Use of continuous subcutaneous insulin infusion versus multiple daily injections in emerging adults with type 1 diabetes is associated with better clinical engagement but not glycaemic control.

BACKGROUND: Limited studies have compared outcomes between emerging adults with type 1 diabetes mellitus (T1D) attending a diabetes transition support programme using multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII). AIMS: To assess glycaemic control and service utilisation in emerging adults with T1D on MDI or CSII attending a young adult diabetes clinic (YAC). METHODS: A retrospective cohort analysis was conducted from January 2013 to December 2015. Data collected included clinic visits per year, after-hours mobile telephone use, diabetic ketoacidosis (DKA) admissions and all HbA1c levels. Independent t-test was used to compare continuous variables whilst Pearson's Chi-squared test was used for categorical variables. Linear mixed effects models explored mean changes in HbA1c levels over time. RESULTS: Over 3 years, 318 youth with T1D (176 MDI, 121 CSII, 21 switched from MDI to CSII) attended our YAC. Aggregated mean HbA1c levels remained similar between modalities (CSII 9.1% vs MDI 9.3%; P = 0.23); however, mean change in HbA1c at 3 years was significantly increased in CSII users at 0.55% (95% CI 0.15-0.95; P < 0.01) compared with no significant change in MDI users. Clinic visits per year were improved in CSII users (CSII 2.8 vs MDI 2.5; P = 0.02), while DKA admissions remained similar between MDI and CSII users (3.6 admissions per 100 patient-years). CONCLUSION: In our YAC cohort, glycaemic control in CSII and MDI users was similar but well below recommended international glycaemic targets (HbA1c level < 7.0%). Despite increased clinical engagement occurring in CSII users, glycaemic deterioration was observed over the 3 years.

Universal Subsidized Continuous Glucose Monitoring Funding for Young People With Type 1 Diabetes: Uptake and Outcomes Over 2 Years, a Population-Based Study.

OBJECTIVE: Continuous glucose monitoring (CGM) is increasingly used in type 1 diabetes management; however, funding models vary. This study determined the uptake rate and glycemic outcomes following a change in national health policy to introduce universal subsidized CGM funding for people with type 1 diabetes aged <21 years. RESEARCH DESIGN AND METHODS: Longitudinal data from 12 months before the subsidy until 24 months after were analyzed. Measures and outcomes included age, diabetes duration, HbA1c, episodes of diabetic ketoacidosis and severe hypoglycemia, insulin regimen, CGM uptake, and percentage CGM use. Two data sources were used: the Australasian Diabetes Database Network (ADDN) registry (a prospective diabetes database) and the National Diabetes Service Scheme (NDSS) registry that includes almost all individuals with type 1 diabetes nationally. RESULTS: CGM uptake increased from 5% presubsidy to 79% after 2 years. After CGM introduction, the odds ratio (OR) of achieving the HbA1c target of <7.0% improved at 12 months (OR 2.5, P < 0.001) and was maintained at 24 months (OR 2.3, P < 0.001). The OR for suboptimal glycemic control (HbA1c ≥9.0%) decreased to 0.34 (P < 0.001) at 24 months. Of CGM users, 65% used CGM >75% of time, and had a lower HbA1c at 24 months compared with those with usage <25% (7.8 ± 1.3% vs. 8.6 ± 1.8%, respectively, P < 0.001). Diabetic ketoacidosis was also reduced in this group (incidence rate ratio 0.49, 95% CI 0.33-0.74, P < 0.001). CONCLUSIONS: Following the national subsidy, CGM use was high and associated with sustained improvement in glycemic control. This information will inform economic analyses and future policy and serve as a model of evaluation diabetes technologies.

Insulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double-blind placebo-controlled, randomised trial.

BACKGROUND: Insulin resistance is an under-recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes. METHODS: We will study 40 adults aged 20-55 years with Type 1 diabetes (HbA1c ≤ 80 mmol/mol [9.5%], fasting C-peptide <0.3 nmol/L) and 20 age-, gender- and body mass index (BMI)-matched controls. Insulin sensitivity will be determined by the two-step hyperinsulinaemic-euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended-release 1500 mg daily or matched placebo for 26 weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low-dose stage of the clamp. CONCLUSION: The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes. TRIAL REGISTRATION: ACTRN12619001440112.

