Cannabis Grow

In the context of adolescent health disparities prevention, this approach may be especially useful for identifying and/or implementing asset-based and youth-led interventions.For example, researchers could directly partner with teachers, service providers, parents, and transgender adolescents of color to gather insights based on survey data and in-depth interviews or focus groups into the individual, interpersonal, and contextual factors that influence adolescent vaping. Indeed, research has found that supportive school, community-based, and family contexts may buffer against substance use and support well-being among transgender adolescents– MM-CBPR is well-suited to examine these influences and identify multiple levers for intervention. There is also a need to examine gender identity disparities in adolescent vaping and co-use of tobacco products, such as combustible cigarettes. While explorations of vaping alone are important given recent increases in vaping prevalence, examinations of co-use and the health effects of co-use relative to vaping alone should be prioritized for prevention planning. Universal HIV testing is a cornerstone in efforts to achieve epidemic control as HIV-infected and unaware people are associated with the majority of HIV transmission events. In particular, during acute and early HIV infection , people who are unaware of their HIV status represent a subgroup with a disproportionate risk of HIV transmission due to high HIV viral loads, ongoing sexual risk behaviors and greater per-contact infectivity. The CDC recommends provision of confidential partner services to provide HIV risk reduction education and HIV testing to the recent sex or needle-sharing partners of newly HIV diagnosed people. By linking recently exposed persons to testing and treatment, this public health intervention has been used to limit the spread of sexually transmitted infections ,dry rack cannabis such as syphilis and gonorrhea, since the early 20th century. In the setting of HIV, however, partner services has had its limitations.

In 2006, Katz et al.estimated that fewer than half of newly HIV-diagnosed persons received partner services at public health departments across the United States. Reasons include that partner services is not mandated by law for HIV infection and more importantly that HIV remains a highly stigmatizing condition with significant implications for direct or indirect disclosure. Not only is partner services underutilized, but it can be limited in finding HIV unawares in the setting of newly diagnosed chronic HIV infection in which persons are often required to recall partners from several years prior. In 2007, the Task Force on Community Preventive Services, in reviewing the efficacy of partner services, showed that 20% of all referred partners were newly diagnosed with HIV. Persons with AEH likely represent a group particularly appropriate for partner services, as recall of recent sexual or needle-sharing partners may be more likely to identify putative transmission partners . Studies of partner services in the setting of recent HIV infection are limited, but demonstrate a greater yield of new HIV diagnoses in the setting of newly diagnosed acute HIV infection as compared with partner services provided to chronically HIV-infected persons. We examined the yield of HIV partner services provided to persons newly diagnosed with AEH in San Diego for identification of HIV-unaware persons, individuals with AEH, genetically linked partners and HIV-uninfected individuals at high risk for acquiring HIV infection.Adults and adolescents were offered confidential and free-of-charge screening for acute, early and established HIV infection at multiple community-based sites in San Diego as part of the San Diego Primary Infection Resource Consortium from 1996 to 2014. Before 2007, a quantitative HIV RNA was performed in HIV antibody–negative persons presenting with signs or symptoms of AEH and behavioral risks for HIV infection . Beginning in 2007, HIV nucleic acid testing was provided to all HIV antibody–negative persons regardless of symptoms and exposures. AHI was defined by a negative or indeterminate HIV antibody test in the presence of detectable HIV-1 RNA, corresponding to Fiebig stages I–II. Consenting antiretroviral -naive individuals with AEH were offered enrollment and longitudinal follow-up in the observational SD PIRC study.Routine clinical laboratories and HIV drug resistance testing were performed at baseline; demographic and behavioral risk data were collected for all individuals.

Longitudinal follow-up included visits at weeks 2, 4, 8, 12 and every 24 weeks thereafter. HIV partner services were offered to all AEH clients and included education and counseling to elicit information about recent sex or needle-sharing partners. Index cases were offered ‘self-disclosure’ , ‘dual-disclosure’ and ‘third-party notification’ for recruiting their recent sex or needle-sharing contacts. Study staff providing partner services received structured partner services training by the California Department of Public Health or Centers for Disease Control and Prevention. These structured trainings were repeated by our study staff every 5 years. The trainings included how to elicit partners from index cases, including prompts and reinterviews, and delivering exposure notifications to partners. Privacy concerns were taken very seriously, in particular when an index case chose third-party notification . Partners successfully contacted were offered free-of-charge HIV testing and counseling through SD PIRC or a testing facility of their choice and linkage to prevention and treatment services. Those with positive HIV test results who reported unknown or negative HIV serostatus before HIV testing were defined as newly HIV diagnosed, whereas those who reported positive serostatus or found to have been diagnosed previously were defined as previously diagnosed. All recruited partners who underwent HIV testing and counseling with the SD PIRC provided behavioral risk information, and recruited partners identified with AEH were also offered enrollment into SD PIRC as index clients . Partnerships were characterized as genetically linked if the HIV population sequence from an index case and their recruited partner were less than or equal to 1.5% genetically different using the Tamura-Nei model. The study focused on sex or needle sharing partners recruited within 6 months of diagnosis of the index case. Statistical analysis was performed using SPSS version 22 and SAS 9.3 . The efficacy of partner services provided to AEH clients was assessed by the number of index cases needed to interview to identify recruited partners: for HIV/STI testing, newly diagnosed with HIV infection, AEH infection and genetically linked index and recruited partners. We compared demographic and behavioral characteristics between HIV-infected and HIV uninfected recruited partners by using two-tailed t tests and two-tailed x2 analyses.

Because both index and recruited partners were occasionally represented in multiple different partnerships, mixed-effects logistic modeling was performed for genetic linkage and new HIV diagnoses. The UCSD Human Research Protections Program approved the study protocol, consent and all study related procedures. All study participants provided voluntary,roll bench written informed consent before any study procedures were undertaken.A total of 574 ART-naive individuals were newly diagnosed with AEH and offered partner services between 1996 and 2014. Among those index clients, 107 provided contact information sufficient to successfully identify and test partner.These 107 index cases identified 119 recruited partners and 128 distinct partnerships . Only for two recruited partners, needle sharing was identified as the most likely mode of HIV transmission . There were nine individuals who served as both index case and recruited partner in distinct partnerships . Index case and recruited partner demographics were not significantly different. The majority of both, index cases and recruited partners were non-Hispanic white men , MSM . The median age of index cases and recruited partners was not significantly different . Behavioral risks were also not significantly different between AEH index cases and recruited partners . In addition, there were no significant demographic or behavioral risk differences between HIV infected and HIV-uninfected recruited partners except for age . Of the 128 distinct partnerships identified, were HIV serodiscordant, and the remaining 76 were HIV seroconcordant. Paired HIV resistance test sequences were available in 62 of 76 seroconcordant partnerships and demonstrated genetic linkage in 38 of these partnerships. Genetic linkage between the index case and recruited partner was used to identify putative transmission pairs and was observed in 50% of recruited partners with AEH and 50% of recruited partners with chronic HIV infection. Behavioral risks were not significantly different between index cases who were part of a genetic cluster and those who were not . Evaluation of the time between identification of the index case and recruited partners showed that those recruited partners enrolled within 30 days of their index were significantly more likely to be newly diagnosed with HIV and genetically linked to their index than partners identified later. The results were robust to whether partnerships were treated as independent or were corrected for belonging to multiple partnerships in the mixed-effects framework.We found that partner services for persons with AEH represents an effective tool to find HIV-unaware persons, particularly when partner services is performed within 30 days of diagnosis. Importantly, more than a third of the newly HIV-diagnosed recruited partners were still in the acute and early phases of HIV infection, that is the phase with the greatest risk of HIV transmission. Partner services also identified putative transmission partners, with genetically linked partners representing 61% of the seroconcordant partnerships. Finally, partner services identified a high-risk HIV-uninfected cohort, whose risk behaviors did not differ from those newly diagnosed with HIV infection. The HIV epidemic is propagated by HIV unawares, particularly during the phase of AEH. We demonstrated that HIV screening within the sexual contact network of persons diagnosed with AEH is an effective strategy to identify HIVunawares in early stages of HIV infection. In this study, one out of three recruited partners was newly diagnosed with HIV infection and one out of seven with AEH.

This was 12 times higher than the overall yield of voluntary community-based HIV screening of MSM with the SD PIRC , the HIV-screening program used to identify the index participants in this study. Also, the recruited partners identified in this study represented a more high-yield cohort than previously documented. In two prior studies of partner services in AHI,7–10% of all recruited partners identified were newly diagnosed with HIV, as compared with 33% in this study. Partner services might contribute to broader public health goals to end the epidemic. Although we found a decrease over time in the number of recruited partners , which may be explained in part by the success of anonymous, internet-based sexual networks, partner services continued to be high yield in terms of identifying HIV-positive individuals . Another key finding was that the immediacy of partner services was essential. Partners identified in the first 30 days of a new AEH diagnosis were more likely to yield a new HIV diagnosis and a putative transmission link to the index case . In addition, 29% of genetic linkages occurred in partnerships in which the recruited partner also had AEH, showing that partner services coupled with phylogenetic analysis could potentially be an effective tool in identifying and targeting real-time transmission outbreaks among AEH persons. The HIV-uninfected recruited partners in this study reported behavioral risks that were comparable with AEH-infected index cases. Because they belonged to the sexual network of an individual with high infectivity, and because their risk behaviors did not differ from HIV-infected recruited partners, this group may represent ideal candidates for focused HIV-prevention services, including preexposure prophylaxis . Limitations of this study included the observational study design and the convenience sampling used to identify the study cohort. Further, this study was performed among MSM and in San Diego, among whom the HIVepidemic may differ from other areas of the world. Despite the fact that new HIV diagnoses within this studies were based on laboratory findings, self-report , and also checked against local HIV clinical and research databases, we can’t rule out that a proportion of recruited partners classified as newly diagnosed may, in fact, have been diagnosed with HIV before. Also, our study participants identified fewer recruited partners when compared with two prior studies of partner services . This is most likely because field-services were not provided in this study, as compared with the two prior studies in which partner services was performed by the local public health departments. In conclusion, our study indicates that provision of partner services to persons with AEH within the first 30 days of diagnosis represents an effective tool for finding HIV-unaware persons, including those with AEH who are at greatest risk of HIV transmission. In addition, partner services in this setting identifies HIV-uninfected partners who may greatly benefit from targeted prevention services, such as PrEP.

HOPE HOME staff collected data on alcohol use, drug use, and depression using validated scales in their 6-month followup visits. We used the closest score to our neurologic assessment and excluded individuals with assessments more than 4 weeks after our neurologic exam. The HOPE HOME staff used the Alcohol Use Disorders Identification Test to assess for alcohol use disorders. HOPE HOME modified the AUDIT by asking about behaviors in the past 6 months, instead of past year. We considered scores of 8–15 as measures of harmful alcohol use, 16–19 as moderate disorders, and 20 and above as evidence of severe alcohol use disorders. HOPE HOME staff also adapted questions from World Health Organization Alcohol, Smoking, and Substance Involvement Screening Test which assesses drug use in the 12 months prior to survey administration to assess drug use in the past 6 months. We asked participants how often they used, had a strong desire or urge to use, experienced health, social, legal or financial problems as a result of using, and failed to do what was normally expected of them due to using the following substances: cannabis, cocaine, amphetamine type stimulants, inhalants, sedatives or sleeping pills, hallucinogens, opioids, or other drugs in the past 6 months. Possible responses were the following: never , once or twice , monthly , weekly , and daily or almost daily . HOPE HOME asked participants if a friend, relative, or anyone else had ever expressed concern about their drug use for the listed substances and if they ever tried and failed to control, cut down, or stop using each listed drug. Possible responses were never , in the past 6 months , and not in the past 6 months . For each substance, we specified substance involvement risk as lower risk , moderate risk , and high risk . HOPE HOME used the Center for Epidemiologic Studies Depression Scale to assess depression in participants, which has shown to be a reliable measure of depression in homeless populations. We asked participants if they experienced various feelings or behaviors rarely ,drying cannabis some or a little of the time , occasionally or a moderate amount of time , or most or all of the time .

