The Role of Cannabis, Cannabidiol and Other Cannabinoids in Chronic Pain. The Perspective of Physicians.

Currently, there is a renewed interest in treatments with medical cannabis and cannabinoids. Based on an increasing number of publications over the last decades that permitted new insights into mechanisms, efficacy and safety of cannabinoids, the use of cannabinergic medications is authorised in an increasing number of European and non-European countries. The alleviation of chronic, painful conditions is, since thousands of years, one of the primary reasons for the use of cannabis. Depending on the country, a wide range of medicinal cannabis preparations are available:ranging from defined cultivars of medical cannabis, mainly varying in their THC:CBD ratio, that are inhaled or taken as whole plant extracts,to highly purified single cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD),or mixtures of two enriched extracts, standardised to a 1:1 ratio of THC:CBD (nabiximols). Although conflicting opinions continue to exist, the majority of reviews in the past concluded that medical cannabis and cannabinoids play a significant role in the management of pain. Surprisingly, systematic studies to date do not support an "entourage effect" of the other plant constituents of cannabis (mainly terpenoids) in treatment of chronic pain. An emerging cannabinoid is CBD which is the only cannabinergic medication available at present that does not cause the typical "cannabis high"; it is not a "controlled substance". However, despite years of research, there is either no study or no well-conducted, head-to-head, comparison available between different cannabis cultivars, between pure cannabinoids, and between pure cannabinoids and extracts. It remains unanswered which is the optimal treatment approach.

Peripheral Nerve Field Stimulation for Chronic Back Pain: Therapy Outcome Predictive Factors.

OBJECTIVE: To identify variables that influence pain reduction following peripheral nerve field stimulation (PNFS) in order to identify a potential responder profile. METHODS: Exploratory univariate and multivariate (random forest) analyses were performed separately on 2 randomized controlled trials and a registry; all included patients with chronic back pain, mainly failed back surgery syndrome. An international expert panel judged the clinical relevance of variables to identify responders by consensus. RESULTS: Variables identified that may help predict PNFS success in patients with back pain include patient and pain characteristics (age, time since onset of pain and spinal surgery, pain medication history, position and size of pain area, pain severity, mixed nociceptive/neuropathic pain, health-related quality of life, depression, functional disability, and leg pain status), implant procedure variables (the number and position of leads, paresthesia coverage, and amount of pain relief during the trial), and programming (number of programs, cathodes, and anodes; pulse rate; pulse width; and percentage of device usage). CONCLUSIONS: While these analyses are exploratory and restricted to a limited sample size, they suggest variables that may play a role in predicting a therapeutic response. These results, however, are informative only and should be cautiously interpreted. Future research to validate the variables in a clinical study is needed.

[Cannabidiol in cancer treatment]. / Cannabidiol bei Tumorerkrankungen.

BACKGROUND: Cannabis was used for cancer patients as early as about 2500 years ago. Experimental studies demonstrated tumor-inhibiting activities of various cannabinoids more than 40 years ago. In view of the status of tetrahydrocannabinol (THC) as a regulated substance, non-psychotomimetic cannabidiol (CBD) is of particular importance. OBJECTIVES: Efficacy of pure CBD in various animal models as well as initial results (case reports) from patients. METHODS: Review of the literature on animal experiments and observations in humans. RESULTS: Preclinical studies, particularly recent ones, including numerous animal models of tumors, unanimously suggest the therapeutic efficacy of CBD. In isolated combination studies, synergistic effects were generally observed. In addition, CBD may potentially play a role in the palliative care of patients, especially concerning symptoms such as pain, insomnia, anxiety, and depression. Further human studies are warranted.

A Pilot Study of Pharyngeal Electrical Stimulation for Orally Intubated ICU Patients with Dysphagia.

