not been studied prospectively.

Nitric Oxide Donor Sodium Nitroprusside Reduces Racemic Ketamine-But Not Esketamine-Induced Pain Relief.

The anesthetic, analgesic and antidepressant drug ketamine produces dissociation with symptoms of psychosis and anxiety, an effect attributed to neuronal nitric oxide depletion following -methyl-d-aspartate blockade. There is evidence that dissociation induced by racemic ketamine, containing both ketamine enantiomers (S- and R-ketamine) but not esketamine (the S-isomer) is inhibited by nitric oxide (NO) donor sodium nitroprusside (SNP). We tested whether a similar intervention would reduce racemic and esketamine-induced analgesia in a randomized double-blind placebo-controlled trial.

Neuropathic and Nociplastic Pain Profiles are Common in Adult Chronic Nonbacterial Osteitis (CNO).

Chronic nonbacterial osteitis (CNO) is a rare musculoskeletal disease causing chronic bone pain. It is known that chronic musculoskeletal pain may involve other mechanisms than nociceptive pain only. We investigate the prevalence of neuropathic and nociplastic pain in adult CNO and their association with clinical characteristics and treatment outcomes.

Reversal of Propofol-induced Depression of the Hypoxic Ventilatory Response by BK-channel Blocker ENA-001: A Randomized Controlled Trial.

Background: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion.

[Pain in cancer].

Patients with cancer often experience pain that significantly interferes with their daily life. In this review paper the authors discuss the different aspects of cancer pain by answering different questions regarding cancer pain. Items that are discussed include measurement of pain, medical and interventional pain treatment, side effects, opioid tolerance and addiction and barriers that preclude proper treatment of pain.

Pharmacology of viable mechanism agnostic respiratory stimulants for the reversal of drug-induced respiratory depression in humans.

Introduction: Drug-induced respiratory depression is potentially fatal and can be caused by various drugs such as synthetic opioids and tranquilizers. The only class of respiratory depressants that has a specific reversal agent are opioids, such as naloxone. These reversal agents have limited utility in situations of polysubstance ingestion with agents from multiple respiratory depressant classes.

Neurocognitive Effect of Biased µ-Opioid Receptor Agonist Oliceridine, a Utility Function Analysis and Comparison with Morphine.

Background: Oliceridine (Olinvyk) is a μ-opioid receptor agonist that in contrast to conventional opioids preferentially engages the G-protein-coupled signaling pathway. This study was designed to determine the utility function of oliceridine versus morphine based on neurocognitive tests and cold pressor test.

Methods: The study had a randomized, double-blind, placebo-controlled, partial block three-way crossover design.

Opioid Overdose: Limitations in Naloxone Reversal of Respiratory Depression and Prevention of Cardiac Arrest.

Opioids are effective analgesics, but they can have harmful adverse effects, such as addiction and potentially fatal respiratory depression. Naloxone is currently the only available treatment for reversing the negative effects of opioids, including respiratory depression. However, the effectiveness of naloxone, particularly after an opioid overdose, varies depending on the pharmacokinetics and the pharmacodynamics of the opioid that was overdosed.

A biomarker of opioid-induced respiratory toxicity in experimental studies.

Opioids are commonly used painkillers and drugs of abuse and have serious toxic effects including potentially lethal respiratory depression. It remains unknown which respiratory parameter is the most sensitive biomarker of opioid-induced respiratory depression (OIRD). To evaluate this issue, we studied 24 volunteers and measured resting ventilation, resting end-tidal PCO (PCO) and the hypercapnic ventilatory response (HCVR) before and at 1-h intervals following intake of the opioid tapentadol.

Oral Oxycodone-Induced Respiratory Depression During Normocapnia and Hypercapnia: A Pharmacokinetic-Pharmacodynamic Modeling Study.

The widely prescribed opioid oxycodone may cause lethal respiratory depression. We compared the effects of oxycodone on breathing and antinociception in healthy young volunteers. After pharmacokinetic/pharmacodynamic (PK/PD) modeling, we constructed utility functions to combine the wanted and unwanted end points into a single function.

Inhaled Δ-tetrahydrocannabinol does not enhance oxycodone-induced respiratory depression: randomised controlled trial in healthy volunteers.

Background: In humans, the effect of cannabis on ventilatory control is poorly studied, and consequently, the effect of Δ-tetrahydrocannabinol (THC) remains unknown, particularly when THC is combined with an opioid. We studied the effect of THC on breathing without and with oxycodone pretreatment. We hypothesised that THC causes respiratory depression, which is amplified when THC and oxycodone are combined.

Cannabis-opioid interaction in the treatment of fibromyalgia pain: an open-label, proof of concept study with randomization between treatment groups: cannabis, oxycodone or cannabis/oxycodone combination-the SPIRAL study.

Background: Opioids continue to be widely prescribed for chronic noncancer pain, despite the awareness that opioids provide only short-time pain relief, lead to dose accumulation, have numerous adverse effects, and are difficult to wean. As an alternative, we previously showed advantages of using pharmaceutical-grade cannabis in a population of chronic pain patients with fibromyalgia. It remains unknown whether combining an opioid with pharmaceutical-grade cannabis has advantages, such as fewer side effects from lesser opioid consumption in chronic pain.

Intraoperative use of the machine learning-derived nociception level monitor results in less pain in the first 90 min after surgery.

In this pooled analysis of two randomized clinical trials, intraoperative opioid dosing based on the nociception level-index produced less pain compared to standard care with a difference in pain scores in the post-anesthesia care unit of 1.5 (95% CI 0.8-2.

Respiratory Effects of Biased Ligand Oliceridine in Older Volunteers: A Pharmacokinetic-Pharmacodynamic Comparison with Morphine.

Background: Oliceridine is a G protein-biased µ-opioid, a drug class that is associated with less respiratory depression than nonbiased opioids, such as morphine. The authors quantified the respiratory effects of oliceridine and morphine in elderly volunteers. The authors hypothesized that these opioids differ in their pharmacodynamic behavior, measured as effect on ventilation at an extrapolated end-tidal Pco2 at 55 mmHg, V̇E55.

Effect of spinal anesthesia-induced deafferentation on pain processing in healthy male volunteers: A task-related fMRI study.

Background: Spinal anesthesia causes short-term deafferentation and alters the crosstalk among brain regions involved in pain perception and pain modulation. In the current study, we examined the effect of spinal anesthesia on pain response to noxious thermal stimuli in non-deafferented skin areas using a functional magnetic resonance imaging (fMRI) paradigm.

Methods: Twenty-two healthy subjects participated in the study.

Carbon dioxide tolerability and toxicity in rat and man: A translational study.

Due the increasing need for storage of carbon dioxide (CO) more individuals are prone to be exposed to high concentrations of CO accidentally released into atmosphere, with deleterious consequences. We tested the effect of increasing CO concentrations in humans (6-12%) and rats (10-50%) at varying inhalation times (10-60 min). In humans, a continuous positive airway pressure helmet was used to deliver the gas mixture to the participants.

-Ketamine oral thin film-Part 2: Population pharmacodynamics of -ketamine, -norketamine and -hydroxynorketamine.

Ketamine is a versatile drug used for many indications and is administered various routes. Here, we report on the pharmacodynamics of sublingual and buccal fast-dissolving oral-thin-films that contain 50 mg of ketamine in a population of healthy male and female volunteers. Twenty volunteers received one or two 50 mg ketamine oral thin films in a crossover design, placed for 10 min sublingually ( = 15) or buccally ( = 5).