No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Rog DJ, Nurmikko TJ, Friede T, Young CA. Randomized, controlled trial of cannabis-based medicine in central pain in multiple sclerosis. Neurology 65: 812-819
Abstract
Central pain in multiple sclerosis (MS) is common and often refractory to treatment.
We conducted a single-center, 5-week (1-week run-in, 4-week treatment), randomized, double-blind, placebo-controlled, parallel-group trial in 66 patients with MS and central pain states (59 dysesthetic, seven painful spasms) of a whole-plant cannabis-based medicine (CBM), containing delta-9-tetrahydrocannabinol:cannabidiol (THC:CBD) delivered via an oromucosal spray, as adjunctive analgesic treatment. Each spray delivered 2.7 mg of THC and 2.5 of CBD, and patients could gradually self-titrate to a maximum of 48 sprays in 24 hours.
Sixty-four patients (97%) completed the trial, 34 received CBM. In week 4, the mean number of daily sprays taken of CBM (n = 32) was 9.6 (range 2 to 25, SD = 6.0) and of placebo (n = 31) was 19.1 (range 1 to 47, SD = 12.9). Pain and sleep disturbance were recorded daily on an 11-point numerical rating scale. CBM was superior to placebo in reducing the mean intensity of pain (CBM mean change -2.7, 95% CI: -3.4 to -2.0, placebo -1.4 95% CI: -2.0 to -0.8, comparison between groups, p = 0.005) and sleep disturbance (CBM mean change -2.5, 95% CI: -3.4 to -1.7, placebo -0.8, 95% CI: -1.5 to -0.1, comparison between groups, p = 0.003). CBM was generally well tolerated, although more patients on CBM than placebo reported dizziness, dry mouth, and somnolence. Cognitive side effects were limited to long-term memory storage.
Cannabis-based medicine is effective in reducing pain and sleep disturbance in patients with multiple sclerosis related central neuropathic pain and is mostly well tolerated.
... 43 The use of MM for chronic secondary musculoskeletal pain was investigated in 15 studies. [44][45][46][47][48][49][50][51][52][53][54][55][56][57][58] These studies included a total of 2,018 patients. More than half of the studies (n = 8) reported significant improvement in pain. ...
... More than half of the studies (n = 8) reported significant improvement in pain. [46][47][48][49]53,[55][56][57] The studies on chronic secondary musculoskeletal pain are shown in Table 4. ...
... However, after excluding studies using mixed treatment, those shorter than 4 weeks and those involving fewer than 20 patients, only 17 studies were available. 42,49,53,55,57,68,70,80,84,[86][87][88][89][91][92][93][94] The analysis of treatment approaches identified distinct phases in the treatment pathway for reducing pain in patients with chronic pain syndromes, which is illustrated in Fig. 4. The qualification of patients is the first key step for patients with chronic pain. Factors that should be considered include the type of the main diagnosis of pain syndrome, the co-occurrence of other conditions that could improve alongside pain, 55,57,88 and exhausted treatment options. ...
Chronic pain affects up to 40% of adults, contributing to high medical expenses, the loss of productivity, reduced quality of life (QoL), and disability. Chronic pain requires detailed diagnostic assessment, treatment and rehabilitation, yet approx. 80% of patients report inadequate pain management. As new treatment options are needed, we aimed to explore the effectiveness of medical cannabis-based products in managing chronic pain, with a particular focus on treatment patterns.We searched the PubMed, Scopus and Web of Science databases using keywords related to cannabinoids and chronic pain syndromes. In total, 3,954 articles were identified, and 74 studies involving 12,562 patients were included. The effectiveness of cannabis-based products varied across studies. Cannabinoids were most effective in treating chronic secondary headache and orofacial pain, chronic secondary musculoskeletal pain, chronic secondary visceral pain, and chronic neuropathic pain. Properly qualifying patients is the first crucial step in managing chronic pain, considering pain characteristics, comorbidities and other treatment options. Treatment should start with low doses of cannabinoids, which are then increased to achieve the desired therapeutic effect while minimizing adverse effects.This narrative review revealed significant gaps in the evidence regarding precise treatment patterns, particularly for the long-term maintenance treatment needed by patients with chronic pain. Medical cannabis can be considered an option for carefully selected patients with chronic pain syndromes when other treatment options fail to achieve an adequate response, and when the potential benefits outweigh the risks. However, there is still a need for well-designed clinical research to establish the long-term efficacy and safety of cannabinoids.
... Considering patients with an advanced MS condition, in the clinical trial conducted Rog et al. [54], the treatment with THC:CBD spray (2.7 mg: 2.5 mg) reduced neuropathic pain scale and numerical rating scale for pain. Intention to treat data analysis presented 89% of patients added reporting the dysesthetic pain and 11% painful spasms. ...
... Furthermore, there were no significant biochemical differences found in blood samples, nor were there any notable changes in vital signs. With that in mind, it is possible to assume that the treatment was well tolerable [54]. ...
... Then, the treatment with THC:CBD did not appear to significantly affect the MS-related neuropsychological outcomes measured. Furthermore, long-term use of THC:CBD did not show significant effects, it requires more studies to evaluate this information [54]. ...
Cannabis sativa is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for Cannabis sativa potential effects, especially tetrahydrocannabinol and cannabidiol. Scientific development has shown interest in the potential of cannabidiol in various health conditions, as it has demonstrated lower adverse events and great pharmacological potential, especially when administered topically. The present study aims to carry out a scoping review, focusing on the use of cannabidiol, in vivo models, for topical administration. Thus, the methodological approach used by the Joanna Briggs Institute was applied, and the studies were selected based on previously established inclusion cri-teria. Even though more information regarding the dose to achieve pharmacological potential is still needed, cannabidiol demonstrated potential in treating and preventing different conditions, such as glaucoma, atopic dermatitis, epidermolysis bullosa, and pyoderma gangrenosum.
... Zhou et al. showed that combining D9-THC and CBD significantly improved behavioral and neurological disability scores by lowering TNF-A and raising brain-derived neurotrophic factor (BDNF) levels. CBD has been reported to be effective in delaying the onset of symptoms and the progression of the disease when oligodendrocyte glycoprotein is used to induce EAE in mice [77][78][79][80]. This effect may be attributed to a reduction in proinflammatory cell counts, microglial and T-cell activation, axonal damage, and cytokine production in the spinal cord. ...
... This suggests that Sativex may modulate sensory-motor integration in response to painful stimulation, which would restore cortical pain-gating mechanisms [18,77]. Rog et al. [78] conducted a randomized control experiment in 2005 to examine the effects of Nabiximols on central NP. Sativex's effectiveness was demonstrated by the significant decrease in pain NRS scores that it caused. ...
... The studies presented here provide the most relevant data on the use of Sativex to enhance sleep metrics. NRS scale was used to assess sleep interruption caused by MS pain in a study [78]. The results revealed a 1.39 odds ratio (OR) for Sativex over placebo [78]. ...
Sativex is a cannabis-based medicine that comes in the form of an oromucosal spray. It contains equal amounts of Δ9-tetrahydrocannabinol and cannabidiol, two compounds derived from cannabis plants. Sativex has been shown to have positive effects on symptoms of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and sleep disorders. It also has analgesic, antiinflammatory, antitumoral, and neuroprotective properties, which make it a potential treatment option for other neurological disorders. The article reviews the results of recent preclinical and clinical studies that support the therapeutic potential of Sativex and the molecular mechanisms behind its neuroprotective benefits in various neurological disorders. The article also discusses the possible advantages and disadvantages of using Sativex as a neurotherapeutic agent, such as its safety, efficacy, availability, and legal status.
... This is particularly disturbing considering the drastic increase in American opioid deaths (68,000) in 2020, 30,31 as well as the largely unexplored analgesic properties of cannabis. 32,33,34,35 To reintroduce and act on a bill like H.R.3617 poses an opportunity for Congress to start catching up with the realities in American homes and communities. ...
... 36 Due to the restrictions imposed by the CSA as well as the negative connotations, it has been nearly impossible to receive federal funding for cannabis research that would elucidate any therapeutic potential. Despite those setbacks, studies indicating that cannabis may indeed have a significant therapeutic value slowly kept emerging, especially outside the U.S. 32,33,34,35 Despite this knowledge, medical doctors, physician assistants, and advanced registered nurse practitioners are only able to authorize the use of cannabis if their state recognizes use for the intended condition. In states without supportive marijuana legislation, this treatment option remains illegal potentially forcing healthcare practitioners to forgo best possible care and violating their Hippocratic Oath. ...
... 47 Evolving research is suggesting that cannabinoids do have analgesic properties and are likely valuable as a full or adjunctive treatment option for refractory and chronic states of pain, especially in palliative care settings. 32,33,34,35,48 As recommendations of the medicinal use of cannabis expand, an ethical dilemma arises for patients and their treating physicians in states that do not have access to medical cannabis. For example, a patient who is eligible for medicinal cannabis treating chronic pain in New York may no longer be eligible if they moved to a state lacking a comprehensive medical cannabis program, such as North Carolina or Kansas. ...
Most Americans are living with state-sanctioned cannabis jurisdiction permitting medicinal, and often, recreational use. Yet, cannabis and its cannabinoids remain on schedule-I of the controlled substances act (CSA), imposing hurdles to much needed research and promulgating outdated ‘War on Drugs’ policies and their disproportionate impact on minorities. Recent advances by the current government to decriminalize past federal cannabis possession convictions and the encouragement to State Governors to follow suit are within the current political climate and public opinion but fall short during times of an ever- faster expansion of cannabis legislation and access by the individual states. Opposing views on federal cannabis legalization have precipitated an indeterminate situation between federal and state legislation prompting inconsistent decision-making, social injustice, and health inequities across the country. The latter can be exemplified by the inconsistencies of qualifying conditions and availability of cannabis for medicinal use. Now, under the new 118th U.S. Congress, it becomes ever more important to re-focus on legislative opportunities such as the ‘Marijuana Opportunity Reinvestment and Expungement (MORE) Act of 2021’ which had been previously passed by the House of Representatives on April 1st, 2022, under the 117th Congress (2021-22). This bill aims to de-schedule and decriminalize use, possession, distribution, sale, and production of medical cannabis on the federal level. Through establishing cannabis business equity and loan programs, it seeks to promote social justice for communities disproportionately affected by the ‘War on Drugs’. This health policy research brief provides a comprehensive view of stakeholder perspectives and positions, as well as potential benefits and drawbacks - all with a historical perspective.
... Evidence summaries and clinical guideline recommendations 1. CBM use for people with chronic pain Forty-seven studies relevant to pain management were reviewed, including 22 RCT, 46-67 11 pre-post studies or uncontrolled trials, 68-78 11 cross-sectional or observational cohort studies, 79-89 and 3 case series. [90][91][92] Most studies (38/47) reported at least moderate benefits of CBM for chronic pain, [46][47][48]50,51,54,55,57,[59][60][61][62][63][64][65][66][67][68][69][70][73][74][75][76][77][78][79][80][82][83][84][86][87][88][89][90][91][92] seven were inconclusive or found insufficient evidence, 49,53,56,58,71,72,85 and two reported mixed results. 52,81 Associated improvements in secondary outcomes, including QoL, functionality, and mood, have also been observed with the use of medical cannabis in addition to reductions in pain severity, intensity, and interference. ...
... 11. CBM use for people living with chronic pain experiencing anxiety Eight studies within this review examined the treatment of anxiety with CBM in people living with chronic pain. 55,61,70,76,[96][97][98][99] Although these studies utilized a variety of CBM approaches, most evidence-including the relatively higher quality studies-reported anxiolytic effects of cannabis. For details of the individual studies, see Appendix K in Supplementary Data. ...
... In contrast to these positive results, three RCTs found no significant difference between nabiximols and placebo in depression scores. 53,55,58 For details of the individual studies, see Appendix L in Supplementary Data. ...