We asked participants about the following experiences: being bothered by things they usually aren’t bothered by, poor appetite, not being able to shake off the blues even with help from family/friends, feeling just as good as other people, having trouble keeping his/her mind on task, feeling depressed, feeling like everything is an effort, feeling hopeful about the future, thinking his/her life had been a failure, fear, restless sleep, happiness, talking less than usual, loneliness, feeling that people were unfriendly, enjoying life, crying spells, sadness, feeling that people disliked him/her, feeling that he or she could not get “going.” Scores of 0–3 for each of the 20 questions were combined for a total score of up to 60. We used a standard threshold score of 16 or more to categorize possible clinical depression. Neurologists [SM and SL] conducted structured neurocognitive histories in all study participants through a phone interview. This included participants’ age, sex, self-reported race, educational attainment, and work experience/stated profession. We also screened participants for comorbidities that are known risk factors for NDDB and/or cognitive decline: traumatic brain injury , stroke/transient ischemic attack, seizures/epilepsy, encephalitis/meningitis, sleep disorders , hypertension, hypercholesterolemia, obesity, diabetes, hearing loss, vision loss, cardiovascular disease, and thyroid disorders . Along with formalized scores for measuring alcohol use and drug use , we obtained informal data on individuals’ use, we defined remote alcohol and illicit drug use as no use within the previous year . We screened for the presence of known specific neurodegenerative disorders among first- and second-degree relatives . We asked the following question to elicit any other pertinent family history from each participant: “Did anyone in your family, including grandparents, parents, aunts or uncles, cousins, brothers or sisters, or children experience progressive loss of mental functions, or thinking abilities, or cognitive functions? Progressive changes in personality or behavior? Progressive difficulties speaking? Progressive difficulties using their arms and legs?” We [SM and/or SL] then assessed each participant’s neurocognitive history following a structured interview based on gold standard evaluation procedures in the UCSF ADRC. Participants were asked to report on perceived changes to their neurocognitive health over the previous “few years” compared to their perceived baseline.

The interview began with a brief assessment of subjective cognitive decline based on a previously published SCD interview, the SCDI . This interview begins with an open-ended question, followed by a brief structured assessment of changes to individual cognitive domains and an assessment of when said cognitive changes began, whether or not the participant felt concerned about said cognitive changes , and if the participant sought medical care for said complaints. This initial assessment was followed by a detailed neurocognitive review of systems that probed the following domains: episodic memory , visuospatial skills , executive function , language , sleep, autonomic, and sensory functions, motor function , and behavioral and emotional processing changes. Participants were scheduled for in-person neurological examinations after completing their phone-based neurocognitive history examinations. Experienced neurologists [SM or SL] performed neurologic examinations in a safe and private outdoor space within the HOPE-HOME study site in Oakland, California. Neurological examinations were conducted using Personal Protective Equipment in accordance with COVID-19 public health recommendations. In addition to all components of a gold standard bedside neurological examination we assessed olfaction using the Brief Smell Identification Test given that hyposmia/anosmia is a known risk factor for NDDB, especially alpha-synuclein associated disease .Trained testers [SM or GA] conducted all neuropsychologic assessments, which were administered on the UCSF Tabletbased Cognitive Assessment Tool platform . The tests were developed and validated by UCSF neuropsychologists to measure cognitive skills that are affected by typical and atypical presentations of NDDB . Participants were asked to report any drug use prior to test administration and were assessed for clinical signs of intoxication. If participants screened positive, they were rescheduled for a different visit. None of the participants in this study showed clinical signs of intoxication during testing. Memory was assessed using Favorites, an associative memory test that requires participants to learn associations between verbal and visual stimuli.

Performance was summarized by the total correct across the 2 learning and 1 delay trials. Executive functions were assessed by Match, which requires participants to quickly match numbers and simple pictures. Performance was summarized by total correct in 2 min. Flanker and Dot Counting tests from the NIH EXAMINER battery provided additional executive assessments . Visuospatial skills was measured by Line Orientation, which requires participants to indicate which of two lines is parallel to a target line. Language was assessed by Animal Fluency . Social cognition was assessed with the Dynamic affect Recognition Test on which participants are asked to identify the emotion expressed in each of a series of short videos relying on nonverbal cues. In total, administration of the TabCAT spanned 30–45 min . Participants’ scores on neuropsychological testing were adjusted for demographic factors using normative data . For Favorites, Match, Line Orientation, and Animal Fluency,ebb flow the scores were corrected for age and education level using a previously published regression approach . Flanker and Dot Counting were corrected for age and sex using the same method. DART was corrected for sex and age using a traditional box norms approach. As the participant sample is disadvantaged relative to reference samples, a conservative impairment threshold was selected. Using the summation of data obtained from structured neurocognitive history, neurological examination, neuropsychological examination, and functional assessment, we assigned each participant into one of four groups to denote each participant’s overall neurocognitive health status: neurocognitively normal, SCD , and mild or major neurocognitive disorder based on criteria from the 5th version of the Diagnostic and Statistical Manual . “Neurocognitively normal” participants were those that did not report or endorse neurocognitive concerns based on our neurocognitive history intake, performed within normal range on neuropsychological examination, and reported intact ADLs and iADLs. Participants with SCD were those who reported and/or endorsed neurocognitive concerns on our neurocognitive history intake but performed within normal range on neuropsychological examination and reported intact ADLs and iADLs. Participants with mild neurocognitive disorder were those who reported and/or endorsed neurocognitive concerns on our neurocognitive history intake and performed below expected on neuropsychological examination yet reported intact ADLs and iADLs. Finally, participants with major neurocognitive disorder were those who reported and/or endorsed neurocognitive concerns on our neurocognitive history intake, performed below expected on neuropsychological examination, and reported significant impairments on their ADLs and/or iADLs.

Subsequently, we screened all neurocognitive signs and symptoms obtained from structured neurocognitive history, neurological examination, neuropsychological examination, and functional assessment, to assign each participant into one or more of the gold standard research diagnostic criteria for NDDB, which included the following criteria: possible Alzheimer’s Dementia , possible behavioral variant frontotemporal dementia , probable corticobasal syndrome , possible CBS, possible Lewy body dementia , amnestic mild cognitive impairment , nonamnestic MCI, possible multiple system atrophy , primary progressive aphasia , possible Parkinson’s disease , possible progressive supranuclear palsy , suggestive PSP, and posterior cortical atrophy . In this manner, we explored possible etiologic diagnoses for the observed neurocognitive deficits observed in participants based solely on clinical data. Lifetime risks for alcohol-related blackouts in many surveys is >50% among drinkers . The high blood alcohol concentrations involved and the compromised cognitive processes inherent in ARBs increase risks for additional serious consequences, including accidents, unwanted sex, and exposure to other forms of violence . In addition to BACs>.20g/dl needed for most blackouts, ARBs are also associated with European American [EA] ancestry, female sex, and several genetically-influenced phenotypes related to heavier drinking, including a low level of response to alcohol, as described further below . However, the relationships among these characteristics and ARBs are complex and their potential interactions have not been adequately evaluated . The link of ethnicity to ARBs may relate to heavier drinking in EAs and, potentially, Hispanics, compared to other populations such as Asian individuals . Ethnic differences may also reflect divergent patterns of alcohol metabolizing enzymes, as Asians have higher rates of mutations in both aldehyde dehydrogenase and alcohol dehydrogenase that produce greater alcohol sensitivities and contribute to lower levels of heavier drinking with subsequent lower rates of ARBs . EAs, Asians, and Hispanics also differ on cultural-based proscriptions against heavy drinking, especially in women , have different rates of low LRs unrelated to alcohol metabolism , and vary regarding typical body mass indices, with the latter likely to affect BACs per drink .This reflects women’s likely lower body weight, less first pass metabolism of alcohol, and higher body fat with corresponding less body water per pound. However, there is overlap between ethnic background and drinking patterns among women, and it is not clear if those two characteristics interact regarding ARBs. Both ethnicity and sex also relate to low LRs to alcohol . However, LR differences across EA, Hispanic, and Asian individuals , and across sexes raise questions about how LR interacts with ethnicity and sex to contribute to ARBs.A recent review highlighted the paucity of prospective studies evaluating how multiple risk factors interact in contributing to ARBs, while controlling for alcohol quantities . In response, the present analyses extracted information from a 55-week prospective study that evaluated educational approaches to preventing heavy drinking on campus . The data tested four hypotheses: Hypothesis 1 states that relationships of ethnicity to ARBs will remain even after controlling for the maximum number of drinks consumed, with the highest ARB prevalence in EA and Hispanic and the lowest rates in Asian students. Hypothesis 2 is that ARB rates will be higher in females, and that the ethnic differences will remain robust after considering sex and controlling for maximum drinks. Hypothesis 3 proposes that low LRs will relate to ARBs, and that ethnic differences will remain even after considering maximum drinks and LR. Hypothesis 4 states that ethnic group status will interact with sex and LR to predict rates of ARBs over 55 weeks.Following University of California, San Diego Human Protections Committee approval, in January, 2014, 18-year-old freshmen were selected from respondents to questionnaires emailed to UCSD students to solicit participants for a 55-week study of ways to diminish heavy drinking in college students .

According to the census, more than one-fifth of state residents were Hispanic or Latino/a in 2015. Colorado’s population growth of nearly eight percent since 2010 ranks third behind only Texas and North Dakota. Politically, Colorado has been trending blue over the past several election cycles. Some have identified the migration of Californians into Colorado as a contributing factor to the state leaning further in the Democratic direction . The state awarded its Electoral College votes in 2008 and 2012 to the Democratic ticket, and the party appears poised to carry the state in 2016. A streak of two consecutive wins for the Democratic Party’s presidential candidates has not happened since Colorado voters supported Franklin Roosevelt in 1932 and 1936. Democrats emerged victorious in the last three gubernatorial elections and won three consecutive elections to the U.S. Senate beginning in 2004. The state’s march toward blue-state status was interrupted in 2014, however, as Republican Representative Cory Gardner defeated incumbent Democratic Senator Mark Udall in a competitive race. Republican candidates in this election cycle swept three of the remaining four statewide races, and the GOP regained control of one chamber of the state legislature. The single bright spot for Democrats on election night 2014 was the reelection of incumbent Governor John Hickenlooper who narrowly edged out Republican challenger Bob Beauprez. Colorado continues to receive national and international attention over the legalization of recreational marijuana, which has important budgetary implications. Though revenues associated with legalized recreational marijuana have fallen short of early government forecasts, pot for cannabis marijuana tax revenue continues to grow steadily. The sale of marijuana to adults over the age of 21 became legal on January 1, 2014.

By the end of the year, the state received $44 million in revenue from recreational marijuana. Combined with the preexisting medical marijuana market, the state received $76 million in 2014 .Despite an improving economy and a new stream of marijuana tax revenue, legislators remain wary about approving new spending measures. This is partly attributable to uncertainty regarding potential tax rebates mandated by the Taxpayer’s Bill of Rights . In the current legislature, Democrats hold a slim majority in the House, while the Republican advantage in the Senate is by a single seat. An analysis of roll call voting in state legislatures concluded that the Colorado Legislature is among the most ideologically polarized in the nation . Divided government, coupled with greater ideological polarization, has made dramatic changes in spending less likely to be successful. Governor Hickenlooper’s approval rating remains above 50 percent, but he faces a divided legislature and does not enjoy substantial political capital, having barely survived a close reelection . When submitting requests to the Office of State Planning and Budget , departments must outline a strategic plan to accompany their request. The governor’s budget request is submitted to the legislature in the fall. After consideration by the Joint Budget Committee , the full legislature typically passes the budget in May in time for the start of the fiscal year on July 1. The constitution mandates a balanced budget. Last November, the priorities reflected in Governor Hickenlooper’s proposed budget for the 2015–2016 fiscal year were similar to those in prior budgets drafted by the governor in collaboration with the OSPB. In his accompanying letter to the six-member JBC, the governor emphasized “enrollment and inflation increases for K-12 education, the return of General Fund support for transportation for the first time since FY 2007‒08 pursuant to S.B. 09‒228, increased caseload in the State’s Medicaid program, an anticipated decrease in the federal Medicaid match rate, the continuation of existing capital construction projects, and essential projects for the state’s information technology infrastructure” .

Spending in just two areas—K-12 education and health and human services—constitute two-thirds of all proposed General Fund appropriations. Governor Hickenlooper’s budget letter detailed how economic progress in Colorado has outpaced the nationwide recovery. In that sense, the budget reflects a cautious optimism about the state’s economic well being. The Bureau of Labor Statistics reports that Colorado’s seasonally adjusted unemployment rate in December 2014 was just 4.0 percent. Tied for seventh lowest in the country , it is a product of 35 consecutive months of job growth. The national unemployment rate for the same month was 5.6 percent. After a decrease in gross state product in 2009, the state has logged increases averaging about 2.5 percent a year for the past four years, and per capita income levels have increased. Against this backdrop of economic improvement, the governor’s budget includes $26.8 billion in total spending with a General Fund allocation of $10.3 billion. The sums represent spending increases from the prior fiscal year of 7.0 percent in total funds and 9.6 percent from the General Fund . During the recent economic recession, General Fund revenue in current dollars decreased over two consecutive fiscal years. Since the low point of the 2009–2010 when the General Fund fell to $6.4 billion, this number has increased by an average of $0.65 billion over the past four years.2 A March 2015 estimate projected that General Fund revenue was on track to grow by nearly nine percent in the current fiscal year, but contraction in oil and gas industry-related ac-tivity is projected to slow revenue gains. The projected General Fund amounts for the fiscal years beginning in 2014 and 2015 are $9.6 billion and $10.3 billion, respectively. One novel aspect of this year’s budget debate is that economic gains are substantial enough that lawmakers will have to consider tax refunds under TABOR. According to TABOR, which voters ratified in the state constitution in 1992, the state must issue tax refunds if revenues exceed the prior year’s spending after accounting for inflation and population growth.

