cannabidiol and Chronic-Disease

Appetite influences perceived quality of life for a dog or cat with cancer. Inappetence often is multifactorial, complicating treatment. Cancer-related anorexia/cachexia syndrome is a metabolic, paraneoplastic syndrome characterized by decreased food intake, involuntary weight loss, and loss of fat and muscle. If weight loss/cachexia has an impact on canine and feline cancer patients as in humans, management may improve survival times and quality of life. The challenge is having effective, proved therapies available for clinical use. Recent Food and Drug Administration approvals for appetite stimulation have renewed interest and discussion and has the potential to alter the course of case management.

Topics: Animals; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Appetite Stimulants; Cachexia; Cannabidiol; Cat Diseases; Cats; Chronic Disease; Dog Diseases; Dogs; Neoplasms; Quality of Life

Increasing evidence suggests that an overactive endocannabinoid system (ECS) may contribute to the development of diabetes by promoting energy intake and storage, impairing both glucose and lipid metabolism, by exerting pro-apoptotic effects in pancreatic beta cells and by facilitating inflammation in pancreatic islets. Furthermore, hyperglycaemia associated with diabetes has also been implicated in triggering perturbations of the ECS amplifying the pathological processes mentioned above, eventually culminating in a vicious circle. Compelling evidence from preclinical studies indicates that the ECS also influences diabetes-induced oxidative stress, inflammation, fibrosis and subsequent tissue injury in target organs for diabetic complications. In this review, we provide an update on the contribution of the ECS to the pathogenesis of diabetes and diabetic microvascular (retinopathy, nephropathy and neuropathy) and cardiovascular complications. The therapeutic potential of targeting the ECS is also discussed.. This article is part of a themed section on Endocannabinoids. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.7/issuetoc.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cannabidiol; Chronic Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Endocannabinoids; Humans; Insulin Resistance; Insulin-Secreting Cells; Obesity; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2

Although not new, the use of cannabis-based drugs for treating chronic pain patients is becoming a hot topic for pain physicians and other specialists due to the constant flow of medical information regarding this pharmacological therapy. Its indication is becoming more clearly targeted towards pain syndromes arising from nerve damage. The number of cases reported, clinical trials and reviews published on this subject exponentially increase year by year. A possible explanation for this may be the fact that neuropathic pain is a highly disabling symptom and, consequently, there is a demand from patients and health professionals for a definitive remedy to treat this pain.. Parallel to the number of articles on the effectiveness, recent articles describing the tolerability of cannabis-based drugs along with a more accurate characterisation of its side-effect profile and/or lack of effectiveness have been published, and they are placing a cautious stop for a more precise prescription of these medications.. This article reviews the current knowledge on the use of Sativex for treating neuropathic pains of different origin, and analyses the balance between the advantages and drawbacks of this therapy.

Topics: Analgesics; Cannabidiol; Chronic Disease; Clinical Trials as Topic; Dronabinol; Drug Combinations; Humans; Neuralgia; Pain Measurement; Plant Extracts

Neuropathic pain encompasses a myriad of painful disease states that are often hard to treat, especially with one single medication. In the comprehensive treatment of neuropathic pain, the concept of complex polypharmacy is a rational approach, accompanied by physical and mental health therapies. Medications primarily used for neuropathic pain generally fall into the categories of anticonvulsants, antidepressants, opioids, and topical agents. Generally, most first-line medications used today show a response rate of approximately 30% to 50% reduction in pain in up to 50% of patients treated. There is no "gold standard" in regard to one medication for neuropathic pain. Some new medications have emerged during the past few years that help to augment the armamentarium of medications used in neuropathic pain. This paper reviews the definition of neuropathic pain and introduces the reader to the evidence-based literature on these new medications available for the treatment of neuropathic pain.

Topics: Analgesics; Animals; Cannabidiol; Chronic Disease; Dronabinol; Duloxetine Hydrochloride; gamma-Aminobutyric Acid; Guidelines as Topic; Humans; Pain; Peripheral Nervous System Diseases; Pregabalin; Thiophenes

