Cannabis Significantly Reduces the Use of Prescription Opioids and Improves Quality of Life in Authorized Patients: Results of a Large Prospective Study.

OBJECTIVES: This article presents findings from a large prospective examination of Canadian medical cannabis patients, with a focus on the impacts of cannabis on prescription opioid use and quality of life over a 6-month period. METHODS: The Tilray Observational Patient Study took place at 21 medical clinics throughout Canada. This analysis includes 1,145 patients who had at least one postbaseline visit, with follow-up at 1, 3, and 6 months. Instruments included a comprehensive cannabis use inventory, the World Health Organization Quality of Life Short Form (WHOQOL-BREF), and a detailed prescription drug questionnaire. RESULTS: Participants were 57.6% female, with a median age of 52 years. Baseline opioid use was reported by 28% of participants, dropping to 11% at 6 months. Daily opioid use went from 152 mg morphine milligram equivalent (MME) at baseline to 32.2 mg MME at 6 months, a 78% reduction in mean opioid dosage. Similar reductions were also seen in the other four primary prescription drug classes identified by participants, and statistically significant improvements were reported in all four domains of the WHOQOL-BREF. CONCLUSIONS: This study provides an individual-level perspective of cannabis substitution for opioids and other prescription drugs, as well as associated improvement in quality of life over 6 months. The high rate of cannabis use for chronic pain and the subsequent reductions in opioid use suggest that cannabis may play a harm reduction role in the opioid overdose crisis, potentially improving the quality of life of patients and overall public health.

Primary Hepatic Neuroendocrine Carcinoma Treated with Doxorubicin and Cyclophosphamide in a Dog.

A 7 yr, 6 mo old male neutered Australian cattle dog cross presented to a referral hospital with a large abdominal mass. An abdominal ultrasound revealed multifocal lesions throughout the liver, which were suspicious for intrahepatic metastasis, with no evidence of extrahepatic metastatic disease. Cytology indicated neoplasia of epithelial origin, with neuroendocrine neoplasia the primary suspicion. The patient was started on a maximally tolerated chemotherapy protocol of doxorubicin and metronomic cyclophosphamide. Stable disease was found on repeat abdominal ultrasounds, and the patient tolerated the protocol well. On completion of five doxorubicin doses, the dog was continued on metronomic cyclophosphamide and meloxicam. Progressive hepatic disease was found at 10 mo. The patient was euthanized 15.5 mo (465 days) after commencing treatment. Histopathology and immunohistochemistry (synaptophysin) performed on liver collected postmortem indicated (primary) hepatic neuroendocrine carcinoma. Primary hepatic neuroendocrine carcinomas are rare in dogs, and there is no standard of care for treatment. To the authors' knowledge, this is the first report of a primary hepatic neuroendocrine carcinoma treated with high-dose doxorubicin and metronomic cyclophosphamide.

BioTIME: A database of biodiversity time series for the Anthropocene.

MOTIVATION: The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene. MAIN TYPES OF VARIABLES INCLUDED: The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record. SPATIAL LOCATION AND GRAIN: BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2). TIME PERIOD AND GRAIN: BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year. MAJOR TAXA AND LEVEL OF MEASUREMENT: BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates. SOFTWARE FORMAT: .csv and .SQL.

Molecular diagnosis of Pneumocystis pneumonia in dogs.

Pneumocystis pneumonia (PCP) is a life-threatening fungal disease that can occur in dogs. The aim of this study was to provide a preliminary genetic characterisation of Pneumocystis carinii f.sp.'canis' (P. canis) in dogs and thereby develop a reliable molecular protocol to definitively diagnose canine PCP. We investigated P. canis in a variety of lung specimens from dogs with confirmed or strongly suspected PCP (Group 1, n = 16), dogs with non-PCP lower respiratory tract problems (Group 2, n = 65) and dogs not suspected of having PCP or other lower respiratory diseases (Group 3, n = 11). Presence of Pneumocystis DNA was determined by nested PCR of the large and small mitochondrial subunit rRNA loci and by a real-time quantitative polymerase chain reaction (qPCR) assay developed using a new set of primers. Molecular results were correlated with the presence of Pneumocystis morphotypes detected in cytological/histological preparations. Pneumocystis DNA was amplified from 13/16 PCP-suspected dogs (Group 1) and from 4/76 dogs of control Groups 2 and 3 (combined). The latter four dogs were thought to have been colonized by P. canis. Comparison of CT values in 'infected' versus 'colonized' dogs was consistent with this notion, with a distinct difference in molecular burden between groups (CT ≤ 26 versus CT range (26

Telling our stories: heroin-assisted treatment and SNAP activism in the Downtown Eastside of Vancouver.