Background: One in five individuals live with chronic pain globally, which often co-occurs with sleep problems, anxiety, depression, and substance use disorders. Although these conditions are commonly managed with cannabinoid-based medicines (CBM), health care providers report lack of information on the risks, benefits, and appropriate use of CBM for therapeutic purposes. Aims: We present these clinical practice guidelines to help clinicians and patients navigate appropriate CBM use in the management of chronic pain and co-occurring conditions. Materials and Methods: We conducted a systematic review of studies investigating the use of CBM for the treatment of chronic pain. Articles were dually reviewed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical recommendations were developed based on available evidence from the review. Values and preferences and practical tips have also been provided to support clinical application. The GRADE system was used to rate the strength of recommendations and quality of evidence. Results: From our literature search, 70 articles met inclusion criteria and were utilized in guideline development, including 19 systematic reviews and 51 original research studies. Research typically demonstrates moderate benefit of CBM in chronic pain management. There is also evidence for efficacy of CBM in the management of comorbidities, including sleep problems, anxiety, appetite suppression, and for managing symptoms in some chronic conditions associated with pain including HIV, multiple sclerosis, fibromyalgia, and arthritis. Conclusions: All patients considering CBM should be educated on risks and adverse events. Patients and clinicians should work collaboratively to identify appropriate dosing, titration, and administration routes for each individual. Systematic Review Registration: PROSPERO no. 135886.
... There is substantial evidence and multiple clinical studies to substantiate the use of these medications for patients with multiple sclerosis (MS), as well as their approved applications for managing chronic pain, cannabis use disorder (CUD), and weight loss in individuals with AIDS [78][79][80][81]. The advancement of a compound that resembles THC shows significant potential. ...
... Interestingly, cannabinoids have also shown anti-inflammatory effects, immunosuppressive properties, and neuroprotection capability in MS [51]. Several clinical trials have studied the use of cannabinoids to manage MS [78][79][80][81]. The molecular effect of cannabinoids in MS and their function in neuroprotection and immunomodulation suggest that cannabinoids are more than a symptomatic treatment. ...
Multiple sclerosis is the predominant autoimmune disorder affecting the central nervous system in adolescents and adults. Specific treatments are categorized as disease-modifying, whereas others are symptomatic treatments to alleviate painful symptoms. Currently, no singular conventional therapy is universally effective for all patients across all stages of the illness. Nevertheless, cannabinoids exhibit significant promise in their capacity for neuroprotection, anti-inflammation, and immunosuppression. This review will examine the traditional treatment for multiple sclerosis, the increasing interest in using cannabis as a treatment method, its role in protecting the nervous system and regulating the immune system, commercially available therapeutic cannabinoids, and the emerging use of cannabis in nanomedicine. In conclusion, cannabinoids exhibit potential as a disease-modifying treatment rather than merely symptomatic relief. However, further research is necessary to unveil their role and establish the safety and advancements in nano-cannabinoid medicine, offering the potential for reduced toxicity and fewer adverse effects, thereby maximizing the benefits of cannabinoids.
... In humans, cannabinoids have shown efficacy in reducing the inflammatory pain associated with MS and arthritis. Studies by Rog et al. (2005) found that administration of an oromucosal spray containing 2.7 mg of ∆9-THC and 2.5 mg of CBD significantly reduced the mean intensity of pain and sleep disturbances compared to placebo [97]. Similarly, Svendsen et al. (2004) demonstrated that the oral synthetic cannabinoid dronabinol significantly lowered pain intensity scores compared to placebo [98]. ...
... In humans, cannabinoids have shown efficacy in reducing the inflammatory pain associated with MS and arthritis. Studies by Rog et al. (2005) found that administration of an oromucosal spray containing 2.7 mg of ∆9-THC and 2.5 mg of CBD significantly reduced the mean intensity of pain and sleep disturbances compared to placebo [97]. Similarly, Svendsen et al. (2004) demonstrated that the oral synthetic cannabinoid dronabinol significantly lowered pain intensity scores compared to placebo [98]. ...
Coronavirus disease-19 (COVID-19) is a highly contagious illness caused by the SARS-CoV-2 virus. The clinical presentation of COVID-19 is variable, often including symptoms such as fever, cough, headache, fatigue, and an altered sense of smell and taste. Recently, post-acute “long” COVID-19 has emerged as a concern, with symptoms persisting beyond the acute infection. Vaccinations remain one of the most effective preventative methods against severe COVID-19 outcomes and the development of long-term COVID-19. However, individuals with underlying health conditions may not mount an adequate protective response to COVID-19 vaccines, increasing the likelihood of severe symptoms, hospitalization, and the development of long-term COVID-19 in high-risk populations. This review explores the potential therapeutic role of cannabinoids in limiting the susceptibility and severity of infection, both pre- and post-SARS-CoV-19 infection. Early in the SARS-CoV-19 infection, cannabinoids have been shown to prevent viral entry, mitigate oxidative stress, and alleviate the associated cytokine storm. Post-SARS-CoV-2 infection, cannabinoids have shown promise in treating symptoms associated with post-acute long COVID-19, including depression, anxiety, post-traumatic stress injury, insomnia, pain, and decreased appetite. While current research primarily focuses on potential treatments for the acute phase of COVID-19, there is a gap in research addressing therapeutics for the early and post-infectious phases. This review highlights the potential for future research to bridge this gap by investigating cannabinoids and the endocannabinoid system as a potential treatment strategy for both early and post-SARS-CoV-19 infection.
... Between 2003 and 2010, a review of 18 trials involving 766 individuals examined the effectiveness of cannabis medications in treating pain, particularly neuropathic pain. The trials were of high quality, with 15 trials showing substantial analgesic effects and improvements in sleep quality [99][100][101][102][103]. The treatments were compared with placebo and smoked cannabis, with no significant side effects observed. ...
Chronic non-cancer pain, defined by the Center for Disease Control and Prevention (CDC) as lasting beyond three months, significantly affects individuals’ quality of life and is often linked to various medical conditions or injuries. Its management is complex. Cannabis, containing the key compounds Delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), has garnered interest for its potential in pain management, though it remains controversial due to its psychoactive effects and illegal status in many countries. THCprovides pain relief by blocking nociceptive stimuli but has psychoactive effects and may potentially induce dependency. CBD has calming and antipsychotic properties. The inhalation of cannabis offers quick relief but poses respiratory risks, while its oral administrations are safer but act more slowly. Short-term cannabis use can impair cognition and motor skills, while long-term use may lead to dependency and cognitive decline, especially if used from an early age. Adverse effects vary by gender and prior use, with addiction mainly linked to THC and influenced by genetics. Despite these risks, patients often report more benefits, such as improved quality of life and reduced opioid use, although the evidence remains inconclusive. The legal landscape for medical cannabis varies globally, with some positive public health outcomes like reduced opioid-related issues in areas where it is legalized. Cannabis shows promise in managing chronic pain, but its psychoactive effects and dependency risks necessitate cautious use. Future research should prioritize long-term clinical trials to establish optimal dosing, efficacy, and safety, aiding in the development of informed guidelines for safe cannabis use in chronic pain management. This review examines the use of cannabis in managing chronic non-cancer pain, focusing on its benefits, drawbacks, mechanisms, delivery methods, and impact on quality of life.
... In a placebo-controlled, crossover trial in a mixed population of Cannabis-experienced and Cannabis-naïve subjects with MS with substantial spasticity, smoked Cannabis (4% delta-9-THC) on 3 occasions reduced the level of spasticity by ~50% compared with smoking placebo cigarette. The side effects of smoked Cannabis were similar to oral delta-9-THC with the addition of unacceptable levels of feeling "high" in some subjects [80]. ...
The potential of botanical cannabinoids as potential anti-inflammatory and neuroprotective agents.
... Although, to date, Epidiolex for epilepsy is the only phytocannabinoid drug with FDA approval (in addition to three synthetic THC-related drugs largely used as anti-emetics), medicinal usage of cannabis, including products with high THC content, is legal in most US states for the treatment of cancer, epilepsy, multiple sclerosis, glaucoma, HIV/AIDS, Parkinson's disease, Crohn's disease, PTSD, ALS, terminal illnesses, and chronic nonmalignant pain, and in children with severe neurological illnesses including cerebral palsy, muscular dystrophy, cystic fibrosis, and osteogenesis imperfecta [30] . In many countries other than the US, the use of medicinal cannabis is not authorized and even criminalized. ...
Aims : Using an investigator-designed survey tool to confirm that adult patients with type 1 Gaucher disease (GD1) often self-prescribe cannabis products to try to alleviate symptoms such as lingering fatigue, chronic bone and joint pain, loss of energy, anxiety, and depression that persist despite enzyme replacement therapy (ERT) or substrate restriction therapy (SRT). Additionally, to explore whether patient reports of symptom relief and adverse side effects relate to frequency and duration of cannabis use.
Methods : We conducted an anonymous, cross-sectional questionnaire study to elicit GD1 patient-reported experiences with cannabis used to alleviate symptoms they attributed to their underlying disease. Eligible participants included individuals with GD1 aged ≥ 18 years, regardless of sex, gender, country of residence, ethnicity, state of health or GD1 treatment status. The questions included basic socio-demography (n = 9), GD diagnosis and pre-treatment signs and symptoms (n = 16), GD treatment information (n = 9), current GD symptoms (n = 12), concurrent manifestations of Parkinson’s disease (n = 6), details of cannabis use (n = 24), perceived effect of cannabis on symptoms (n = 13), and interest in participating in future studies (n = 2).
Results: 159 GD1 adults (81.5% US) responded to advertisements on patient online sites or to informational posts in advocacy group newsletters. The most frequent pre-treatment symptoms were fatigue (83.8%), bone or joint pain (79.7%), and bleeding problems (73.0%). Hemostasis substantially improved, but pain, achiness, fatigue, and anxiety often persisted. Sixty-two respondents (39%) reported very heterogeneous cannabis use. There was a positive association between the severity of persistent symptoms and the likelihood of cannabis use. Cannabis users reported improvements in muscle pain (84.3%), bone pain (82.4%), joint pain (82.4%), anxiety (70.6%), and general achiness (66.7%). However, moderate and extreme bone manifestations, fatigue, breathing problems, memory loss, and episodic dyscoordination were more prevalent among frequent users of inhaled cannabis than among non-users.
Conclusion: Our results justify further investigations to determine the efficacy and safety of cannabis specifically for GD1 patients. Although randomized controlled trials would be optimal, well-designed observational GD registry studies may be a more practical approach. Although some patients may be reluctant to talk openly with their doctors about cannabis, they should routinely be queried about such use by primary care physicians and GD specialists who, in turn, must be able to provide informed guidance on safety, dosage, and potential interactions with other medications the patient is using.
... Los cannabinoides tienen un efecto modesto en el dolor central en la esclerosos múltiple. 79 ...
Los ensayos randomizados, doble ciegos, controlados con placebo sobre el dolor neuropático son cada vez más comunes y por ende se necesita una revisión actualizada de la evidencia disponible. Los estudios fueron identificados por medio de búsquedas en MEDLINE y EMBASE. Los valores del número necesario a tratar (NNT) y número necesario a dañar (NND) se utilizaron para comparar la eficacia y seguridad de los diferentes tratamientos para un número de condiciones dolorosas neuropáticas. Se incluyeron ciento setenta y cuatro estudios, lo que representa un 66% de incremento en los ensayos randomizados, controlados con placebo publicados en los últimos 5 años. Se examinó la polineuropatía dolorosa (más comúnmente debida a diabetes) en 69 estudios, neuralgia post-herpética en 23, mientras que la injuria nerviosa periférica, dolor central, neuropatía por HIV, y neuralgia de trigémino fueron estudiados con menor frecuencia. Los antidepresivos tricíclicos, los inhibidores de la recaptación de serotonina y noradrenalina, los anticonvulsivantes gabapentina y pregabalina, y los opioides son las clases de drogas para las cuales existe la mejor evidencia de un efecto clínico relevante. A pesar del 66% de incremento en los ensayos publicados, sólo se obtuvo una limitada mejoría en el tratamiento del dolor neuropático. Una amplia proporción de pacientes con dolor neuropático permanece con un insuficiente alivio del dolor. Este hecho exige otras opciones de tratamiento para abordar el dolor neuropático crónico. Para evaluar la hipótesis de que una clasificación basada en el mecanismo puede ayudar a mejorar el tratamiento de pacientes individuales, se necesitan ensayos farmacológicos de gran escala que apunten a identificar los posibles subgrupos de pacientes que tengan probabilidades de responder a drogas específicas.
... Cannabinoids act via CB1 and CB2 receptors within the endocannabinoid system, which plays a role in pain management. Although its full benefits for NP are still under investigation, data suggest that cannabis with a CBD:THC ratio of 1:1 or higher can reduce pain in patients with MS [113]. The use of cannabinoids and their safety profile as beneficial in NP management have been established by the American Academy of Neurology [114]. ...
Multiple sclerosis is a chronic infammatory disease that afects the central nervous system and can cause various types of
pain including ongoing extremity pain, Lhermitte’s phenomenon, trigeminal neuralgia, and mixed pain. Neuropathic pain is
a major concern for individuals with multiple sclerosis as it is directly linked to myelin damage in the central nervous system
and the management of neuropathic pain in multiple sclerosis is challenging as the options available have limited efcacy and
can cause unpleasant side efects. The literature search was conducted across two databases, PubMed, and Google Scholar.
