Medical cannabis and stigma: A qualitative study with patients living with chronic pain.

AIMS AND OBJECTIVES: To explore the ways in which stigma is experienced, and what strategies are used to manage stigma among patients using medical cannabis to ease suffering from chronic pain. BACKGROUND: Various jurisdictions have legalised medical cannabis in recent decades. Despite increasing prevalence and more liberal attitudes towards medical cannabis, it is possible that patients who use medical cannabis experience stigma. DESIGN: A phenomenological qualitative study. METHODS: Fifteen patients living with chronic pain and licensed by the Israeli Ministry of Health to use medical cannabis to treat pain symptoms for at least 1 year participated in semi-structured interviews. Transcribed data were analysed using thematic analysis to identify themes related to stigma. The manuscript is in correspondence to SRQR EQUATOR checklist. RESULTS: Expressions of stigma were more related to 'felt' than 'enacted' stigma. Stigma related to decisions to delay onset of medical cannabis treatment and the ways in which participants managed medical cannabis use during their everyday lives. Participants dissociated themselves from recreational cannabis users, by presenting themselves as responsible normative individuals and engaging in a form of normalisation known as 'normification', emphasising their own discrete and controlled medical cannabis use and cannabis' benefits. CONCLUSIONS: Patients experienced 'felt' stigma which had consequences for their self-presentations and medical cannabis use. This suggests that medical cannabis is not normalised in Israel and interventions may be needed to handle stigma related to medical cannabis. RELEVANCE TO CLINICAL PRACTICE: The findings emphasise the effects of 'felt' stigma on patients. Aiming to increase the effectiveness of medical cannabis treatment and reducing harms, we suggest that particular focus should be placed on managing stigma at the intrapersonal level. In addition, there may be a need to address stigma at the societal level including social interactions with friends, family and medical personnel.

Negative experiences of patients using medicinal cannabis: A systematic review of qualitative studies.

AIMS AND OBJECTIVES: In this study, we systematically reviewed qualitative studies concerning patients' experience with medicinal cannabis (MC) use, to gain insight into the negative effects of MC. BACKGROUND: Over the past decades, the use of MC for therapeutic purposes has increased. However, there is conflicting and insufficient data on possible negative physiological and psychological effects of MC treatment. DESIGN: A systematic review was conducted and the PRISMA guidelines were adopted. Literature searches were conducted using PubMed, PsycINFO and EMBASE. Critical Appraisal Skills Programme (CASP) qualitative checklist used to assess risk of bias in the included studies. METHODS: We included studies focusing on conventional medical treatment using cannabis-based products, approved by a physician for a particular health issue. RESULTS: Of the 1230 articles identified in the initial search, eight articles were included in the review. Following the compilation of themes in the eligible studies, six themes were identified: (1) MC approval; (2) administrative barriers; (3) social perception; (4) MC misuse/widespread effect; (5) adverse effects; and (6) dependence or addiction. These were grouped into two meta-themes: (1) administrative and social aspects of MC use; and (2) experiences of the effects of medicinal cannabis. CONCLUSIONS: Our findings call for specific attention to unique consequences associated with MC use. Further research is needed in order to assess the degree to which negative experiences associated with MC use may affect various aspects of patients' medical condition. RELEVANCE TO CLINICAL PRACTICE: Describing the complex experience of MC treatment and its spectrum of consequences for patients may enable physicians, therapists and researchers to provide more attentive and accurate MC treatment to their patients. PATIENT OR PUBLIC CONTRIBUTION: In this review, patients' narratives were explored, yet the research methods did not directly involve patients or the public.

Diagnosis, management and impact on patients' lives of cancer-related neuropathic pain (CRNP): A European survey.

