Long-term medical cannabis use and risk factors for diversion: Report on physician's guidance and patients' behaviour.

OBJECTIVES: Various jurisdictions have legalized cannabis for medical purposes. As with all psychoactive medications, medical cannabis carries a risk of diversion and accidental ingestion. These risks may be particularly high among long-term medical cannabis patients as safety practices may become less salient to patients once the treatment becomes part of everyday life. The current study examines whether patients who have used medical cannabis for longer periods differ from those who have used for shorter periods in terms of sociodemographic background and other key aspects of medical cannabis use. Furthermore, the study examines the relationship between length of medical cannabis treatment and risk factors related to storage and diversion. Finally, the study examines the extent to which oncologists provide information to their patients about safe storage and disposal. METHODS: One hundred twenty-one medical cannabis oncology patients were interviewed face-to-face and 55 oncologists participated in a survey about safe storage and disposal practices related to medical cannabis. RESULTS: Length of medical cannabis treatment was related to administration by smoking and using higher monthly dosages. In terms of risk for unsafe storage and diversion, length of medical cannabis was positively associated with using cannabis outside the home and having been asked to give away medical cannabis. Physicians did not report providing information to patients regarding safe storage and disposal practices in a regular manner. SIGNIFICANCE OF RESULTS: Results suggest that there is an ongoing risk of unsafe storage and diversion over the course of medical cannabis treatment. Oncologists may need to give more consistent and continued training in safe storage and disposal practices, especially among long-term medical cannabis patients.

Understanding the role of service providers, land use, and resident characteristics on the occurrence of mental health crisis calls to the police.

Similar to concentrations of crime, mental health calls have been found to concentrate at a small number of places, but few have considered the context of places where mental health calls occur. The current study examines the influence of the physical and social context of street segments, particularly the role of service providers, land use features of the street and nearby area, and characteristics of residents on the likelihood of a mental health crisis call to the police occurring on the street. The findings demonstrate that the social context, such as offending and drug use among residents, levels of social cohesion and community involvement, and drug and violent crime influenced the occurrence of mental health crisis calls. Findings from this study make theoretical and practical contributions to a number of disciplines by improving our understanding of where mental health crisis calls occur and why they are found at specific places.

Perspectives of people with mental health problems at hot spots: Attitudes and perceptions of safety, crime, and the police.

People who live in places with high levels of crime and disorder are more likely to experience mental illness compared with those who do not live in these types of place (Weisburd et al., 2018; Weisburd & White, 2019). The increased police presence on high crime streets may also increase the likelihood that these individuals will encounter law enforcement. There is a strong body of literature focused on the relationship between neighborhoods and the physical and mental health of residents (e.g. Arcaya et al., 2016; Duncan & Kawachi, 2018; Leventhal & Brooks-Gunn, 2003), but there are very few studies that look at the perceptions of people with mental illness directly, particularly as they relate to the environment of the street on which they live and attitudes toward the police. In turn, existing studies generally look at the most serious mental health problems (e.g. schizophrenia), ignoring more common mental health concerns such as post-traumatic stress disorder (PTSD) and depression. This paper uses self-report data from a large in-person survey of people who live on crime hot spot and non-hot spot streets in order to assess attitudes among a broader group of persons with mental health problems. Furthermore, we examine the interaction between living in crime hot spots and non-hot spots and perceptions of these residents. Our findings in this broader sample confirm earlier studies that identify greater fear and less trust of the police among persons with mental illnesses. At the same time, our findings suggest that fear of crime and perceptions of police are moderated by living in a crime hot spot.

Storage and disposal of medical cannabis among patients with cancer: Assessing the risk of diversion and unintentional digestion.

BACKGROUND: Increasingly more jurisdictions worldwide are legalizing medical cannabis. Major concerns related to such policies are that improper storage and disposal arrangements may lead to the diversion and unintentional digestion of cannabis. These concerns are particularly acute among patients with cancer because they take home medical cannabis for extended periods and have high rates of treatment termination and mortality shortly after the onset of treatment with medical cannabis. Therefore, leftover cannabis is potentially particularly prevalent, and potentially improperly stored, in households of current and deceased patients with cancer. The current study investigated the risk of medical cannabis diversion and unintentional digestion among oncology patients treated with medical cannabis and caregivers of recently deceased patients who were treated with medical cannabis. METHODS: A total of 123 oncology patients treated with medical cannabis and 37 caregivers of deceased oncology patients treated with medical cannabis were interviewed regarding practices and the information received concerning the safe storage and disposal of medical cannabis, as well as experiences of theft, diversion, and unintentional digestion. RESULTS: High rates of suboptimal storage were reported and caregivers were found to be particularly unlikely to have received information regarding the safe storage and disposal of medical cannabis. Few incidences of theft, diversion, and unintentional digestion were reported. CONCLUSIONS: Oncologists and other health care providers have an important, yet unfilled, role to play with regard to educating patients and caregivers of the importance of the safe storage and disposal of medical cannabis. Interventions designed to alert patients treated with medical cannabis and their caregivers to the problem of diversion, along with strategies to limit it, have the potential to limit diversion and unintentional exposure to medical cannabis. Cancer 2016;122:3363-3370. © 2016 American Cancer Society.