Eligible studies included clinical trials, observational studies, meta-analyses, systematic reviews, and narrative reviews.
The objective of this article is to provide an overview of literature on pharmacological and non-pharmacological strategies
employed in the management of neuropathic pain in multiple sclerosis. Pharmacological options include cannabinoids,
muscle relaxants (tizanidine, baclofen, dantrolene), anticonvulsants (benzodiazepines, gabapentin, phenytoin, carbamazepine,
lamotrigine), antidepressants (duloxetine, venlafaxine, tricyclic antidepressants), opioids (naltrexone), and botulinum toxin
variants, which have evidence from various clinical trials. Non-pharmacological approaches for trigeminal neuralgia may
include neurosurgical methods. Non-invasive methods, physical therapy, and psychotherapy (cognitive behavioral therapy,
acceptance and commitment therapy and mindfulness-based stress reduction) may be recommended for patients with
neuropathic pain in multiple sclerosis. The choice of treatment depends on the severity and type of pain as well as other
factors, such as patient preferences and comorbidities. There is a pressing need for healthcare professionals and researchers
to prioritize the development of better strategies for managing multiple sclerosis-induced neuropathic pain.
... Another plant-based cannabinoid medicine approved for therapeutic uses is Sativex (see Table 1), which contains an almost equal concentration of THC and CBD, is administered orally as an ethanolic spray, and is prescribed for people with multiple sclerosis with moderate to severe spasticity and, in some countries, for neuropathic pain [28]. In terms of potential psychoactivity, Sativex has been reported to be generally well tolerated and does not produce the 'feeling high' effect in most users that THC can usually produce [29]. ...
The Medical Cannabis Access Programme in Ireland currently provides access to cannabis to patients with one of three conditions when other treatments have not been successful. The three conditions are spasticity (stiff and/or rigid muscles) associated with multiple sclerosis, nausea and vomiting associated with chemotherapy, and severe epilepsy.
This evidence review was conducted to inform a Department of Health review of the current Medicinal Cannabis Access Programme on the suitability of cannabis-based products for medical conditions. We found evidence to support the use of prescribed medicinal cannabis for certain conditions for which it is currently approved in Ireland, such as nausea and vomiting in cancer and spasticity in multiple sclerosis. There was also evidence of a significant benefit for neuropathic or nerve pain, which can occur with conditions such as multiple sclerosis, diabetes or spinal cord injury.
For most other conditions, including anxiety and pain in conditions such as cancer, rheumatic diseases and fibromyalgia, there is no conclusive evidence to confirm the efficacy of prescribed medicinal cannabis.
Regarding the safety of prescribed medicinal cannabis, the review found that although serious adverse events do not appear to be common, there is some evidence that some side effects such as dizziness, dry mouth, sedation, and headache can occur. Mixed evidence was found, however, on the likelihood of other adverse events such as drowsiness, nausea, and any psychiatric disorder adverse events. Our findings are similar to those reported by other overviews.
This review was an overview of reviews. While traditional systematic reviews gather evidence from existing original research studies (primary studies), an overview of reviews gathers evidence from existing systematic reviews. We focused on systematic reviews of studies of adults who received prescribed medicinal cannabis containing natural or synthetic cannabidiol (CBD) or tetrahydrocannabinol (THC) or their derivatives, and excluded evidence on cannabis for recreational use or for medicinal use without prescription/medical supervision.
The 47 included systematic reviews covered research from the last 30+ years on a wide range of medical conditions, including cancer, multiple sclerosis, rheumatic diseases, chronic pain, and mental health and neuropsychological conditions. The evidence review revealed a fragmented body of research – many types of medicinal cannabis exist, making it difficult to gather a strong body of evidence for one particular formulation for a given condition or complaint. Further high-quality research is needed based on randomised controlled trials. In the meantime, this review will help inform decision making in relation to future policy on the use of prescribed medicinal cannabis along with input from patient groups, clinicians, and service planners.
... Of the 10 studies that were included (total N = 510), seven included patients with multiple sclerosis. No evidence was found for cognitive impairment when comparing performance under treatment and control conditions; only one study reported impairment, and this was specific to a measure of long-term memory storage [24]. There has been speculation that CBD may attenuate THC effects [25,26], which could explain the lack of cognitive impairment observed in the studies included in the review, but recent evidence suggests that this is unlikely and that coadministration of CBD may even increase blood THC concentrations [17,[27][28][29]. ...
Medical cannabis use is increasing in Australia and other jurisdictions, yet little is known about the effects of medical cannabis on cognitive function. Findings from studies of non-medical (‘recreational’) cannabis may not be applicable to patients using prescribed medical cannabis to manage a health condition.
In this semi-naturalistic, open-label trial, patients with various health conditions attended a single laboratory session in which they self-administered a standard dose of prescribed medical cannabis as per instructions on the pharmacy label. We assessed cognitive performance using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and Druid application (app) prior to and following (CANTAB: + 3 h; Druid: + 3 and 5.5 h) medical cannabis self-administration. We also assessed subjective drug effects prior to and following (1, 2 and 4 h) medical cannabis self-administration using a range of 0–10 cm visual analogue scales (‘stoned’, ‘sedated’, ‘relaxed’, ‘comfortable’, ‘anxious’ and ‘confident’). Data were analyzed using linear fixed-effect models.
Participants (N = 40; 22 females) were prescribed a range of products including orally administered oils (n = 23) and flower for vaporization (n = 17). Participants had a mean (standard deviation [SD]) age of 41.38 (12.66) years and had been using medical cannabis for a mean (SD) of 10.18 (8.73) months. Chronic non-cancer pain was the most common indication for medical cannabis use (n = 20), followed by sleep disorder (n = 18) and anxiety (n = 11). The mean (SD) delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) dose administered by participants was 9.61 (8.52) mg/9.15 (10.11) mg among those using an oil, and 37.00 (24.53) mg/0.38 (1.58) mg among those who vaporized flower, respectively. Participants’ performance improved over time on the CANTAB Multitasking Test and Rapid Visual Information Processing test (both p-values <0.001). All other changes in cognitive performance measures over time were non-significant (p > 0.05). Vaporization of flower was associated with significantly stronger subjective feelings of ‘stoned’ and ‘sedated’ relative to oils (both p < 0.001).
These findings suggest that prescribed medical cannabis may have minimal acute impact on cognitive function among patients with chronic health conditions, although larger and controlled trials are needed.
... In central post-stroke neuropathy, amitriptyline [79] and lamotrigine [80] have proven efficacy, whereas conflicting results have emerged from pregabalin [59]. In MS-related central pain, duloxetine, levetiracetam [81], and cannabinoids have been found to be effective [82,83]. Following spinal cord injury, trials have shown benefits from lamotrigine, botulinum toxin, and pregabalin [84][85][86], whereas conflicting results have been observed for amitriptyline and gabapentin [59]. ...
Neuropathic pain, traditionally considered a chronic condition, is increasingly encountered in the emergency department (ED), accounting for approximately 20% of patients presenting with pain. Understanding the physiology and key clinical presentations of neuropathic pain is crucial for ED physicians to provide optimal treatment. While diagnosing neuropathic pain can be challenging, emphasis should be placed on obtaining a comprehensive medical history and conducting a thorough clinical examination. Patients often describe neuropathic pain as a burning or shock-like sensation, leading them to seek care in the ED after ineffective relief from common analgesics such as paracetamol and NSAIDs. Collaboration between emergency medicine specialists, neurologists, and pain management experts can contribute to the development of evidence-based guidelines specifically tailored for the emergency department setting. This article provides a concise overview of the common clinical manifestations of neuropathic pain that may prompt patients to seek emergency care.
... evaluating CBM on peripheral NP in a design very similar to the present study (outcome measure and number of patients) did not find an effect of CBD, THC, or the combination of THC and CBD on peripheral neuropathic pain [18]. Furthermore, no effect of Dronabinol (synthetic THC) was found on central pain in the study by Schimrigk [20,21]. However, in a larger 14 weeks RCT by Langford et al. (2012) also investigating nabiximols the primary endpoint of a 30% pain reduction was not met [22]. ...
Patients with multiple sclerosis (MS) and spinal cord injury (SCI) commonly sustain central neuropathic pain (NP) and spasticity. Despite a lack of consistent evidence, cannabis-based medicine (CBM) has been suggested as a supplement treatment. We aimed to investigate the effect of CBM on NP and spasticity in patients with MS or SCI. We performed a randomized, double-blinded, placebo-controlled trial in Denmark. Patients aged ≥18 years with NP (intensity >3, ≤9 on a numerical rating scale (NRS0-10) and/or spasticity (>3 on NRS0-10) were randomized to treatment consisting of either delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), a combination of THC&CBD in maximum doses of 22.5 mg, 45 mg and 22.5/45 mg per day, respectively, or placebo. A baseline registration was performed before randomization. Treatment duration was six weeks followed by a one-week phaseout. Primary endpoints were the intensity of patient-reported NP and/or spasticity. Between February 2019 and December 2021, 134 patients were randomized (MS n = 119, SCI n = 15), where 32 were assigned to THC, 31 to CBD, 31 to THC&CBD, and 40 to placebo. No significant difference was found for: mean pain intensity (THC 0.42 (−0.54–1.38), CBD 0.45 (−0.47–1.38) and THC&CBD 0.16 (−0.75–1.08)), mean spasticity intensity (THC 0.24 (−0.67–1.45), CBD 0.46 (−0.74–1.65), and THC&CBD 0.10 (−1.18–1.39), secondary outcomes (patient global impression of change and quality of life), or any tertiary outcomes. We aimed to include 448 patients in the trial; however, due to COVID-19 and recruitment challenges, fewer were included. Nevertheless, in this four-arm parallel trial, no effect was found between placebo and active treatment with THC or CBD alone or in combination on NP or spasticity in patients with either MS or SCI. The trial was registered with the EU Clinical Trials Register EudraCT (2018-002315-98).
... 4 O Pesquisas atuais reforçam a classificação apresentada nessa cartilha e ainda acrescentam o uso terapêutico da maconha em epilepsias como evidência conclusiva. [5][6][7][8][9][10][11][12][13] Entretanto, pelo modesto número de pesquisas feitas nessas áreas, observa-se ainda limitação de evidências seguras no uso de produtos derivados de Cannabis nas seguintes condições citadas: 14 É preciso compreender que os benefícios do uso dos produtos derivados de Cannabis podem ser proporcionados não apenas para as pessoas com os problemas citados, mas também para os familiares e cuidadores que os acompanham. Por isso, é necessário ampliar de forma quantitativa e qualitativa as pesquisas e informar a população sobre o uso medicinal da maconha, no intuito de reduzir o preconceito social intrínseco associado à planta e melhorar a qualidade de vida das pessoas. ...
O uso medicinal de Cannabis tem registros históricos que datam aproximadamente de 3.000 anos a.C. e persistiu em diversos momentos da história. Os estudos clínicos sobre esse uso iniciaram-se na década de 1960, porém as pesquisas foram interrompidas em razão da política proibicionista do uso de Cannabis, reconhecido como droga ilícita. O retorno das pesquisas nos anos 1990 ratificou os efeitos terapêuticos dessa planta, tornando-a um potencial recurso a ser ofertado pelo Sistema Único de Saúde, com acesso pela Atenção Primária à Saúde. Com este ensaio, propomos refletir sobre o papel da Medicina de Família e Comunidade enquanto especialidade relevante no manejo terapêutico de Cannabis medicinal. Essa reflexão parte dos princípios da especialidade e do Sistema Único de Saúde, assim como é fundamentada nas evidências clínicas quanto ao uso medicinal da maconha.
Background: Neuropathic pain (NP) is a chronic condition caused by abnormal neuronal excitability in the nervous system. Current treatments for NP are often ineffective or poorly tolerated. Hence, we reviewed the efficacy and safety of novel drugs or devices that target neuronal excitability in NP patients compared with placebo, sham, or usual care interventions.
Methods: Six databases were searched for parallel randomized controlled trials (RCTs) reporting novel devices (rTMS, SCS, and TENS) or drugs (EMA401, capsaicin 8% patch, and Sativex) for NP. Data were extracted and quality was assessed using the ROB2 tool. The random-effects inverse variance method was used for analysis.