OBJECTIVE: This study assessed the impact of cancer-related neuropathic pain (CRNP) on patients and the importance of the patient-healthcare professional (HCP) relationship in diagnosis and management. METHODS: A quantitative online survey was conducted involving adult patients from 13 European countries who had been diagnosed with treatable cancer and experienced symptoms of peripheral neuropathy. RESULTS: Of 24,733 screened respondents, 549 eligible persons met the inclusion criteria and completed the questionnaire. Among individuals still experiencing pain, 75% rated it as 'severe' or 'moderate'. In addition, 61% reported a negative impact on day-to-day activities, and 30% said they had stopped working as a result. A third of respondents had received no diagnosis of CRNP despite reporting painful symptoms to an HCP. HCPs spending enough time discussing pain and understanding the impact on patients' lives were each associated with an increased likelihood of a formal CRNP diagnosis. Compared with individuals currently in active cancer treatment, cancer survivors were less likely to have a diagnosis of CRNP or regular pain conversations with HCPs. CONCLUSION: CRNP remains under-recognised despite its substantial impact on patients' lives. Clinical practice may be improved by strengthening patient-HCP relationships around pain discussions and increasing the focus on pain management among cancer survivors.

The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

Volitional limbic neuromodulation exerts a beneficial clinical effect on Fibromyalgia.

Volitional neural modulation using neurofeedback has been indicated as a potential treatment for chronic conditions that involve peripheral and central neural dysregulation. Here we utilized neurofeedback in patients suffering from Fibromyalgia - a chronic pain syndrome that involves sleep disturbance and emotion dysregulation. These ancillary symptoms, which have an amplificating effect on pain, are known to be mediated by heightened limbic activity. In order to reliably probe limbic activity in a scalable manner fit for EEG-neurofeedback training, we utilized an Electrical Finger Print (EFP) model of amygdala-BOLD signal (termed Amyg-EFP), that has been successfully validated in our lab in the context of volitional neuromodulation. We anticipated that Amyg-EFP-neurofeedback training aimed at limbic down modulation would improve chronic pain in patients suffering from Fibromyalgia, by reducing sleep disorder improving emotion regulation. We further expected that improved clinical status would correspond with successful training as indicated by improved down modulation of the Amygdala-EFP signal. Thirty-Four Fibromyalgia patients (31F; age 35.6 ±â€¯11.82) participated in a randomized placebo-controlled trial with biweekly Amyg-EFP-neurofeedback sessions or sham neurofeedback (n = 9) for a total duration of five consecutive weeks. Following training, participants in the real-neurofeedback group were divided into good (n = 13) or poor (n = 12) modulators according to their success in the neurofeedback training. Before and after treatment, self-reports on pain, depression, anxiety, fatigue and sleep quality were obtained, as well as objective sleep indices. Long-term clinical follow-up was made available, within up to three years of the neurofeedback training completion. REM latency and objective sleep quality index were robustly improved following the treatment course only in the real-neurofeedback group (time × group p < 0.05) and to a greater extent among good modulators (time × sub-group p < 0.05). In contrast, self-report measures did not reveal a treatment-specific response at the end of the neurofeedback training. However, the follow-up assessment revealed a delayed improvement in chronic pain and subjective sleep experience, evident only in the real-neurofeedback group (time × group p < 0.05). Moderation analysis showed that the enduring clinical effects on pain evident in the follow-up assessment were predicted by the immediate improvements following training in objective sleep and subjective affect measures. Our findings suggest that Amyg-EFP-neurofeedback that specifically targets limbic activity down modulation offers a successful principled approach for volitional EEG based neuromodulation treatment in Fibromyalgia patients. Importantly, it seems that via its immediate sleep improving effect, the neurofeedback training induced a delayed reduction in the target subjective symptom of chronic pain, far and beyond the immediate placebo effect. This indirect approach to chronic pain management reflects the substantial link between somatic and affective dysregulation that can be successfully targeted using neurofeedback.

Cannabis-based medicines for chronic pain management: current and future prospects.