TABOR refunds have not been possible for at least a decade. The governor’s budget includes a rebate forecast in the amount of $167.2 million.3 Legislators may ask voters to forego refunds in lieu of providing spending in a number of areas. The governor’s budget letter outlines several contingency plans where additional legislation or voter approval may be necessary to enact the spending items it includes. The governor’s 2015–2016 budget proposed increasing appropriations from the General Fund for most state departments. Table 1 provides summary data comparing the proposed budget with spending levels from the prior year. The first items discussed in the governor’s budget letter concern education,dry racks which is among the governor’s highest priorities. Since Governor Hickenlooper previously campaigned for passage of Amendment 66—a tax increase to fund K-12 education— it is not surprising to see his budget propose increases in education funding in the aftermath of its defeat. Put to voters on the 2013 ballot, Amendment 66 proposed an approximate 10 percent increase in the tax rate on income up to $75,000 and a 25 percent increase on income beyond $75,000. According to the state, the amendment would have raised taxes by $950 million in the first year following adoption. Despite the fact that supporters of the amendment raised in excess of $10 million to promote the measure, Colorado voters overwhelmingly rejected the tax increase with 64 percent of the electorate voting against it. Following this resounding defeat, the governor’s proposed budget seeks to increase education funding. The defeat of the tax increase to fund education could make more modest increases in education spending more acceptable to Republican legislators. Many Democratic lawmakers who supported the tax increase view the governor’s increase in K-12 spending as all the more necessary. Accordingly, the budget for the upcoming fiscal year increases total spending on K-12 education by 8.1 percent , an increase in per pupil funding of nearly $475 that brings total per pupil funding to about $7,500. Spending on higher education will increase by over $100 million after agreement was reached in 2014 on legislation limiting undergraduate tuition increases to no more than six percent in exchange for greater direct support from the state budget.General Fund increases for public institutions of higher education was set at about $75 million. This amount allocated to the governing boards of higher education institutions reflects an increase of 12.5 percent in General Fund spending. An additional $30 million would be allocated to a new Colorado Opportunity Scholarship Initiative, which would go toward student scholarships funded jointly by public and private sources. The budget from the previous year included about $60 million from the General Fund to institutional support with $40 million designated for student financial aid. After education, the second largest increase in spending is proposed to go to the Department of Health Care Policy and Financing where, as in previous years, caseload increases have necessitated greater funding. Accordingly, the budget includes an increase of $82 million from the General Fund. An additional $154.7 million in General Fund spending is pegged for future casework and modernization related to Medicaid, children’s health plans, and other health programs. Another notable increase in health care spending is a proposed increase of $11.4 million for 1.0 percent raises in provider and targeted service rates.

Nearly $7 million of a $25 million General Fund increase in Department of Human Services spending is proposed to allow counties to hire 130 additional child welfare caseworkers, and mental health and juvenile correctional institutions are scheduled to hire more than 100 new full-time employees. The governor’s budget continues to make investments in improving the Department of Corrections. Interest in directing greater funds to this area grew after the murder of Department of Corrections Director Tom Clements in 2013. The new director, Rick Raemisch, has championed meaningful prison reform. After increasing General Fund spending for the department by more than six percent last year, the 2015–2016 budget proposes a more modest increase of 4.0 percent, or nearly $30 million. The department estimates a small increase in the number of offenders housed in its facilities, and greater funding will allow the department to improve operations and facilities, including the addition of 330 beds. The state expects to hire more than 20 full-time employees to better assist people in the criminal justice system with mental health issues. A 1.0 percent provider rate increase is also included in the budget. The only departments with proposed reductions in General Fund spending were Public Health and Environment, Public Safety, and Revenue. Funding requested for the Department of Public Safety is 8.5 percent lower due to the absence of nearly $10 million in funding allocated to purchase aircraft and equipment for an aerial firefighting fleet. These funds made it into the prior year’s budget after the state experienced one of the most devastating wildfire seasons in its history. Partially filling this void is a proposed additional $2.7 million in funding to go toward two new Colorado Bureau of Investigation forensic labs and a 1.0 percent increase for state community corrections program providers. Funding proposed for the Department of Public Health and Environment is 28 percent lower largely due to the absence of appropriations made last year to help communities recover from widespread flooding that occurred in September 2013. General Fund spending for the Department of Revenue is slated for reduction with the loss of a one-time appropriation of $6.2 million in the prior year’s budget to help the department modernize its operations. These anomalies explain most of the larger cuts in General Fund spending. The budget preserves the status quo in most areas with a few targeted increases.In 2012, when nearly 55 percent of Colorado voters cast ballots in favor of legalizing recreational marijuana use by adults over the age of 21 the state’s counties were nearly evenly divided on the issue. Thirty-three of the 64 counties had a majority voting in favor of legalization, while 31 counties were had more no voters. One of many reasons for the ultimate success of the measure was that localities were given the option to prohibit marijuana business.”5 A year-end analysis in The Denver Post noted that 23 Colorado counties currently permit marijuana cul-tivation, sales, or both . Within these counties, 53 cities or towns permit recreational marijuana sale. As of March 2015, the state had licensed a total of 341 retail stores to sell marijuana. Including those authorized to sell medicinal marijuana, the number of outlets is over 500 .6 A study by the Marijuana Policy Group found that the demand for marijuana in the state likely far exceeds prior estimates, although the total amount of tax revenue generated by the first year of legal recreational sales fell short of expectations .

Using gene array analysis, we have observed that the relative levels of CB1, CB2, GPR18 and TRPV2 as well as of the fatty acid amide hydrolase gene transcripts were not significantly affected by the cannabinoid treatments and their levels did not exceed the 2-fold induction or 50% reduction by either CBD or THC treatment. On the other hand, we show here that LPS markedly down regulates CB2 and GPR55 and that this down regulation is not affected by either CBD or THC pretreatment. This result is in agreement with our previous report showing that LPS markedly down regulates CB2 and GPR55 mRNAs in BV- 2 microglial cells and in microglial primary cultures. Network analysis and signaling pathways A relationship between CBD-mediated oxidative stress response and glutathione depletion was previously reported . More recently, we showed that CBD-specific gene expression profile in BV-2 cells displays changes normally occurring under either nutrient limiting conditions or proteasome inhibition, and that are attributed to activation of GCN2/eIF2a/ p8/ATF4/CHOP-Trib3 pathway leading to autophagy as well as to apoptotic cell death. The Trib3 gene product seem to be of high importance to the CBD effect due to its ability to serve as a master regulator of an array of pathways including AP-1, ER stress, Akt/PKB and NF-kB . Trib3 expression is significantly upregulated by CBD as well as by THC and as observed here, remains upregulated after LPS treatment . According to these gene array studies and the qPCR results, LPS by itself does not significantly affect the expression of Trib3 mRNA. IPA interactome analysis of the micro-arrays data reveals an interaction between the CBD-upregulated Trib3 and the NF-kB transcription factor pathway . This interaction seems to be responsible for the attenuation by CBD of the transcription of many pro-inflammatory genes. There are several indications suggesting interaction between these two pathways. First, a direct interaction between p65/RelA and Trib3 protein which induces inhibition of PKA dependent p65 phosphorylation, was described . Second, Trib3 protein can negatively regulate the serinethreonine kinase Akt/PKB, a downstream effector of PI3K that has been implicated in the potentiation of NF-kB-induced transcription of pro-inflammatory mediators.

This negative regulation of Akt activity by the highly induced Trib3 gene product could point to the mechanism for the CBD-mediated regulation of LPS-stimulated gene expression. Indeed,cannabis grow set up the effect of CBD treatment on a number of LPS-stimulated genes as reported here is reminiscent of the effects described for the PI3K inhibitor and for the NFkB inhibitor in the murine macrophage cell line RAW264.7 activated with LPS. Both PI3K and NFkB signaling pathways exert important roles in gene expression in response to LPS, but they are not overlapping. Specifically, treatment with CBD repressed a number of typical pro-inflammatory genes stimulated by LPS, which are known to be NFkB dependent and of other genes including Csf3, Il-1b, Il-1a and Cox2/Ptgs2, which are under the control of both PI3K and NFkB pathways. Finally, Trib3 was documented to interfere with the inflammatory MAPK signaling via direct interaction with MEK-1 and MKK7 leading to attenuation of AP-1 mediated transcriptional activity in cancer HeLa cells. AP-1 is a transcription factor involved in the regulation of inflammation-mediated cellular functions and has been shown to be inhibited by Nrf2-activating agents. Indeed, our IPA network analysis indicates that the observed decrease in mRNA levels for a number of genes is probably related to a reduction in AP-1 dependent transcription. Additionally, according to these IPA results, this repression is reinforced by combined treatments of CBD and LPS as observed by the induction of FosL1 gene product, another negative regulator of AP-1 . Trib3 has been shown to down regulate PPARc transcription and serve as a potent negative regulator of adipocyte differentiation and PPARc is a molecular target for CBD that could be involved in mediating transcriptional effects in BV-2 microglial cells. Indeed, CBD has been shown to bind to PPARc in vitro as well as to activate its transcriptional activity in 3T3L1 fibroblast and in HEK293 transfected cells. In addition, Necela et al., described a regulatory feedback loop in which PPARc represses NF-kB-mediated inflammatory signaling in unstimulated macrophages. Moreover, they show that upon activation of TLR4 in LPS-stimulated macrophages, NF-kB drives down PPARc expression.

These results are in agreement with our results showing that LPS highly down regulates the expression of Pparg1 and Pparg2 in BV-2 cells. The profiles of CBD-induced gene expression with either resting or LPS-activated BV-2 cells, show that CBD stimulates the transcription of several anabolic genes encoding amino acid bio-synthetic enzymes, amino acid transporters and aminoacyltRNA synthetases known to be activated by ATF4, a basic leucine zipper transcription factor, that is increased when cultured cells are deprived of amino acids or subjected to endoplasmic reticulum stress . The divergent types of stress converge on a single event—phosphorylation of the translation initiation factor eIF2a, resulting in a general translational pause followed by selective increase in ATF4 mRNA translation and subsequent stimulation of expression of ATF4 target genes. Many of the CBD-affected transcripts are indeed classified as Nrf2-mediated oxidative stress response genes, including enzymes involved in the biosynthesis of glutathione. Thus, the observed CBD-mediated induction of ATF4-dependent anabolic genes may serve to replenish the amino acids reduced during the elevated turnover of GSH . The mechanism underlying CBD action presumably engages generation of ROS which in turn depletes intracellular GSH. Perturbations in redox tone and GSH levels activate the ‘‘phase 2 response’’, a mechanism used by cells to mitigate oxidative stress . As we have previously shown, many of the ‘‘phase 2’’ gene products are significantly upregulated by CBD. Our present results show that CBD, and less so THC, have immuno suppressive and protective activities that are reminiscent of other clinically applied drugs such as glucocorticoids , rexinoids and synthetic triterpenoids. GCs are immunomodulatory agents known to act as suppressive and protective mediators against inflammation. GCs are known to clear antigens by stimulating cell trafficking as well as scavenger systems and matrix metallo proteinases while they stop cellular immune responses by inhibiting antigen presentation and T cell activation.

Synthetic oleanane triterpenoids were shown to be highly effective in many in vivo models in the prevention and treatment of cancer and other diseases with an inflammatory component. Molecular targets of SO include KEAP1 , PPARc, IkB kinase, TGF-b signaling and STAT signaling. SO are among the most potent known inducers of the phase 2 response both in vivo and in vitro and affect the expression of several key cell cycle proteins . In some cancer cells, SO signal through PPARc to inhibit proliferation. The rexinoids bind almost exclusively to the RXRs and are involved in regulation of development, cell proliferation, differentiation and apoptosis. Because RXRs heterodimerize with other receptors , rexinoids modulate the actions of many steroid-like molecules that control metabolism and cellular energetics. In view of these results, triterpenoids and rexinoids are defined as multifunctional drugs. Their targets are either regulatory proteins that control the activity of transcription factors or transcription factors themselves . These complex modulatory activities exerted by GCs,grow rack systems rexinoids and SO display a panorama of effects that closely resembles the complex actions of CBD.Humans support the growth and maintenance of diverse sets of microbes in niches in contact with the environment including skin, lungs, mouth and gut. Studies of these microbes in the gut and oral cavity have uncovered key interactions between bacteria and human hosts in a wide variety of normal and pathological states. Many of these interactions are inferred from correlations between the composition of the microbial populations and changes in health status. For example, in gingivitis, an increase in Gram negative and anaerobic bacteria causes inflammation in the mouth.Our understanding of the basis for changes in microbial composition, and of how these changes influence human phenotypes, is still a work in progress. Clearly environmental factors and host genetic factors have important influences, perhaps best demonstrated to date by studies in the gut.By this approach, informed hypotheses about human genes that may conceivably influence a particular microbiological phenotype are tested with family or population-based studies to identify human variants that are statistically consistent with the hypothesis.