Results: In our review of 30 RCTs with 4251 participants, device-based interventions were found to be more effective in reducing pain scores than control interventions (SMD = −1.27, 95% CI: −1.92 to −0.62). However, high heterogeneity was seen (p<0.01, I2 = 91%), attributable to the etiology of NP (R2 = 58.84%) and year of publication (R2 = 49.49%). Funding source and type of control comparator were ruled out as cause of heterogeneity. Although drug interventions did not differ from placebo interventions in absolute pain reduction (SMD = −1.21, 95% CI: −3.55 to 1.13), when comparing relative change in pain intensity from baseline, drug interventions were found to be effective (SMD = 0.29, 95% CI: 0.04–0.55). Asymmetry in the funnel plot was visualized, suggesting publication bias. Certainty of evidence was very low according to GRADE assessment.
Conclusions: Our review indicates that device-based interventions are more effective than control interventions in reducing pain intensity in NP. Nevertheless, available evidence is limited due to heterogeneity and publication bias, prompting the need for more high-quality RCTs to confirm the efficacy and safety of these interventions.
Cannabis sativa L. has been an important medicinal and recreational plant since ancient times due to the presence of cannabinoids. Recently, there has been resurgence in cannabis research on account of phytochemical cannabidiol (CBD) oweing to its immense medicinal properties. This study reports the morphological, anatomical, phytochemical and molecular characterization of C. sativa collected from different regions in North India for diversity analysis and high-CBD accessions. The plant height, stem diameter, leaf length, and number of primary branches significantly differed (p < 0.05) among the accessions. There is considerable diversity in the size, shape and surface ornamentation of C. sativa seeds. However, the shape, size and annulus diameter of the pollen grains exhibited a narrow range in subtropical climates. The collenchymatous tissue revealed diversity among the accessions, producing wavy stems in most male accessions. The northern Indian cannabis populations are dominated by intermediate chemotypes, where both CBD and tetrahydrocannabinol (THC) are present. CBD-rich fibre-type accessions are rarely found in nature. We found one CBD-rich accession with 0.19% THC and 1.36% CBD content, which could be a potential parental line for future breeding programmes. Dendrogram clustering and population structure analysis grouped the accessions into two major subpopulations irrespective of chemotype and sex. Overall, this comprehensive study provides valuable insights into the diversity of Indian C. sativa accessions, laying a foundation for further breeding and conservation efforts for CBD-rich Indian Cannabis germplasms.
The landscape of medical cannabis has evolved dramatically over the past few decades. Once stigmatized and illegal in most parts of the world, cannabis is now recognized for its potential therapeutic benefits, supported by an expanding body of scientific research. However, the transition from prohibition to medical recognition is shaped by complex interactions among scientific advancements, public perception and regulatory frameworks for its legalization. This review examines the recent breakthroughs in medical cannabis research, explores the shifting public perceptions and the stigma associated with its use and discusses strategies for enhancing the safety of medical cannabis. We also synthesize the connections between scientific research, public perception and safety considerations in the uses of medical cannabis, providing a comprehensive understanding of how these elements influence each other and shape the future of medical cannabis use for patient adherence.
Cannabinoids represent a highly researched group of plant-derived ingredients. The substantial investment of funds from state and commercial sources has facilitated a significant increase in knowledge about these ingredients. Cannabinoids can be classified into three principal categories: plant-derived phytocannabinoids, synthetic cannabinoids and endogenous cannabinoids, along with the enzymes responsible for their synthesis and degradation. All of these compounds interact biologically with type 1 (CB1) and/or type 2 (CB2) cannabinoid receptors. A substantial body of evidence from in vitro and in vivo studies has demonstrated that cannabinoids and inhibitors of endocannabinoid degradation possess anti-inflammatory, antioxidant, antitumour and antifibrotic properties with beneficial effects. This review, which spans the period from 1940 to 2024, offers an overview of the potential therapeutic applications of natural and synthetic cannabinoids. The development of these substances is essential for the global market of do-it-yourself drugs to fully exploit the promising therapeutic properties of cannabinoids.
Introduction:
Multiple sclerosis (MS) is an inflammatory and degenerative autoimmune condition, resulting frequently in a disabling condition. Significant improvements of long-term prognosis have been recently achieved with an early and more aggressive use of disease modifying therapies (DMTs). Addressing the complexity of managing its progressive forms remains a significant challenge.
Areas covered:
This review provides an update on DMTs for relapsing-remitting MS (RRMS) and progressive MS and their efficacy, safety, and mechanism of action, emphasizing the critical role of biomarkers in optimizing treatment decisions. Moreover, some key information on drugs used to manage symptoms such as pain, fatigue, spasticity and urinary problems will be provided. The literature search was conducted using PubMed, Embase, and Cochrane Library databases covering the period from January 2000 to January 2024.
Expert opinion:
Major advances have been achieved in the treatment of RRMS. Treatment should start immediately as soon as the neurologist is confident with the diagnosis and its choice should be based on the prognostic profile and on the patient's propensity to accept drug-related risks. The therapeutic landscape for progressive MS is quite disappointing and necessitates further innovation. Personalized medicine, leveraging biomarker insights, holds promise for refining treatment efficacy and patient outcomes.
ABSTRACT: Trigeminal neuralgia (TN) is a condition characterised by intense, paroxysmal pain, i.e. sudden, intermittent attacks in the orofacial region innervated by the branches of the trigeminal nerve. Episodes of pain generally occur spontaneously, but can be triggered by stimuli that are innocuous to most individuals, such as the touch of a finger on a specific area of the face or even habitual tasks such as putting on make-up, brushing teeth, chewing and even talking. The limited knowledge about the aetiology and pathophysiology of trigeminal neuralgia means that its treatment remains a major challenge for health professionals. Early and accurate diagnosis of TN is fundamental to the success of therapeutic interventions and can reduce or eliminate pain episodes. Pharmacological therapy is usually the first option, but it must be individualised and tailored to the patient's particularities and general condition. Some studies have shown the effectiveness of cannabinoids in promoting analgesia in chronic pain of various etiologies, especially neuropathic pain associated with diabetes, human immunodeficiency virus, multiple sclerosis, severe rheumatoid arthritis and fibromyalgia. They have also shown satisfactory results for controlling pain of oncological origin, post-traumatic pain, post-surgical pain, neuropathic pain and peripheral neuropathies. Over the last decade, interest in cannabis in medicine and dentistry has increased, and several countries, including the United States and Canada, have produced their own legislation on it and cannabis-based medicines. This study aimed to carry out a scoping review of the available literature, taking into account the efficacy, indications and doses used of cannabinoids in the NT. The databases used were Pubmed, ScienceDirect and LILACS. Articles were included in English, Portuguese and Spanish, with no year restriction. A total of 70 relevant articles were identified, however after excluding duplicates, 49 articles were selected for title evaluation and were submitted for reading. After screening, 5 full-text articles were
evaluated. One article was excluded because it was a literature review and three studies met the eligibility criteria and were included in the review for data extraction and evaluation. The studies analysed highlight the therapeutic potential of cannabinoids in the management of TN and other forms of neuropathic pain. They emphasise the efficacy of both synthetic and natural cannabinoids in mitigating pain sensitivity in patients diagnosed with multiple sclerosis and post-stroke pain syndrome
with associated TN. Although they suggest that cannabinoids may represent an alternative for cases of neuropathic pain that are refractory to conventional treatments, among others NT. Scientific evidence on this therapeutic agent is still insufficient, although some studies have shown benefits. However, more clinical trials are needed to raise the level of evidence about the benefits of this treatment, to fully understand its long-term effects and to establish the best dosage and safety practices.
KEYWORDS: Trigeminal neuralgia; Cannabinoids
Multiple sclerosis (MS) is a complex autoimmune disease characterized by inflammation, demyelination, and neurodegeneration, with oxidative stress playing a pivotal role in its pathogenesis. Recognizing the importance of mitigating oxidative damage, this abstract provides a succinct overview of the therapeutic potential of specific antioxidants—Ginkgo biloba, melatonin, curcumin, Edaravone, and N-acetyl cysteine—in the context of MS. Ginkgo biloba, a renowned herbal supplement, possesses robust antioxidant and anti-inflammatory properties. Preclinical phase studies suggest it can modulate immune responses, reduce neuroinflammation, and potentially impede MS progression. Melatonin, a potent antioxidant hormone, displays neuroprotective and immunomodulatory effects, positioning it as a promising adjunct therapy for MS. Curcumin, the active component of turmeric, demonstrates anti-inflammatory and antioxidant actions, offering potential benefits in reducing neuroinflammation and promoting remyelination. Edaravone, a free radical scavenger approved for neurodegenerative disorders, holds promise in alleviating MS-related oxidative stress. N-acetyl cysteine, a glutathione precursor, exhibits neuroprotective and anti-inflammatory properties, making it a potential therapeutic avenue for MS. This chapter will delve into the therapeutic potential of these antioxidants for MS management through a discussion of preclinical and clinical trials.
Cannabis use and cannabis use disorders have taken on a new social significance as a result of partial legalization. In 2021 a total of 4.5 million adults (8.8%) in Germany used the drug. The number of users as well as problematic use have risen in the last decade. Cannabis products with a high delta-9-tetrahydrocannabinol (THC) content and their regular use lead to changes in cannabinoid receptor distribution in the brain and to modifications in the structure and functionality of relevant neuronal networks. The consequences of cannabinoid use are particularly in the psychological functioning and can include intoxication, harmful use, dependence with withdrawal symptoms and cannabis-induced mental disorders. Changes in the diagnostics between ICD-10 and ICD-11 are presented. Interdisciplinary S3 guidelines on cannabis-related disorders are currently being developed and will be finalized shortly.
Interest in medical cannabis and cannabis-based medicinal products (CBMPs) has increased greatly in recent years. Two cannabinoids are of principal importance; delta-9-tetrahydrocannabinol (∆9-THC), the primary psychoactive component, and also cannabidiol (CBD), considered non-intoxicating. Each has distinct mechanisms of action and different therapeutic potentials. CBMPs differ in their ∆9-THC and CBD components; predominantly ∆9-THC, balanced formulations with equivalent ∆9-THC and CBD elements, and CBD-predominant products. In this narrative review, we evaluate the published evidence for the clinical benefits of CBMPs and overall benefits in well-being. We also review the overall safety profile and discuss the potential for dependence with CBMPs. Evidence can be drawn from a wide range of randomized and other controlled studies and from observational real-world studies. Most data from observational registry studies are supportive of ∆9-THC-based products (∆9-THC-predominant or balanced CBMPs) in the management of chronic neuropathic pain. Balanced products are also effective in reducing spasticity in multiple sclerosis. Most CBMPs show benefit in providing symptomatic benefits in reducing anxiety, nausea, and in improving sleep, but the place of specific products is more subtle, and choice guided by specific circumstances. Symptomatic improvements are accompanied by improved quality of life and well-being. Safety data indicate that CBMPs are generally well tolerated in most patients without specific contraindications. The majority of adverse effects are non-serious, and transient; most are principally associated with ∆9-THC and are dose-dependent. In contrast to recreational cannabis use, there is little evidence from clinical studies that CBMPs have any potential for dependence.
Aim
Cannabis-based medication has recently been made available in the NHS for reducing pain and spasticity in patients with multiple sclerosis (MS). The currently available preparation of Sativex (nabiximols) contains a combination of botanical cannabis extracts with cannabidiol (CBD) and tetrahydrocannabinol (THC) with almost equal amounts in addition to minor cannabinoids and terpenoids and is delivered via an oro-mucosal spray. The present study aims to examine the use and trends in prescribing cannabinoid-based Sativex to control pain in patients diagnosed with MS.
Methods
Primary care prescribing data for cannabinoid-based Sativex (2013-2022) from the Prescription Cost Analysis were extracted and analysed. Linear regression analyses were performed to examine prescription trends and prescription costs (average change per year).
Results
There was a general increasing trend in the number of prescriptions each year, from 4.42 items dispensed per 100,000 people in 2013 to 5.15 in 2022. Overall, prescription items for cannabinoid-based Sativex increased by 0.34% per year (95% CI:−3.98, 4.67, p = 0.860) on average between 2013 and 2022. On average, a 2.43% (95% CI: −5.78, 0.92, p = 0.133) increase per year was observed for the costs of cannabinoid-based Sativex from 2013 to 2022.
Conclusion
The results suggested that cannabinoid-based Sativex should be considered an option due to its effectiveness, acceptable tolerance, and safety profile in the prescribing of Sativex.