PURPOSE OF REVIEW: The medicinal use of cannabis has recently become the focus of much medical, as well as political, attention. This reality of growing use but limited evidence creates unique dilemmas for the prescribing clinician. The purpose of this review is to explore current evidence and gaps in knowledge and offer some practical considerations. RECENT FINDINGS: There is robust preclinical data regarding the relevance of the endocannabinoid system to many pain-relevant processes. However, evidence to support cannabis-based medicines clinical use is still lacking. The best evidence to date is in managing neuropathic pain, although whether effects are clinically significant remains undetermined. However, the safety profile of cannabinoids seems favorable, especially by comparison to other medications used for pain control. SUMMARY: The endocannabinoid system is undoubtedly a new and exciting pharmaceutical target for chronic pain management, but transition from preclinical to clinical studies has so far proved difficult. Although it is reasonable to consider cannabinoids for otherwise unresponsive pain, care should be taken in frail clinical populations. As this has become a socioeconomic and political issue in which agendas often take precedence over due diligence, there is a pressing need for unbiased empirical data and high quality evidence to better inform prescribers and patients.

Postoperative Pain Management Among Native and Non-native Israeli Citizens-Data From the European PAIN-OUT Registry.

PURPOSE: It has been widely reported that minority groups receive inferior emergency pain management. We aimed to determine whether this is true in the postoperative setting, as effective postoperative analgesia is an essential component of high quality medical care. DESIGN: A retrospective case-control study of paired 248 postsurgical Israeli patients. METHODS: Data were gathered from the European Union's "PAIN-OUT" registry. Quality of care measures, composite pain score, composite side effect score, and composite emotional score were analyzed. FINDINGS: Composite pain, side effect, and emotional scores were significantly higher among natives compared with non-natives. Opioid consumption did not differ between the two groups. CONCLUSIONS: In this study, immigration status was not a predictor of inferior postoperative analgesia. In contrast, non-natives benefited more from analgesic care. We suggest this stems from differing patient expectations and attitudes toward pain management between the groups, with higher expectations for analgesia on the part of native patients accounting for these observations.

An Internet-Based Survey to Assess Clinicians' Knowledge and Attitudes Towards Opioid-Induced Hypogonadism.

BACKGROUND: Long-term opioid therapy for chronic pain management requires regularly assessing and documenting benefits and side effects. Opioid-induced sex hormone disturbances are a complication that needs to be assessed routinely and perhaps not only when suspected. There is abundant literature about its prevalence, clinical consequences, and treatment, yet routine hormone screening and appropriate treatment are seldom performed in pain clinics. Ignorance, skepticism, and/or indifference are possible reasons explaining why opioid-induced hypogonadism (OIH) remains underdiagnosed among chronic pain patients. METHODS: This was an Internet-based survey reaching out to pain clinicians to assess their knowledge and attitudes regarding OIH. RESULTS: A total of 135 responses were received, representing a 23.7% response rate. Analysis of responses showed that 47% of responders were somewhat familiar with this complication, but their knowledge about the prevalence and the time to develop varied. Screening for OIH is ordered based on suspicion of its presence (50%), but not routinely (38%). Lack of knowledge was the most frequent reason adduced for not screening for OIH. Sex-related symptoms and signs are the most relevant reasons leading to suspicion and screening of OIH. Upon laboratory confirmation, most responders refer their patients to endocrinology (82%) for further management since most (60%) believe that testosterone replacement would improve their patients' health. CONCLUSIONS: Knowledge and attitudes towards OIH varied among this population of pain clinicians invited to participate in the research. Lack of knowledge and incertitude seem to impact the attitudes towards screening and treating OIH. Better medical training at undergraduate and postgraduate levels as well as continuous medical education may contribute to raising awareness about this complication and providing early treatment.

[MEDICAL MARIJUANA DEPENDENCE AMONG CHRONIC PAIN PATIENTS SUFFERING FROM DEPRESSION AND ANXIETY].