Combining Three Cohorts of World Trade Center Rescue/Recovery Workers for Assessing Cancer Incidence and Mortality.

Three cohorts including the Fire Department of the City of New York (FDNY), the World Trade Center Health Registry (WTCHR), and the General Responder Cohort (GRC), each funded by the World Trade Center Health Program have reported associations between WTC-exposures and cancer. Results have generally been consistent with effect estimates for excess incidence for all cancers ranging from 6 to 14% above background rates. Pooling would increase sample size and de-duplicate cases between the cohorts. However, pooling required time consuming steps: obtaining Institutional Review Board (IRB) approvals and legal agreements from entities involved; establishing an honest broker for managing the data; de-duplicating the pooled cohort files; applying to State Cancer Registries (SCRs) for matched cancer cases; and finalizing analysis data files. Obtaining SCR data use agreements ranged from 6.5 to 114.5 weeks with six states requiring >20 weeks. Records from FDNY (n = 16,221), WTCHR (n = 29,372), and GRC (n = 33,427) were combined de-duplicated resulting in 69,102 unique individuals. Overall, 7894 cancer tumors were matched to the pooled cohort, increasing the number cancers by as much as 58% compared to previous analyses. Pooling resulted in a coherent resource for future research for studies on rare cancers and mortality, with more representative of occupations and WTC- exposure.

Reducing Type 1 Diabetes Mortality: Role for Adjunctive Therapies?

Individuals with type 1 diabetes (T1D) frequently fail to achieve glycemic goals and have excess cardiovascular risk and premature death. Adjunctive agents may play a role in reducing morbidity, mortality, and the adverse sequelae of insulin treatment. A surge in type 2 diabetes drug development has revealed agents with benefits beyond glucose lowering, including cardiovascular risk reduction. Could these benefits translate to T1D? Specific trials for T1D demonstrate substantial hemoglobin (Hb)A1c reductions with sodium glucose cotransporter inhibitors (SGLTis) and glucagon-like peptide (GLP)1 agonists, and modest improvements with metformin, dipeptidyl peptidase-4 inhibitor (DPP4i), and pramlintide. Studies exploring cardiovascular risk reduction are warranted. This review synthesizes the emerging literature for researchers and clinicians treating people with T1D. Challenges in T1D research are discussed.

Systemic Autoimmune Disease Among Adults Exposed to the September 11, 2001 Terrorist Attack.

OBJECTIVE: Autoimmune disease is an emerging condition among persons exposed to the September 11, 2001 attack on the World Trade Center (WTC). Components of the dust cloud resulting from the collapse of the WTC have been associated with development of a systemic autoimmune disease, as has posttraumatic stress disorder (PTSD). We undertook this study to determine whether dust exposure and PTSD were associated with an increased risk of systemic autoimmune disease in a 9/11-exposed cohort. METHODS: Among 43,133 WTC Health Registry enrollees, 2,786 self-reported having a post-9/11 systemic autoimmune disease. We obtained informed consent to review medical records to validate systemic autoimmune disease diagnoses for 1,041 enrollees. Diagnoses of systemic autoimmune diseases were confirmed by classification criteria, rheumatologist diagnosis, or having been prescribed systemic autoimmune disease medication. Controls were enrollees who denied having an autoimmune disease diagnosis (n = 37,017). We used multivariable log-binomial regression to examine the association between multiple 9/11 exposures and risk of post-9/11 systemic autoimmune disease, stratifying by responders (rescue, recovery, and clean-up workers) and community members (e.g., residents, area workers). RESULTS: We identified 118 persons with systemic autoimmune disease. Rheumatoid arthritis was most frequent (n = 71), followed by SjÓ§gren's syndrome (n = 22), systemic lupus erythematosus (n = 20), myositis (n = 9), mixed connective tissue disease (n = 7), and scleroderma (n = 4). Among 9/11 responders, those with intense dust cloud exposure had almost twice the risk of systemic autoimmune disease (adjusted risk ratio 1.86 [95% confidence interval 1.02-3.40]). Community members with PTSD had a nearly 3-fold increased risk of systemic autoimmune disease. CONCLUSION: Intense dust cloud exposure among responders and PTSD among community members were associated with a statistically significant increased risk of new-onset systemic autoimmune disease. Clinicians treating 9/11 survivors should be aware of the potential increased risk of systemic autoimmune disease in this population.

