cannabidiol and Pain--Intractable

This study compared the efficacy of a tetrahydrocannabinol:cannabidiol (THC:CBD) extract, a nonopioid analgesic endocannabinoid system modulator, and a THC extract, with placebo, in relieving pain in patients with advanced cancer. In total, 177 patients with cancer pain, who experienced inadequate analgesia despite chronic opioid dosing, entered a two-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. Patients were randomized to THC:CBD extract (n = 60), THC extract (n = 58), or placebo (n = 59). The primary analysis of change from baseline in mean pain Numerical Rating Scale (NRS) score was statistically significantly in favor of THC:CBD compared with placebo (improvement of -1.37 vs. -0.69), whereas the THC group showed a nonsignificant change (-1.01 vs. -0.69). Twice as many patients taking THC:CBD showed a reduction of more than 30% from baseline pain NRS score when compared with placebo (23 [43%] vs. 12 [21%]). The associated odds ratio was statistically significant, whereas the number of THC group responders was similar to placebo (12 [23%] vs. 12 [21%]) and did not reach statistical significance. There was no change from baseline in median dose of opioid background medication or mean number of doses of breakthrough medication across treatment groups. No significant group differences were found in the NRS sleep quality or nausea scores or the pain control assessment. However, the results from the European Organisation for Research and Treatment of Cancer Quality of Life Cancer Questionnaire showed a worsening in nausea and vomiting with THC:CBD compared with placebo (P = 0.02), whereas THC had no difference (P = 1.0). Most drug-related adverse events were mild/moderate in severity. This study shows that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.

Topics: Adult; Aged; Cannabidiol; Dose-Response Relationship, Drug; Double-Blind Method; Dronabinol; Drug Combinations; Endpoint Determination; Female; Humans; Male; Middle Aged; Neoplasms; Pain, Intractable

This pilot study aimed to assess the safety, tolerability, pharmacokinetics and exploratory analgesic effect of a novel water-soluble oro-buccal nanoparticle spray of a cannabis-based medicine (MDCNS-01) in patients with advanced incurable malignancy with unrelieved pain from opioid analgesic. The study was a non-blinded single arm 2 stage study. Stage I was a single escalating dose (n = 5) [2.5 mg Δ9-THC and 2.5 mg CBD) versus a 3-fold escalated dose. Stage II was an up-titrated dose in patients with advanced cancers and intractable pain (n = 25). During Stage I with an increased cannabis-based medicine dose, maximum observed plasma concentrations of cannabinoids were dose dependant. The water-soluble formulation in the current study resulted in a higher median (min, max) systemic exposure of Δ9-THC than CBD (AUC from 2.5 mg each of Δ9-THC and CBD, was 1.71 ng mL.h-1 (1.1, 6.6) and 0.65 ng mL.h-1 (0.49, 4.1), respectively). During stage II a subgroup of patients diagnosed with breast and prostate cancers with bone metastases, had the highest mean pain score improvement from baseline of 40% (unadjusted) and 33% (adjusted for rescue medication use). For all patients the most reported adverse events were mild or moderate drowsiness affecting 11 (44%) and 4 (6%) patients, respectively, and nausea and vomiting that affected 18 (72%) patients. The water-soluble cannabis-based medicine provided acceptable bioavailability for Δ9-THC/CBD, appeared safe and tolerable in advanced incurable cancers with uncontrolled pain with preliminary evidence of analgesic efficacy.

Topics: Analgesics; Analgesics, Opioid; Cannabidiol; Cannabinoids; Cannabis; Dronabinol; Humans; Male; Nanoparticles; Neoplasms; Pain, Intractable; Pilot Projects; Water

Since 2013 in the Italian market has been introduced the Nabiximols, a drug containing two of the main active cannabinoids: Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and cannabidiol (CBD). This drug has been approved in Italy in the treatment of Multiple Sclerosis (MS). It is an oral spray formulation and each puff of 100μl contains 2.7mg of Δ(9)-THC and 2.5mg of CBD. In the present study we analyzed urine and blood samples collected from a group of 20 patients treated with Nabiximols in order to evaluate: blood Δ(9)-THC concentrations in relation to the dose administered and the duration of treatment and the potentiality of this medication to be used for drug habit.. The study was conducted on a sample group of patients affected by MS, of both sexes, age: 49-61 years, treated with Nabiximols for short (28 days) or long-term. The results of our study allow affirming that it is unlikely to use this medication for drug habit or to sale it in the black market because of the low blood concentrations available and of its high costs. These statements were confirmed by: (a) the low Δ(9)-THC concentrations in the pharmaceutical formulation; (b) the low blood concentrations produced by Nabiximols administration, more than 10 times smaller than the blood concentrations known to produce psychotropic effects; (c) the presence of CBD (Δ(9)-THC natural antagonist); (d) the route of administration (inhaled, not smoked).

Topics: Administration, Inhalation; Analgesics, Non-Narcotic; Cannabidiol; Cannabinoids; Dronabinol; Drug Combinations; Female; Forensic Toxicology; Humans; Male; Middle Aged; Multiple Sclerosis; Pain, Intractable

Topics: Administration, Oral; Affect; Cannabidiol; Dose-Response Relationship, Drug; Dronabinol; Drug Combinations; Germany; Humans; Marijuana Abuse; Marijuana Smoking; Medical Marijuana; Multiple Sclerosis; Pain, Intractable; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Receptors, Cannabinoid; Risk Factors; Wasting Syndrome