gw-1000 and Neoplasms

Answer questions and earn CME/CNE Marijuana has been used for centuries, and interest in its medicinal properties has been increasing in recent years. Investigations into these medicinal properties has led to the development of cannabinoid pharmaceuticals such as dronabinol, nabilone, and nabiximols. Dronabinol is best studied in the treatment of nausea secondary to cancer chemotherapy and anorexia associated with weight loss in patients with acquired immune deficiency syndrome, and is approved by the US Food and Drug Administration for those indications. Nabilone has been best studied for the treatment of nausea secondary to cancer chemotherapy. There are also limited studies of these drugs for other conditions. Nabiximols is only available in the United States through clinical trials, but is used in Canada and the United Kingdom for the treatment of spasticity secondary to multiple sclerosis and pain. Studies of marijuana have concentrated on nausea, appetite, and pain. This article will review the literature regarding the medical use of marijuana and these cannabinoid pharmaceuticals (with emphasis on indications relevant to oncology), as well as available information regarding adverse effects of marijuana use.

Topics: Analgesics, Non-Narcotic; Antiemetics; Canada; Cannabidiol; Clinical Trials as Topic; Dronabinol; Drug Combinations; Evidence-Based Medicine; Humans; Medical Marijuana; Multiple Sclerosis; Neoplasms; Pain; Treatment Outcome; United Kingdom; United States

To estimate prevalence of continuous use (persistence) of prescribed cannabinoid medications for up to 1 year from initial prescription in Manitoba, Canada and predictors of duration of use.. A retrospective, population-based, cohort study using administrative data from the Manitoba Population Research Data Repository located at the Manitoba Centre for Health Policy, Canada.. People without a record of a previous prescription who were prescribed a cannabinoid medication from 1 April 2004 to 1 April 2016 followed for 1 year from the date of first prescription.. Continuous prescribed cannabinoid medication use was defined as use without a gap exceeding 60 days between prescriptions. The primary outcome was prevalence of continuous prescribed cannabinoid medication use for up to 1 year. A secondary outcome was duration of continuous use. Predictors were socio-demographic characteristics, medical diagnoses and type of cannabinoid medication.. Among 5452 new users, 18.1% [95% confidence interval (CI) = 17.08-19.12] were still using cannabinoids at 1 year. Median duration of use was 31 days [interquartile range (IQR) = 25-193]. This was highest for nabilone (33 days, IQR = 25-199) and lowest for nabiximols (20 days, IQR = 7-30). Use was longest among 19-45- and 46-64-year-old users and those with the highest socio-economic status. Fibromyalgia [hazard ratio (HR) = 0.89, 95% CI = 0.84-0.95], osteoarthritis (HR = 0.91, 95% CI = 0.82-0.97) and substance use disorder (HR = 0.85, 95% CI = 0.76-0.94) diagnoses were associated with longer use (HR for discontinuation-HR < 1 less discontinuation and longer use). A diagnosis of cancer was associated with shorter use (HR = 2.73, 95% CI = 2.02-3.67).. In Manitoba, Canada approximately 18% of people prescribed cannabinoid medication continue using for at least 1 year. Duration of use varies with type of cannabinoid medication, age, socio-economic status and dagnosis.

Topics: Adolescent; Adult; Aged; Cannabidiol; Cannabinoids; Dronabinol; Drug Combinations; Duration of Therapy; Female; Fibromyalgia; Humans; Male; Manitoba; Medication Adherence; Middle Aged; Neoplasms; Osteoarthritis; Prescription Drugs; Retrospective Studies; Social Class; Substance-Related Disorders; Young Adult

Although the global incidence of cutaneous melanoma is increasing, survival rates for patients with metastatic disease remain <10%. Novel treatment strategies are therefore urgently required, particularly for patients bearing BRAF/NRAS wild-type tumors. Targeting autophagy is a means to promote cancer cell death in chemotherapy-resistant tumors, and the aim of this study was to test the hypothesis that cannabinoids promote autophagy-dependent apoptosis in melanoma. Treatment with Δ(9)-Tetrahydrocannabinol (THC) resulted in the activation of autophagy, loss of cell viability, and activation of apoptosis, whereas cotreatment with chloroquine or knockdown of Atg7, but not Beclin-1 or Ambra1, prevented THC-induced autophagy and cell death in vitro. Administration of Sativex-like (a laboratory preparation comprising equal amounts of THC and cannabidiol (CBD)) to mice bearing BRAF wild-type melanoma xenografts substantially inhibited melanoma viability, proliferation, and tumor growth paralleled by an increase in autophagy and apoptosis compared with standard single-agent temozolomide. Collectively, our findings suggest that THC activates noncanonical autophagy-mediated apoptosis of melanoma cells, suggesting that cytotoxic autophagy induction with Sativex warrants clinical evaluation for metastatic disease.

Topics: Adaptor Proteins, Signal Transducing; Animals; Apoptosis; Apoptosis Regulatory Proteins; Autophagy; Beclin-1; Cannabidiol; Cannabinoids; Cannabinol; Cell Death; Cell Line, Tumor; Cell Proliferation; Cell Survival; Dacarbazine; Dronabinol; Drug Combinations; Humans; Male; Melanoma; Membrane Proteins; Mice; Mice, Nude; Microscopy, Confocal; Neoplasm Metastasis; Neoplasm Transplantation; Neoplasms; Plant Extracts; Proto-Oncogene Proteins B-raf; ras Proteins; Skin Neoplasms; Temozolomide

Topics: Analgesics; Analgesics, Opioid; Antineoplastic Agents; Cannabidiol; Cannabinoids; Clinical Trials as Topic; Dronabinol; Drug Combinations; Drugs, Investigational; Humans; Neoplasms; Neuralgia; Pain; Palliative Care; Plant Extracts