Attitudes towards mental health, mental health research and digital interventions by young adults with type 1 diabetes: A qualitative analysis.

BACKGROUND: Young people with type 1 diabetes are at increased risk of mental disorders. Whereas treatment need is high, difficulty recruiting young people with type 1 diabetes into psychosocial studies complicates development, testing and dissemination of these interventions. OBJECTIVE: Interviews with young adults with type 1 diabetes were conducted to examine attitudes towards mental health and mental health research, including barriers and motivators to participation in mental health studies and preferred sources of mental health support. The interviews were audio-taped, transcribed and evaluated via thematic analysis. SETTING AND PARTICIPANTS: Young adults with type 1 diabetes were recruited via social media channels of 3 advocacy organizations. A total of 31 young adults (26 females and 5 males) with an average age of 22 years were interviewed between October 2015 and January 2016. RESULTS: Participants were largely unaware of their increased vulnerability to common mental health problems and knew little about mental health research. Major barriers to participation included perceived stigma and lifestyle issues and low levels of trust in researchers. Opportunities to connect with peers and help others were described as key motivators. Psychological distress was considered normal within the context of diabetes. A need for some level of human contact in receiving psychosocial support was expressed. DISCUSSION AND CONCLUSION: Findings provide valuable insights into the complex dynamics of engaging young adults with type 1 diabetes in mental health studies. Interviewees provided practical suggestions to assist investigation and delivery of psychosocial interventions for this vulnerable group.

The effectiveness of a monetary incentive offer on survey response rates and response completeness in a longitudinal study.

BACKGROUND: Achieving adequate response rates is an ongoing challenge for longitudinal studies. The World Trade Center Health Registry is a longitudinal health study that periodically surveys a cohort of ~71,000 people exposed to the 9/11 terrorist attacks in New York City. Since Wave 1, the Registry has conducted three follow-up surveys (Waves 2-4) every 3-4 years and utilized various strategies to increase survey participation. A promised monetary incentive was offered for the first time to survey non-respondents in the recent Wave 4 survey, conducted 13-14 years after 9/11. METHODS: We evaluated the effectiveness of a monetary incentive in improving the response rate five months after survey launch, and assessed whether or not response completeness was compromised due to incentive use. The study compared the likelihood of returning a survey for those who received an incentive offer to those who did not, using logistic regression models. Among those who returned surveys, we also examined whether those receiving an incentive notification had higher rate of response completeness than those who did not, using negative binomial regression models and logistic regression models. RESULTS: We found that a $10 monetary incentive offer was effective in increasing Wave 4 response rates. Specifically, the $10 incentive offer was useful in encouraging initially reluctant participants to respond to the survey. The likelihood of returning a survey increased by 30% for those who received an incentive offer (AOR = 1.3, 95% CI: 1.1, 1.4), and the incentive increased the number of returned surveys by 18%. Moreover, our results did not reveal any significant differences on response completeness between those who received an incentive offer and those who did not. CONCLUSIONS: In the face of the growing challenge of maintaining a high response rate for the World Trade Center Health Registry follow-up surveys, this study showed the value of offering a monetary incentive as an additional refusal conversion strategy. Our findings also suggest that an incentive offer could be particularly useful near the end of data collection period when an immediate boost in response rate is needed.

Building Capacity in Community-Based Participatory Research Partnerships Through a Focus on Process and Multiculturalism.

BACKGROUND: In health research, investigators and funders are emphasizing the importance of collaboration between communities and academic institutions to achieve health equity. Although the principles underlying community-academic partnered research have been well-articulated, the processes by which partnerships integrate these principles when working across cultural differences are not as well described. OBJECTIVES: We present how Project GRACE (Growing, Reaching, Advocating for Change and Empowerment) integrated participatory research principles with the process of building individual and partnership capacity. METHODS: We worked with Vigorous Interventions In Ongoing Natural Settings (VISIONS) Inc., a process consultant and training organization, to develop a capacity building model. We present the conceptual framework and multicultural process of change (MPOC) that was used to build individual and partnership capacity to address health disparities. CONCLUSIONS: The process and capacity building model provides a common language, approach, and toolset to understand differences and the dynamics of inequity. These tools can be used by other partnerships in the conduct of research to achieve health equity.