Introduction Perceptions of cannabis as a potential medical treatment for mood and anxiety disorders have been increasing in the context of legalizations, availability, and medical cannabis programs, though current evidence predominately indicates risks and negative effects of cannabis use (CU) on mental health outcomes. This study aims to understand motivations, perceptions, effects, and patterns of CU in individuals with mood and anxiety disorders.
Methods Thirty-six adult patients diagnosed with mood or anxiety disorders, obsessive-compulsive disorder, or posttraumatic stress disorder who were currently using cannabis completed an in-depth qualitative interview on individual motivations, perceptions, experiences, effects, and patterns of their CU. The thematic analysis focused on phases of CU and sources of cannabis products and information.
Results Reported motivations for initiation of CU included curiosity, peer pressure, and dissatisfaction with conventional treatments. Factors such as psychotropic effects and coping with mental health symptoms and insomnia contributed to the continuation of CU. More negative effects, including cognitive dysfunction, worsening of mood, and anxiety symptoms, were acknowledged with ongoing CU. Concerning findings included common initiation of CU before age 18, combined medical and recreational CU, rare consultation of medical professionals on CU, and potential effects and harms.
Discussion Findings indicate individual complexity of motivations, perceptions, and patterns of CU in the study population. The reported potential beneficial effects of specific cannabis products should be further investigated. Findings emphasize patient-provider dialogue on both CU and conventional treatments. Information from this study can contribute to and inform the development of education, prevention, and intervention strategies.
Objective
The objective of this study is to evaluate the comparative benefits and harms of opioids and cannabis for medical use for chronic non-cancer pain.
Design
Systematic review and network meta-analysis.
Data sources
EMBASE, MEDLINE, CINAHL, AMED, PsycINFO, PubMed, Web of Science, Cannabis-Med, Epistemonikos and the Cochrane Library (CENTRAL) from inception to March 2021.
Study selection
Randomised trials comparing any type of cannabis for medical use or opioids, against each other or placebo, with patient follow-up ≥4 weeks.
Data extraction and synthesis
Paired reviewers independently extracted data. We used Bayesian random-effects network meta-analyses to summarise the evidence and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach to evaluate the certainty of evidence and communicate our findings.
Results
Ninety trials involving 22 028 patients were eligible for review, among which the length of follow-up ranged from 28 to 180 days. Moderate certainty evidence showed that opioids provide small improvements in pain, physical functioning and sleep quality versus placebo; low to moderate certainty evidence supported similar effects for cannabis versus placebo. Neither was more effective than placebo for role, social or emotional functioning (all high to moderate certainty evidence). Moderate certainty evidence showed there is probably little to no difference between cannabis for medical use and opioids for physical functioning (weighted mean difference (WMD) 0.47 on the 100-point 36-item Short Form Survey physical component summary score, 95% credible interval (CrI) −1.97 to 2.99), and cannabis resulted in fewer discontinuations due to adverse events versus opioids (OR 0.55, 95% CrI 0.36 to 0.83). Low certainty evidence suggested little to no difference between cannabis and opioids for pain relief (WMD 0.23 cm on a 10 cm Visual Analogue Scale (VAS), 95% CrI −0.06 to 0.53) or sleep quality (WMD 0.49 mm on a 100 mm VAS, 95% CrI −4.72 to 5.59).
Conclusions
Cannabis for medical use may be similarly effective and result in fewer discontinuations than opioids for chronic non-cancer pain.
PROSPERO registration number
CRD42020185184.
We investigate the impacts of state legalization of products containing cannabidiol (CBD), a non‐psychoactive alternative to marijuana, on opioid prescribing rates. Research suggests that legalized medical marijuana may reduce opioid prescriptions, though no empirical link between CBD and opioids has been ascertained. Using county‐level prescribing rates between 2010 and 2019, as well as state‐level morphine milligram equivalent (MME) consumption of 8 common opioids, we estimate that state adoption of limited access cannabis product (CBD) laws leads to no change in opioid prescribing rates. Using supply‐side access measures for access to CBD through legal and open dispensaries, we find that the ability to purchase CBD legally leads to 6.6% to 8.1% fewer opioid prescriptions at pre‐legalization means, which suggests that access to CBD products is essential when evaluating the impacts of legalization; synthetic control model estimates suggest that legal and open dispensaries reduce opioid prescribing rates by nearly 3.5% 2 years post‐legalization. We also find that mandating CBD be purchased with an ID or through a patient registry offsets most potential benefits of CBD legalization. Our results provide the first empirical evidence that: (i) state legalization of prescription CBD alone does not reduce opioid usage; (ii) regulations limiting purchasing, such as ID laws, negate nearly all of the benefits of demand‐side legalization; and (iii) supply‐side access, either via interstate purchasing or legal and open dispensaries, are vital in using pain‐management substances to fully combat the opioid epidemic.
Mounting evidence suggests safety and tolerability of cannabis-derived and psychedelic drugs as potential novel therapeutics for psychiatric, as well as sleep and pain disorders. Evidence concerning the therapeutic efficacy of these compounds remains controversial, although some promising preliminary results are available for them in specific disorders. For example, CBD is approved as medication for treatment-refractory epilepsy, while MDMA and psilocybin are being tested in phase 3 clinical trials respectively for treatment-refractory PTSD and MDD. Despite encouraging preliminary results, further preclinical and clinical trials are required to validate these findings. Most importantly, more systematic research is required to assess the potential long-term side effects that might arise following the use of cannabinoids and psychedelic compounds in psychiatric settings.
Chronic neuropathic pain is a debilitating pain syndrome caused by damage to the nervous system that is poorly served by current medications. Given these problems, clinical studies have pursued extracts of the plant Cannabis sativa as alternative treatments for this condition. The vast majority of these studies have examined cannabinoids which contain the psychoactive constituent delta‐9‐tetrahydrocannabinol (THC). While there have been some positive findings, meta‐analyses of this clinical work indicates that this effectiveness is limited and hampered by side‐effects. This review focuses on how recent preclinical studies have predicted the clinical limitations of THC‐containing cannabis extracts, and importantly, point to how they might be improved. This work highlights the importance of targeting channels and receptors other than cannabinoid CB1 receptors which mediate many of the side‐effects of cannabis.
image
Background
The opioid crisis continues in full force, as physicians and caregivers are desperate for resources to help patients with opioid use and chronic pain disorders find safer and more accessible non-opioid tools.
Main body
The purpose of this article is to review the current state of the opioid epidemic; the shifting picture of cannabinoids; and the research, policy, and current events that make opioid risk reduction an urgent public health challenge. The provided table contains an evidence-based clinical framework for the utilization of cannabinoids to treat patients with chronic pain who are dependent on opioids, seeking alternatives to opioids, and tapering opioids.
Conclusion
Based on a comprehensive review of the literature and epidemiological evidence to date, cannabinoids stand to be one of the most interesting, safe, and accessible tools available to attenuate the devastation resulting from the misuse and abuse of opioid narcotics. Considering the urgency of the opioid epidemic and broadening of cannabinoid accessibility amidst absent prescribing guidelines, the authors recommend use of this clinical framework in the contexts of both clinical research continuity and patient care.
Purpose of Review
The use of cannabinoid-based medicines in symptomatic treatment for people with multiple sclerosis (MS) is high. This review aimed to assess benefit and harms of cannabinoids, including synthetic, herbal and plant-derived cannabinoids, for reducing symptoms in adults with MS.
Recent Findings
Cannabinoids exert effects of potential relevance to MS: their action of neuroinflammation suppression, their immunomodulatory and neuroprotective effects in the central nervous system could benefit people with MS. Nabiximols is approved and available for people with MS and moderate or severe spasticity in many countries, and cannabinoids are also licensed in several countries for the treatment of chronic neuropathic pain.
Summary
Compared with placebo, cannabinoids likely reduce the severity of spasticity and improve well-being in the short term. Their effect on chronic neurological pain is uncertain. Serious adverse events are not increased; however, withdrawals due to adverse events are slightly greater in the cannabinoid group than in the placebo group. Most of the included trials had major weaknesses. Studies of high quality, with large sample sizes and longer follow-up period, are needed. Moreover, further research is needed in order to assess the short-and long-term adverse effects of these drugs.
Neuropathic pain is a disabling condition caused by various diseases and can profoundly impact the quality of life. Unfortunately, current treatments often do not produce complete amelioration and can be associated with potential side effects. Recently, herbal drugs have garnered more attention as an alternative or a complementary treatment. In this article, we summarized the results of randomized clinical trials to evaluate the effects of various phytomedicines on neuropathic pain. In addition, we discussed their main bioactive components and potential mechanisms of action to provide a better view of the application of herbal drugs for treating neuropathic pain.
An updated third edition of this award-winning book provides a comprehensive overview of the complex associations between cannabis and mental illness. Organised into easy to navigate sections, the book has been fully revised to feature eight entirely new chapters covering important novel aspects. Marijuana and Madness incorporates new research findings on the potential use of cannabinoids, and synthetic cannabinoids, in an array of mental illnesses, balanced against the potential adverse effects. The associations between cannabis and psychosis, developing putative models of 'cannabis induced' psychosis and pathways to schizophrenia are all covered. The book importantly discusses the impact of exposure to cannabis at various stages of neurodevelopment (in utero, in childhood, and during adolescence) and it thoroughly reviews the treatments for cannabis dependence and health policy implications of the availability of increasingly high potency cannabis. This book will quickly become an essential resource for all members of the mental health team.
Multiple sclerosis (MS) is a complicated condition in which the immune system attacks myelinated axons in the central nervous system (CNS), destroying both myelin and axons to varying degrees. Several environmental, genetic, and epigenetic factors influence the risk of developing the disease and how well it responds to treatment. Cannabinoids have recently sparked renewed interest in their therapeutic applications, with growing evidence for their role in symptom control in MS. Cannabinoids exert their roles through the endogenous cannabinoid (ECB) system, with some reports shedding light on the molecular biology of this system and lending credence to some anecdotal medical claims. The double nature of cannabinoids, which cause both positive and negative effects, comes from their actions on the same receptor. Several mechanisms have been adopted to evade this effect. However, there are still numerous limitations to using cannabinoids to treat MS patients. In this review, we will explore and discuss the molecular effect of cannabinoids on the ECB system, the various factors that affect the response to cannabinoids in the body, including the role of gene polymorphism and its relation to dosage, assessing the positive over the adverse effects of cannabinoids in MS, and finally, exploring the possible functional mechanism of cannabinoids in MS and the current and future progress of cannabinoid therapeutics.
Introduction:
Medical cannabis is an increasingly prevalent treatment for a wide variety of indications, yet there is still no uniformly accepted protocol for the titration of cannabinoid doses. We aimed to develop a model to predict the stable THC and CBD dosages after six months of treatment using available baseline patient characteristics.
Methods:
In this prospective study, we included all consecutive adult patients (age 18 and above) who exclusively used a single method of cannabis delivery. Telephone interviews were conducted six months post-treatment initiation to assess changes in symptoms and side effects. We prospectively analyzed THC and CBD dosages with respect to demographic variables and patient characteristics in two main groups divided according to cannabis administration method - inhalation or sublingual oil.
Results:
A total of 3,554 patients were included in the study (2,724 exclusively inhaled cannabis and 830 exclusively consumed cannabis as sublingual oil). The daily THC and CBD doses were significantly higher in the inhalation group than in the sublingual group (p<.001). None of the four models predicting THC and CBD doses in the two groups had satisfactory prediction ability (adjusted R-squared between 0.007 and 0.09). Male gender, unemployed status, tobacco smoking and a lack of concern about cannabis treatment were associated with a higher inhaled THC dose (p<.001).
Conclusion:
Models based on patient characteristics failed to accurately predict the final titration doses of CBD and THC for both inhalation and sublingual administration. Clinical guidelines should maintain a highly individual approach for cannabinoid dosing.
Carbamazepine is widely used to treat paroxysmal neurological symptoms and pain. We report on five patients with multiple sclerosis in whom disability was seriously enhanced by treatment with carbamazepine at comparatively low dosages. It is possible to misinterpret worsening of symptoms as an exacerbation of multiple sclerosis.
A 48 year old man had had symptoms of multiple sclerosis for three years, at first intermittent but eventually progressive, with mainly ataxia and spastic weakness of the legs. He also had disabling oscillopsia …
Objective To establish whether cannabis is an effective and safe treatment option in the management of pain. Design Systematic review of randomised controlled trials. Data sources Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches. Study selection Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score. Data extraction Independent data extraction; discrepancies resolved by consensus. Data synthesis 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common.
Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies.
To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy.
Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997.
Outpatient clinics at 20 sites.