INTRODUCTION: In recent years, medical marijuana (MM) is increasingly being used for the treatment of chronic pain. Depression and anxiety have been identified as risk factors for the problematic use of prescription opioids, yet their contribution to developing MM dependence hasn't been explored up to date. In this study we explored the association between depression and anxiety severity and the risk for cannabis dependence among chronic pain patients prescribed MM. METHODS: Participants were 324 chronic pain patients prescribed MM with no cuncurrent opioid treatment. All participants were screened for depression using the Patient Health Questionnaire (PHQ-9), for anxiety using the Generalized Anxiety Disorder questionnaire (GAD-7) and for problematic use of MM according to DSM-IV criteria for cannabis dependence using the AUDADI-IT questionnaire. Logistic regression analyses controlling for additional sociodemographic and clinical factors were conducted. RESULTS: Generally, prevalence of cannabis dependence was higher among participants with levels of depression and anxiety levels compared to those without depression or anxiety. However, after controlling for confounders only participants with severe depression were significantly more likely (Adjusted Odds Ratio=5.86) to screen positive for cannabis dependence compared to those without depression. CONCLUSIONS: Severe depression may be a risk factor for problematic use of MM among chronic pain patients. Increasing use of MM calls for further explotartion of potential risk factors which may predict problematic MM use among this population.

Depressive personality vulnerability in chronic physical pain: Centrality of sociotropy.

OBJECTIVE: Chronic physical pain is one of modern medicine's principal challenges. Recently, there has been a keen research interest in the role of depressive personality vulnerability (DPV) in the course of chronic pain. This is the first attempt to examine the role of three leading DPV dimensions-sociotropy, autonomy, and self-criticism-in chronic pain. METHOD: Chronic pain patients (N = 428) were assessed four times as to their pain, disability, anxious depression, and pain-based catastrophizing. At Time 1, sociotropy, autonomy, and self-criticism were also assessed. The effects of sociotropy, autonomy, and self-criticism on pain, disability, anxious depression, and pain-based catastrophizing were examined using structural equation modeling analyses. RESULTS: All DPV dimensions uniquely predicted Time 1, but not Time 2, anxious depression. Sociotropy predicted Time 1 pain and catastrophizing over and above anxious depression, as well as an increase in catastrophizing over time. Autonomy predicted a decrease in catastrophizing and disability, and Time 1 anxious depression predicted an increase in self-criticism. CONCLUSIONS: Sociotropy appears to be a unique dimension of DPV in chronic pain.

Increased Sympathetic Outflow Induces Adaptation to Acute Experimental Pain.

BACKGROUND: There are interrelationships between the autonomic nervous system and pain. This study aims to explore the effect of different autonomic manipulations on pain perception and modulation. METHODS: Twenty healthy subjects (10 men and 10 women, mean age 25 ± 3 years) participated in this single-blinded, semi-randomized, controlled study, which included 2 study visits. Warm detection thresholds, heat pain thresholds, conditioned pain modulation (CPM), and pain adaptation were tested before and after administration of phenylephrine, clonidine, yohimbine, and saline. RESULTS: Changes in heart rate and blood pressure were found after all the pharmacological interventions. The only effect on pain measures was that yohimbine enhanced pain adaptation capacity while phenylephrine reduced it (P = 0.032). Several significant correlations were found between autonomic and pain parameters; greater decreases in heart rate after phenylephrine were associated with reduced pain ratings (r2 = 0.288, P = 0.018). In addition, enhanced pain adaptation was associated with higher total vascular resistance (r2 = 0.442, P = 0.01). CONCLUSIONS: Different effects of acute autonomic manipulations on experimental pain were found: an increase in sympathetic tone induced by yohimbine led to reduced pain sensitivity; a decrease in sympathetic tone with no effect on vagal-parasympathetic tone induced by phenylephrine led to reduction in pain adaptation capacity; and a decrease in sympathetic tone and increase in vagal parasympathetic tone by clonidine led to no change in pain adaptation capacity. While increased sympathetic outflow does facilitate pain adaptation, activation of either the sympathetic or parasympathetic limbs of the autonomic nervous system does not affect pain thresholds or CPM. Finally, a correlation exists between nociception and cardiovascular parameters only due to baroreflex activation.