OBJECTIVE: Dysphagia is a common disorder in neurological and non-neurological intensive care unit (ICU) patients and can lead to aspiration pneumonia, prolonged ventilation, and delayed extubation. Dysphagia is an independent predictor of increased mortality. In dysphagic stroke patients with tracheotomy, the use of pharyngeal electric stimulation (PES), an emerging technique to treat dysphagia, has been shown to improve airway protection and shorten time to decannulation. The objective of this study was to determine whether patients who receive PES have a lower prevalence of pneumonia and frequency of reintubation. DESIGN: Secondary analysis of a non-blinded interventional subject sample from a large clinical study with a historical age, pathology, and severity-matched control group. SETTING: ICU of a tertiary care medical center. PATIENTS: In this pilot non-blinded study, a group of 15 intubated patients in a general and a neurologic ICU received PES while orally intubated during ICU stay. A control group (n = 25) matched for age, type, and region of pathology, and severity of illness expressed by Simplified Acute Physiology Score and Therapeutic Intervention Scoring System was used to compare for pneumonia and need for reintubation. MAIN RESULTS: Patients treated with PES had significantly lower prevalence of pneumonia (4 vs 21, p = 0.00046) and frequency of reintubation (0 vs 6, p = 0.046) when compared to controls. CONCLUSION: Although limited by its small size and non-blinded design, this is the first study demonstrating the benefits of PES in ICU patients still orally intubated, thus offering a potential new method to reduce morbidity, mortality, and economic burden in a mixed ICU population. In order to further investigate and strengthen our findings, a statistically powered, randomized controlled study is recommended.

[Electrical muscle stimulation in combination with heat for patients with chronic, nonspecific low back pain : A randomized, double-blind, stratified, placebo-controlled clinical trial]. / Elektrische Muskelstimulation in Kombination mit Wärme bei Patienten mit chronischen unspezifischen Rückenschmerzen : Eine randomisierte, stratifizierte, doppelblinde, placebokontrollierte klinische Studie.

BACKGROUND: Chronic non-specific low back pain (LBP) causes more disability than any other medical condition worldwide. Electrical muscle stimulation in combination with heat (EMS/H) for management of LBP has yet not been properly studied. Our hypothesis was that EMS/H provides better pain relief and improves subjective and objective data compared to standard treatment. METHODS: Between 2015 and 2017, we conducted a 6 week randomized, double-blind, stratified, placebo controlled clinical trial, comparing two different forms of EMS/H with placebo treatment with a follow-up 12 weeks after randomization. Patients >18 years with LBP for >6 months and a pain intensity of numerical rating scale (NRS) ≥4/10 were enrolled. RESULTS: A total of 100 patients were recruited. Patients were representative of a LBP population with moderate to severe pain (NRS 5.7/10). After 18 treatments, we found a statistically significant pain reduction, which was also observed at the 12 week follow-up. CONCLUSION: EMS/H is an effective and safe method for managing LBP. A clinically relevant and persisting pain reduction, a stable decrease in self-perceived disability, an improvement in both mood and affective characterization as well as sensory characterization of pain, muscle strength and endurance may have a significant impact on the management of LBP.

The use of cannabis in supportive care and treatment of brain tumor.

Cannabinoids are multitarget substances. Currently available are dronabinol (synthetic delta-9-tetrahydrocannabinol, THC), synthetic cannabidiol (CBD) the respective substances isolated and purified from cannabis, a refined extract, nabiximols (THC:CBD = 1.08:1.00); and nabilone, which is also synthetic and has properties that are very similar to those of THC. Cannabinoids have a role in the treatment of cancer as palliative interventions against nausea, vomiting, pain, anxiety, and sleep disturbances. THC and nabilone are also used for anorexia and weight loss, whereas CBD has no orexigenic effect. The psychotropic effects of THC and nabilone, although often undesirable, can improve mood when administered in low doses. CBD has no psychotropic effects; it is anxiolytic and antidepressive. Of particular interest are glioma studies in animals where relatively high doses of CBD and THC demonstrated significant regression of tumor volumes (approximately 50% to 95% and even complete eradication in rare cases). Concomitant treatment with X-rays or temozolomide enhanced activity further. Similarly, a combination of THC with CBD showed synergistic effects. Although many questions, such as on optimized treatment schedules, are still unresolved, today's scientific results suggest that cannabinoids could play an important role in palliative care of brain tumor patients.

Peripheral nerve field stimulation (PNFS) in chronic low back pain: a prospective multicenter study.