Preliminary evidence suggests that cannabidiol (CBD) may be effective in the treatment of neurodegenerative disorders; however, CBD has never been evaluated for the treatment of cognitive impairments associated with schizophrenia (CIAS).. This study compared the cognitive, symptomatic, and side effects of CBD versus placebo in a clinical trial.. This study was a 6-week, randomized, placebo-controlled, parallel group, fixed-dose study of oral CBD (600 mg/day) or placebo augmentation in 36 stable antipsychotic-treated patients diagnosed with chronic schizophrenia. All subjects completed the MATRICS Consensus Cognitive Battery (MCCB) at baseline and at end of 6 weeks of treatment. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and biweekly.. There was no main effect of time or drug on MCCB Composite score, but a significant drug × time effect was observed (p = 0.02). Post hoc analyses revealed that only placebo-treated subjects improved over time (p = 0.03). There was a significant decrease in PANSS Total scores over time (p < 0. 0001) but there was no significant drug × time interaction (p = 0.18). Side effects were similar between CBD and placebo, with the one exception being sedation, which was more prevalent in the CBD group.. At the dose studied, CBD augmentation was not associated with an improvement in MCCB or PANSS scores in stable antipsychotic-treated outpatients with schizophrenia. Overall, CBD was well tolerated with no worsening of mood, suicidality, or movement side effects.. https://clinicaltrials.gov/ct2/show/NCT00588731.

Topics: Administration, Oral; Adult; Affect; Antipsychotic Agents; Cannabidiol; Chronic Disease; Cognition; Cognitive Dysfunction; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Mental Status and Dementia Tests; Middle Aged; Outpatients; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Treatment Outcome

Three Cannabis Based Medicinal Extracts (CBMEs) for sublingual use became available in 2000. A total of 34 'N of 1' studies were undertaken using this novel therapy for patients with chronic, mainly neuropathic, pain and associated symptoms to explore efficacy, tolerability, safety and dosages. Three CBMEs (Delta9 Tetrahydrocannabinol (THC), Cannabidiol (CBD) and a 1:1 mixture of them both) were given over a 12-week period. After an initial open-label period, the CBMEs were used in a randomised, double-blind, placebo controlled, crossover trial. Extracts which contained THC proved most effective in symptom control. Regimens for the use of the sublingual spray emerged and a wide range of dosing requirements was observed. Side-effects were common, reflecting a learning curve for both patient and study team. These were generally acceptable and little different to those seen when other psycho-active agents are used for chronic pain. These initial experiences with CBME open the way to more detailed and extensive studies.

Topics: Administration, Sublingual; Adult; Aged; Analgesics, Non-Narcotic; Cannabidiol; Chronic Disease; Cross-Over Studies; Depressive Disorder; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Pain; Pain Measurement; Patient Selection; Sleep; Treatment Outcome

Chronic methamphetamine (meth) abuse can lead to certain deficits in the hippocampal function by affecting the hippocampal neurogenesis and plasticity. To determine whether cannabidiol (CBD) can promote proliferation and maturation of neuronal progenitor cells, this study investigated the CBD effect on neurogenesis in the hippocampal dentate gyrus (DG) following chronic exposure to meth in rats. The rats received 2 mg/kg of meth twice a day for ten days. Next, immunofluorescence was performed to evaluate the effect of intracerebroventricular (ICV) administration of CBD (50 μg/5 μL) over an abstinence period (ten days) on the expression levels of neurogenesis markers, such as Ki67, NeuN, and doublecortin (DCX). Moreover, neuronal degeneration in the hippocampus was assessed using Nissl staining. According to our findings, repeated ICV administration of CBD improved cell proliferation and neurogenesis and increased the number of Ki-67 and DCX-positive cells in the abstinence period. Meanwhile, meth treatment subjects caused a significant decrease in the number of neurogenesis makers, as compared to the control group. The neurogenesis markers (Ki-67 and DCX) could be somewhat reversed, while NeuN did not show any significant increase in the CBD group. Our findings demonstrated that CBD can induce neuroprotective effects by modulating neurogenesis. Therefore, it can provide a promising therapeutic approach to improve cognitive performance following chronic exposure to psychostimulant drugs, including meth.

Topics: Amphetamine-Related Disorders; Animals; Cannabidiol; Cell Proliferation; Central Nervous System Stimulants; Chronic Disease; Dentate Gyrus; Hippocampus; Injections, Intraventricular; Male; Methamphetamine; Neural Stem Cells; Neurogenesis; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Topics: Animals; Cannabidiol; Chronic Disease; Cobalt; Depression; Limbic System; Microinjections; Neuralgia; Piperazines; Piperidines; Prefrontal Cortex; Pyrazoles; Pyridines; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Serotonin, 5-HT1A; Sciatica; Serotonin 5-HT1 Receptor Antagonists; Swimming; Synapses