Examples include MHC genes,SLC11A1, the MEFV gene,FUT2 gene, and loci linked to susceptibility to infectious disease. While often successful, the candidate gene approach is limited by the ability to formulate hypotheses given current knowledge. They are neither comprehensive nor sufficient to identify the entire range of human genes involved in population changes associated with complex phenotypes or with maintenance of the composition of the “normal” micro-biome. In addition the significant inter-individual variation in micro-biome composition often masks specific effects of human genes if insufficient numbers of individuals are studied. Moreover, the micro-biome of a niche includes complex mixtures of organisms and is in part defined by interactions among its members making the identification of a “microbial phenotype” complicated. The oral micro-biome is one of the most diverse microbial niches in the human body, including over 600 different microorganisms . It is in continual contact with the environment, and has been shown to be susceptible to many environmental effects. These environmental factors include tobacco use , romantic partners, and cohabitation. The microbes reside in sub-niches along the oral cavity including on the tongue, cheek, and teeth. The salivary micro-biome has been shown to be representative of many the oral micro-biome niches, which is thought to be due to the fact that microorganisms from the oral cavity surfaces shed into the saliva. Previous salivary micro-biome studies have identified specific micro-biota that are present in almost all individuals, referred to as the core micro-biome. Saliva is also accessible, making it ideal for surveys of populations for micro-biome studies. In this paper, we describe an unbiased approach to studying the effects of human genes on the oral micro-biome with a two-step strategy. The first step utilizes twin information to establish heritable phenotypes related to the micro-biome; and the second identifies DNA sequence variation associated with the identified highly heritable traits. From 16S rRNA sequence information, a large number of potential phenotypes can be explored with the twin studies to allow identification of the most heritable and therefore the phenotypes most likely to be mapped in the association study. A key strength of this approach lies in the independence of the data underlying the two steps reducing multiple testing and type 1 effects on the power to carry out the test for association. The ability to refine a phenotype prior to carrying out an association study can lead to greater likelihood of detecting specific SNPs that influence it. We show, with the largest oral micro-biome twin study to date, that multiple phenotypes of the salivary micro-biome are heritable. Using these phenotypes, we identify promising host gene candidates in a genome wide association study of an separate sample that may play a role in establishing the oral micro-biome.Twin samples were obtained from the Colorado Twin Registry . The twin sample included 366 monozygotic pairs , 263 same sex, and 123 opposite sex dizygotic pairs . Unrelated individuals were ascertained from community and clinical samples participating in the Colorado Center for Antisocial Drug Dependence and isolation of DNA from saliva and characterization of their genotypes was as previously described.Pooled DNA from triplicate PCR with the 16S V4 hyper variable primers 515F/806R was done according to the Earth Microbiome Project 16S rRNA amplicon Protocol, with unique barcode indices for multiplex sequencing on the forward primer. Concentration of pooled products was determined by picogreen. 240 ng from each sample was pooled for multiplex paired-end sequence determination on the Illumina MiSeq platform.Samples from 1504 twins of whom 111 within-twin longitudinal samples with at least 3500 reads and DNA samples from 1481 unrelated individuals with at least 3000 reads produced 2664 and 2679 OTUs respectively. All samples were rarefied to 2500 sequences to retain as many samples as possible to improve power with little effect to results.To avoid analyses of OTUs that were the result of sequencing or PCR error, OTUs that were not present in at least 2 subjects and observed at least 10 times were removed, resulting in 895 OTUs in the twins and 931 OTUs in the unrelated individuals. One of the unrelated individuals was later removed during analysis due to cryptic relatedness leaving 1480 people in the unrelated sample.β-diversity was analyzed via Bray Curtis and UniFrac using QIIME and R.

As a result, a young child treated with amphetamines would not necessarily have an increased risk for abuse of other stimulants by the time he or she reached adolescence – when illicit drugs are more readily found. In contrast, if the onset of treatment were to start in the early teens , drug-seeking behavior would peak just as illicit substances became more available. This hypothesis is supported by one study that found that ADHD individuals whose treatment persisted into adolescence were more likely to become dependent on cigarettes than those whose treatment ended earlier. The individuals whose treatment had stopped before adolescence went through the sensitization/withdrawal process before cigarettes became available to them, either through legal or illegal means. The effect of amphetamine is also hypothesized to be greater under both temporal and environmental cues previously associated with administration. It is likely that a child treated at a younger age would move out of an environment previously associated with amphetamine and therefore have a decreased sensitivity to amphetamine at an older age compared to an individual who started treatment in adolescence. The child treated at a younger age would therefore be less likely to abuse their prescription and eventually other illicit drugs. Thus, ADHD treatment at a younger age seems to have little or no effect on drug abuse during adolescence and adulthood,cannabis grow equipment while treatment that continues into adolescence may raise the risk of non-prescription stimulant abuse. Lastly, adolescents typically experience much more stressful environments as more responsibility is given to them at both home and school. The stress of adolescence may synergize with the effects described above, and thus further increase the likelihood of stimulant abuse. On the other hand, if amphetamine prescription is initiated before adolescence, the individual will not have the same added level of stress, and thus will be less driven to abuse their medication or drugs with similar effects.

Although much evidence points to an increased risk of substance abuse with amphetamine treatment, many investigators have concluded that amphetamine use does not increase a patient’s likelihood of later developing SUD, and that it may actually exert a protective effect against substance abuse later in life based on population-level studies – that is, some have concluded that stimulant-based treatment of ADHD early in life may decrease drug abuse later in life. For instance, Barkley and colleagues, the same group whose results indicated a significant increase in cocaine use amongst ADHD patients treated with stimulants, still concluded that treatment of ADHD had no effect on the likelihood of using a number of drugs. A similar study that followed 56 medicated and 19 unmedicated patients found that there was no association between treatment and drug abuse. A study that followed 285 treated and 84 untreated ADHD patients also concluded that SUD did not develop as a result of stimulant treatment. A meta-analysis of several studies also found that for any category of drug use, stimulant treatment decreased the risk that an individual would abuse drugs in general. Review papers on the subject of SUD and its relationship with ADHD have also come to the conclusion that childhood treatment with stimulants is negatively correlated with substance abuse.Although many studies conclude that stimulant treatment is protective against the development of SUD when prescribed to ADHD patients, the validity of these studies is questionable. For instance, many of the studies that come to this conclusion are funded in full or in part by drug companies such as Pfizer or Eli Lilly, which manufacture ADHD medications.Reviews and meta-analyses are particularly dubious when a conflicting financial interest exists, because they may select papers that suggest a desired result. In addition, studies with larger sample sizes and meta analyses tend to group all types of substance abuse into one category, or simply distinguish between “drug abuse” and “alcohol/ tobacco use” categories. Large bins of categorization produce a confounding variable, because stimulant drugs are known to reinforce and prime other stimulant drugs most reliably. The fact that amphetamine treatment has been suggested to protect against or have no correlation with the use of depressants such as marijuana or alcohol makes placing all drugs of abuse into one category especially problematic. The decreased risk factor for depressant use and the increased risk factor for stimulant use interfere with each other when considered together, thus concealing any specific trends that might exist.

Of two predominant studies that separated “substance abuse” into individual drugs or drug subcategories, one study found a significant increase in cocaine use, while the other found no significant increase. However, the latter study had a small sample size of 56 medicated ADHD patients and 19 non-medicated patients. It is possible that if larger sample sizes were obtained, a significant increase would have become apparent. This conclusion seems increasingly likely since the prevalence of stimulant abuse in society is generally not as high as for other drugs such as cannabis or alcohol, especially amongst ADHD patients in general. Therefore, a much larger sample size is needed to compare stimulant-specific abuse amongst ADHD patients. Furthermore, if treatment with stimulants does in fact exert a protective effect against general drug abuse and not illicit stimulant abuse, the analysis of drug abuse in general as a single category would actually downplay the increase in stimulant abuse amongst patients. Untreated subjects would be much more likely than treated subjects to participate in non-stimulant abuse, confounding a large portion of studies. Based on the idea that those with a later onset of treatment have a higher potential for stimulant abuse, it is probable that if the age of treatment onset were compared, patients with a later onset of treatment would show a specific increase in illicit stimulant abuse in adolescence and possibly into adulthood. However, those treated at a younger age may not have a statistically higher percentage of abuse of any drug. If it is true that subjects treated earlier are less likely to abuse stimulants than those treated later in adolescence, any study that does not compare age of onset and likelihood to develop stimulant-specific abuse possesses a significant weakness. Most of the studies that come to the conclusion of a negative correlation between amphetamine treatment and substance abuse fail to accurately assess age of treatment onset when evaluating data, thus mixing information from individuals that may have a higher risk of drug dependence with those that may have a lower risk of drug dependence because of age of treatment onset. Finally, none of these studies take into account the differences between methylphenidate and amphetamine. Since amphetamine has been shown to have an increased potential for abuse compared to methylphenidate and other ADHD medications, these studies therefore downplay the exposure to risk of substance dependence that is put forth with amphetamine prescription.

The majority of population studies that have concluded that stimulant-based treatment has no effect on the development of substance abuse later in life fail to take into account all of the factors necessary to produce accurate correlations.Current knowledge regarding the effects of amphetamines on stimulant-specific abuse in animals and general drug abuse in humans is not consistent. Studies on animal models have concluded that amphetamines specifically raise the tendency to self-administer stimulants, such as cocaine and nicotine,mobile vertical rack largely due to the sensitization of the rewarding effects of amphetamine that results in drug-seeking behavior.On the other hand, other population-level studies based on surveys and meta-analyses have concluded that stimulant prescription has no correlation with the development of substance abuse. These studies, however, all possess one or more of the following flaws: failing to distinguish between stimulants and depressants in terms of drugs abused by patients; failing to distinguish between amphetamine medication and other stimulant treatment; working with sample sizes far too small to accurately reflect the level of dependence that might develop to stimulants, specifically; and failing to consider the age of the patient at treatment onset. Taken together, evidence suggests that amphetamine treatment of ADHD causes a small increase in potential for stimulant drug abuse and possibly a decreased potential abuse of depressants. The risk for developing stimulant abuse is likely dependent on age of onset of stimulant prescription, with those treated in adolescence and young adulthood at a higher risk. However, there are no conclusive studies to verify this hypothesis. Considering that the amphetamine treatment for ADHD is on the rise, it would be prudent for an independent research group concerned with the health of ADHD patients to conduct a large scale study that accounts for the variables mentioned above, using a large population of both treated and untreated ADHD patients to test specific dependence of stimulant class drugs that arise from treatment with amphetamines. Another potential method of study might include comparing the number of formerly treated ADHD versus untreated ADHD patients amongst a population known to have abused stimulants, adjusting for the percentage of treated versus untreated ADHD individuals amongst the ADHD population. A conclusive study on this matter would allow parents, schools, and physicians to more accurately consider the treatments available for children with ADHD.The expression of cannabinoid receptors by human leukocytes suggests that both endogenous ligands and inhaled marijuana smoke might exert immuno regulatory properties that are distinct from their effects on the brain . Furthermore, while brain cells exclusively express cannabinoid receptor type 1 , leukocytes express both CB1 and CB2, with CB2 reported as the predominant sub-type .

Both CB1 and CB2 are transmembrane G-protein coupled receptors that inhibit the generation of cyclic adenosine monophosphate and can signal through a variety of pathways including PI3-kinase, MAP kinase, NF-κB, AP-1, and NF-AT . The resulting effects on host immunity have primarily been studied in animal models and suggest a coordinated down-regulation of cellular responses that can occur through altered trafficking, selective apoptosis, or functional skewing of antigen presenting cells and T cells away from T helper type 1 or Th17 response patterns . Similar results have been observed when purified human T cells are stimulated in vitro in the presence of Δ9-tetrahydrocannabinol . However, the extent to which the effects are observed in humans in vivo is unclear. Daily administration of marijuana or oral THC to research subjects in a prospective and randomized study had no obvious effect on T cell proliferation or cytokine production when blood cells were subsequently isolated and stimulated in vitro . Sipe et al. examined the distribution and function of a common polymorphism in the human CB2 gene associated with the replacement of a glutamine by an arginine at amino acid position. Functionally, lymphocytes from subjects with either of these genotypes proliferated normally when stimulated with anti-CD3 antibody. However, when stimulated in the presence of an endocannabinoid, lymphocytes expressing the glutamine residue at position 63 were markedly inhibited while those expressing the arginine were only modestly suppressed. The arginine substitution also correlated with the prevalence of autoimmune disease in the subjects tested. Collectively, this body of work suggests that cannabinoids are biologically active immune regulators in humans. Expanding upon this hypothesis, we examined the expression of cannabinoid receptors by human monocytes and the impact of THC on their differentiation into monocyte-derived dendritic cells . Exposing monocytes to THC blocked many of the features normally associated with their differentiation into functional DC and impaired their capacity for T cell activation. Furthermore, the T cell activation that did occur was associated with a change in T cell phenotype and cytokine secretion. However, the impact of THC was partially overcome when DC and T cells were exposed to a combination of activation signals and exogenous cytokines. Our findings suggest that cannabinoids are capable of altering the differentiation and activation of cells involved in human cell-mediated immunity. As an initial step in understanding the potential interaction between cannabinoids and human monocyte-derived DC, monocytes were evaluated for the expression of the CB1 and CB2 receptor sub-types by RT-PCR and flow cytometry . RT-PCR studies were carried out on monocytes that had been purified to >90% purity by either negative depletion or fluorescent cell sorting. mRNA encoding for both CB1 and CB2 were detected, although expression of CB2 predominated whether analyzed by standard RT-PCR or by an automated quantitative RT-PCR using cells from 4 different donors.