Nonfatal injuries 1 week after hurricane sandy--New York city metropolitan area, October 2012.

On October 29, 2012, Hurricane Sandy (Sandy) made landfall in densely populated areas of New York, New Jersey, and Connecticut. Flooding affected 51 square miles (132 square kilometers) of New York City (NYC) and resulted in 43 deaths, many caused by drowning in the home, along with numerous storm-related injuries. Thousands of those affected were survivors of the World Trade Center (WTC) disaster of September 11, 2001 (9/11) who had previously enrolled in the WTC Health Registry (Registry) cohort study. To assess Sandy-related injuries and associated risk factors among those who lived in Hurricane Sandy-flooded areas and elsewhere, the NYC Department of Health and Mental Hygiene surveyed 8,870 WTC survivors, who had provided physical and mental health updates 8 to 16 months before Sandy. Approximately 10% of the respondents in flooded areas reported injuries in the first week after Sandy; nearly 75% of those had more than one injury. Injuries occurred during evacuation and clean-up/repair of damaged or destroyed homes. Hurricane preparation and precautionary messages emphasizing potential for injury hazards during both evacuation and clean-up or repair of damaged residences might help mitigate the occurrence and severity of injury after a hurricane.

Mental health of those directly exposed to the World Trade Center disaster: unmet mental health care need, mental health treatment service use, and quality of life.

Mental health service utilization several years following a man-made or natural disaster can be lower than expected, despite a high prevalence of mental health disorders among those exposed. This study focused on factors associated with subjective unmet mental health care need (UMHCN) and its relationship to a combination of diagnostic history and current mental health symptoms, 5-6 years after the 9-11-01 World Trade Center (WTC) disaster in New York City, USA. Two survey waves of the WTC Health Registry, after exclusions, provided a sample of 36,625 enrollees for this analysis. Important differences were found among enrollees who were categorized according to the presence or absence of a self-reported mental health diagnosis and symptoms indicative of post-traumatic stress disorder or serious psychological distress. Persons with diagnoses and symptoms had the highest levels of UMHCN, poor mental health days, and mental health service use. Those with symptoms only were a vulnerable group much less likely to use mental health services yet reporting UMHCN and poor mental health days. Implications for delivering mental health services include recognizing that many persons with undiagnosed but symptomatic mental health symptoms are not using mental health services, despite having perceived need for mental health care.

Gastroesophageal reflux symptoms and comorbid asthma and posttraumatic stress disorder following the 9/11 terrorist attacks on World Trade Center in New York City.

OBJECTIVES: Excess gastroesophageal reflux disease (GERD) was reported in several populations exposed to the September 11 2001 (9/11) terrorist attacks on the World Trade Center (WTC). We examined new onset gastroesophageal reflux symptoms (GERS) since 9/11 and persisting up to 5-6 years in relation to 9/11-related exposures among the WTC Health Registry enrollees, and potential associations with comorbid asthma and posttraumatic stress disorder (PTSD). METHODS: This is a retrospective analysis of 37,118 adult enrollees (i.e., rescue/recovery workers, local residents, area workers, and passersby in lower Manhattan on 9/11) who reported no pre-9/11 GERS and who participated in two Registry surveys 2-3 and 5-6 years after 9/11. Post-9/11 GERS (new onset since 9/11) reported at first survey, and persistent GERS (post-9/11 GERS reported at both surveys) were analyzed using log-binomial regression. RESULTS: Cumulative incidence was 20% for post-9/11 GERS and 13% for persistent GERS. Persistent GERS occurred more often among those with comorbid PTSD (24%), asthma (13%), or both (36%) compared with neither of the comorbid conditions (8%). Among enrollees with neither asthma nor PTSD, the adjusted risk ratio (aRR) for persistent GERS was elevated among: workers arriving at the WTC pile on 9/11 (aRR=1.6; 95% confidence interval (CI) 1.3-2.1) or working at the WTC site > 90 days (aRR=1.6; 1.4-2.0); residents exposed to the intense dust cloud on 9/11 (aRR=1.5; 1.0-2.3), or who did not evacuate their homes (aRR=1.7; 1.2-2.3); and area workers exposed to the intense dust cloud (aRR=1.5; 1.2-1.8). CONCLUSIONS: Disaster-related environmental exposures may contribute to the development of GERS. GERS may be accentuated in the presence of asthma or PTSD.