To examine whether cannabis use predicts medication overuse headache (MOH) in patients with chronic migraine (CM).. Electronic chart review was conducted by combining the terms "CM," "medication overuse," "cannabis," "cannabidiol," and "tetrahydrocannabinol" for patients seen at our headache clinics from 2015 to 2019. Of 729 charts consecutively screened, 368 met our inclusion criteria, that is, adult patients with CM with ≥1-year CM duration. The following variables were extracted from the included patient charts: MOH diagnosis, age, sex, migraine frequency, current CM duration, current cannabis use duration, overused acute migraine medications, current MOH duration, and types of cannabis products used. Logistic regression was used to identify variables predicting MOH while controlling for remaining predictors. Agglomerative hierarchical clustering (AHC) was conducted to explore natural clusters using all predictor variables.. There were 212 patients with CM and MOH (cases; median age 43 years, interquartile range [IQR] 33-54; 177 [83%] females) and 156 patients with CM without MOH (referents; median age 40 years, IQR 31-49; 130 [83%] females). MOH was present in 81% (122/150) of current cannabis users compared with 41% (90/218) in those without cannabis use-adjusted odds ratio 6.3 (95% CI: 3.56 to 11.1, p < 0.0001). Current cannabis use was significantly associated with opioid use (Spearman's rho 0.26, p < 0.0001). Both current cannabis use (rho 0.40, p < 0.0001) and opioid use (rho 0.36, p < 0.0001) were significantly associated with MOH. Similarly, AHC revealed two major natural clusters. Cluster I patients featured 9.3 times higher current cannabis use, 9.2 times higher current opioid use, and 1.8 times higher MOH burden than those in Cluster II (p < 0.0001).. Cannabis use was significantly associated with increased prevalence of MOH in CM. Bidirectional cannabis-opioid association was observed-use of one was associated with use of the other. Advising patients with CM and MOH to reduce cannabis use may help treat MOH effectively.

Topics: Adult; Analgesics, Non-Narcotic; Analgesics, Opioid; Cannabidiol; Chronic Disease; Dronabinol; Female; Headache Disorders, Secondary; Humans; Male; Medical Marijuana; Middle Aged; Migraine Disorders; Prescription Drug Overuse

The symptomatic treatment of myotonia and myalgia in patients with dystrophic and non-dystrophic myotonias is often not satisfactory. Some patients anecdotally report symptoms' relief through consumption of cannabis.. A combination of cannabidiol and tetrahydrocannabinol (CBD/THC) was prescribed as compassionate use to six patients (four patients with myotonic dystrophy types 1 and 2, and 2 patients with CLCN1-myotonia) with therapy-resistant myotonia and myalgia. CBD/THC oil was administered on a low dose in the first 2 weeks and adjusted to a higher dose in the following 2 weeks. Myotonia behaviour scale (MBS), hand-opening time, visual analogue scales (VAS) for myalgia and myotonia, and fatigue and daytime sleepiness severity scale (FSS, ESS) were performed weekly to monitor treatment response.. All patients reported an improvement of myotonia especially in weeks 3 and 4 of treatment: MBS improved of at least 2 points in all patients, the hand-opening time variously improved in 5 out of 6 patients. Chronic myalgia was reported by both DM2 patients at baseline, one of them experienced a significant improvement of myalgia under treatment. Some gastrointestinal complaints, as abdominal pain and diarrhoea, improved in 3 patients; however, 4 out of 6 patients reported new-onset constipation. No other relevant side effect was noticed.. These first empirical results suggest a potentially beneficial role of CBD/THC in alleviating myotonia and should encourage further research in this field including a randomized-controlled trial on larger cohorts.

Topics: Adult; Aged; Cannabidiol; Cannabinoid Receptor Modulators; Chronic Disease; Cohort Studies; Compassionate Use Trials; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Muscular Dystrophies; Myalgia; Myotonia; Oils; Treatment Outcome