Preemptive Analgesia in Hip Arthroscopy: A Randomized Controlled Trial of Preemptive Periacetabular or Intra-articular Bupivacaine in Addition to Postoperative Intra-articular Bupivacaine.

PURPOSE: To evaluate and compare the efficacy of intra-articular and periacetabular blocks for postoperative pain control after hip arthroscopy. METHODS: Forty-two consecutive patients scheduled for hip arthroscopy were randomized into 2 postoperative pain control groups. One group received preemptive intra-articular 20 mL of bupivacaine 0.5% injection, and the second group received preemptive periacetabular 20 mL of bupivacaine 0.5% injection. Before closure all patients received an additional dose of 20 mL of bupivacaine 0.5% intra-articularly. Data were compared with respect to postoperative pain with visual analog scale (VAS) and analgesic consumption, documented in a pain diary for 2 weeks after surgery. RESULTS: Twenty-one patients were treated with intra-articular injection, and 21 patients with peri-acetabular injection. There were no significant differences with regards to patient demographics or surgical procedures. VAS scores recorded during the first 30 minutes postoperatively and 18 hours after surgery were significantly lower in the periacetabular group compared with in the intra-articular group (0.667 ± 1.49 vs 2.11 ± 2.29; P < .045 and 2.62 ± 2.2 vs 4.79 ± 2.6; P < .009). There were no differences between the groups with regard to analgesic consumption. CONCLUSIONS: Periacetabular injection of bupivacaine 0.5% was superior to intra-articular injection in pain reduction after hip arthroscopy at 30 minutes and 18 hours postoperatively. However, total analgesic consumption over the first 2 postoperative weeks and VAS pain measurements were not significantly affected. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Pain Modulation and Autonomic Function: The Effect of Clonidine.

OBJECTIVE: The α2-agonist clonidine is an analgesic agent, whose yet uncertain action may involve either increase in pain modulation efficiency, change in autonomic function, and/or decrease in anxiety level. The present study aimed to examine the effect of oral clonidine on pain perception in healthy subjects in order to reveal its mode of action. DESIGN: Randomized, double-blind, placebo-controlled study. SUBJECTS: Forty healthy subjects. METHODS: Subjects received either 0.15 mg oral clonidine or placebo. We measured pain parameters of heat pain thresholds, tonic heat stimulus, mechanical temporal summation, offset analgesia (OA) and conditioned pain modulation (CPM); autonomic parameters of deep breathing ratio and heart rate variability indices obtained before, during, and after tonic heat stimulus; and psychological parameters of anxiety and pain catastrophizing. RESULTS: Clonidine decreased systolic blood pressure (P = 0.022) and heart rate (P = 0.004) and increased rMSSD (P = 0.020), though no effect was observed on pain perception, pain modulation, and psychological parameters. Autonomic changes were correlated with pain modulation capacity; for OA, the separate slope model was significant (P = 0.008); in the clonidine group, more efficient OA was associated with lower heart rate (r = 0.633, P = 0.005), unlike in the placebo group. CONCLUSIONS: The change in autonomic function that was related to the increase in pain modulation capacity, and the lack of change in anxiety, suggest a combined modulatory-autonomic mode of analgesic action for clonidine.

Is adenosine a modulator of peripheral vasoconstrictor responses?

