Nocebo effects are adverse treatment outcomes that cannot be attributed to active treatment components. A common example is the experiencing of side effects after reading the side effect... Show moreNocebo effects are adverse treatment outcomes that cannot be attributed to active treatment components. A common example is the experiencing of side effects after reading the side effect description on a medication leaflet. Nocebo hyperalgesia, i.e., increased pain sensitivity due to nocebo effects, can be acquired via learning in both healthy and clinical populations, and has a large social and economic impact on healthcare. In the current dissertation, we investigated the experimental learning mechanisms behind the acquisition and recovery of nocebo hyperalgesia in healthy individuals and in patients with fibromyalgia, and the potential differences between groups. Additionally, we investigated the predictors of nocebo hyperalgesia acquisition and recovery to identify individuals who are more susceptible to these effects. Lastly, we stepped outside of the lab-settings and in an electronic diary study, examined the role of (experimentally-induced) nocebo hyperalgesia in daily pain progression of patients with fibromyalgia. The current dissertation offers insights for better understanding the expectancy and learning mechanisms behind nocebo hyperalgesia in individuals with and without chronic pain. These can be useful for the future design of personalised learning-based interventions for targeting nocebo effects on pain. Show less
Dam, C.J. van; Velzen, M. van; Kramers, C.; Schellekens, A.; Olofsen, E.; Niesters, M.; Dahan, A. 2023
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... Show moreBackground 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.Methods Trial design: a single-center, randomized, three-arm, open-label, exploratory trial.Trial population: 60 patients with fibromyalgia according to the 2010 definition of the American College of Rheumatologists.Intervention: Patients will be randomized to receive up to 4 daily 5 mg oral oxycodone sustained release (SR) tablet, up to 5 times 150 mg inhaled cannabis (Bediol (R), containing 6.3% delta(9)-tetrahydrocannabinol and 8% cannabidiol), or the combination of both treatments. Treatment is aimed at self-titration with the daily maximum doses given. Treatment will continue for 6 weeks, after which there is a 6-week follow-up period.Main trial endpoint: The number of side effects observed during the course of treatment using a composite adverse effect score that includes the following 10 symptoms: dizziness (when getting up), sleepiness, insomnia, headache, nausea, vomiting, constipation, drug high, hallucinations, and paranoia.Secondary and tertiary endpoints include pain relief and number of oxycodone doses and cannabis inhalations.Discussion The trial is designed to determine whether self-titration of oxycodone and cannabis will reduce side effects in chronic pain patients with fibromyalgia. Show less
Donk, T. van de; Niesters, M.; Kowal, M.A.; Olofsen, E.; Dahan, A.; Velzen, M. van 2019
The balance between safety and efficacy is important in pharmacotherapy. When the indication of a registered drug shifts to another disease or a different patient population, studies on safety and... Show moreThe balance between safety and efficacy is important in pharmacotherapy. When the indication of a registered drug shifts to another disease or a different patient population, studies on safety and efficacy need to be performed. Ketamine is a relatively __old__ drug and used for almost 50 years as an anesthetic. Recently there has been a renewed interest for the treatment of therapy-resistant chronic pain with subanesthetic doses of ketamine. This thesis describes the effects of S-ketamine in patients with chronic pain (CRPS-1 and fibromyalgia patients) and healthy volunteers. In chronic pain patients (e.g. CRPS-1) pain relief can last for months after long-term intravenous ketamine infusions, but short-term S-ketamine had no long-term efficacy in fibromyalgia patients. S-ketamine can cause a wide range of side-effects which limits its use. Therefore studies were performed in healthy volunteers to expand the knowledge on S-ketamine and the main metabolite S-norketamine to further characterize side-effects (specifically neurocognitive effects). S-norketamine does not contribute to S-ketamine__s analgesic effects and can therefore not serve as an alternative. Show less