BACKGROUND: This article highlights the experiences of a peer-run group, SALOME/NAOMI Association of Patients (SNAP), that meets weekly in the Downtown Eastside of Vancouver, British Columbia, Canada. SNAP is a unique independent peer- run drug user group that formed in 2011 following Canada's first heroin-assisted treatment trial (HAT), North America Opiate Medication Initiative (NAOMI). SNAP's members are now made up of former research participants who participated in two heroin-assisted trials in Vancouver. This article highlights SNAP members' experiences as research subjects in Canada's second clinical trial conducted in Vancouver, Study to Assess Longer-term Opioid Medication Effectiveness (SALOME), that began recruitment of research participants in 2011. METHODS: This paper draws on one brainstorming session, three focus groups, and field notes, with the SALOME/NAOMI Association of Patients (SNAP) in late 2013 about their experiences as research subjects in Canada's second clinical trial, SALOME in the DTES of Vancouver, and fieldwork from a 6-year period (March 2011 to February 2017) with SNAP members. SNAP's research draws on research principles developed by drug user groups and critical methodological frameworks on community-based research for social justice. RESULTS: The results illuminate how participating in the SALOME clinical trial impacted the lives of SNAP members. In addition, the findings reveal how SNAP member's advocacy for HAT impacts the group in positive ways. Seven major themes emerged from the analysis of the brainstorming and focus groups: life prior to SALOME, the clinic setting and routine, stability, 6-month transition, support, exiting the trial and ethics, and collective action, including their participation in a constitutional challenge in the Supreme Court of BC to continue receiving HAT once the SALOME trial ended. CONCLUSIONS: HAT benefits SNAP members. They argue that permanent HAT programs should be established in Canada because they are an effective harm reduction initiative, one that also reduces opioid overdose deaths.

Discovery of potent inhibitors of the lysophospholipase autotaxin.

The autotaxin-lysophosphatidic acid (ATX-LPA) axis has been implicated in several disease conditions including inflammation, fibrosis and cancer. This makes ATX an attractive drug target and its inhibition may lead to useful therapeutic agents. Through a high throughput screen (HTS) we identified a series of small molecule inhibitors of ATX which have subsequently been optimized for potency, selectivity and developability properties. This has delivered drug-like compounds such as 9v (CRT0273750) which modulate LPA levels in plasma and are suitable for in vivo studies. X-ray crystallography has revealed that these compounds have an unexpected binding mode in that they do not interact with the active site zinc ions but instead occupy the hydrophobic LPC pocket extending from the active site of ATX together with occupying the LPA 'exit' channel.

Protein engineering enables a soakable crystal form of human CDK7 primed for high-throughput crystallography and structure-based drug design.

Cyclin dependent kinase 7 (CDK7) is an important therapeutic kinase best known for its dual role in cell cycle regulation and gene transcription. Here, we describe the application of protein engineering to generate constructs leading to high resolution crystal structures of human CDK7 in both active and inactive conformations. The active state of the kinase was crystallized by incorporation of an additional surface residue mutation (W132R) onto the double phosphomimetic mutant background (S164D and T170E) that yielded the inactive kinase structure. A novel back-soaking approach was developed to determine crystal structures of several clinical and pre-clinical inhibitors of this kinase, demonstrating the potential utility of the crystal system for structure-based drug design (SBDD). The crystal structures help to rationalize the mode of inhibition and the ligand selectivity profiles versus key anti-targets. The protein engineering approach described here illustrates a generally applicable strategy for structural enablement of challenging molecular targets.

Scalable Synthesis of an Acid Stable Analogue of Hippuristanol.

Hippuristanol is a marine derived steroidal natural product with promising anticancer activity. However, instability at low pH has precluded its development as an efficient therapy. We addressed this limitation by replacing one of the oxygen atoms of the spiroketal moiety with a carbon atom. Key steps in the synthesis include a Meyer-Schuster/Nazarov cascade, a hypoiodite mediated oxyfunctionalization, and the late-stage installation of a hydroxyl group on the C-ring of the steroid.

Yet they failed to do so: recommendations based on the experiences of NAOMI research survivors and a call for action.