The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale.
Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo.
The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results.
Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06).
Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.
To establish whether cannabis is an effective and safe treatment option in the management of pain.
Systematic review of randomised controlled trials.
Electronic databases Medline, Embase, Oxford Pain Database, and Cochrane Library; references from identified papers; hand searches.
Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. Validity of trials was assessed independently with the Oxford score.
Independent data extraction; discrepancies resolved by consensus.
20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5-20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5-3 mg were about as effective as codeine 50-120 mg, and oral benzopyranoperidine 2-4 mg was less effective than codeine 60-120 mg and no better than placebo. Adverse effects, most often psychotropic, were common.
Cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. Their widespread introduction into clinical practice for pain management is therefore undesirable. In acute postoperative pain they should not be used. Before cannabinoids can be considered for treating spasticity and neuropathic pain, further valid randomised controlled studies are needed.
To determine whether plant-derived cannabis medicinal extracts (CME) can alleviate neurogenic symptoms unresponsive to standard treatment, and to quantify adverse effects.
A consecutive series of double-blind, randomized, placebo-controlled single-patient cross-over trials with two-week treatment periods.
Patients attended as outpatients, but took the CME at home.
Twenty-four patients with multiple sclerosis (18), spinal cord injury (4), brachial plexus damage (1), and limb amputation due to neurofibromatosis (1).
Whole-plant extracts of delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), 1:1 CBD:THC, or matched placebo were self-administered by sublingual spray at doses determined by titration against symptom relief or unwanted effects within the range of 2.5-120 mg/24 hours. Measures used: Patients recorded symptom, well-being and intoxication scores on a daily basis using visual analogue scales. At the end of each two-week period an observer rated severity and frequency of symptoms on numerical rating scales, administered standard measures of disability (Barthel Index), mood and cognition, and recorded adverse events.
Pain relief associated with both THC and CBD was significantly superior to placebo. Impaired bladder control, muscle spasms and spasticity were improved by CME in some patients with these symptoms. Three patients had transient hypotension and intoxication with rapid initial dosing of THC-containing CME.
Cannabis medicinal extracts can improve neurogenic symptoms unresponsive to standard treatments. Unwanted effects are predictable and generally well tolerated. Larger scale studies are warranted to confirm these findings.
1',1'dimethylheptyl-Delta8-tetrahydrocannabinol-11-oic acid (CT-3), a potent analog of THC-11-oic acid, produces marked antiallodynic and analgesic effects in animals without evoking the typical effects described in models of cannabinoids. Therefore, CT-3 may be an effective analgesic for poorly controlled resistant neuropathic pain.
To examine the analgesic efficacy and safety of CT-3 in chronic neuropathic pain in humans.
Randomized, placebo-controlled, double-blind crossover trial conducted in Germany from May-September 2002.
Twenty-one patients (8 women and 13 men) aged 29 to 65 years (mean, 51 years) who had a clinical presentation and examination consistent with chronic neuropathic pain (for at least 6 months) with hyperalgesia (n = 21) and allodynia (n = 7).
Patients were randomized to two 7-day treatment orders in a crossover design. Two daily doses of CT-3 (four 10-mg capsules per day) or identical placebo capsules were given during the first 4 days and 8 capsules per day were given in 2 daily doses in the following 3 days. After a washout and baseline period of 1 week each, patients crossed over to the second 7-day treatment period.
Visual analog scale (VAS) and verbal rating scale scores for pain; vital sign, hematologic and blood chemistry, and electrocardiogram measurements; scores on the Trail-Making Test and the Addiction Research Center Inventory-Marijuana scale; and adverse effects.
The mean differences over time for the VAS values in the CT-3-placebo sequence measured 3 hours after intake of study drug differed significantly from those in the placebo-CT-3 sequence (mean [SD], -11.54 [14.16] vs 9.86 [21.43]; P =.02). Eight hours after intake of the drug, the pain scale differences between groups were less marked. No dose response was observed. Adverse effects, mainly transient dry mouth and tiredness, were reported significantly more often during CT-3 treatment (mean [SD] difference, -0.67 [0.50] for CT-3-placebo sequence vs 0.10 [0.74] for placebo-CT-3 sequence; P =.02). There were no significant differences with respect to vital signs, blood tests, electrocardiogram, Trail-Making Test, and Addiction Research Center Inventory-Marijuana scale. No carryover or period effects were observed except on the Trail-Making Test.
In this preliminary study, CT-3 was effective in reducing chronic neuropathic pain compared with placebo. No major adverse effects were observed.
To evaluate the effect of the oral synthetic delta-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis.
Randomised double blind placebo controlled crossover trial.
Outpatient clinic, University Hospital of Aarhus, Denmark.
24 patients aged between 23 and 55 years with multiple sclerosis and central pain.
Orally administered dronabinol at a maximum dose of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated by a three week washout period.
Median spontaneous pain intensity (numerical rating scale) in the last week of treatment.
Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0 to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). On the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo. The number of patients with adverse events was higher during active treatment, especially in the first week of treatment. The functional ability of the multiple sclerosis patients did not change.
Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.
Context:
Pain is the most disturbing symptom of diabetic peripheral neuropathy. As many as 45% of patients with diabetes mellitus develop peripheral neuropathies.
Objective:
To evaluate the effect of gabapentin monotherapy on pain associated with diabetic peripheral neuropathy.
Design:
Randomized, double-blind, placebo-controlled, 8-week trial conducted between July 1996 and March 1997.
Setting:
Outpatient clinics at 20 sites.
Patients:
The 165 patients enrolled had a 1- to 5-year history of pain attributed to diabetic neuropathy and a minimum 40-mm pain score on the Short-Form McGill Pain Questionnaire visual analogue scale.
Intervention:
Gabapentin (titrated from 900 to 3600 mg/d or maximum tolerated dosage) or placebo.
Main outcome measures:
The primary efficacy measure was daily pain severity as measured on an 11-point Likert scale (0, no pain; 10, worst possible pain). Secondary measures included sleep interference scores, the Short-Form McGill Pain Questionnaire scores, Patient Global Impression of Change and Clinical Global Impression of Change, the Short Form-36 Quality of Life Questionnaire scores, and the Profile of Mood States results.
Results:
Eighty-four patients received gabapentin and 70 (83%) completed the study; 81 received placebo and 65 (80%) completed the study. By intent-to-treat analysis, gabapentin-treated patients' mean daily pain score at the study end point (baseline, 6.4; end point, 3.9; n = 82) was significantly lower (P<.001) compared with the placebo-treated patients' end-point score (baseline, 6.5; end point, 5.1; n = 80). All secondary outcome measures of pain were significantly better in the gabapentin group than in the placebo group. Additional statistically significant differences favoring gabapentin treatment were observed in measures of quality of life (Short Form-36 Quality of Life Questionnaire and Profile of Mood States). Adverse events experienced significantly more frequently in the gabapentin group were dizziness (20 [24%] in the gabapentin group vs 4 [4.9%] in the control group; P<.001) and somnolence (19 [23%] in the gabapentin group vs 5 [6%] in the control group; P = .003). Confusion was also more frequent in the gabapentin group (7 [8%] vs 1 [1.2%]; P = .06).
Conclusion:
Gabapentin monotherapy appears to be efficacious for the treatment of pain and sleep interference associated with diabetic peripheral neuropathy and exhibits positive effects on mood and quality of life.
22 out of 235 patients with undoubted or suspected MS, treated during 1966-1973, had paroxysmal symptoms during the course of their disease. Paroxysmal dysarthria and ataxia (7 cases), and tonic seizures (5 cases) were the most common types of attacks. Some types of attacks (paroxysmal hemiataxia and crossed paresthesia, paroxysmal itching, diplopia as the single paroxysmal symptom) do not seem to have been described previously. A patient with tonic seizures caused by a localized, traumatic lesion of the cervical spinal cord is also described. It is suggested that the paroxysmal phenomena in MS are caused by a transversely spreading ephaptic activation of axons within a partially demyelinated lesion in fiber tracts somewhere in the central nervous system. The different paroxysmal phenomena are discussed in the light of this hypothesis.
Context Cognitive impairments are associated with long-term cannabis use, but
the parameters of use that contribute to impairments and the nature and endurance
of cognitive dysfunction remain uncertain.Objective To examine the effects of duration of cannabis use on specific areas
of cognitive functioning among users seeking treatment for cannabis dependence.Design, Setting, and Participants Multisite retrospective cross-sectional neuropsychological study conducted
in the United States (Seattle, Wash; Farmington, Conn; and Miami, Fla) between
1997 and 2000 among 102 near-daily cannabis users (51 long-term users: mean,
23.9 years of use; 51 shorter-term users: mean, 10.2 years of use) compared
with 33 nonuser controls.Main Outcome Measures Measures from 9 standard neuropsychological tests that assessed attention,
memory, and executive functioning, and were administered prior to entry to
a treatment program and following a median 17-hour abstinence.Results Long-term cannabis users performed significantly less well than shorter-term
users and controls on tests of memory and attention. On the Rey Auditory Verbal
Learning Test, long-term users recalled significantly fewer words than either
shorter-term users (P = .001) or controls (P = .005); there was no difference between shorter-term
users and controls. Long-term users showed impaired learning (P = .007), retention (P = .003), and retrieval
(P = .002) compared with controls. Both user groups
performed poorly on a time estimation task (P<.001
vs controls). Performance measures often correlated significantly with the
duration of cannabis use, being worse with increasing years of use, but were
unrelated to withdrawal symptoms and persisted after controlling for recent
cannabis use and other drug use.Conclusions These results confirm that long-term heavy cannabis users show impairments
in memory and attention that endure beyond the period of intoxication and
worsen with increasing years of regular cannabis use.
Anecdotal evidence and preclinical and clinical data indicate that cannabis and individual cannabinoids can suppress muscle spasticity/spasm and pain associated with multiple sclerosis (MS). Anecdotal data come from the responses to a questionnaire by 112 patients with MS who self-medicated with cannabis. The preclinical data come from animal experiments showing that cannabinoid receptor agonists are antinociceptive and can depress motor function, reduce the severity of primary generalised dystonia, and decrease inflammation and the intensity of behavioural signs of experimental autoimmune encephalomyelitis. The clinical data derive from 7 clinical trials, albeit involving small numbers of patients, which indicate that cannabis itself, the cannabinoid -tetrahydrocannabinol (-THC) and the synthetic analogue of -THC nabilone can reduce the intensity of several symptoms in patients with MS or spinal cord injury, including spasticity, pain, tremor and nocturia.These data provide sufficient evidence to warrant a large scale clinical trial to attempt to provide an objective and conclusive answer to the questions of whether cannabis and cannabinoids are effective in MS and, if they are, whether these effects are achievable at dose levels that do not provoke unacceptable adverse effects. Likely drug candidates for a clinical trial include -THC and nabilone, both of which are already licensed medicines. When taken orally, -THC seems to undergo variable absorption and to have a narrow therapeutic window. This makes it difficult to predict an oral dose that will be both effective and tolerable, so prompting a need for better cannabinoid formulations, cannabinoid vehicles and modes of administration.There is also a need to establish whether cannabis has any therapeutic advantages over individual cannabinoids such as -THC and, if so, to investigate the basis for this. In addition, it will be worth seeking out a way of separating the therapeutic properties of cannabinoids from their unwanted effects, particularly their psychotropic effects, and several strategies for achieving this goal are described.To succeed, any clinical study with cannabinoids will require sufficient funding, the use of adequate outcome measures, and the committed involvement of scientists and physicians who have appropriate cannabinoid and clinical expertise.
ABSTRACT– A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
Background: Multiple sclerosis is associated with muscle stiffness, spasms, pain, and tremor. Much anecdotal evidence suggests that cannabinoids could help these symptoms. Our aim was to test the notion that cannabinoids have a beneficial effect on spasticity and other symptoms related to multiple sclerosis. Methods: We did a randomised, placebo-controlled trial, to which we enrolled 667 patients with stable multiple sclerosis and muscle spasticity. 630 participants were treated at 33 UK centres with oral cannabis extract (n=211), Δ9-tetrahydrocannabinol (Δ9-THC; n=206), or placebo (n=213). Trial duration was 15 weeks. Our primary outcome measure was change in overall spasticity scores, using the Ashworth scale. Analysis was by intention to treat. Findings: 611 of 630 patients were followed up for the primary endpoint. We noted no treatment effect of cannabinoids on the primary outcome (p=0·40). The estimated difference in mean reduction in total Ashworth score for participants taking cannabis extract compared with placebo was 0·32 (95% CI −1·04 to 1·67), and for those taking Δ9-THC versus placebo it was 0·94 (−0·44 to 2·31). There was evidence of a treatment effect on patient-reported spasticity and pain (p=0·003), with improvement in spasticity reported in 61% (n=121, 95% CI 54·6–68·2), 60% (n=108, 52·5–66·8), and 46% (n=91, 39·0–52·9) of participants on cannabis extract, Δ9-THC, and placebo, respectively. Interpretation: Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale. However, though there was a degree of unmasking among the patients in the active treatment groups, objective improvement in mobility and patients' opinion of an improvement in pain suggest cannabinoids might be clinically useful.