Our study of social network effects confirms that adults with SUD and MDD will likely benefit from efforts to restructure their social networks by increasing the number of abstinent/non-using supports and decreasing the number of contacts who use substances regularly. Results also suggested that both regular maintenance of positive social networks and avoiding momentary shifts that increase the density of regular users are likely important for avoiding future increases in drinking. For individuals who are unable to enact sustained changes in social networks, our research suggests that placement into constrained environments can assist in attenuating the negative influence of a social network comprised of greater numbers of substance abusers. While this series of studies makes important research and clinical contributions, especially with respect to the treatment and long-term recovery of patients with substance dependence and MDD, overall limitations should be noted. Perhaps most notable among these limitations are the restricted demographic characteristics of our sample which curtails the immediate generalizability of these findings. This is a common limitation of clinical trials of treatments for addictive disorders , and while these results may be widely applicable due to the high prevalence of MDD in substance use treatment settings , replication in other samples is needed before generalizing these findings to a population with a wider range of demographic characteristics. Many of our patients also had post-traumatic stress disorder. While we tested effects of PTSD on substance use outcomes, we did not explore more intricate effects that are of interest due to the high prevalence of PTSD in this population. Temporal precedence between variables was not always tested , and even models demonstrating temporal precedence did not fulfill all criteria for examining mechanisms of change . There is still some debate as to whether some of the process variables we studied are true mechanisms,indoor cannabis grow system or just risk markers of some underlying characteristics that better enable patients to limit drinking and drug use .

Regardless of these distinctions, our studies make important contributions to the literature because these variables have not been studied extensively in patients with SUDs and co-occurring psychiatric disorders, but further research is needed to demonstrate these processes can be manipulated in ways that improve the effectiveness of interventions. Because these studies involved secondary analyses of existing data, we were somewhat limited by characteristics of measures utilized in the original clinical trial. Our measures of 12-step attendance and affiliation were brief and did not differentiate between different meetings , which may have allowed better investigation of disparate findings with respect to alcohol vs. drug use. Our social network measure did not capture features of social support examined in prior studies, such as whether network members actively supported patients’ abstinence efforts . Furthermore, although we examined complex mediating and moderating effects on long-term substance use, there are potential relationships among mediating variables that we did not investigate.Considering the results of these four studies in the context of prior research in substance-dependence samples, there are numerous interesting lines of research for future inquiry. While we found that impairment predicted overall levels of 12-step affiliation, we did not test whether impairment relates to specific 12-step behaviors or impacts rates of post-treatment changes in 12-step attendance or affiliation. Because the rate of change in 12-step affiliation may be especially important, as demonstrated in Study 2, future research might further investigate the role of impairment on changes in 12-step affiliation in patients with substance dependence and MDD. Prior studies also found that neurocognitive functioning moderated social network effects , and given that social networks predicted substance use and impairment moderated the effects of other contextual variables , this question is worth exploring in patients with substance dependence and co-occurring psychiatric disorders.

Studies have demonstrated that patients’ pre-existing social network characteristics may moderate the effects of certain interventions, such that treatments specializing in altering the structure of social networks are especially useful for patients with networks comprised primarily of substance users . It is currently unknown whether social networks or many other baseline characteristics impacted whether patients in our sample had better outcomes from TSF or ICBT, which may help guide decisions about the appropriateness of certain interventions for patients with substance dependence and psychiatric disorders. Further work is needed to determine if particular aspects of psychosocial therapy are responsible for initiating change in mediating or moderating variables, and how to optimally package interventions for dissemination. A prior study of alcohol-dependent patients found that receiving a specific craving module moderated relations between negative mood and drinking . Given that patients in our study received distinct modules that focused on different aspects of coping, and depression predicted future substance use, it may be worth investigating whether receipt of certain therapy modules had intended effects on reducing “self-medicating” patterns of drinking. Homework compliance has been found to predict outcomes in CBT for cocaine dependence and may be an important mechanism of intervention effects on substance use , suggesting that compliance with group therapy homework may have influenced therapeutic process variables in our sample. By identifying modifiable variables that predict future substance use , our research identifies important proximal targets for newly developed interventions or modifications to existing therapies. Since the publication of the short and long-term results of our trial, there is somewhat stronger evidence for the efficacy of integrated psychosocial therapies , but given the historically poor treatment outcomes for patients with substance dependence and MDD, further development and refinement of interventions is necessary to improve the long-term treatment outcomes within this population. The corresponding predicted reduction from the Poisson regression is approximately 2.1 percent for the minimum wage and 2.3 percent for the EITC. However, the precision of the estimates is too low to conclude that this difference is statistically significant. For additional robustness, we estimate augmented specifications controlling for state linear and quadratic time trends. The results are qualitatively consistent across these specifications ; however the precision of the estimates is reduced to the point where the estimated effects of the EITC are no longer statistically significant, possibly reflecting the limited variation in state policies during the sample period. Next, we present the estimated event study models of suicide deaths.

Figure 2 plots the estimated event time coefficients together with 95 percent confidence intervals. Panel presents results for the minimum wage. Recall that if the parallel trends assumption holds, we should expect the data to exhibit parallel pre-trends, i.e. the estimated event time coefficients should not be different from zero for the years leading up to a minimum wage increase . Overall, point estimates are indeed small in magnitude during the pre-period; and they are not significantly different from zero at the five percent level. At time 0, the estimated event time coefficients exhibit a significant discontinuous downward shift, consistent with the negative effect of the minimum wage presented in Tables 2-4. Separating the sample by gender, minimum wage event study estimates for men are somewhat more concerning – while the estimated pre-trends are not statistically significantly different from zero,PIPP horticulture the point estimates are nonetheless consistently positive. Such differential pre-trends could mean that the negative effect for men is biased downward, reflecting in part differential mortality patterns in states that implement higher minimum wages. For women, estimated pre-trends are small and close to zero, supporting parallel pre-trends. Moreover, the drop at time zero is statistically significant at the five percent level. Unlike the minimum wage, which raises pre-tax wages at the time of implementation, the direct impact of state EITC policies on disposable earnings may operate with a lag, as eligible families receive EITC payments only after filing taxes for the previous year. Absent any labor supply response, state EITCs would start affecting outcomes only in their second year, which is the first year eligible workers receive the additional payments. Meanwhile, the research consensus suggests that higher EITCs have positive employment effects, especially among single mothers. For these groups, expanded EITCs could have an additional, contemporaneous effect on pre-tax income as well as on associated downstream outcomes, as workers increase their labor supply knowing they will earn a larger EITC payment when they receive their tax refund the following year.The models find parallel pretrends for the pooled sample as well as for men and women separately. In the pooled sample, a small negative effect appears in year 0 , followed by a discontinuous downward shift in estimated event time coefficients the following year. This pattern is consistent with the effects of the EITC on suicides operating primarily through increased tax refunds in hand — as people start receiving larger tax refunds once the policy has been in effect a full year. For men, while there are no effects on suicides in year 0, event time coefficients drop sharply in year 1. For women meanwhile, the coefficient path starts falling immediately at year 0 followed by larger negative effects in year 1 and later years. This pattern is consistent with the literature that finds that positive labor supply responses to the EITC are found mainly among women. Appendix figures and show estimated results with further model varieties: Appendix figure shows results for minimum wages, but incorporating additional minimum wage changes by reporting outcomes for less than the full [-5,4] window around the policy change. Appendix figure presents results from the more parsimonious event study specification of equation . For the minimum wage, this specification indicates no significant shift in male suicide mortality around minimum wage changes. Meanwhile, estimated minimum wage event studies for the pooled sample and for women are remarkably consistent across the two specifications. For state EITCs, results are similar across specifications. To summarize, the estimated event study models indicate that the parallel pre-trend assumption holds, supporting our identifying assumption of parallel trends. In addition, the patterns indicate negative causal effects: the number of suicides tends to drop sharply after the implementation of higher minimum wages and state EITC. Our analysis to this point has focused on mortality outcomes of individuals with high school or less education, who have greater exposure to minimum wages relative to our placebo sample of individuals with a bachelor’s degree or higher. This same intuition should hold more generally: within the sample of less-educated adults, reductions in suicides should be larger among groups that are more exposed to the policies we study. To test this prediction, we use earnings and hours data from the CPS MORG to estimate exposures to the minimum wage for various groups of workers with high school education or less. We slice the sample by gender and age , yielding 10 sub-samples. We define group-level exposure to the minimum wage as the share of workers who earn less than 110 percent of the current minimum wage. To capture exposure to the EITC, we use the CPS ASEC, calculating for each demographic group the share of workers who receive the credit. We then estimate the panel models of suicide deaths from equation for each sub-sample. Intuitively, if minimum wages and EITCs reduce suicide deaths by raising incomes of affected workers, estimated effects should be larger and more negative for groups that have higher exposure. That is, the estimated effects should be negatively correlated with exposure. Conversely, a lack of correlation between effect size and exposure would provide evidence against our hypothesis that higher minimum wages reduce suicides by raising incomes of low wage workers. Figure 3 plots the estimated effects on suicide against exposure. The top panel shows effects for minimum wages, while the lower panel shows effects for EITCs. For both policies, the figure indicates that effect estimates and exposure are negatively correlated: on average, populations with higher exposure tend to experience more substantial drops in suicide. The line of best fit is downward sloping; for minimum wages, the slope is significantly different from zero at the 1 percent level, while the slope for EITC exposure is significant at the 5 percent level. We also find similar downward patterns when we plot effects versus exposure separately for men and women . To summarize, Figure 3 indicates that the reduction in suicides is greater among the groups that are more likely to be affected by higher minimum wages. This finding lends support to our hypothesized mechanism that minimum wages reduce suicides by lifting low-income groups out of poverty.

These studies also suggest that measures of exceptionally poor performance are perhaps better indicators of impairment than continuous performance scores or dichotomous classifications of samples based on arbitrary cutpoints. Despite evidence that patients with psychiatric comorbidity comprise the majority of patients in clinical settings and have greater neurocognitive deficits than patients with substance dependence only previous studies have not explored the impact of neurocognitive impairment on treatment outcomes for patients with comorbidity. The current study addresses this area of need by examining the effects of neurocognitive impairment on substance use outcomes in patients treated for substance dependence and MDD. Greater neurocognitive impairment at baseline predicted lower self-efficacy and lower 12-step affiliation, and our analyses confirmed that these proximal variables mediated the effects of impairment on future drinking and drug use. Previous studies found similar relationships between impairment and self-efficacy , and our study extends these findings to patients with comorbid MDD. Self-efficacy is typically defined as the confidence to abstain from substance use in high-risk situations, and patients with greater impairment apparently had lower confidence they could manage these situations without using substances. The specific mechanisms underlying these effects are unclear, but it is possible that impaired patients engaged less fully in TSF and ICBT or experienced less perceived benefit from therapy sessions. In one recent study poorer cognitive ability predicted lower acquisition of coping skills in CBT . Future studies might explore whether reduced coping skills or difficulty engaging in other aspects of group treatment explain lower self-efficacy for cognitively impaired patients.

Patients with greater impairment had lower levels of 12-step affiliation,mobile grow systems suggesting they had greater difficulty engaging in 12-step practices that common in both therapy conditions but were only specifically targeted in TSF. This may help explain why patients with poorer neurocognitive functioning had better long-term substance use in ICBT than in TSF . While it was originally hypothesized that patients with poorer neurocognitive functioning would fare worse in ICBT due to the cognitive demands of the treatment, the current study shows that impaired patients had difficulty frequently attending 12-step meetings or engaging in 12-step behaviors. The direction of this finding contradicts those of previous studies, which found that levels of AA affiliation were significantly greater for impaired patients . It is possible that for patients with substance dependence and MDD, neurocognitive impairment represents an additional and especially disabling risk factor leading to limited engagement in 12-step practices. Patients with greater neurocognitive impairment were also found to have greater depressive symptoms during the course of the study. Similar results were found in a sample of depressed, hazardous drinkers, as patients with better cognitive functioning had greater reductions in depressive symptoms during CBT . We hypothesized that neurocognitive effects on depressive symptoms would impact substance use outcomes, given that egative affect is a frequent precursor to relapse in patients with comorbid MDD , and is consistently tied to substance use over time , suggesting that greater depression severity within these patients is frequently a potential trigger for future substance use. This hypothesis was confirmed by mediation analyses demonstrating that greater depressive symptoms predicted greater future alcohol and drug use and mediated the effects of neurocognitive impairment on these outcomes. Our previous work tied reductions in depression during treatment to 12-step meeting attendance, and it is possible that reduced engagement in 12- step contributed to greater depression for cognitive impaired patients. Alternatively, these patients may have had difficulty with other elements of treatment that limited their improvement in depressive symptoms.