BACKGROUND: This article highlights the experiences of a unique group. In January 2011, Dave Murray organized a group of participants from the North American Opiate Medication Initiative (NAOMI) heroin-assisted treatment clinical trials from 2005 to 2008 in the Downtown Eastside of Vancouver (DTES), B.C., Canada. The NAOMI Patients Association (NPA) is an independent group that currently meets every Saturday in the DTES. Currently, all members of the NPA are former participants in the heroin stream of the clinical trial. The NPA offers support, education, and advocacy to its members. METHODS: Drawing on brainstorming sessions and focus groups that were conducted in the summer of 2011, this paper highlights the experiences of NPA members in their own words. RESULTS: The findings provide a lens to understand how becoming a research subject for the NAOMI trial impacted the lives of NPA members, both positive and negative. The NPA members discuss ethics, consent, recommendations for future HAT programs and studies, and ongoing advocacy.

Individual and community predictors of maternal smoking in the city of Baltimore: what can be learned from a predominantly minority case controlled study?

This case control study of 1,000 birth certificates examined what individual and community factors predicted maternal smoking in Baltimore, Maryland. Conditional multinomial logistic regression results indicated women who were White were more likely to start smoking at a young age, but as they got older, they were less likely to smoke. Minority women were more likely to start smoking at a later age. Also, White women were more likely to smoke as the rate of poverty increased, while for minority women, smoking was unrelated to whether they lived in higher or lower poverty areas. Medical assistance status, community education level, and crime rate were not found to be related to smoking status.

Discovery, Characterization, and Structure-Based Optimization of Small-Molecule In Vitro and In Vivo Probes for Human DNA Polymerase Theta.

Human DNA polymerase theta (Polθ), which is essential for microhomology-mediated DNA double strand break repair, has been proposed as an attractive target for the treatment of BRCA deficient and other DNA repair pathway defective cancers. As previously reported, we recently identified the first selective small molecule Polθ in vitro probe, 22 (ART558), which recapitulates the phenotype of Polθ loss, and in vivo probe, 43 (ART812), which is efficacious in a model of PARP inhibitor resistant TNBC in vivo. Here we describe the discovery, biochemical and biophysical characterization of these probes including small molecule ligand co-crystal structures with Polθ. The crystallographic data provides a basis for understanding the unique mechanism of inhibition of these compounds which is dependent on stabilization of a "closed" enzyme conformation. Additionally, the structural biology platform provided a basis for rational optimization based primarily on reduced ligand conformational flexibility.

Heroin and the illegal drug overdose death epidemic: A history of missed opportunities and resistance.

BACKGROUND: Due to prohibitionist policies and practices, a poisoned illegal drug supply, and inadequate access to flexible substitution programs, Canada is currently experiencing the worst illegal drug overdose death epidemic in its history. In examining past policies, practices, and discourse that support heroin regulation and drug prohibition, the drivers of the current illegal drug overdose death epidemic in Canada are brought more clearly into focus. METHODS: This article provides a critical socio-historical analysis of heroin (opioid) regulation with a focus on Canadian federal and provincial policies in the province of B.C., especially the city of Vancouver. Drawing from primary and secondary sources, this article provides a critical socio-historical analysis of heroin (opioid) regulation in Canada. RESULTS: Examining Canada's history of heroin criminalization provides a window to understand the systemic discrimination against people who use illegal heroin and other opioids. From its inception, heroin prohibition has worked to brutally punish a small segment of the population, especially those who are poor, racialized, and gendered. Negative heroin discourse and stereotyping about people who use heroin had an effect, shaping drug law, policing, prisons, and policy and treatment options. CONCLUSION: Little attention has been given to the increase in heroin possession offences across Canada over nine consecutive years and the lack of heroin substitution programs. Resistance to drug prohibition and criminal approaches to drug use emerged in the 1950s and continue today. Those most affected by drug policies demand inclusion and representation, access to a legal heroin supply, and the establishment and maintenance of heroin buyer clubs, contesting the very foundations of drug control in the twenty-first century.

A highly charged field: Mapping energies, currents and desires for reform in Canadian expert responses to drug law.