The medical necessity for medicinal cannabis: prospective, observational study evaluating the treatment in cancer patients on supportive or palliative care.

Background. Cancer patients using cannabis report better influence from the plant extract than from synthetic products. However, almost all the research conducted to date has been performed with synthetic products. We followed patients with a medicinal cannabis license to evaluate the advantages and side effects of using cannabis by cancer patients. Methods. The study included two interviews based on questionnaires regarding symptoms and side effects, the first held on the day the license was issued and the second 6-8 weeks later. Cancer symptoms and cannabis side effects were documented on scales from 0 to 4 following the CTCAE. The distress thermometer was used also. Results. Of the 211 patients who had a first interview, only 131 had the second interview, 25 of whom stopped treatment after less than a week. All cancer or anticancer treatment-related symptoms showed significant improvement (P < 0.001). No significant side effects except for memory lessening in patients with prolonged cannabis use (P = 0.002) were noted. Conclusion. The positive effects of cannabis on various cancer-related symptoms are tempered by reliance on self-reporting for many of the variables. Although studies with a control group are missing, the improvement in symptoms should push the use of cannabis in palliative treatment of oncology patients.

[New mechanisms involved in the pathogenesis of pituitary adenomas]. / Nuevos mecanismos involucrados en la patogénesis de adenomas hipofisarios.

We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In addition ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17 beta-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17 beta-estradiol with Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4 physically interacts with the ER alpha/ER beta. We show for the first time the role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP-4/E2.

Involvement of bone morphogenetic protein 4 (BMP-4) in pituitary prolactinoma pathogenesis through a Smad/estrogen receptor crosstalk.

Pituitary tumor development involves clonal expansion stimulated by hormones and growth factorscytokines. Using mRNA differential display, we found that the bone morphogenetic protein (BMP) inhibitor noggin is down-regulated in prolactinomas from dopamine D2-receptor-deficient mice. BMP-4 is overexpressed in prolactinomas taken from dopamine D2-receptor-deficient female mice, but expression of the highly homologous BMP-2 does not differ in normal pituitary tissue and prolactinomas. BMP-4 is overexpressed in other prolactinoma models, including estradiol-induced rat prolactinomas and human prolactinomas, compared with normal tissue and other pituitary adenoma types (Western blot analysis of 48 tumors). BMP-4 stimulates, and noggin blocks, cell proliferation and the expression of c-Myc in human prolactinomas, whereas BMP-4 has no action in other human pituitary tumors. GH3 cells stably transfected with a dominant negative of Smad4 (Smad4dn; a BMP signal cotransducer) or noggin have reduced tumorigenicity in nude mice. Tumor growth recovered in vivo when the Smad4dn expression was lost, proving that BMP-4Smad4 are involved in tumor development in vivo. BMP-4 and estrogens act through overlapping intracellular signaling mechanisms on GH3 cell proliferation and c-myc expression: they had additive effects at low concentrations but not at saturating doses, and their action was inhibited by blocking either pathway with the reciprocal antagonist (i.e., BMP-4 with ICI 182780 or 17beta-estradiol with Smad4dn). Furthermore, coimmunoprecipitation studies demonstrate that under BMP-4 stimulation Smad4 and Smad1 physically interact with the estrogen receptor. This previously undescribed prolactinoma pathogenesis mechanism may participate in tumorigenicity in other cells where estrogens and the type beta transforming growth factor family have important roles.

Nuevos mecanismos involucrados en la patogenesis de adenomas hipofisarios / New mechanisms involved in the pathogenesis of pituiatary adenomas

We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In addition ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17 beta-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17 beta-estradiol with Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4 physically interacts with the ER alpha/ER beta. We show for the first time the role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP-4/E2

Nuevos mecanismos involucrados en la patogénesis de adenomas hipofisarios. / [New mechanisms involved in the pathogenesis of pituitary adenomas]

We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In addition ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17 beta-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17 beta-estradiol with Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4 physically interacts with the ER alpha/ER beta. We show for the first time the role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP-4/E2.

Nuevos mecanismos involucrados en la patogenesis de adenomas hipofisarios / New mechanisms involved in the pathogenesis of pituiatary adenomas

We studied Smad-4dn tumors generated from lactosomatotrophic GH3 cells stably transfected with a dominant negative form of Smad-4 (a bone morphogenetic protein-4, BMP-4, signal co-transducer) which had reduced tumorigenicity in nude mice, but had showed a late increase in tumor size. We found that they had lost in vivo the expression of Smad-4dn and had recovered c-Myc expression. In accordance, BMP-4 is overexpressed and stimulates the expression of c-Myc in human prolactinomas, but not in other human pituitary adenomas or normal pituitary. In addition ICI 182,780 inhibited BMP-4 stimulated c-Myc expression and BMP-4 and 17 beta-estradiol in combination had an additive effect on GH3 cell proliferation. Their action was inhibited by blocking BMP-4 with ICI 182,780 or 17 beta-estradiol with Smad-4dn. Furthermore, co-immunoprecipitation studies demonstrate that Smad-4 physically interacts with the ER alpha/ER beta. We show for the first time the role of BMP-4 in prolactinoma pathogenesis, involving a functional cross-talk BMP-4/E2 (AU)