Investigation of neurocognitive impairment as a moderator revealed complex interactions with therapeutic process variables in the prediction of drinking and drug use.Greater 12-step affiliation predicted lower future drinking to a greater extent for impaired patients. Although the direction of this finding is contrary to effects observed in previous, similar studies , other research found the effects of baseline social support on future drinking were greater for impaired patients . Our sample differed from these studies in that all patients had comorbid MDD, and our results suggest at greater levels of depression severity, the benefits of engaging with external sources of support are especially useful. That is, 12-step affiliation was most predictive of future drinking for patients with severe impairment, especially when they were severely depressed. Although prior research has found relatively reduced benefits of AA practices for patients with MDD , our results suggest the opposite may be true for patients with neurocognitive impairment, as they may experience relatively greater benefits from 12- step affiliation. Neurocognitive impairment also moderated the effects of depression on future drug use, but in the opposite direction than expected: relations between depressive symptoms and future drug use were stronger for patients with less impairment. Although rates of drug use in the sample were low overall, patients with little or no impairment had a greater tendency to use drugs frequently following periods of more severe depressive symptoms. Because previous studies of neurocognitive effects on treatment have largely focused on alcohol users without MDD or depressive symptoms, the mechanisms underlying this unexpected finding are unclear. Others have speculated that cognitively impaired patients may be relatively less capable of the planning required to re-initiate substance use . Relations between depression and drinking were not moderated by impairment, suggesting this could be the case for drug use but not necessarily for alcohol. This interaction was also less robust, as it was not statistically significant when controlling for prior self-efficacy and 12-step affiliation. Future studies are needed to determine whether this finding is consistent in other samples of drug dependent patients, with or without comorbid MDD. Limitations of this study should be noted. The results may not be immediately generalizable to the broad population of patients with psychiatric comorbidity, as we only studied patients with MDD, and our sample was comprised of veterans who were predominantly male and Caucasian.

Clinical trials of treatment for alcohol and drug dependence frequently suffer these demographic limitations, and replication of these findings in a wider range of patients is needed before broader generalizations can be made. Although we examined complex mediated and moderated pathways to substance use, there are untested relationships among the variables in this study that merit further exploration. Greater self-efficacy has been associated with greater 12-step affiliation, which could be one factor explaining lower self-efficacy for patients with greater neurocognitive impairment. Because the effects of mediating variables were examined in separate HLMs, we did not test whether each variable relates independently to future substance use, which can be examined in “multiple mediator” models that help demonstrate which mediating processes may be most crucial for limiting future substance use. Although this study met several conceptual criteria for examining mechanisms of change , further criteria are required to conclude with greater confidence that these process variables are mechanisms of change or casual factors for limiting long-term substance use. Despite decades of clinical research developing and testing behavioral interventions for substance dependence, evidence-based interventions are only moderately effective ,cannabis grow supplies with a substantial number of patients returning to substance use following treatment . Furthermore, many of the largest randomized trials have found equivalent outcomes across distinct treatment conditions , and theoretically distinct treatments often fail to produce differential change on hypothesized mechanisms of action , suggesting we may know little about the underlying mechanisms of change within addiction treatment. Consequently, researchers have increasingly turned towards process-focused investigations aimed at identifying how treatments work, for whom they are effective, and which modifiable factors are most integral for maintaining positive change , with hopes of improving the overall likelihood that substance dependence treatment will result in long-term change. The past decade has seen vast growth in process-oriented studies in the general addictions treatment field . However, very little of this work has involved samples of patients with other psychiatric disorders, despite evidence that these patients comprise the majority in many treatment settings . Among individuals with substance dependence, major depression is the most common co-occurring Axis I disorder in the general population and in treatment settings . Patients with co occurring MDD typically cost more to treat and have poorer treatment outcomes than patients without this MDD , suggesting it is especially important to identify core therapeutic processes within these patients.

However, because little process-oriented research has involved patients with substance dependence and MDD, it is not known whether previous findings generalize to this highly prevalent, costly, and disrupted population. Studies of mediators of treatment outcome are essential to the general area of “treatment process” research. Within treatment studies, investigations of mediators typically examine an intermediate factor that may explain the effect of treatment “dose” on a clinical outcome . These studies have the potential to inform the development of more efficient and portable interventions by identifying the skills or behaviors targeted by interventions that are most responsible for producing positive change. In previous studies examining mediation, lower marijuana use in CBT + contingency management compared to contingency management alone was mediated by enhanced self-efficacy , and better abstinence rates in TSF were explained by greater commitment to abstinence . Importantly, statistical mediation is only one of several conditions to be met before declaring a variable is a mechanism of change, as temporal precedence, specificity, and experimental manipulation of the variable must also be demonstrated . In practice these criteria are rarely.Study 4 has been submitted for publication in Journal of Consulting and Clinical Psychology, as following: Worley, M.J., Tate, S.R., Tapert, S.F., Granholm, E.G., & Brown, S.A. Neurocognitive impairment interacts with 12-step affiliation and depression to predict future drinking in depressed, substance-dependent veterans. The dissertation author was the primary author of this manuscript under review. Despite decades of clinical research developing and testing behavioral interventions for substance dependence, evidence-based interventions are only moderately effective ,with a substantial number of patients returning to substance use following treatment . Furthermore, many of the largest randomized trials have found equivalent outcomes across distinct treatment conditions , and theoretically distinct treatments often fail to produce differential change on hypothesized mechanisms of action , suggesting we may know little about the underlying mechanisms of change within addiction treatment. Consequently, researchers have increasingly turned towards process-focused investigations aimed at identifying how treatments work, for whom they are effective, and which modifiable factors are most integral for maintaining positive change , with hopes of improving the overall likelihood that substance dependence treatment will result in long-term change. The past decade has seen vast growth in process-oriented studies in the general addictions treatment field . However, very little of this work has involved samples of patients with other psychiatric disorders, despite evidence that these patients comprise the majority in many treatment settings . Among individuals with substance dependence, major depression is the most common co-occurring Axis I disorder in the general population and in treatment settings . Patients with co occurring MDD typically cost more to treat and have poorer treatment outcomes than patients without this MDD , suggesting it is especially important to identify core therapeutic processes within these patients. However, because little process-oriented research has involved patients with substance dependence and MDD, it is not known whether previous findings generalize to this highly prevalent, costly, and disrupted population. Studies of mediators of treatment outcome are essential to the general area of “treatment process” research. Mediators are third variables that statistically explain an association between a predictor and outcome . Within treatment studies, investigations of mediators typically examine an intermediate factor that may explain the effect of treatment “dose” on a clinical outcome . These studies have the potential to inform the development of more efficient and portable interventions by identifying the skills or behaviors targeted by interventions that are most responsible for producing positive change. In previous studies examining mediation, lower marijuana use in CBT + contingency management compared to contingency management alone was mediated by enhanced self-efficacy , and better abstinence rates in TSF were explained by greater commitment to abstinence . Importantly, statistical mediation is only one of several conditions to be met before declaring a variable is a mechanism of change, as temporal precedence, specificity, and experimental manipulation of the variable must also be demonstrated .

Similar results were found in our sample of veterans with comorbid MDD, where patients receiving group Twelve-Step Facilitation had increased levels of 12-step affiliation during treatment . However, it is not known whether comorbid patients can sustain high levels of 12-step participation after the conclusion of TSF therapy, and if any changes in long-term participation will impact substance use. Surprisingly few studies of substance-dependent samples have directly examined post treatment change in 12-step involvement, but some investigations have found no decline in 12-step attendance or affiliation in the first six months or one year following treatment. Patients with comorbid MDD could have greater difficulty sustaining 12-step involvement, possibly due to persistent depressive symptoms interfering with meeting attendance, difficulty making social connections with group members, or group resistance to the use of psychotropic medication . Difficulty sustaining 12-step involvement may contribute to the poorer long-term treatment outcomes for patients with comorbid MDD, but to date this question has not been examined empirically. This study involves secondary analyses of a sample of veterans enrolled in a 6- month trial of group TSF and Integrated Cognitive Behavioral Therapy for treatment of comorbid substance dependence and major depression . Utilizing latent growth curve models which explicitly model individual patterns of change in specified variables,mobile vertical rack we had three primary aims related to 12-step involvement and post-treatment substance use during the one-year follow-up period.

First, we aimed to describe the post-treatment trajectories of 12-step affiliation and meeting attendance separately for the TSF and ICBT groups. Secondly, we examined if the post-treatment trajectories of 12-step affiliation and meeting attendance differed between TSF and ICBT, hypothesizing that patients in TSF would have difficulty sustaining within-treatment levels of 12-step affiliation and attendance and evince greater decline in these variables during follow-up. Thirdly, we examined if post treatment change in 12-step affiliation and meeting attendance predicted post-treatment change in drinking and drug use. We hypothesized that greater reductions in 12-step affiliation and meeting attendance would predict greater increases in drinking and drug use, and that these effects would mediate the superior long-term treatment effects observed for the ICBT condition. The sample for this study includes 201 veterans who participated in a trial of outpatient group psychotherapy for comorbid substance dependence and MDD . We included all participants from the trial who completed at least one follow-up assessment from end-of-treatment to the one year follow-up . Demographics of the sample are presented in Table 5. Study inclusion criteria were lifetime dependence on alcohol, cannabis, or stimulants with recent use, and major depressive disorder with at least one episode occurring independently of substance use. Exclusion criteria included opiate dependence with intravenous administration, bipolar or psychotic disorder, residing excessively far from the research facility, or memory impairments prohibiting accurate recall in study assessments. The procedures for this study were approved by the University of California, San Diego and VA San Diego Healthcare System Institutional Review Boards. Participant referrals were obtained from the VASDHS dual diagnosis clinic by research study staff, who conducted brief screenings prior to meeting with eligible veterans to explain study procedures and obtain informed consent. Participating veterans consented to 6 months of group psychotherapy, recording of sessions, psychotropic medication management appointments, random urine screens, and research assessments conducted at intake and at 3-month intervals for an 18-month period. Veterans agreed to receive no other formal treatment for substance use or depression for the duration of group psychotherapy. Group psychotherapy was initiated on a rolling basis, with starts occurring every 2 weeks.

After completing the intake assessment participants were sequentially allocated to the treatment condition with the next start date. For Twelve-Step Facilitation we modified the TSF protocol from Project MATCH to allow group delivery and discussion of multiple substances. For development of Integrated Cognitive Behavioral Therapy , material was adapted from two empirically-supported treatments: group cognitive-behavioral therapy for depression and cognitive-behavioral relapse prevention from Project MATCH . The two treatments were identically structured with a series of three modules, with each module designed to cover a specific 12-step or cognitive-behavioral topic. Group sessions occurred twice/week for the first 3 months of group treatment, when each topic was covered in a one-month block.Interventions were co-delivered by senior clinicians and doctoral students trained via manual review, direct observation, and weekly supervision. Therapists were rotated across treatment conditions on a regular basis , and adherence to protocol was assessed via videotape review.In LGM a series of repeated measures are used to indicate each individual’s underlying latent “growth curve” on one or more variables. This process creates separate growth curves for each individual, described by “growth factors” such as latent intercept and latent slope . Estimates of the sample mean and variance are obtained for each growth factor, and covariates can be used to predict individual differences in the initial level or rate of change over time. One distinct advantage of LGM is the ability to examine relations between the rates of change in multiple longitudinal processes, as warranted by the aims of this study. Because we were primarily concerned with the 12-month follow-up period, the end-of-treatment time point served as the initial level for each LGM. Thus, in each LGM the latent intercept represents the level at end-of-treatment, while latent slopes represent rates of increase or decrease during the 12 months of follow-up . For each study variable we first fit unconditional growth models to determine the optimal shape of the growth trajectory, before incorporating treatment group as a predictor in conditional models. This allowed us to test whether treatment condition predicted variability in the intercepts and slopes. In the final LGMs for PDD and PDDRG we specified growth curve mediation models , to determine if the slope of 12-step affiliation or meeting attendance mediated the relationship between treatment group and the slope of PDD or PDDRG.