Down-regulation of diacylglycerol lipase-alpha during neural stem cell differentiation: identification of elements that regulate transcription.

The diacylglycerol lipases (DAGLalpha and DAGLbeta) synthesize 2-arachidonoylglycerol (2-AG), a full agonist at cannabinoid receptors. Dynamic regulation of DAGL expression underpins its role in axonal growth and guidance during development, retrograde synaptic signalling at mature synapses, and maintenance of adult neurogenesis. We show here that DAGLalpha expression is dramatically down-regulated when neural stem (NS) cells are differentiated toward a gamma-aminobutyric acidergic neuronal phenotype. To understand how DAGLalpha expression might be controlled, we sought to identify the core promoter region and regulatory elements within it. The core promoter was identified and shown to contain both an enhancer and a suppressor region. Deletion analysis identified two elements, including a GC-box, that specifically promote expression in NS cells. Bioinformatic analysis identified three candidate transcription factors that might regulate DAGLalpha expression in NS cells by binding to the GC box; these were specificity protein 1 (Sp1), early growth response element 1 (EGR1), and zinc finger DNA-binding protein 89 (ZBP-89). However, Sp1 was the only factor that could bind to the GC-box. A specific mutation within the GC-box that inhibited Sp1 binding reduced DAGLalpha promoter activity in NS cells. Likewise, a dominant negative Sp1 was shown to bind to the GC-box and to suppress DAGLalpha promoter activity specifically in NS cells. Finally, like DAGLalpha, Sp1 was down-regulated during neuronal differentiation. A full characterization of the DAGLalpha promoter will help to elucidate the upstream pathways that regulate DAGLalpha expression in NS cells and their progeny.

BDNF regulates neuronal sensitivity to endocannabinoids.

The diacylglycerol lipases (DAGLalpha/beta) synthesize 2-arachidonylglycerol (2-AG), the major endocannabinoid in the developing and adult brain (eCB). This lipid acts on cannabinoid receptors to regulate axonal growth and guidance, activity-dependent synaptic plasticity and adult neurogenesis, and can also protect neurons from excitotoxicity. 2-AG action is generally terminated by monoacylglycerol lipase (MAGL), however we know very little about the mechanisms that regulate neuronal sensitivity to eCBs. In the present study we show that the brain-derived neurotrophic factor (BDNF) can determine neuronal sensitivity to eCBs. In this context, in cultured cerebellar granule neurons (CGNs) BDNF increases the expression of CB1 receptor transcripts and decreases expression of MAGL transcripts. Using phosphorylation of Akt as the readout, we show that BDNF can promote a stable increase in neuronal sensitivity to eCBs. For example, concentrations of 2-AG and noladin either (NE) that normally do not lead to Akt phosphorylation in control neurons do so in neurons pre-treated with BDNF. In addition, Akt phosphorylation in response to a wide range of concentrations of NE was always greater in neurons pre-treated with BDNF. Our data suggests the existence of a positive feedback loop that might sustain neuronal survival in the normal brain.

Asthma and posttraumatic stress symptoms 5 to 6 years following exposure to the World Trade Center terrorist attack.