Use of cannabidiol (CBD) has markedly increased in the past 5 years, concurrent with marketing claims that over-the-counter CBD can be used to treat almost any health condition. However, the reasons why individuals use CBD remain unclear.. To assess whether individuals are using CBD for diagnosable conditions that have evidence-based therapies.. This case series assessed claimed treatment applications reported by CBD users in public testimonials shared on the Reddit forum r/CBD. The r/CBD forum was selected because it includes a large, naturally occurring sample of 104 917 registered individuals who publicly discuss their experiences using CBD. All r/CBD posts were obtained from January 1, 2014, through August 31, 2019. A random sample of posts was drawn (n = 3000) and filtered to include posts in which self-identified CBD users testified why they take CBD (n = 376).. Self-reported use of CBD for medicinal purposes.. Cannabidiol testimonials were divided into 11 subcategories corresponding with the condition's medical subspecialty and 2 subcategories corresponding with wellness benefits. Posts were allowed to receive more than 1 label.. Of the 376 posts labeled as testimonials, 90.0% (95% CI, 86.8%-92.8%) of testimonials claimed that CBD treated the individual's diagnosable conditions. Psychiatric conditions (eg, autism or depression) were the most frequently cited subcategory, mentioned in 63.9% (95% CI, 59.0%-69.1%) of testimonials, followed by orthopedic (26.4%; 95% CI, 21.8%-31.1%), sleep (14.6%; 95% CI, 11.3%-18.5%), and neurological (6.9%; 95% CI, 4.4%-9.6%) conditions. Testimonials also claimed that CBD treated gastroenterological conditions (3.9%; 95% CI, 1.9%-6.1%), as well as addiction, cardiological, dermatological, ophthalmological, oral health, and sexual health conditions (<2.0% each). By contrast, just 29.5% (95% CI, 24.8%-34.2%) of testimonies claimed any wellness benefit, with most citing mental wellness (eg, "quieting my mind") (29.5% [95% CI, 24.2%-34.4%]); 1.4% (95% CI, 0.3%-2.8%) claimed a physical wellness benefit (eg, "exercise performance").. The findings of this case series suggest a need for regulation of factors associated with CBD being used to treat diagnosable conditions, engagement of health care professionals with patients on their potential CBD use, and implementation of public health campaigns that encourage the public to seek treatment advice from health care professionals regarding evidence-based therapies.

Topics: Adaptation, Psychological; Adult; Cannabidiol; Cannabinoids; Chronic Disease; Female; Humans; Male; Mental Disorders; Middle Aged; Narration; Patient Satisfaction; Self Report; Treatment Outcome

Diabetes and aging are risk factors for cognitive impairments after chronic cerebral hypoperfusion (CCH). Cannabidiol (CBD) is a phytocannabinoid present in the Cannabis sativa plant. It has beneficial effects on both cerebral ischemic diseases and diabetes. We have recently reported that diabetes interacted synergistically with aging to increase neuroinflammation and memory deficits in rats subjected to CCH. The present study investigated whether CBD would alleviate cognitive decline and affect markers of inflammation and neuroplasticity in the hippocampus in middle-aged diabetic rats submitted to CCH. Diabetes was induced in middle-aged rats (14 months old) by intravenous streptozotocin (SZT) administration. Thirty days later, the diabetic animals were subjected to sham or CCH surgeries and treated with CBD (10 mg/kg, once a day) during 30 days. Diabetes exacerbated cognitive deficits induced by CCH in middle-aged rats. Repeated CBD treatment decreased body weight in both sham- and CCH-operated animals. Cannabidiol improved memory performance and reduced hippocampal levels of inflammation markers (inducible nitric oxide synthase, ionized calcium-binding adapter molecule 1, glial fibrillary acidic protein, and arginase 1). Cannabidiol attenuated the decrease in hippocampal levels of brain-derived neurotrophic factor induced by CCH in diabetic animals, but it did not affect the levels of neuroplasticity markers (growth-associated protein-43 and synaptophysin) in middle-aged diabetic rats. These results suggest that the neuroprotective effects of CBD in middle-aged diabetic rats subjected to CCH are related to a reduction in neuroinflammation. However, they seemed to occur independently of hippocampal neuroplasticity changes.

Topics: Age Factors; Animals; Blood Glucose; Brain; Cannabidiol; Cerebrovascular Circulation; Chronic Disease; Comorbidity; Diabetes Mellitus, Experimental; Male; Rats; Rats, Wistar; Treatment Outcome

The G protein-coupled receptor 55 (GPR55) is a novel cannabinoid receptor, whose exact role in anxiety remains unknown. The present study was conducted to explore the possible mechanisms by which GPR55 regulates anxiety and to evaluate the effectiveness of O-1602 in the treatment of anxiety-like symptoms. Mice were exposed to two types of acute stressors: restraint and forced swimming. Anxiety behavior was evaluated using the elevated plus maze and the open field test. We found that O-1602 alleviated anxiety-like behavior in acutely stressed mice. We used lentiviral shRNA to selective ly knockdown GPR55 in the medial orbital cortex and found that knockdown of GPR55 abolished the anxiolytic effect of O-1602. We also used Y-27632, a specific inhibitor of ROCK, and U73122, an inhibitor of PLC, and found that both inhibitors attenuated the effectiveness of O-1602. Western blot analysis revealed that O-1602 downregulated the expression of GluA1 and GluN2A in mice. Taken together, these results suggest that GPR55 plays an important role in anxiety and O-1602 may have therapeutic potential in treating anxiety-like symptoms.

