Nabilone administration in refractory chronic diarrhea: a case series.

BACKGROUND: Daily cannabis assumption is currently associated with several physical and mental health problems, however in the past it was prescribed for a multitude of symptoms, including vomiting, abdominal pain and diarrhea. Through the years, the endocannabinoid system has been recognized in the homeostatic mechanisms of the gut, as well as in the physiological control of intestinal motility and secretion. Accordingly, cannabinoids may be a promising therapy against several gastrointestinal conditions, such as abdominal pain and motility-related disorders. CASE PRESENTATION: We retrospectively analysed the efficacy and safety of a CB1-receptor agonist administered in six patients with refractory chronic diarrhea, between April 2008 and July 2016. After three months of therapy, oral nabilone improved the health of nearly all patients, with visible improvements in reducing diarrheal symptoms and weight gain. Most of the benefits persisted through the three-month follow-up. Only one patient interrupted the treatment after one month, due to severe fatigue and mental confusion; the symptoms disappeared in the follow-up period. CONCLUSIONS: These findings encourage the study of cannabinoids acting on CB1 receptors in chronic gastrointestinal disorders, especially in refractory chronic diarrhea, offering a chance for a substantial improvement in the quality of life of selected patients, with a reasonable safety profile.

Pharmacokinetics and tolerability of oral cannabis preparations in patients with medication overuse headache (MOH)-a pilot study.

PURPOSE: The recent release of a medical cannabis strain has given a new impulse for the study of cannabis in Italy. The National Health Service advises to consume medical cannabis by vaporizing, in decoction or oil form. This is the first study that explores the pharmacokinetics and tolerability of a single oral dose of cannabis as decoction (200 ml) or in olive oil (1 ml), as a first step to improve the prescriptive recommendations. METHODS: This is a single-center, open-label, two-period crossover study designed to assess the pharmacokinetics and tolerability of oral cannabis administered to 13 patients with medication overuse headache (MOH). A liquid chromatography tandem-mass spectrometry (LC-MS/MS) method was conducted for the quantification of THC, CBD, 11-OH-THC, THC-COOH, THC-COOH-glucuronide, THCA-A, and CBDA. Blood pressure, heart rate, and a short list of symptoms by numerical rating scale (NRS) were assessed. RESULTS: Decoctions of cannabis showed high variability in cannabinoids content, compared to cannabis oil. For both preparations, THCA-A and CBDA were the most widely absorbed cannabinoids, while THC and CBD were less absorbed. The most important differences concern the bioavailability of THC, higher in oil (AUC0-24 7.44, 95% CI 5.19, 9.68) than in decoction (AUC0-24 3.34, 95% CI 2.07, 4.60), and the bioavailability of CBDA. No serious adverse events were reported. CONCLUSIONS: Cannabis decoction and cannabis oil showed different pharmacokinetic properties, as well as distinct consequences on patients. This study was performed in a limited number of patients; future studies should be performed to investigate the clinical efficacy in larger populations.

Migraine preventive drug-induced weight gain may be mediated by effects on hypothalamic peptides: the results of a pilot study.

AIMS: This study was aimed to verify changes in the levels of hypothalamic neuropeptides in migraineurs under preventive treatment with amitryptiline and flunarizine. Thirty-nine migraine patients with a body mass index <25 kg/m(2) and without endocrinological or metabolic diseases were assigned to two treatment groups, one receiving amitryptiline, the other flunarizine, for 3 months. Orexin-A, orexin-B and neuropeptide-Y plasma levels were measured at the basal time, at the 1st, 2nd and 3rd months of preventive treatment. RESULTS: A statistically significant reduction in plasma orexin-A and orexin-B levels emerged in both groups. Conversely, plasma neuropeptide-Y levels were markedly increased, with the highest levels at the 2nd and 3rd months, in both patient groups. Orexin-A levels were also negatively correlated to weight gain in both groups during the treatment period. CONCLUSIONS: These results suggest that changes in the levels of hypothalamic orexinergic peptides may contribute to body weight increase occurring in migraineurs during amitryptiline or flunarizine prophylactic treatment.