A representative sample of 117 patients with definite multiple sclerosis (MS) was interviewed on pain syndromes. Chronic syndromes lasting more than one month included dysaestesthesia, low back pain, spasms, tonic seizures, tightening and painful sensations in the extremities. Acute syndromes included neuralgia, L'Hermitte's sign and pain associated with optic neuritis. Thirty-five per cent were pain-free. Of the remaining patients had 45% pain at the time of the examination, 32% indicated pain among the most severe symptoms of MS and 23% had pain at the onset of MS. The number of patients with pain at the time of the examination increased with age and duration of disease. Patients with pain were significantly more often spastic and significantly more often sought alternative treatment forms. No difference was found for mean age, sex, physical impairment, duration of disease from onset of MS, depressive score and score of delayed verbal memory.
Since multiple sclerosis (MS) is believed to be an immune-mediated disease, it follows that its therapies should be directed towards modulating the immune system. Current MS treatments, which include the use of exogenous steroids that are immunosuppressive, do not meet therapeutic objectives. delta 9-Tetrahydrocannabinol (THC), an active component of marijuana, has been shown to be immunosuppressive. To test THC's ability to suppress an immune-mediated disease, experimental autoimmune encephalomyelitis (EAE), the laboratory model of MS, was used. Lewis rats and strain 13 guinea pigs were administered THC either before inoculation for EAE or treated with THC after injection. Control animals received placebo. The effect of dose, in addition to the timing of treatment, was also investigated. All animals treated with placebo developed severe clinical EAE 10-12 days post-injection (d.p.i.) and more than 98% died by 15 d.p.i. THC-treated animals had either no clinical signs or mild signs with delayed onset (13-15 d.p.i.) with survival greater than 95%. Examination of central nervous system tissue revealed a marked reduction of inflammation in the THC-treated animals. Therefore, as THC has been shown to inhibit both clinical and histologic EAE, it may prove to be a new and relatively innocuous agent for the treatment of immune-mediated diseases.
One method of evaluating the degree of neurologic impairment in MS has been the combination of grades (0 = normal to 5 or 6 = maximal impairment) within 8 Functional Systems (FS) and an overall Disability Status Scale (DSS) that had steps from 0 (normal) to 10 (death due to MS). A new Expanded Disability Status Scale (EDSS) is presented, with each of the former steps (1,2,3 . . . 9) now divided into two (1.0, 1.5, 2.0 . . . 9.5). The lower portion is obligatorily defined by Functional System grades. The FS are Pyramidal, Cerebellar, Brain Stem, Sensory, Bowel & Bladder, Visual, Cerebral, and Other; the Sensory and Bowel & Bladder Systems have been revised. Patterns of FS and relations of FS by type and grade to the DSS are demonstrated.
A self-assessment scale has been developed and found to be a reliable instrument for detecting states of depression and anxiety in the setting of an hospital medical outpatient clinic. The anxiety and depressive subscales are also valid measures of severity of the emotional disorder. It is suggested that the introduction of the scales into general hospital practice would facilitate the large task of detection and management of emotional disorder in patients under investigation and treatment in medical and surgical departments.
Neuropathic pain syndromes are commonly seen in clinical practice and are frequently used as pain models in testing new therapies. However, no pain scale exists with the primary purpose to measure pain in neuropathic syndromes. This paper describes the development and preliminary validation of the Neuropathic Pain Scale (NPS), which is designed to assess distinct pain qualities associated with neuropathic pain. Results support the discriminant and predictive validity of the NPS items. Moreover, the NPS items appear to be sensitive to treatments known to impact neuropathic pain. These findings provide support for the further development of the NPS.
Pain is a frequent and distressing complaint in patients with multiple sclerosis (MS) and may present a difficult therapeutic problem. Conventional therapy is moderately effective and includes, among others, a variety of anticonvulsant medications. Gabapentin (Neurontin) is a new generation antiepileptic drug which appears to be advantageous in treatment of intractable pain of reflex sympathetic dystrophy. This study investigates the benefits of open-label treatment with gabapentin for pain control in 25 patients with MS. Excellent to moderate pain relief was obtained in a substantial number of patients. Throbbing pains and needles, and cramping pains responded best, and dull aching pains responded least to the medication. There was no significant change in distribution and type of pain as a result of this treatment. Mild to moderate side effects were observed. Cautious escalation of the dose of gabapentin is advisable in MS patients. Further clinical trials with larger patient groups are recommended.
The increased awareness of the impact and complexity of management of symptoms in multiple sclerosis has resulted in advances in the understanding of their mechanisms, and in improvements in their measurement and management. It has also highlighted the paucity of evidence-based practice in this area and the need to develop agreed and comprehensive management strategies.
Postherpetic neuralgia (PHN) is a syndrome of often intractable neuropathic pain following herpes zoster (shingles) that eludes effective treatment in many patients.
To determine the efficacy and safety of the anticonvulsant drug gabapentin in reducing PHN pain.
Multicenter, randomized, double-blind, placebo-controlled, parallel design, 8-week trial conducted from August 1996 through July 1997.
Sixteen US outpatient clinical centers.
A total of 229 subjects were randomized.
A 4-week titration period to a maximum dosage of 3600 mg/d of gabapentin or matching placebo. Treatment was maintained for another 4 weeks at the maximum tolerated dose. Concomitant tricyclic antidepressants and/or narcotics were continued if therapy was stabilized prior to study entry and remained constant throughout the study.
The primary efficacy measure was change in the average daily pain score based on an 11-point Likert scale (0, no pain; 10, worst possible pain) from baseline week to the final week of therapy. Secondary measures included average daily sleep scores, Short-Form McGill Pain Questionnaire (SF-MPQ), Subject Global Impression of Change and investigator-rated Clinical Global Impression of Change, Short Form-36 (SF-36) Quality of Life Questionnaire, and Profile of Mood States (POMS). Safety measures included the frequency and severity of adverse events.
One hundred thirteen patients received gabapentin, and 89 (78.8%) completed the study; 116 received placebo, and 95 (81.9%) completed the study. By intent-to-treat analysis, subjects receiving gabapentin had a statistically significant reduction in average daily pain score from 6.3 to 4.2 points compared with a change from 6.5 to 6.0 points in subjects randomized to receive placebo (P<.001). Secondary measures of pain as well as changes in pain and sleep interference showed improvement with gabapentin (P<.001). Many measures within the SF-36 and POMS also significantly favored gabapentin (P< or =.01). Somnolence, dizziness, ataxia, peripheral edema, and infection were all more frequent in the gabapentin group, but withdrawals were comparable in the 2 groups (15 [13.3%] in the gabapentin group vs 11 [9.5%] in the placebo group).
Gabapentin is effective in the treatment of pain and sleep interference associated with PHN. Mood and quality of life also improve with gabapentin therapy.
Painful tonic spasms (PTS) are now regarded as a typical symptom of multiple sclerosis but pathologic or radiologic findings rarely have been described. We report clinical and magnetic resonance imaging records of five original cases. In all of them, lesions likely responsible for unilateral PTS involved the motor pathway at the level of the posterior limb of the internal capsule or the cerebral peduncle on the opposite side. Closeness of motor fibers seems to be the most important underlying anatomic factor because it enables involvement of a higher proportion of axons by a single demyelinating lesion and radial spread of ephaptic activation. In turn, preservation of the underlying pyramidal-spinal tract could make it easier for the pathologic discharge to reach the peripheral effectors and generate PTS.
A postal survey showed that the majority of 49 leading international neurologists involved with multiple sclerosis research felt that currently existing outcome measures for this illness were inadequate, and that there was a need for a new measure which should be patient orientated, multidimensional, and not biased towards any particular disability. The Guy's Neurological Disability Scale (GNDS) was subsequently devised as a simple and user-friendly clinical disability scale capable of embracing the whole range of disabilities which could be encountered in the course of multiple sclerosis. It has 12 separate categories which include cognition, mood, vision, speech, swallowing, upper limb function, lower limb function, bladder function, bowel function, sexual function, fatigue, and 'others'. The GNDS was found to be acceptable to neurologists and patients, reliable, responsive, and valid as a measure of disability. The scale was also found to be valid when applied by non-neurologists, over the phone, or via a postal questionnaire.
Tricyclic antidepressants and carbamazepine have become the mainstay in the treatment of neuropathic pain. Within the last decade, controlled trials have shown that numerous other drugs relieve such pain. We identified all placebo-controlled trials and calculated numbers needed to treat (NNT) to obtain one patient with more than 50% pain relief in order to compare the efficacy with the current treatments, and to search for relations between mechanism of pain and drug action. In diabetic neuropathy, NNT was 1.4 in a study with optimal doses of the tricyclic antidepressant imipramine as compared to 2.4 in other studies on tricyclics. The NNT was 6.7 for selective serotonin reuptake inhibitors, 3.3 for carbamazepine, 10.0 for mexiletine, 3.7 for gabapentin, 1.9 for dextromethorphan, 3.4 for tramadol and levodopa and 5.9 for capsaicin. In postherpetic neuralgia, the NNT was 2.3 for tricyclics, 3.2 for gabapentin, 2.5 for oxycodone and 5.3 for capsaicin, whereas dextromethorphan was inactive. In peripheral nerve injury, NNT was 2.5 for tricyclics and 3.5 for capsaicin. In central pain, NNT was 2.5 for tricyclics and 3. 4 for carbamazepine, whereas selective serotonin reuptake inhibitors, mexiletine and dextromethorphan were inactive. There were no clear relations between mechanism of action of the drugs and the effect in distinct pain conditions or for single drug classes and different pain conditions. It is concluded that tricyclic antidepressants in optimal doses appear to be the most efficient treatment of neuropathic pain, but some of the other treatments may be important due to their better tolerability. Relations between drug and pain mechanisms may be elucidated by studies focusing on specific neuropathic pain phenomena such as pain paroxysms and touch-evoked pain.
Mammalian tissues contain at least two types of cannabinoid receptor, CB(1) and CB(2), both coupled to G proteins. CB(1) receptors are expressed mainly by neurones of the central and peripheral nervous system whereas CB(2) receptors occur centrally and peripherally in certain non-neuronal tissues, particularly in immune cells. The existence of endogenous ligands for cannabinoid receptors has also been demonstrated. The discovery of this 'endocannabinoid system' has prompted the development of a range of novel cannabinoid receptor agonists and antagonists, including several that show marked selectivity for CB(1) or CB(2) receptors. It has also been paralleled by a renewed interest in cannabinoid-induced antinociception. This review summarizes current knowledge about the ability of cannabinoids to produce antinociception in animal models of acute pain as well as about the ability of these drugs to suppress signs of tonic pain induced in animals by nerve damage or by the injection of an inflammatory agent. Particular attention is paid to the types of pain against which cannabinoids may be effective, the distribution pattern of cannabinoid receptors in central and peripheral pain pathways and the part that these receptors play in cannabinoid-induced antinociception. The possibility that antinociception can be mediated by cannabinoid receptors other than CB(1) and CB(2) receptors, for example CB(2)-like receptors, is also discussed as is the evidence firstly that one endogenous cannabinoid, anandamide, produces antinociception through mechanisms that differ from those of other types of cannabinoid, for example by acting on vanilloid receptors, and secondly that the endocannabinoid system has physiological and/or pathophysiological roles in the modulation of pain.