Topics: Acute Disease; Amides; Animals; Anti-Anxiety Agents; Anxiety; Cannabidiol; Chronic Disease; Cyclohexanes; Estrenes; Gene Knockdown Techniques; Injections, Intraperitoneal; Male; Mice, Inbred C57BL; Prefrontal Cortex; Pyridines; Pyrrolidinones; Receptors, Cannabinoid; Resorcinols; Restraint, Physical; Signal Transduction; Stress, Psychological; Swimming

Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient's quality of life. Its treatment is complex and sometimes the outcome is insufficient. Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies.. To quantify the clinical response of a group of patients with spastic chronic spinal cord injury to the orally administered drug delta-9-tetrahydrocannabinol-cannabidiol (Sativex ®) as medication for use in special situations.. The research consists of a six-month observational study in patients with chronic spinal cord injuries with refractory spasticity. The variables collected were: modified Ashworth scale, Penn spasm frequency scale, Numeric Rating Scale, and Visual Analogue Scale for pain. Additionally, clinical variables and side effects of the treatment were also collected.. Fifteen patients took part in this study. A significant improvement was observed on three of the scales recorded: modified Ashworth scale (z = -2.97; p = 0.003), Penn spasm frequency scale (z = -2.76; p = 0.006) and Numeric Rating Scale (z = -3.21; p = 0.001). The use of the drug was withdrawn in two patients due to side effects.. Sativex can be considered an alternative in patients with spasticity associated with chronic spinal cord injury for whom other therapeutic measures have been insufficient. Further studies need to be conducted before the use of this drug can be recommended and so as to define a complete profile of its long-term side effects.. Delta-9-tetrahidrocannabinol-cannabidiol en el tratamiento de la espasticidad en la lesion medular cronica: una experiencia clinica.. Introduccion. La espasticidad en la lesion medular cronica es una condicion que puede repercutir negativamente en la calidad de vida del paciente. Su tratamiento es complejo y, en ocasiones, el resultado es insuficiente. Recientemente, en la esclerosis multiple los cannabinoides se han empleado con exito en el tratamiento de la espasticidad refractaria a otras terapias. Objetivo. Cuantificar la respuesta clinica de un grupo de pacientes con lesion medular cronica espastica al farmaco delta-9-tetrahidrocannabinol-cannabidiol (Sativex ®), de administracion oral, como medicamento de uso en situaciones especiales. Pacientes y metodos. Estudio observacional durante seis meses en lesionados medulares cronicos con espasticidad refractaria. Las variables recogidas fueron: escala modificada de Ashworth, escala de frecuencia de espasmos de Penn, Numeric Rating Scale y escala visual analogica del dolor. De forma adicional se recogieron variables clinicas y efectos secundarios del tratamiento. Resultados. Quince pacientes tomaron parte en el estudio. Se observo mejoria significativa en tres de las escalas registradas: escala de Ashworth modificada (z = -2,97; p = 0,003), escala de frecuencia de espasmos de Penn (z = -2,76; p = 0,006) y Numeric Rating Scale (z = -3,21; p = 0,001). Se suspendio el uso del farmaco en dos pacientes por efectos secundarios. Conclusiones. Sativex se muestra como una alternativa en pacientes con espasticidad asociada a lesion medular cronica, en las que otras medidas terapeuticas resultan insuficientes. Son necesarios mas estudios para recomendar el uso de este farmaco y definir un perfil completo de sus efectos adversos a largo plazo.

