cannabidiol and Peripheral-Nervous-System-Diseases

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Asthma; Humans; Ion Channel Gating; Neurons; Pain; Peripheral Nervous System Diseases; Pulmonary Disease, Chronic Obstructive; Transient Receptor Potential Channels

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

Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ(9) -tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15-week randomized, double-blind, placebo-controlled parallel group study.. In total, 303 patients with PNP associated with allodynia were screened; 128 were randomized to THC/CBD spray and 118 to placebo, in addition to their current analgesic therapy. The co-primary efficacy endpoints were the 30% responder rate in PNP 0-10 numerical rating scale (NRS) score and the mean change from baseline to the end of treatment in this score. Various key secondary measures of pain and functioning were also investigated.. At the 30% responder level, there were statistically significant treatment differences in favour of THC/CBD spray in the full analysis (intention-to-treat) dataset [p = 0.034; 95% confidence interval (CI): 1.05-3.70]. There was also a reduction in mean PNP 0-10 NRS scores in both treatment groups that was numerically higher in the THC/CBD spray group, but which failed to reach statistical significance. Secondary measures of sleep quality 0-10 NRS score (p = 0.0072) and Subject Global Impression of Change (SGIC) (p = 0.023) also demonstrated statistically significant treatment differences in favour of THC/CBD spray treatment.. These findings demonstrate that, in a meaningful proportion of otherwise treatment-resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified.

Topics: Adult; Aged; Aged, 80 and over; Analgesics; Cannabidiol; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Female; Humans; Male; Middle Aged; Neuralgia; Pain Measurement; Peripheral Nervous System Diseases; Treatment Outcome

Cannabinoids are known to have analgesic properties. We evaluated the effect of oro-mucosal sativex, (THC: CBD), an endocannabinoid system modulator, on pain and allodynia, in 125 patients with neuropathic pain of peripheral origin in a five-week, randomised, double-blind, placebo-controlled, parallel design trial. Patients remained on their existing stable analgesia. A self-titrating regimen was used to optimise drug administration. Sixty-three patients were randomised to receive sativex and 62 placebo. The mean reduction in pain intensity scores (primary outcome measure) was greater in patients receiving sativex than placebo (mean adjusted scores -1.48 points vs. -0.52 points on a 0-10 Numerical Rating Scale (p=0.004; 95% CI: -1.59, -0.32). Improvements in Neuropathic Pain Scale composite score (p=0.007), sleep NRS (p=0.001), dynamic allodynia (p=0.042), punctate allodynia (p=0.021), Pain Disability Index (p=0.003) and Patient's Global Impression of Change (p<0.001) were similarly greater on sativex vs. placebo. Sedative and gastrointestinal side effects were reported more commonly by patients on active medication. Of all participants, 18% on sativex and 3% on placebo withdrew during the study. An open-label extension study showed that the initial pain relief was maintained without dose escalation or toxicity for 52 weeks.

Topics: Administration, Intranasal; Adolescent; Adult; Aged; Analgesics; Cannabidiol; Double-Blind Method; Dronabinol; Drug Combinations; Female; Humans; Hyperesthesia; Male; Middle Aged; Neuralgia; Pain Measurement; Peripheral Nervous System Diseases; Plant Extracts; Psychomotor Performance; Time Factors; Treatment Outcome

To assess the safety, dosing, and preventive effects of cannabidiol (CBD) on chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving oxaliplatin- or paclitaxel-based chemotherapy.. Patients with cancer scheduled to undergo treatment with carboplatin and paclitaxel (Carbo-Tax) or capecitabine and oxaliplatin (CAPOX) received 150 mg CBD oil twice daily (300 mg/daily) for 8 days beginning 1 day before initiation of chemotherapy. Ten CIPN-specific patient-reported outcome (PRO) measures were captured at baseline and each day after the first cycle of chemotherapy for 8 days. Multi-frequency vibrometry (MF-V) was captured at baseline and day 4 ± 1 after initiation of chemotherapy. Controls were obtained from a similar patient cohort that did not receive CBD. Adverse events were captured using the CTCAE ver. 4.03.. From March to December 2021, 54 patients were recruited. CBD-treated patients were significantly older (p = 0.013/0.037, CAPOX/Carbo-Tax) compared to controls. Patients receiving CBD and CAPOX or Carbo-Tax showed significantly lower (better) change in Z-scores in high-frequency MF-V (125 and 250 Hz) compared to controls. This difference was most pronounced for patients receiving Carbo-Tax (- 1.76, CI-95 = [- 2.52; - 1.02] at 250 Hz). CAPOX patients treated with CBD had significantly lower peak baseline-adjusted difference in three PRO items on cold sensitivity to touch, discomfort swallowing cold liquids, and throat discomfort (- 2.08, - 2.06, and - 1.81, CI-95 = [- 3.89; - 0.12], NRS 0-10). No significant differences in PRO items were found for patients receiving Carbo-Tax. Possible side effects included stomach pain (grades 1-2) for patients receiving CAPOX.. CBD attenuated early symptoms of CIPN with no major safety concerns. Long-term follow-up is ongoing. Results should be confirmed in a larger, randomized study.. NCT 04,167,319 (U.S National Library of Medicine; ClinicalTrials.gov). Date of registration: November 18, 2019.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cannabidiol; Humans; Oxaliplatin; Paclitaxel; Peripheral Nervous System Diseases

Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a noneuphoria producing constituent of cannabis that has the potential to relieve pain. The aim of this study was to determine whether CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy. Osteoarthritis was induced in male Wistar rats (150-175 g) by intra-articular injection of sodium monoiodoacetate (MIA; 3 mg). On day 14 (end-stage OA), joint afferent mechanosensitivity was assessed using in vivo electrophysiology, whereas pain behaviour was measured by von Frey hair algesiometry and dynamic incapacitance. To investigate acute joint inflammation, blood flow and leukocyte trafficking were measured on day 1 after MIA. Joint nerve myelination was calculated by G-ratio analysis. The therapeutic and prophylactic effects of peripheral CBD (100-300 μg) were assessed. In end-stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (P < 0.0001; n = 8). Acute, transient joint inflammation was reduced by local CBD treatment (P < 0.0001; n = 6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (P < 0.0001; n = 8), and was also found to be neuroprotective (P < 0.05; n = 6-8). The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints. These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.

Topics: Animals; Arthralgia; Cannabidiol; Disease Models, Animal; Inflammation; Iodoacetic Acid; Knee Joint; Male; Osteoarthritis; Osteoarthritis, Knee; Pain; Peripheral Nervous System Diseases; Rats, Wistar

The taxane chemotherapeutic paclitaxel frequently produces peripheral neuropathy in humans. Rodent models to investigate mechanisms and treatments are largely restricted to male rats, whereas female mouse studies are lacking. We characterized a range of paclitaxel doses on cold and mechanical allodynia in male and female C57Bl/6 mice. Because the nonpsychoactive phytocannabinoid cannabidiol attenuates other forms of neuropathic pain, we assessed its effect on paclitaxel-induced allodynia. Paclitaxel produced allodynia that was largely dose independent and more robust in female mice, and this effect was prevented by treatment with cannabidiol. Our preliminary findings therefore indicate that cannabidiol may prevent the development of paclitaxel-induced allodynia in mice and therefore be effective at preventing dose-limiting paclitaxel-induced peripheral neuropathy in humans.

Topics: Analgesics; Animals; Behavior, Animal; Cannabidiol; Cold Temperature; Disease Models, Animal; Female; Hyperalgesia; Male; Mice; Mice, Inbred C57BL; Paclitaxel; Pain Measurement; Pain Threshold; Peripheral Nervous System Diseases; Physical Stimulation; Sex Factors; Time Factors

GW Pharmaceuticals is developing GW-1000 (Sativex), a narrow ratio delta9-tetrahydrocannabinol:cannabidiol product for the potential treatment of multiple sclerosis, spinal cord injury, neurogenic pain and peripheral neuropathy. In March 2003, the company filed for approval for the treatment of MS with the UK Medicines Control Agency, and in May 2004, filed for new drug submission with Health Canada.

Topics: Administration, Oral; Analgesics; Animals; Biological Availability; Canada; Cannabidiol; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dronabinol; Drug Approval; Drug Combinations; Drug Evaluation, Preclinical; Drug Industry; Humans; Hyperalgesia; Investigational New Drug Application; Mice; Molecular Structure; Multiple Sclerosis; Patents as Topic; Peripheral Nervous System Diseases; Phytotherapy; Plant Extracts; Plant Preparations; Randomized Controlled Trials as Topic; Spinal Cord Injuries; Structure-Activity Relationship