While many experts consider major changes to legal approaches to drug use necessary, achieving such change has proven to be difficult. The political process is often seen as integral to bringing about change, largely due to orthodox understandings of the 'nature' of law, in which law is made by parliaments and capable of revision in only limited instances. In recent years, theorists such as Bruno Latour (2009, 2013), Andreas Philippopoulos-Mihalopoulos (2015) and Serge Gutwirth (2015) have taken a more expansive view of the nature of law and its effects. According to these theorists, law also emerges from outside the political process, including through various practices such as those of professionals working within legal systems, and those engaged in resistance, navigation and subversion (Seear, 2020). This article explores these processes using Karen Barad's (2015) work on lightning. As we will explain, Barad presents lightning as a 'queer', non-linear, uncertain and indeterminate phenomenon, using it to understand causation in new ways. Along with Barad's ideas, the article draws on interview data (N = 35) collected for two research projects in Canada. These interviews were conducted with senior drug use-related policy makers, service providers, advocates and lawyers based in British Columbia and Ontario, Canada. The interviews explore how key Canadian experts view drug law, debates about law and policy and whether they support reform. We also explore how these experts navigate the criminalisation of drugs and whether any insights can be drawn from their practices, including their attempts to navigate, subvert or change the law. First we consider experts' concern about current prohibitionist legal frameworks, finding it widespread, along with appetite for change. Second, we examine experts' accounts of strategies used for working around or challenging punitive frameworks. We find that change, like lightning, is complicated and messy; simplistic approaches to changes are not always possible, and may in fact make matters worse. There are multiple, unpredictable effects in engaging and resisting law, and thus difficulty in tackling criminalisation in any clear and simple way. Practices and processes of responding to and resisting drug-use criminalisation can thus be understood in terms that reflect the 'queer', indeterminate, unpredictable and multidirectional nature of Barad's lightning. In concluding, we note that this way of understanding legal processes and resistance has implications for the future of Canadian drug policy, including debates about whether it is possible to work within a framework of overarching criminalisation.

The impact of non-medical cannabis legalization and other exposures on retention in longitudinal cannabis research: a survival analysis of a prospective study of Canadian medical cannabis patients.

BACKGROUND: Despite repeated calls by medical associations to gather evidence on the harms and benefits of cannabis, there are ongoing methodological challenges to conducting observational and clinical studies on cannabis, including a high rate of patients that are lost to follow-up (LTFU). This study explores factors potentially associated with retention in a large prospective study of Canadian medical cannabis patients, with the goal of reducing the probability that patients will be lost to follow-up in future cannabis research. METHODS: The Tilray Observational Patient Study (TOPS) was a multi-site, prospective study assessing the impact of medical cannabis over 6 months in a broad population of authorized Canadian cannabis patients. The study took place from 2016 to 19, and we conducted a series of exploratory analyses including a Kaplan-Meier survival analysis and logistic regressions to assess the potential association between study retention and variables including patient characteristics, cannabis and prescription drug use, quality of life, and the legalization of non-medical cannabis. RESULTS: Overall, 1011 participants were included in this analysis, contributing 287 patient-years of data. Retention was 728 (72%) at 3 months, and 419 (41.4%) at 6 months. Our analyses found significantly lower adjusted odds of retention following legalization (AOR 0.28, 95% CI 0.18-0.41), and in patients that used prescription opioids at baseline (AOR 0.62, 95% CI 0.46-0.85), while increased odds of retention were found in patients with a higher baseline psychological score (AOR 1.43, 95% CI 1.08-1.90) or that used anti-seizure medications at baseline (AOR 1.91, 95% CI 1.30-2.81). DISCUSSION: TOPS provided a unique opportunity to examine patient characteristics and other variables that may be associated with retention in prospective medical cannabis studies. Our findings highlight some of the challenges of conducting medical cannabis research at a time when patients have a multitude of cannabis access options, including legal adult dispensaries and a robust illicit market. High LTFU rates can impact the validity of studies, and potentially lead to misestimations of the harms and benefits of medical cannabis use. Despite being a multi-site prospective study, this was a convenience sample, thereby limiting the generalizability of these findings. Additionally, data regarding the use of cannabis was self-reported by patients, so is subject to potential recall bias. CONCLUSION: We found evidence that external policy changes that affect access to cannabis such as the legalization of non-medical adult use and patient characteristics associated with patient physical/psychological capacity can impact retention in prospective medical cannabis studies. Evidence-based strategies to reduce study burden on participants, such as minimizing in-person visits by providing digitized internet-based surveys and phone or telemedicine follow-up options as well as ensuring adequate participant compensation could improve retention. Additionally, policy-related changes aimed at improving access to medical cannabis, including increased cost-coverage and community-based distribution, could encourage patients to remain in the federal medical cannabis program and thereby reduce LTFU in associated studies.

Self-reported reductions in tobacco and nicotine use following medical cannabis initiation: Results from a cross-sectional survey of authorized medical cannabis patients in Canada.