CONTEXT: The World Trade Center Health Registry provides a unique opportunity to examine long-term health effects of a large-scale disaster. OBJECTIVE: To examine risk factors for new asthma diagnoses and event-related posttraumatic stress (PTS) symptoms among exposed adults 5 to 6 years following exposure to the September 11, 2001, World Trade Center (WTC) terrorist attack. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal cohort study with wave 1 (W1) enrollment of 71,437 adults in 2003-2004, including rescue/recovery worker, lower Manhattan resident, lower Manhattan office worker, and passersby eligibility groups; 46,322 adults (68%) completed the wave 2 (W2) survey in 2006-2007. MAIN OUTCOME MEASURES: Self-reported diagnosed asthma following September 11; event-related current PTS symptoms indicative of probable posttraumatic stress disorder (PTSD), assessed using the PTSD Checklist (cutoff score > or = 44). RESULTS: Of W2 participants with no stated asthma history, 10.2% (95% confidence interval [CI], 9.9%-10.5%) reported new asthma diagnoses postevent. Intense dust cloud exposure on September 11 was a major contributor to new asthma diagnoses for all eligibility groups: for example, 19.1% vs 9.6% in those without exposure among rescue/recovery workers (adjusted odds ratio, 1.5 [95% CI, 1.4-1.7]). Asthma risk was highest among rescue/recovery workers on the WTC pile on September 11 (20.5% [95% CI, 19.0%-22.0%]). Persistent risks included working longer at the WTC site, not evacuating homes, and experiencing a heavy layer of dust in home or office. Of participants with no PTSD history, 23.8% (95% CI, 23.4%-24.2%) reported PTS symptoms at either W1 (14.3%) or W2 (19.1%). Nearly 10% (9.6% [95% CI, 9.3%-9.8%]) had PTS symptoms at both surveys, 4.7% (95% CI, 4.5%-4.9%) had PTS symptoms at W1 only, and 9.5% (95% CI, 9.3%-9.8%) had PTS symptoms at W2 only. At W2, passersby had the highest rate of PTS symptoms (23.2% [95% CI, 21.4%-25.0%]). Event-related loss of spouse or job was associated with PTS symptoms at W2. CONCLUSION: Acute and prolonged exposures were both associated with a large burden of asthma and PTS symptoms 5 to 6 years after the September 11 WTC attack.

An overview of 9/11 experiences and respiratory and mental health conditions among World Trade Center Health Registry enrollees.

To date, health effects of exposure to the September 11, 2001 disaster in New York City have been studied in specific groups, but no studies have estimated its impact across the different exposed populations. This report provides an overview of the World Trade Center Health Registry (WTCHR) enrollees, their exposures, and their respiratory and mental health outcomes 2-3 years post-9/11. Results are extrapolated to the estimated universe of people eligible to enroll in the WTCHR to determine magnitude of impact. Building occupants, persons on the street or in transit in lower Manhattan on 9/11, local residents, rescue and recovery workers/volunteers, and area school children and staff were interviewed and enrolled in the WTCHR between September 2003 and November 2004. A total of 71,437 people enrolled in the WTCHR, for 17.4% coverage of the estimated eligible exposed population (nearly 410,000); 30% were recruited from lists, and 70% were self-identified. Many reported being in the dust cloud from the collapsing WTC Towers (51%), witnessing traumatic events (70%), or sustaining an injury (13%). After 9/11, 67% of adult enrollees reported new or worsening respiratory symptoms, 3% reported newly diagnosed asthma, 16% screened positive for probable posttraumatic stress disorder (PTSD), and 8% for serious psychological distress (SPD). Newly diagnosed asthma was most common among rescue and recovery workers who worked on the debris pile (4.1%). PTSD was higher among those who reported Hispanic ethnicity (30%), household income < $25,000 (31%), or being injured (35%). Using previously published estimates of the total number of exposed people per WTCHR eligibility criteria, we estimate between 3,800 and 12,600 adults experienced newly diagnosed asthma and 34,600-70,200 adults experienced PTSD following the attacks, suggesting extensive adverse health impacts beyond the immediate deaths and injuries from the acute event.

A diacylglycerol lipase-CB2 cannabinoid pathway regulates adult subventricular zone neurogenesis in an age-dependent manner.

The subventricular zone (SVZ) is a major site of neurogenesis in the adult. We now show that ependymal and proliferating cells in the adult mouse SVZ express diacylglycerol lipases (DAGLs), enzymes that synthesise a CB1/CB2 cannabinoid receptor ligand. DAGL and CB2 antagonists inhibit the proliferation of cultured neural stem cells, and the proliferation of progenitor cells in young animals. Furthermore, CB2 agonists stimulate progenitor cell proliferation in vivo, with this effect being more pronounced in older animals. A similar response was seen with a fatty acid amide hydrolase (FAAH) inhibitor that limits degradation of endocannabinoids. The effects on proliferation were mirrored in changes in the number of neuroblasts migrating from the SVZ to the olfactory bulb (OB). In this context, CB2 antagonists reduced the number of newborn neurons appearing in the OB in the young adult animals while CB2 agonists stimulated this in older animals. These data identify CB2 receptor agonists and FAAH inhibitors as agents that can counteract the naturally observed decline in adult neurogenesis that is associated with ageing.