Topics: Adult; Aged; Cannabidiol; Chronic Disease; Dronabinol; Drug Combinations; Female; Humans; Male; Middle Aged; Muscle Spasticity; Spinal Cord Injuries; Treatment Outcome

Febrile infection-related epilepsy syndrome (FIRES) is a devastating epilepsy affecting normal children after a febrile illness. FIRES presents with an acute phase with super-refractory status epilepticus and all patients progress to a chronic phase with persistent refractory epilepsy. The typical outcome is severe encephalopathy or death. The authors present 7 children from 5 centers with FIRES who had not responded to antiepileptic drugs or other therapies who were given cannabadiol (Epidiolex, GW Pharma) on emergency or expanded investigational protocols in either the acute or chronic phase of illness. After starting cannabidiol, 6 of 7 patients' seizures improved in frequency and duration. One patient died due to multiorgan failure secondary to isoflourane. An average of 4 antiepileptic drugs were weaned. Currently 5 subjects are ambulatory, 1 walks with assistance, and 4 are verbal. While this is an open-label case series, the authors add cannabidiol as a possible treatment for FIRES.

Topics: Acute Disease; Anticonvulsants; Cannabidiol; Child; Chronic Disease; Drug Resistant Epilepsy; Epileptic Syndromes; Fever; Humans; Infections; Male; Status Epilepticus; Treatment Outcome

The endocannabinoid system in mice plays a role in models of human cirrhosis and hepatic encephalopathy (HE), induced by a hepatotoxin. We report now the therapeutic effects of cannabidiol (CBD), a non-psychoactive constituent of Cannabis sativa, on HE caused by bile duct ligation (BDL), a model of chronic liver disease.. CBD (5mg/kg; i.p.) was administered over 4weeks to mice that had undergone BDL.. Cognitive function in the eight arm maze and the T-maze tests, as well as locomotor function in the open field test were impaired by the ligation and were improved by CBD. BDL raised hippocampal expression of the TNF-alpha-receptor 1 gene, which was reduced by CBD. However, BDL reduced expression of the brain-derived neurotrophic factor (BDNF) gene, which was increased by CBD. The effects of CBD on cognition, locomotion and on TNF-alpha receptor 1 expression were blocked by ZM241385, an A(2)A adenosine receptor antagonist. BDL lowers the expression of this receptor.. The effects of BDL apparently result in part from down-regulation of A(2)A adenosine receptor. CBD reverses these effects through activation of this receptor, leading to compensation of the ligation effect.

Topics: Adenosine A2 Receptor Antagonists; Animals; Bile Ducts; Brain-Derived Neurotrophic Factor; Cannabidiol; Chronic Disease; Cognition; Cognition Disorders; Cyclooxygenase 2; Disease Models, Animal; Female; Gait Disorders, Neurologic; Hepatic Encephalopathy; Ligation; Liver Diseases; Mice; Mice, Inbred Strains; Motor Activity; Receptor, Adenosine A2A; Receptors, Tumor Necrosis Factor, Type I; RNA, Messenger; Treatment Outcome; Triazines; Triazoles

Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund's adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.5-20 mg/kg to neuropathic and 20 mg/kg to adjuvant-injected rats) from day 7 to day 14 after the injury, or intraplantar injection, reduced hyperalgesia to thermal and mechanical stimuli. In the neuropathic animals, the anti-hyperalgesic effect of cannabidiol (20 mg/kg) was prevented by the vanilloid antagonist capsazepine (10 mg/kg, i.p.), but not by cannabinoid receptor antagonists. Cannabidiol's activity was associated with a reduction in the content of several mediators, such as prostaglandin E(2) (PGE(2)), lipid peroxide and nitric oxide (NO), and in the over-activity of glutathione-related enzymes. Cannabidiol only reduced the over-expression of constitutive endothelial NO synthase (NOS), without significantly affecting the inducible form (iNOS) in inflamed paw tissues. Cannabidiol had no effect on neuronal and iNOS isoforms in injured sciatic nerve. The compound's efficacy on neuropathic pain was not accompanied by any reduction in nuclear factor-kappaB (NF-kappaB) activation and tumor necrosis factor alpha (TNFalpha) content. The results indicate a potential for therapeutic use of cannabidiol in chronic painful states.

Topics: Administration, Oral; Animals; Cannabidiol; Cannabinoid Receptor Antagonists; Cannabis; Capsaicin; Chronic Disease; Dinoprostone; Freund's Adjuvant; Hyperalgesia; Inflammation; Lipid Peroxides; Male; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Pain; Pain Measurement; Rats; Rats, Wistar; Sciatic Neuropathy; Tumor Necrosis Factor-alpha

Topics: Analgesics, Opioid; Cannabidiol; Cannabinoids; Carbazoles; Chronic Disease; Dronabinol; Drug Combinations; Humans; Ibuprofen; Oxycodone; Oxymorphone; Pain; Plant Extracts; Serotonin Receptor Agonists; Tryptamines