To test the significance of mediated effects we used asymmetric 95% confidence intervals obtained with the bias-corrected bootstrap procedure , which has shown greater power to detect mediated effects than other formal mediation tests . All LGMs utilized the maximum likelihood procedure,cannabis grow system which incorporates all available data from each participant under the assumption of missing at random.We then used the LGMs for 12-step and affiliation to predict individual differences in the end-of-treatment level and rate of change in alcohol and drug use from Month 6 to Month 18. In separate models the slopes for 12- step affiliation and meeting attendance were utilized as mediating variables between treatment group and the slopes for PDD and PDDRG , to test whether the greater increases in PDD over time for TSF patients were explained by greater decreases in 12-step variables. Results from these analyses are presented in Table 7. The PDD intercept was significantly and negatively correlated with the intercepts for 12-step affiliation and meeting attendance, indicating that individuals with greater levels of affiliation and meeting attendance at end-of-treatment were also drinking less frequently at end-of-treatment. The PDD intercept was significantly and positively correlated with the slopes for 12-step affiliation and attendance, indicating that individuals with lower PDD at end-of-treatment had greater decreases in their 12-step affiliation and attendance during follow-up. Finally, the slopes for 12-step affiliation and meeting attendance were strongly, negatively predictive of PDD slope. This indicated that individuals with greater decreases in 12-step affiliation and meeting attendance from Month 6 to Month 18 had greater increases in PDD over time. As shown by asymmetric 95% confidence intervals obtained via the bias-corrected bootstrap procedure, the indirect effects of treatment group on PDD through slopes of 12-step affiliation and meeting attendance were statistically significant. These results indicate that the greater relative increases in PDD for the TSF patients were mediated by their greater relative decreases in 12-step affiliation and meeting attendance. There were no significant relations between intercepts and slopes of the 12-step variables and PDDRG , indicating that the end-of-treatment level and change during follow-up for drug use frequency was unrelated to end-of-treatment level or change during follow-up for 12-step affiliation or meeting attendance. This study examined post-treatment change in 12-step affiliation and meeting attendance and related effects on substance use outcomes in a sample of veterans with comorbid substance dependence and major depression who received six months of group treatment with TSF or ICBT. Because fewer studies of mediating variables have focused on substance-dependent patients with psychiatric comorbidity, there is relatively less knowledge about processes that sustain long-term change in their substance use outcomes. This study adds to the existing literature by examining post-treatment trajectories of change in 12-step affiliation and attendance in comorbid patients, determining whether treatment condition predicts individual differences in these trajectories, and reporting the mediational effects of reduced 12-step involvement on long-term substance use outcomes.

Veterans in the TSF condition had greater levels of 12-step affiliation and meeting attendance at end-of-treatment than those in ICBT. This is consistent with prior studies of this sample and shows that a professionally-delivered TSF intervention can enable greater levels of 12-step involvement than other psychotherapies during active treatment. However, veterans in TSF also evinced a significant nonlinear decline in both 12-step affiliation and meeting attendance during the one year follow-up, while those in ICBT had no significant change. Previous studies of non-comorbid patients found no post-treatment decline in affiliation or meeting attendance following 12-step interventions . Our contrasting findings suggest comorbid MDD may interfere with continued attendance at 12-step meetings and affiliation with prescribed 12-step behaviors, even when patients are relatively successful at achieving these goals during active TSF. Potential explanatory mechanisms behind this finding are beyond our current scope, but could be related to persistent depressive symptoms and related low motivation, the sudden absence of accountability provided by a formal treatment group, or difficulty in establishing firm social bonds in 12-step meetings for patients with comorbid MDD. Some patients were evidently successful at sustaining 12-step affiliation as revealed by significant individual variance estimates, but modifications to TSF or continued contact may be necessary to achieve the desired long-term results in the majority of patients with comorbid MDD. Independent of treatment condition, individuals with greater decreases in 12-step affiliation and meeting attendance also had greater increases in drinking frequency during the one-year follow-up. As evidenced by strong standardized coefficients in our latent growth curve models, post-treatment change in 12-step involvement likely plays a large role in determining whether patients with comorbid substance dependence and MDD experience post-treatment increases in drinking. Similar to a prior report of follow-up substance use outcomes in this sample , the current study found patients in TSF had greater post-treatment increases in drinking frequency than those in the ICBT condition. We also determined this group difference was mediated through reductions in 12-step affiliation and meeting attendance, which provides a possible explanation for the worse outcomes over time for TSF and supports the long-term efficacy of ICBT. During follow-up the ICBT group as a whole did not increase or decrease in 12-step affiliation or meeting attendance, but their mean levels of attendance and affiliation remained consistently greater than zero. Although it was not a prescribed element of treatment, there is apparently a subset of patients in ICBT who continue 12- step involvement. Superior long-term patterns in other mediating variables may have also occurred for the ICBT condition, and future studies will explore other potential factors related to their superior post-treatment drinking outcomes.Limitations of this study include the restricted demographic characteristics of the veteran sample which curtails the immediate generalizability of these findings. Because we tested relations between concurrent changes in 12-step involvement and substance use, we cannot make conclusions about causal relationships, but other elements of our design and findings enhance the plausibility of causal conclusions . Our measures did not differentiate between different types of 12-step meetings , which could have helped explain the lack of findings for drug use outcomes, and future work might benefit from more detailed measures of 12-step involvement. Also, because our 12-step measures were relatively brief, there may have been important aspects of these behaviors we did not consider. Among adults with substance use disorders major depressive disorder is the most common co-occurring Axis I psychiatric disorder, affecting a large percentage of those diagnosed with alcohol or drug dependence .

Analyses of APGAR scores were for the years 1978-2013 because APGAR scores were not reported on birth certificates prior. Cases missing outcome data were typically dropped from analyses. The main exposure variables were time-varying state-level indicators regarding whether states had particular policies in the month and year of conception. These policies were: Mandatory Warning signs, Priority Treatment for Pregnant Women, Priority Treatment for Pregnant Women and Women with Children, Reporting Requirements for Data and Treatment Purposes, Prohibitions on Criminal Prosecution, Civil Commitment, Reporting Requirements for Child Protective Services Purposes, and Child Abuse/Child Neglect. These policies have been detailed elsewhere and are briefly described in Table 1. The first policies, Reporting Requirements for CPS and Child Abuse/Child Neglect, went into effect in Massachusetts in 1974. Next, Washington DC adopted Mandatory Warning Signs in 1985 and Kansas adopted Reporting Requirements for Data and Treatment Purposes in 1986. In 1989, California established Priority Treatment for Pregnant Women, and both Florida and Washington established Priority Treatment for Pregnant Women and Women with Children. Kentucky, Missouri, and Virginia put Prohibitions on Criminal Prosecution into effect in 1992. South Dakota and Wisconsin established Civil Commitment in 1998. All policies were still in effect in at least four states in 2013. Each policy indicator variable is dichotomous, coded as 0 if it was not in effect for that state in the month/year of conception and 1 if it was in effect for the month/year of conception. Linking the policy indicators to the month and year of conception improves the accuracy of exposure timing . Models controlled for both individual-level maternal characteristics and for state level characteristics and policies in effect during the pregnancy.

Individual-level maternal characteristics included maternal age, race, marital status, education, nativity,growing cannabis and parity. If data for individual-level controls were missing, we created a missing category to include all available data. Version of birth certificate was also included as an indicator variable. State-level controls included state- and year- specific poverty, unemployment, per capita cigarette consumption, and per capita total ethanol consumption, as well as indicators for whether government control of wine sales and government control of spirit sales were in effect for that state in that year. Data for state-level controls came from secondary sources, including the U.S. Census, the U.S. Centers for Disease Control and Prevention, APIS, the National Highway Traffic Safety Administration, National Beverage Control Association, and published research . State-level per capita cigarette consumption and per capital alcohol consumption were included because these variables could not be controlled at the individual-level due to lack of data documented on birth certificates in the earlier years and concerns with the quality of these data in the later years . Multi-variable logistic regression was used for all outcomes. Regression models included all policy indicators simultaneously, fixed effects for state and year, state specific cubic time trends, and adjusted for both individual and state-level control variables. Regression models also accounted for clustering of standard errors according to mother’s state of residence. Taking the most conservative approach, analyses included year fixed effects and birth certificate version indicator variables to account for changes in Vital Statistics data gathering over time as well as other relevant events in those states and years. State-specific cubic time trends were added to address possible concerns with endogeneity. All analyses were performed in Stata v14.2. Sensitivity analyses We performed a number of sensitivity analyses post hoc. First, we assessed each policy individually in multi-variable regression models and found no differences compared to models including all policies simultaneously. Second, because information regarding Hispanic ethnicity was not available until 1989, we analyzed data for births for 1989-2013 separately using a combined race/ethnicity variable; results did not change.

Finally, we fit both the preliminary and final models using a 10% sample of the full dataset, and compared these results to those from the full dataset; results did not differ between the 10% sample and full datasets. This is the first study to comprehensively assess whether state-level policies targeting alcohol use in pregnancy are related to adverse birth outcomes, outcomes that indicate measurable harms due to alcohol use during pregnancy. We find that most policies targeting alcohol use during pregnancy – MWS, CACN, CC, PCP, RRDATA, and PTPREG – appear associated with increased adverse birth outcomes, possibly due to some of these policies leading women to avoid prenatal care. In addition, it appears that generally applicable alcohol policies – specifically retail control of wine sales and any other policies that lead to decreased population-level consumption – are associated with improved birth outcomes. Although the magnitudes of effects are generally small, they are still meaningful in such a large population. Overall, these findings do support our hypotheses that policies punishing alcohol use during pregnancy are associated with increased adverse birth outcomes and may lead to avoidance of prenatal care. They do not, however, support our hypothesis that the more supportive policies – including Mandatory Warning Signs – are associated with decreased adverse birth outcomes. They also are inconsistent with our expectation that supportive policies would be unlikely to be associated with prenatal care utilization. With a few exceptions , scholars have consistently distinguished policies targeting substance use during pregnancy as either supportive or punitive; our study findings do not support this distinction. Rather, our findings suggest that state level policies targeting alcohol use during pregnancy at best do not improve birth outcomes and, at worst, lead to increases in adverse birth outcomes and lead women to avoid prenatal care. This pattern of findings is not completely surprising for three key reasons. First, qualitative research has found that information that leads women to worry that their substance use has already irreversibly harmed their fetus leads women to avoid prenatal care .

Similarly, our findings suggest that rather than providing women with information that helps them change their behavior and engage with health care services that may support such behavior change, MWS may operate by scaring women and leading women to avoid such help. Second, this same previous qualitative research has found that policies related to CPS and child removal lead women to avoid prenatal care. Our findings related to CACN policies are consistent with this previous research, and extend prior findings by indicating that this avoidance of prenatal care may be linked to worse birth outcomes. This is crucial,cannabis grow tray as ongoing research on alcohol outcomes has found some associations between states with CACN and less alcohol use during pregnancy . The current analyses show that even though defining alcohol use during pregnancy as child abuse/neglect is associated with decreases in self-reports of binge and heavy alcohol during pregnancy, this does not translate to better birth outcomes. Third, and perhaps most vitally, previous research indicates that policy making related to alcohol use during pregnancy appears more related to policy making in the area of reproductive rights than to policy making that reduces public health harms from alcohol use in the population overall . This means that the problem of alcohol use during pregnancy likely has not benefited from the same public health policy development process used to address public health harms from alcohol use in the general population. The current results show that reduced population-level alcohol consumption and government control over wine retail sales are associated with improved birth outcomes, which is in line with previous studies; therefore policymakers and public health professionals who wish to improve birth outcomes through state-level policies targeting substance use should look to the broader alcohol policy field for lessons and approaches, rather than continuing with the types of policies currently in effect. We do note that some of the patterns of findings are more difficult to understand. For example, the policy that mandates priority treatment for pregnant women was related to lower odds of inadequate PCU, but higher odds of low birthweight, premature birth, and late PCU. These mixed findings could be because the policy indicator does not capture actual treatment availability. States prioritizing treatment for pregnant women might have fewer treatment slots than states without such laws, meaning our finding could be just an indication of lack of treatment availability; future research should examine this. Laws giving pregnant women priority could also prevent women from getting treatment prior to becoming pregnant, especially in states with limited treatment availability. Similarly, laws giving pregnant women priority might prevent other people – including partners of women who become pregnant – from getting treatment, leading to adverse birth outcomes due to harms from others’ drinking. Our findings are inconsistent with the only other published study that examined associations between MWS and adverse birth outcomes across both states and time. In that study, MWS were associated with decreased odds of very low birthweight and very preterm birth .