BACKGROUND: Despite decades of campaigns aimed at reducing tobacco/nicotine (T/N) use and the development of many different T/N reduction and cessation strategies, the impacts on international public health remain significant. Some studies have found an association between medical and non-medical cannabis use and T/N use, although the evidence on whether cannabis/cannabinoids increase or decrease the odds of reducing or ceasing T/N use remain contradictory. This paper explores the self-reported use of cannabis and associated changes in T/N use among a Canadian medical cannabis patient population. METHODS: This study examines the impact of medical cannabis on T/N use by comparing self-reported patterns of use before and after the initiation of medical cannabis. Participants completed an online cross-sectional survey examining demographics, patterns of medical cannabis use, and the impact of medical cannabis on the use of T/N and other substances. The survey also included novel measures examining whether patients intended to use medical cannabis to reduce T/N use or had experience with other pharmacological or psychobehavioral T/N cessation strategies. We conducted a series of descriptive analyses and univariate and multivariate logistic regressions to explore the potential association between primary variables of interest and T/N reduction and cessation. RESULTS: In total, the study recruited 2102 individuals, of whom 650 were current or former T/N users. Following initiation of medical cannabis use 320 (49%) T/N users self-reported reductions in use, with 160 (24.6%) reporting no T/N use in the 30 days prior to the survey. Odds of T/N cessation were greater among those who were age 55 or older (Adjusted Odds Ratio [AOR] = 2.56, 95% Confidence Interval [CI] 1.53-4.26), or those who reported >25 T/N uses per day in the pre-period (AOR = 2.11, 95% CI 1.14-3.92). Specific intent to use medical cannabis to quit resulted in significantly greater odds of reducing T/N use (AOR = 2.79, 95% CI 1.49-5.22); however, involvement with traditional T/N cessation treatments (pharmacological or psychobehavioral) was negatively associated with T/N cessation (AOR 0.39, 95% CI 0.18-0.86). CONCLUSIONS: Results from this retrospective survey of medical cannabis users suggest that initiation of medical cannabis use was associated with self-reported reductions and/or cessation of T/N use in nearly half of study participants. In light of the significant morbidity, mortality, and health care costs related to T/N dependence, future research should further evaluate the potential of cannabis-based treatments to support efforts to reduce or cease T/N use.

Scoring of senescence signalling in multiple human tumour gene expression datasets, identification of a correlation between senescence score and drug toxicity in the NCI60 panel and a pro-inflammatory signature correlating with survival advantage in peritoneal mesothelioma.

BACKGROUND: Cellular senescence is a major barrier to tumour progression, though its role in pathogenesis of cancer and other diseases is poorly understood in vivo. Improved understanding of the degree to which latent senescence signalling persists in tumours might identify intervention strategies to provoke "accelerated senescence" responses as a therapeutic outcome. Senescence involves convergence of multiple pathways and requires ongoing dynamic signalling throughout its establishment and maintenance. Recent discovery of several new markers allows for an expression profiling approach to study specific senescence phenotypes in relevant tissue samples. We adopted a "senescence scoring" methodology based on expression profiles of multiple senescence markers to examine the degree to which signals of damage-associated or secretory senescence persist in various human tumours. RESULTS: We first show that scoring captures differential induction of damage or inflammatory pathways in a series of public datasets involving radiotherapy of colon adenocarcinoma, chemotherapy of breast cancer cells, replicative senescence of mesenchymal stem cells, and progression of melanoma. We extended these results to investigate correlations between senescence score and growth inhibition in response to ~1500 compounds in the NCI60 panel. Scoring of our own mesenchymal tumour dataset highlighted differential expression of secretory signalling pathways between distinct subgroups of MPNST, liposarcomas and peritoneal mesothelioma. Furthermore, a pro-inflammatory signature yielded by hierarchical clustering of secretory markers showed prognostic significance in mesothelioma. CONCLUSIONS: We find that "senescence scoring" accurately reports senescence signalling in a variety of situations where senescence would be expected to occur and highlights differential expression of damage associated and secretory senescence pathways in a context-dependent manner.

Sociodemographic characteristics of cannabis smokers and the experience of cannabis withdrawal.