OBJECTIVES: The goal of this study was to evaluate the long-term efficacy and safety of peripheral nerve field stimulation (PNFS) for chronic low back pain (cLBP). MATERIALS AND METHODS: In this prospective, multicenter observational study, 118 patients were admitted to 11 centers throughout Austria and Switzerland. After a screening visit, all patients underwent a trial stimulation period of at least seven days before implantation of the permanent system. Leads were placed in the subcutaneous tissues of the lower back directly in the region of greatest pain. One hundred five patients were implanted with a permanent stimulating system. Patients' evaluation of pain and functional levels were completed before implantation and one, three, and six months after implantation. Adverse events, medication usage, and coverage of the painful area and predictive value of transcutaneous electrical nerve stimulation (TENS) were monitored. RESULTS: All pain and quality-of-life measures showed statistically significant improvement during the treatment period. These included the average pain visual analog scale, the Oswestry Disability Questionnaire, the Becks Depression Inventory, and the Short Form-12 item Health survey. Additionally, medication usage with opioids, nonsteroidal anti-inflammatory drugs, and anti-convulsants showed a highly significant reduction. Complications requiring surgical intervention were reported in 9.6% of the patients. The degree of coverage of painful areas seems to be an important criterion for efficacy of PNFS, whereas TENS is presumably no predictor. CONCLUSIONS: This prospective, multicenter study confirms that PNFS is an effective therapy for the management of cLBP. Significant improvements in many aspects of the pain condition were measured, and complications were minimal.

Subcutaneous target stimulation (STS) in chronic noncancer pain: a nationwide retrospective study.

Stimulation of primary afferent neurons offers a new approach for the control of localized chronic pain. We describe the results with a new neurostimulation technique, subcutaneous target stimulation (STS), for the treatment of chronic focal noncancer pain. STS applies permanent electrical stimulation directly at the painful area via a percutaneous-placed subcutaneous lead. We reported the clinical outcomes of 111 patients with focal chronic, noncancer pain treated with STS in this first nationwide, multicenter retrospective analysis. The indications for STS were low back pain (n = 29) and failed back surgery syndrome (back pain with leg pain) (n = 37), cervical neck pain (n = 15), and postherpetic neuralgia (n = 12). Pain intensity was measured on a numerical rating scale (NRS) before and after implantation. Data on analgesic medication, stimulation systems, position, and type of leads and complications were obtained from the patients' records. After implantation, the mean pain intensity improved by more than 50% (mean NRS reduction from 8.2 to 4.0) in the entire patient group (P = 0.0009). This was accompanied by a sustained reduction in demand for analgesics. In all the patients, the STS leads were positioned directly at the site of maximum pain. Lead dislocation occurred in 14 patients (13%), infections in 7 (6%), and in 6 cases (5%), lead fractures were observed. The retrospective data analysis revealed that STS effectively provided pain relief in patients suffering from refractory focal chronic noncancer pain and that STS is an alternative treatment option. Prospective controlled studies are required to confirm these retrospective findings. This article presents a new minimally invasive technique for therapy-resistant focal pain.

The prolonged intake of L-arginine-L-aspartate reduces blood lactate accumulation and oxygen consumption during submaximal exercise.

L-arginine-L-aspartate is widely used by athletes for its potentially ergogenic properties. However, only little information on its real efficacy is available from controlled studies. Therefore, we evaluated the effects of prolonged supplementation with L-arginine-L-aspartate on metabolic and cardiorespiratory responses to submaximal exercise in healthy athletes by a double blind placebo-controlled trial. Sixteen healthy male volunteers (22 ± 3 years) performed incremental cycle spiroergometry up to 150 watts before and after intake of L-arginine-L-aspartate (3 grams per day) or placebo for a period of 3 weeks. After intake of L-arginine-L-aspartate, blood lactate at 150 watts dropped from 2.8 ± 0.8 to 2.0 ± 0.9 mmol·l(-1) (p < 0.001) and total oxygen consumption during the 3-min period at 150 watts from 6.32 ± 0.51 to 5.95 ± 0.40 l (p = 0.04) compared to placebo (2.7 ± 1.1 to 2.7 ± 1.4 mmol·l(-1); p = 0.9 and 6.07 ± 0.51 to 5.91 ± 0.50 l; p = 0.3). Additionally, L-arginine-L-aspartate supplementation effected an increased fat utilisation at 50 watts. L-arginine and L-aspartate seem to have induced synergistic metabolic effects. L-arginine might have reduced lactic acid production by the inhibition of glycolysis and L-aspartate may have favoured fatty acid oxidation. Besides, the results indicate improved work efficiency after L-arginine-L-aspartate intake. The resulting increases of submaximal work capacity and exercise tolerance may have important implications for athletes as well as patients. Key PointsAmino acids are among the most common nutritional supplements taken by athletes. They are involved in numerous metabolic pathways that affect exercise metabolism.Three weeks of L-arginine-L-aspartate supplementation resulted in lower blood lactate concentrations and oxygen consumption, diminished glucose and enhanced fat oxidation, and reduced heart rate and ventilation during submaximal cycle exercise.This implies increased submaximal work capacity and exercise tolerance, which may have important implications for both athletes as well as patients.