This discrepancy could be because the previous study 1) only examined MWS without accounting for other policies; 2) used data only for the years 1989-2006; 3) examined different outcomes; 4) only used a subset of states; 5) did not link policy data to individual outcomes based on the month of conception; 6) controlled for state-level policies alcohol and tobacco policies and not actual per capita consumption; and/or 7) controlled for individual-level alcohol use data from birth certificates, which are of poor quality and which could be more likely to be assessed and documented in cases of adverse birth outcomes. Notably, our post hoc sensitivity analyses of race/ethnicity only utilized the years 1989-2013, indicating that the discrepancies between our findings and Cil’s probably are not due to the different time frames. Strengths and Limitations This is the first study to examine all policies related to alcohol use in pregnancy simultaneously across all 50 states using a time frame long enough to capture the period before any laws were enacted . Furthermore, for most of the time frame the data include the entire population of singleton births born in the United States and for the years 1972-1984 include a 50% sample, which makes questions regarding inference and generalizability essentially irrelevant. Another major advantage of these data over, for example, survey data regarding alcohol use during pregnancy, is that biases due to self-report are not present here. Finally, our results were robust across various model specifications, further strengthening our conclusions. The main limitation of this study is that Vital Statistics birth certificate data are not collected for research purposes; therefore, we cannot adjust for maternal-level alcohol or tobacco use. Although maternal alcohol and tobacco use have been recorded on birth certificates since 1989, these data have been shown to be invalid We adjusted for state-level alcohol and tobacco consumption instead. Another limitation is that race has been measured inconsistently on birth certificate data over time. Only in 1989 did states begin to document ethnicity as well as race, although this was phased in over the 1990s. Our primary analyses did not account for ethnicity, e.g. White Hispanic and White Non-Hispanic women are in a single group. Such an approach is reasonable because birth outcomes are similar between White non Hispanic and Hispanic births, both of which differ from Black birth outcomes. We applied approaches developed later to correct for implausible gestational age values to earlier years of Vital Statistics to improve consistency. Also, for these analyses, we focused specifically on policies targeting alcohol use during pregnancy. Preliminary examinations of these policies suggest that many of them may also address drug use. Future research is needed to explore whether the findings generalize to policies targeting drug use during pregnancy.Stress-induced analgesia is mediated by the activa tion of endogenous pain inhibitory systems. Both opioid dependent and opioid-independent forms of SIA have been identified . These mechanisms are differentially activated according to stressor parameters and duration . SIA elicited by intermittent foot shock is blocked by opioid antagonists , whereas SIA elicited by continuous foot shock is blocked by cannabinoid antagonists . We recently demonstrated that this nonopioid form of SIA is mediated by mobilization of two en docannabinoids, 2-arachidonoylglycerol and ananda mide, in the dorsal midbrain . Opioid and nonopioid SIA share similar neuroanatomical substrates. For example, opioid and cannabinoid receptors populate brain regions regulating nociceptive responding, such as the periaqueductal gray and the raphe nuclei of the medulla. Like opioids, cannabinoids modu late distinct circuits within the midbrain PAG and the brainstem rostral ventromedial medulla .

Reproductive health researchers and practitioners have documented that perceptions of the risk of pregnancy and of STIs shape sexual and reproductive behavior in addition to pregnancy intention and access to contraceptive methods. These perceptions and behaviors are partly the result of individual tolerance for risk and uncertainty. Tversky and Kahneman instigated a robust area of inquiry by first describing how risk preferences shape choices and behavior. These same theories of how humans make decisions under uncertainty may shed light on differences in reproductive outcomes. Economists concerned with explaining behavior, including wealth accumulation, focus on measures of economic preferences that govern differences in decision-making. These preferences, including the willingness to assume risk, strongly predict financial behavior and outcomes. Analyses that examine how risk preferences may extend beyond financial behavior to explain behavior in other domains, including health, appear less frequently in the literature. A particularly unexplored area of research concerns how risk preferences affect decision-making surrounding reproduction, contraceptive behavior, and sexual risk taking, where intention-behavior inconsistencies are widely acknowledged. This paper tests the hypothesis that the propensity to take risk manifests not only in the financial decisions commonly studied by decision theorists, but also in less-well studied choices that affect reproductive health. I explore whether individual measures of financial risk tolerance predict important reproductive outcomes of sexual and contraceptive behavior using data from the 1997 cohort of the National Longitudinal Survey of Youth . National and international public health priorities include reduction of unintended pregnancy. Defined as pregnancies that are mistimed or unwanted, unintended pregnancies comprised 45% of all pregnancies to women aged 15-44 in the United States in 2011. Half of those pregnancies ended in abortion.

Epidemiologic literature, moreover,cannabis growing supplies reports associations between unintended pregnancy and negative health and mental health outcomes for mothers and children. Women who experience unintended pregnancies also are more likely to report perceived stress, low social support, and depressive feelings.Evidence further suggests a connection between unintended pregnancy and risk behaviors during pregnancy, such as smoking and alcohol drinking. It is estimated that unintended pregnancies cost the US more than $20 billion per year in expenses for births, abortions and miscarriages. Unintended pregnancies, like many health outcomes, are differentially experienced in the population. They concentrate among women of color and low-income women. Young age, low education, previous pregnancies, non-married status, and living in an urban neighborhood, explain some but not all of the concentration of unintended pregnancy among poor and minority women. Nonuse or inconsistent use of contraception is common among women at risk of unintended pregnancy, meaning those sexually active with a stated desire not to get pregnant.Reproductive health literature reports inconsistencies between intention and behavior regarding contraceptive use and pregnancy. A California study following young women who initiated a new method of contraception and who reported not wanting to be pregnant within a year found high rates of discontinuation over the year. An analysis of a nationally representative dataset found that 25% of non Hispanic black women, 16% of Hispanic women, and 14% of non-Hispanic white women did not use contraception despite risk of unintended pregnancy. Additional studies have shown disparities in contraception use for non-Hispanic black and Hispanic women. These differences may result, at least in part, from lack of information about method availability, especially long acting methods. Research on contraceptive attitudes has reported fear of side effects and mismatches of desired method features to selected method features to be a reason for nonuse. Other research suggests that provider biases may also lead to disparities in information: in one such study, providers of contraceptive counseling recommended IUDs to low-income women of color more often than to white women.

Misperception of pregnancy risk may also result in reduced contraceptive use and subsequent unintended pregnancy regardless of knowledge of available methods. A study of family planning patients found, for example, that underestimation of the likelihood of conception predicted unprotected sex. Foster et al. found that nearly 46% of women engaged in unprotected intercourse in the past three months underestimated the risk of conception.A study of women seeking abortion services found that the majority of women had an inaccurately estimated the risk of pregnancy prior to conception. Structural and psychosocial factors also affect unintended pregnancy risk. Relationship factors, including reproductive coercion, drive contraceptive decision-making and ability to use contraception even in contexts where pregnancy is not desired. A qualitative study exploring determinants of inconsistent use found that eroticism of unprotected sex and the risk of conception was a powerful explanatory factor. Additionally many women, particularly young, poor, and uninsured women, lack access to reproductive healthcare. Micro economists have long attempted to explain differences in choices given equal information. Much of this work falls under the rubric of “behavioral economics,” the study of decisional biases and preferences. Primary questions in the field include: what leads people to behave in ways inconsistent with intentions? Given that differences in information alone unlikely explain differences among groups in unintended pregnancy, looking to behavioral economics for suggestions of other determinants seems warranted. Risk preferences, frequently studied in social science, are strong determinants of financial decision-making, including investment and savings. While elicitation methods vary, a common approach to assess preferences includes a series of questions assessing willingness to take gambles with lifetime income. People willing to take fewer gambles are generally deemed risk averse and those more willing to take gambles are risk tolerant. Behavioral economists have argued that risk preferences in humans arise from loss aversion or the tendency to risk more to avoid a loss than to realize a gain even if the prospective losses and gains are equal.

The argument has garnered credibility in comparison to a standard economic model, which assumes “rational agents” who make choices to maximize utility and who would, therefore, exhibit indifference in choices between equal loss and gain.One seminal study found that a measure of financial risk tolerance predicted risk behavior including smoking and drinking. Barky validated the now widely used measure of risk preferences in a nationally representative sample in the Health and Retirement Study . Risk aversion has also been linked to cancer screening behavior , smoking, heavy drinking, obesity, and non-use of a seat belt. Despite results from the above studies, and the widely-held belief that loss aversion and risk preferences affect choices under uncertainty, surprisingly little attention has been paid to these measures as determinants of sexual and reproductive behavior. In the best example of this limited literature, Schmidt hypothesized that when the risk of pregnancy appears highly uncertain, risk preferences help explain variability in timing of childbearing . She found risk tolerance correlated with earlier childbearing at young ages and earlier timing of marriage. She suggested that the association between early childbearing and increased risk tolerance may be a product of less contraceptive use, although she did not directly test this connection. With exception, much work argues that risk preferences vary with age, income and gender. Gender differences in risk aversion, with females expressing greater aversion, have been hypothesized to arise from different reproductive investment strategies. A few studies have shown that risk tolerant women more likely delay marriage,cannabis indoor growing indicating the apparent importance of risk tolerance to demographic behavior. Schmidt found that the effect of risk tolerance on fertility timing varied by marital status, such that for both married and unmarried women, higher risk tolerance predicted early birth at young ages. Among married women it was also associated with delayed fertility later in life. In this paper, I ask whether propensity to risk-taking in financial decisions affects reproductive behavior. Using data from the 1997 cohort of the National Longitudinal Survey of Youth , I examine several outcomes relevant to reproductive health: sex with high-risk partners, number of sex partners, consistency of contraception use, and effectiveness of contraceptive method. I conduct stratified analyses for contraceptive consistency and effective method use among unmarried and non-cohabitating women and among married or cohabitating women. Number of sexual partners. Respondents were asked the number of partners they had sexual intercourse with since the last interview. As this variable was highly right-skewed, I truncated responses above five to greater than or equal to five partners. Consistent contraceptive use. I derived a measure of consistency of contraceptive use from several questions in the survey. Respondents are first asked the number of times they had sex and then the number of times they used a condom or other birth control. If they could not recall the number, they were asked the proportion of the time that they used a method.

Combining the frequency of intercourse and condom or birth control use questions allowed me to create a percent condom or birth control variable. This is variable categorized into nonuse , inconsistent use , and perfect consistent use . I recoded anyone that reported sterilization as a consistent user even if they reported a lower birth control usage percent. Contraceptive method type. Respondents were asked: “ thinking of all the times that you have had sexual intercourse since the last interview, how many of those times did you or your sexual partner or partners use a condom or female condom?” if they replied 1 or greater, I coded them as using condoms. The following question assessed additional contraceptive use asking which “one of these methods did you or your partner use most often, either with or without a condom or female condom?” Respondents could select one of the following: withdrawal , rhythm , spermicide , diaphragm , IUD , morning after pill , birth control pills, Depo-Provera or injectables, Norplant, patch or ring , cap or shield , had vasectomy or tubal ligation, or no other method. Since the questions were asked separately, condom use could be in addition to or in absence of other contraception use. Contraceptive method effectiveness. I grouped contraceptive methods together based on typical use pregnancy prevention effectiveness rates using categories of low effectiveness , medium effectiveness , and high effectiveness . Participants were coded as medium effectiveness with condoms only if condoms were reported as the only method. Confounding variables were selected a priori based on literature as characteristics that would affect both risk aversion and sexual behavior and included: age, race/ethnicity, education, religion, marital status, parity, insurance, poverty. Age serves as an important control variable, as both risk aversion and fertility intention and contraceptive behavior change with age. Age was assigned at year of risk preference measurement and ranges from 26-32. Race/ethnicity information was recorded at entry into the cohort in 1997. Respondents self-reported race ethnicity, which I divided into Hispanic, non-Hispanic white, non-Hispanic black, and mixed race/other. For multivariable models, I dropped the mixed race/other respondents due to positivity concerns. Education influences risk perception as well as fertility timing and method choice. Risk aversion has been shown to decrease with later schooling and age. I categorize educational attainment into the following categories: some high school, high school degree, some college, and college degree or higher. In addition to age, reproductive history is an important predictor of current reproductive behavior. I therefore include a control for parity . Unintended pregnancy may carry different meaning in the context of being partnered and not partnered. While there is evidence that partnership may affect risk preference and also sexual behavior, I would not expect a different relationship of risk preferences to high risk sex by partnership status. Partnership status can be thought of as an effect modifier to the relationship between risk preferences and contraceptive behavior. Additionally relationship context and power may influence ability to use contraception. Marital status is categorized as: never married/not cohabitating, never married/cohabitating, currently married, and widowed, separated or divorced. While each wave of NLSY97 contains detailed information on contraceptive method use and type, no wave measures pregnancy intention. I cannot, therefore, attribute nonuse to wanting pregnancy or use to wanting to avoid pregnancy. I attempt to indirectly assess intention through fertility expectations. First I include a measure of fertility expectations assessed with the following question: “In five years, what is the percent chance that you will have child?” Respondents report a range of 0-100%. I code ‘don’t know’ responses as 50%. While expectations may differ from intention, they have been shown to access the same construct .