Pain intensity is frequently measured on an 11-point pain intensity numerical rating scale (PI-NRS), where 0=no pain and 10=worst possible pain. However, it is difficult to interpret the clinical importance of changes from baseline on this scale (such as a 1- or 2-point change). To date, there are no data driven estimates for clinically important differences in pain intensity scales used for chronic pain studies. We have estimated a clinically important difference on this scale by relating it to global assessments of change in multiple studies of chronic pain. Data on 2724 subjects from 10 recently completed placebo-controlled clinical trials of pregabalin in diabetic neuropathy, postherpetic neuralgia, chronic low back pain, fibromyalgia, and osteoarthritis were used. The studies had similar designs and measurement instruments, including the PI-NRS, collected in a daily diary, and the standard seven-point patient global impression of change (PGIC), collected at the endpoint. The changes in the PI-NRS from baseline to the endpoint were compared to the PGIC for each subject. Categories of "much improved" and "very much improved" were used as determinants of a clinically important difference and the relationship to the PI-NRS was explored using graphs, box plots, and sensitivity/specificity analyses. A consistent relationship between the change in PI-NRS and the PGIC was demonstrated regardless of study, disease type, age, sex, study result, or treatment group. On average, a reduction of approximately two points or a reduction of approximately 30% in the PI-NRS represented a clinically important difference. The relationship between percent change and the PGIC was also consistent regardless of baseline pain, while higher baseline scores required larger raw changes to represent a clinically important difference. The application of these results to future studies may provide a standard definition of clinically important improvement in clinical trials of chronic pain therapies. Use of a standard outcome across chronic pain studies would greatly enhance the comparability, validity, and clinical applicability of these studies.
The authors conducted a randomized, double-blind, placebo-controlled, twofold crossover study in 16 patients with MS who presented with severe spasticity to investigate safety, tolerability, and efficacy of oral Delta(9)-Tetrahydrocannabinol (THC) and Cannabis sativa plant extract. Both drugs were safe, but adverse events were more common with plant-extract treatment. Compared with placebo, neither THC nor plant-extract treatment reduced spasticity. Both THC and plant-extract treatment worsened the participant's global impression.
Varicella-zoster virus causes chickenpox and can reemerge later in life to cause herpes zoster or shingles. One of the most common and disabling complications of herpes zoster is postherpetic neuralgia (PHN).
This article reviews the current primary literature about the efficacy and tolerability of gabapentin for the treatment of PHN. Gabapentin pharmacokinetics and drug interactions are also reviewed.
A literature search in the English language was conducted using OVID Web, which contained the following databases: MEDLINE (1966-present), EMBASE (1980-2002), Current Contents/Clinical Medicine (1999-2002), Cochrane Controlled Trials Register (1898-present), Cochrane Database of Systemic Reviews (fourth quarter, 2002), and International Pharmaceutical Abstracts (1970-2002). Search terms used were postherpetic neuralgia; zoster; gabapentin; neuropathic pain; pain; pharmacoeconomic; cost; controlled clinical trial; randomized, controlled trial; postherpetic neuralgia and gabapentin; gabapentin and pain; treatment and postherpetic neuralgia; gabapentin and age; gabapentin and gender; gabapentin and ethnicity; and gabapentin and pharmacokinetics.
Gabapentin displays nonlinear absorption kinetics, is minimally protein bound (< 3%), has a high mean (SD) volume of distribution (50.4 [8.0] L), and is excreted via the kidneys as unchanged drug. Two randomized, placebo-controlled, parallel-group, multicenter clinical trials demonstrated the effectiveness of gabapentin at doses of up to 3600 mg/d to significantly reduce pain (P < 0.01 and P < 0.001), improve sleep (P < 0.01), and improve some parameters on the Short Form-McGill Pain Questionnaire (P < 0.05). Dizziness and somnolence were the most common side effects leading to withdrawal from the trials. The recommended dosage in adults is 300 mg at bedtime on day 1,300 mg BID on day 2, and 300 mg TID on day 3, titrating up as needed to 2400 to 3600 mg/d. To reduce adverse events in patients with renal impairment, the dose should be adjusted based on the patient's creatinine clearance.
Gabapentin appears to be effective and well tolerated for the short-term treatment of PHN. However, future controlled studies are needed to determine whether the effectiveness of gabapentin for PHN is maintained for > 2 months, to establish the optimal dose of gabapentin for PHN, and to compare the efficacy of gabapentin with that of other pharmacologic agents used for the treatment of PHN.
The efficacy and safety of sustained-release tramadol compared to placebo in the treatment of post-herpetic neuralgia were evaluated in a multicenter, randomized, double-blind, parallel-group study in 127 outpatients. Treatment was administrated for 6 weeks. The dose of tramadol could be increased from 100 mg/day to 400 mg/day (300 mg/day in patients more than 75 years old). Groups were compared on changes in pain intensity on a Visual Analogue Scale (VAS) between inclusion and the 6th week of treatment (covariance analysis as main analysis and repeated measures analysis as complementary analysis) in the per protocol (PP) population. The randomized population comprised 127 patients aged 35-85 years, mostly females (72.4%). Groups were comparable at inclusion both in the intent to treat (ITT) population (63 patients in the tramadol group and 62 patients in the placebo group) and in the PP population (53 patients in the tramadol group and 55 patients in the placebo group). Mean pain intensity on day 43 adjusted on day 1 (covariance analysis) was significantly lower in the tramadol group than in the placebo group in both the PP (P=0.0499), and the ITT (P=0.031) populations. The two groups significantly differed on change in pain intensity over time (repeated measures analysis) in the ITT population (P=0.012). The percentage of pain relief over the 6th week was significantly higher in the tramadol group than in the placebo group (P=0.017). During the 6th week, patients in the tramadol group required less rescue medication than patients in the placebo group (P=0.022). No significant difference was found between groups either in pain intensity on a 5-point Verbal Scale (VRS) or in quality of life measurements. Tramadol was administered at an average dosage of 275.5 (89.7) mg/day after a 1-week dose-adaptation period. Tramadol was well tolerated. No notable difference appeared between groups either in the percentage of patients with treatment-associated adverse events (TAAE) (29.7% in the tramadol group and 31.8% in the placebo group) or in the total number of TAAE (31 in the tramadol group and 28 in the placebo group).
Multiple sclerosis is associated with muscle stiffness, spasms, pain, and tremor. Much anecdotal evidence suggests that cannabinoids could help these symptoms. Our aim was to test the notion that cannabinoids have a beneficial effect on spasticity and other symptoms related to multiple sclerosis.
We did a randomised, placebo-controlled trial, to which we enrolled 667 patients with stable multiple sclerosis and muscle spasticity. 630 participants were treated at 33 UK centres with oral cannabis extract (n=211), Delta9-tetrahydrocannabinol (Delta9-THC; n=206), or placebo (n=213). Trial duration was 15 weeks. Our primary outcome measure was change in overall spasticity scores, using the Ashworth scale. Analysis was by intention to treat.
611 of 630 patients were followed up for the primary endpoint. We noted no treatment effect of cannabinoids on the primary outcome (p=0.40). The estimated difference in mean reduction in total Ashworth score for participants taking cannabis extract compared with placebo was 0.32 (95% CI -1.04 to 1.67), and for those taking Delta9-THC versus placebo it was 0.94 (-0.44 to 2.31). There was evidence of a treatment effect on patient-reported spasticity and pain (p=0.003), with improvement in spasticity reported in 61% (n=121, 95% CI 54.6-68.2), 60% (n=108, 52.5-66.8), and 46% (n=91, 39.0-52.9) of participants on cannabis extract, Delta9-THC, and placebo, respectively.
Treatment with cannabinoids did not have a beneficial effect on spasticity when assessed with the Ashworth scale. However, though there was a degree of unmasking among the patients in the active treatment groups, objective improvement in mobility and patients' opinion of an improvement in pain suggest cannabinoids might be clinically useful.
The study sought to determine if symptoms and signs cluster differentially in groups of patients with increasing evidence of neuropathic pain (NP). We prospectively looked at symptoms and signs in 214 patients with suspected chronic NP of moderate to severe intensity. According to a set of clinical criteria the patients were a priori classified as having the so-called 'Definite NP' (n = 91), 'Possible NP' (n = 71), or 'Unlikely NP' (n = 52). A recording of symptoms including pain descriptors, intensity of five categories of pain, Short Form McGill Pain Questionnaire, and Major Depression Inventory were done. Sensory tests including repetitive pinprick stimulation, examination for cold-evoked pain by an acetone drop and brush-evoked pain were carried out in the maximal pain area and in a control area. High intensity of superficial ongoing pain, and touch or cold provoked pain was associated with chronic pain classified as definite or possible neuropathic. Intensity of deep ongoing pain, and 'paroxysms' was similar in the three groups. Brush-evoked pain was more frequent in definite NP. The McGill Pain Questionnaire and the used pain descriptors could not distinguish between the three clinical categories. Although certain symptoms (touch or cold provoked pain) and signs (brush-evoked allodynia) are more prominent in patients with definite or possible NP, we found considerable overlap with the clinical presentation of patients with unlikely NP.
Pregabalin, an alpha2-delta ligand with analgesic, anxiolytic, and anticonvulsant activity, has been evaluated for treatment of neuropathic pain. The authors assessed the efficacy and tolerability of pregabalin (75, 300, 600 mg/day) vs placebo in patients with diabetic peripheral neuropathy (DPN).
Patients with a 1- to 5-year history of DPN and average weekly pain score of > or =4 on an 11-point numeric pain-rating scale were enrolled in a 5-week, double-blind, multicenter, placebo-controlled study. Patients (n = 338) were randomized to receive one of three doses of pregabalin or placebo TID. Pregabalin 600 mg/day was titrated over 6 days; lower doses were initiated on day 1.
Patients in the 300- and 600-mg/day pregabalin groups showed improvements in endpoint mean pain score (primary efficacy measure) vs placebo (p = 0.0001). Improvements were also seen in weekly pain score, sleep interference score, patient global impression of change, clinical global impression of change, SF-McGill Pain Questionnaire, and multiple domains of the SF-36 Health Survey. Improvements in pain and sleep were seen as early as week 1 and were sustained throughout the 5 weeks. Responders (patients with > or =50% reduction in pain compared to baseline) were 46% (300 mg/day), 48% (600 mg/day), and 18% (placebo). Pregabalin was well tolerated with a low discontinuation rate. The most common adverse events were dizziness and somnolence.
In patients with diabetic peripheral neuropathy, pregabalin demonstrated early and sustained improvement in pain and a beneficial effect on sleep, which were confirmed by positive patient global impression. Pregabalin was well tolerated at all doses.
Central pain Textbook of pain
- J Biovie
- Pd
- Melzack
Biovie J. Central pain. In: Wall, PD, Melzack R, eds. Textbook of pain, 4th ed. Hong Kong: Harcourt, 1999:879–914.
Validation and reliability of the Neuropathic Pain Scale in multiple sclerosis:S111. Abstract. 818 NEUROLOGY 65 September (2 of 2) 2005 14. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols
- Dj Rog
- Young
Rog DJ, Young CA. Validation and reliability of the Neuropathic Pain Scale in multiple sclerosis. Mult Scler 2001;7:S111. Abstract. 818 NEUROLOGY 65 September (2 of 2) 2005 14. Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 1983; 13:227–231.
Paroxysmal attacks in multiple sclerosis Tramadol in post-herpetic neuralgia: a randomized, placebo-controlled trial
- Po Osterman
- Westerberg
- F Boureau
- P Legallicier
- Kabir
- Ahmadi
Osterman PO, Westerberg CE. Paroxysmal attacks in multiple sclerosis. Brain 1975;98:189–202. 26. Boureau F, Legallicier P, Kabir-Ahmadi M. Tramadol in post-herpetic neuralgia: a randomized, placebo-controlled trial. Pain 2003;104:323–
Classification of chronic pain
- H Mersky
- N Bogduk
Mersky H, Bogduk N. Classification of chronic pain. Seattle: IASP
Press, 1994.
The psychological effects of cannabis in MS: impact on cognition, pain, mood and fatigue
- D W Langdon
- A J Thompson
- K P Johnson
Langdon DW, Thompson AJ, Johnson KP, et al. The psychological effects of cannabis in MS: impact on cognition, pain, mood and fatigue.
Mult Scler ECTRIMS 2003;9:S27. Abstract.
Pain and central nervous system disease: the central pain syndromes
- J J Bonica
Bonica JJ. Introduction: semantic, epidemiologic, and educational issues. In: Casey, KL, eds. Pain and central nervous system disease: the
central pain syndromes. New York: Raven Press, 1991:21.
More than just a headache In the editioral Familikal hemiplegic migraine: More than just a headache–593) by Benatar and Ford, Dr. Ford's middle initial was incorrect. The author's correct name is Corey C
- Familial Hemiplegic Migraine
Familial hemiplegic migraine: More than just a headache
In the editioral " Familikal hemiplegic migraine: More than just a headache " (Neurology 2005;64:592–593) by Benatar and Ford, Dr.
Ford's middle initial was incorrect. The author's correct name is Corey C. Ford.