BACKGROUND: Local vasoconstrictor reflexes, the vascular myogenic response (VMR) and the veno-arterial reflex (VAR) are necessary for the maintenance of regional blood flow and systemic arterial blood pressure during orthostatic stress. Their molecular mechanism is unknown. We postulated that adenosine is involved in the activation of these local reflexes. METHODS: This hypothesis was tested in 10 healthy male volunteers (age 29 ± 3 years, BMI 24 ± 1 kg/m(2)). We used veno-occlusive plethysmography method for the assessment of forearm arterial blood flow at baseline and upon causing local venous congestion by inflating a second cuff to 40 mmHg for 4 min (VAR) and during placement of the forearm 40 cm below cardiac level for 4 min (VMR). These measurements were repeated after local infusion of either saline or aminophylline, non-selective adenosine blockers, using the Bier block method. RESULTS: Rest baseline forearm blood flow was comparable in both arms. Saline did not affect the baseline forearm blood flow. However, aminophylline causes a significant increase in baseline forearm blood flow of 34 ± 6 % (p = 0.002). VAR demonstrated a decrease in forearm blood flow of 49 ± 4.5 % and after saline infusion it remained unchanged, 49 ± 5 % (p = 0.92). However, aminophylline causes significant decrease in the VAR by 35 ± 3 % (p = 0.02). But, both, saline and aminophylline did not affect the VMR. CONCLUSION: Arterial vasoconstriction triggered by venous congestion, which is the veno-arterial reflexis seems to be modulated by adenosine, at least partially. This "sensory" reflex requires further pharmacologic physiologic investigation.

Longitudinal associations between depression, anxiety, pain, and pain-related disability in chronic pain patients.

OBJECTIVE: The current study sets out to examine the longitudinal relationship between pain, pain-related disability, and symptoms of depression and anxiety. The latter symptoms are highly prevalent in chronic pain and seriously impede functioning and quality of life. Nevertheless, the direction of the relationship involving these variables among individuals with chronic pain is still unclear. METHODS: Four-hundred twenty-eight individuals with chronic pain (238 women, mean age 54.84 years, mean pain duration 85.21 months) treated at two pain clinics completed questionnaires regarding their pain (Short-Form McGill Pain Questionnaire), depression (Center for Epidemiological Studies-Depression Scale), state anxiety (State-Trait Anxiety Inventory), and pain-related disability (Pain Disability Index) at four time points, with an average of 5 months between measurements. Cross-lagged, structural equation modeling analyses were performed, enabling the examination of longitudinal associations between the variables. RESULTS: Significant symptoms of both depression and anxiety were reported by more than half of the sample on all waves. A latent depression/anxiety variable longitudinally predicted pain (ß = .27, p < .001) and pain-related disability (ß = .38, p < .001). However, neither pain (ß = .10, p = .126) nor pain-related disability (ß = -.01, p = .790) predicted depression/anxiety. CONCLUSIONS: Among adult patients with chronic pain treated at specialty pain clinics, high levels of depression and anxiety may worsen pain and pain-related disability.

Oral Delta-9-Tetrahydrocannabinol (THC) Increases Parasympathetic Activity and Supraspinal Conditioned Pain Modulation in Chronic Neuropathic Pain Male Patients: A Crossover, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Disordered autonomic nervous system regulation and supraspinal pain inhibition have been repeatedly described in chronic pain. We aimed to explore the effects of δ-9-tetrahydrocannabinol (THC), an emerging treatment option, on autonomic nervous system and central pain modulation measures in patients with chronic pain. METHODS: Twelve male patients with chronic radicular neuropathic pain participated in a randomized, double-blind, crossover, placebo-controlled, single-administration trial. Low/high frequency (LF/HF) heart rate variability (HRV) ratio and conditioned pain modulation (CPM) response were measured and resting-state functional magnetic resonance imaging (MRI) was performed at baseline and after sublingual administration of either 0.2 mg/kg oral THC or placebo. RESULTS: THC significantly reduced the LF/HF ratio compared with placebo (interaction effect F(1,11) = 20.5; p < 0.005) and significantly improved CPM responses (interaction effect F(1,9) = 5.2; p = 0.048). The THC-induced reduction in LF/HF ratio correlated with increased functional connectivity between the rostral ventrolateral medulla and the dorsolateral prefrontal cortex [T(10) = 6.4, cluster p-FDR < 0.005]. CONCLUSIONS: THC shifts the autonomic balance towards increased parasympathetic tone and improves inhibitory pain mechanisms in chronic pain. The increase in vagal tone correlates with connectivity changes in higher-order regulatory brain regions, suggesting THC exerts top-down effects. These changes may reflect a normalizing effect of THC on multiple domains of supraspinal pain dysregulation. CLINICAL TRIAL REGISTRY NUMBER: NCT02560545.

Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

Introduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. Methods: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, "responders" (≥30% reduction in weekly pain at any time point) were identified. Results: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months (F(3,450) = 26.22, P < 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were "responders" but could not be identified by baseline parameters. "Responders" exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious. Conclusion: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.

Medical cannabis for refractory cancer-related pain in a specialised clinical service: a cross-sectional study.

BACKGROUND AND OBJECTIVES: Cancer-related pain management in advanced stages presents a significant challenge that often requires a multidisciplinary approach. Although advancements in pharmacological and interventional therapies, a considerable number of patients still suffer from refractory pain, leading to unmet clinical needs. This study shares our experience with medical cannabis (MC) as a potential therapy for this specific population of patients with cancer-related refractory pain. METHODS: In a cross-sectional study, 252 consecutive refractory cancer-related pain patients (mean age=61.71, SD=14.02, 47.6% males) filled out detailed self-report questionnaires. Of these, 126 patients (55%) were treated with MC and 105 patients (45%) were not. RESULTS: Most patients received pain management from their oncologist, not a pain specialist. MC was mainly started for pain relief, sleep difficulties and anorexia. About 70% of patients reported subjective improvement from MC, with almost 40% reporting a significant improvement in coping with their illness. Side effects were generally mild, with fatigue and dizziness being the most common (21.78% and 23.46%, respectively). No patient required dedicated medical care for side effects. Of non-users, 65% had tried MC before and stopped due to lack of effectiveness or side effects (39.7% and 34.6%, respectively). CONCLUSION: Refractory cancer pain necessitates innovative approaches. This registry highlights that MC can effectively improve symptoms in non-responsive patients, with favourable safety profiles for this vulnerable population.

Face validity of the ICD-10 criteria of substance abuse and dependence for patients prescribed cannabis-based medicines for chronic pain-A survey of pain medicine physicians in Canada, Germany and Israel.

BACKGROUND AND OBJECTIVE: A major concern with cannabis-based medicines (CbM) and medical cannabis (MC) is the risk of abuse and dependence. The face validity of the International Classification of Diseases (ICD-10) criteria for cannabis dependence in patients prescribed CbM for chronic pain has not been assessed. DATABASES AND DATA TREATMENT: Physicians from Canada, Germany and Israel were recruited via the mailing lists of national pain societies. To be eligible, physicians had to have prescribed CbM for chronic pain treatment in the past 12 months. Participants were asked to rate the appropriateness of items adapted from the substance use module of the Composite International Diagnostic Interview Version 3.0 to assess dependence in the context of chronic pain treatment with CbM and the appropriateness of two additional items. In case of disagreement, participants were asked to give reasons. Furthermore, they were asked to suggest potential additional criteria. RESULTS: On average 69.0% of 178 participating physicians indicated agreement with the appropriateness of the ICD-10 criteria, while 20.6% indicated disagreement. The highest disagreement rate was observed for the item on repeated use despite legal problems (35.4% disagreement or strong disagreement). Reasons for disagreement were summarized into six content categories using qualitative methods of analysis. Additional criteria suggested by participants were summarized into 10 content categories. CONCLUSIONS: A collaboration of psychiatrists and pain physicians is required to define criteria and develop instruments to capture abuse and dependence of CbM in chronic pain patients. SIGNIFICANCE: Sixty-nine per cent of 178 pain medicine physicians in Canada, Germany and Israel who participated in a survey on the appropriateness of the ICD-10 criteria for cannabis abuse and dependence for patients prescribed cannabis-derived products for chronic pain assessed the criteria as appropriate, whereas 20.6% deemed the criteria as not appropriate.