BACKGROUND: Cannabis withdrawal can be a negative reinforcer for relapse, but little is known about its association with demographic characteristics. OBJECTIVES: Evaluate the association of demographic characteristics with the experience of cannabis withdrawal. METHODS: Retrospective self-report of a "serious" cannabis quit attempt without formal treatment in a convenience sample of 104 non-treatment-seeking, adult cannabis smokers (mean age 35 years, 52% white, 78% male) with no other current substance use disorder (except tobacco) or chronic health problems. Reasons for quitting, coping strategies to help quit, and 18 specific withdrawal symptoms were assessed by questionnaire. RESULTS: Among withdrawal symptoms, only anxiety, increased sex drive, and craving showed significant associations with age, race, or sex. Women were more likely than men to report a physical withdrawal symptom (OR = 3.2, 95% CI = .99-10.4, p = .05), especially upset stomach. There were few significant demographic associations with coping strategies or reasons for quitting. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This small study suggests that there are few robust associations between demographic characteristics and cannabis withdrawal. Future studies with larger samples are needed. Attention to physical withdrawal symptoms in women may help promote abstinence.

Problematizing the DSM-5 criteria for opioid use disorder: A qualitative analysis.

BACKGROUND: This paper includes the voices of people who are members of a peer-led drug user group (SNAP) in Canada who are receiving heroin-assisted treatment (HAT) outside of a clinical trial. Drawing from critical drug studies, we problematize the criteria for severe opioid use disorder (OUD) from the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, by exploring SNAP members' experiences in relation to heroin-assisted treatment, and examining how SNAP participants' narratives challenge conventional notions of what constitutes severe opioid use disorder. METHOD: Drawing on critical analysis and research guidelines developed by drug user unions and organizations, and critical methodological frameworks on ethical community-based-and-responsive research for social justice, in this paper we focus on semi-structured interviews conducted with 36 SNAP members at the Vancouver Area Network of Drug Users site in the Downtown Eastside of Vancouver, Canada. We included opened ended questions about experiences prior to receiving HAT, experiences while receiving HAT, experiences of drug use and cessation, and future hopes. RESULTS: Although SNAP participants were diagnosed as suffering from OUD, the DSM-5 criteria for OUD fails to encompass their diverse experiences of opioid use. Nor does the DSM diagnosis capture the complexities of their lived experience. The DSM OUD constructs an idea of addiction and the addicted person based on a list of symptoms thought to be associated with extended use of opioids. The problem with this is that many of these "symptoms" of drug use are, in the case of SNAP participants, tied to contextual issues of living in the DTES, experiencing structural vulnerability, and being the target of punitive drug policies and laws. CONCLUSION: To label someone as having a severe disorder shifts the focus from political and social issues, including the lived experiences of people who use heroin. The DSM-5 de-contextualizes drug use. How addiction and heroin are constituted has political implications that will determine what types of services and programs will be set up. Treating a disorder, or a person with a disorder, requires a much different approach than understanding heroin use as a habit. SNAP, and their allies, are rupturing conventional ideas about heroin and taken for granted assumptions about people who use heroin.

Reductions in alcohol use following medical cannabis initiation: results from a large cross-sectional survey of medical cannabis patients in Canada.

BACKGROUND: Evidence details how cannabis can influence the use of other psychoactive substances, including prescription medications, alcohol, tobacco and illicit drugs, but very little research has examined the factors associated with these changes in substance use patterns. This paper explores the self-reported use of cannabis as a substitute for alcohol among a Canadian medical cannabis patient population. METHODS: Data was derived from a survey of 2102 people enrolled in the Canadian medical cannabis program. We included 973 (44%) respondents who reported using alcohol on at least 10 occasions over a 12 month period prior to initiating medical cannabis, and then used retrospective data on the frequency and amount of alcohol use pre-and post medical cannabis initiation to determine which participant characteristics and other variables were associated with reductions and/or cessation of alcohol use. RESULTS: Overall, 419 (44%) participants reported decreases in alcohol usage frequency over 30 days, 323 (34%) decreased the number of standard drinks they had per week, and 76 (8%) reported no alcohol use at all in the 30 days prior to the survey. Being below 55 years of age and reporting higher rates of alcohol use in the pre-period were both associated with greater odds of reducing alcohol use, and an intention to use medical cannabis to reduce alcohol consumption was associated with significantly greater odds of both reducing and ceasing alcohol use altogether. CONCLUSIONS: Our findings suggest that medical cannabis initiation may be associated with self-reported reductions and cessation of alcohol use among medical cannabis patients. Since alcohol is the most prevalent recreational substance in North America, and its use results in significant rates of criminality, morbidity and mortality, these findings may result in improved health outcomes for medical cannabis patients, as well as overall improvements in public health and safety.