In 2007, an estimated 22.3 million people in the United States, aged 12 or older, were classified as meeting the criteria for either substance dependence or abuse. Therapists have long sought to discover the most effective way to address these disorders in therapy; though short-term gains are often seen following inpatient or outpatient treatment, these gains often dissipate over time. Individuals who attend support groups such as Alcoholics or Narcotics Anonymous or SMART Recovery show much better prognoses over time than those who receive formal treatment alone. The current research is a secondary analysis of data collected by the Drug Abuse Treatment Outcome Study. A path analysis is conducted to examine the relationships between symptoms of depression, symptoms of anxiety, and motivation for treatment as they relate to post-treatment support group attendance. These variables form a path model which is analyzed so that each individual regression takes into account the other regressions in the model. Symptoms of depression are found to be significantly positive predictors of motivation for treatment, and motivation for treatment is found to be a significantly positive predictor of support group attendance. Implications of these findings for clinical practice and future directions for research are included in discussion of the results. / Master of Science

Recent research studies and clinical trials have suggested that psychedelic therapy with psychological support can offer beneficial and synergistic effects in reducing or eliminating substance use disorder (SUD) patterns and symptoms. However, very little is known about SUD healthcare providers' perceptions of the usage of psychedelic-assisted therapy in SUD treatment. The present study assesses biomedical SUD healthcare providers' perceptions and concerns to better understand potential barriers to the effective implementation of psychedelic-based therapies and formulate further recommendations for research efforts surrounding them. This study collected data through a short survey and qualitative semi-structured interviews from nine participants involved in SUD patient treatment and care. Open discussion was encouraged in the interviews which were recorded and transcribed using the Otter app. Data was analyzed using Charmaz's two-step coding process, which identified common themes and specific issues about translating psychedelic-assisted therapy into clinical application. Four interconnected themes were identified: personal responsibility, patient safety and expectations, a call for further research, and societal structures as barriers. The findings of this study indicate that SUD healthcare providers have optimism and openness surrounding psychedelic-assisted therapy and generally view it as a positive treatment. However, this optimism was often followed by concerns for safety, legality, and the providers' role in this treatment. Participants also expressed a critical need for further research with rigorous clinical trials to explore the effectiveness of psychedelics in a therapeutic setting. The results provided in this study act as basis for engaging with biomedical SUD healthcare providers to address concerns about psychedelic-assisted therapy in future research for SUD treatment.

Pathological gambling and substance use disorders are highly prevalent and comorbid among veteran populations. These disorders also share genetic influences, although the underlying constructs and magnitude of their influence remain unclear. This project utilized the Hierarchical Taxonomy of Psychopathology (HiTOP) as a framework for modeling the underlying dimensions of psychopathology as latent factors and modeled genetic and environmental influences on substance use disorders and pathological gambling. Study 1 examined the structure of psychopathology for 15 common mental disorders in a sample of Vietnam-era veteran twins from the Harvard Drug Study (nMZ = 3,748 and nDZ = 2,996) to determine the appropriate location for pathological gambling within the HiTOP framework. The best fitting model included internalizing and externalizing spectra and an illicit substance use subfactor. Pathological gambling (loading = .30) loaded onto the externalizing spectrum with legal substance use, conduct disorder, antisocial personality disorder, and a subfactor that subsumed all six illicit substance use disorders. The best fitting model in Study 1 did not support the existence of a ‘p’ factor underlying all psychopathology. In Study 2, genetic and environmental components were modeled for the 15 disorders and 3 latent factors modeled in Study 1. Additive genetics explained from 10% (generalized anxiety disorder, panic disorder) to 49% (nicotine use) of the variance in specific disorders and from 24% (internalizing) to 46% (externalizing) of the variance of latent factors. Only cocaine use and conduct disorder demonstrated significant variance attributable to shared environment, the entirety of which occurred at the disorder-specific level. Only 9% of the genetic variance associated with alcohol use was shared across disorders, whereas 100% of genetic variance in cocaine and hallucinogen use was shared with latent factors. In total, 12% of the variance in risk for pathological gambling was associated with additive genetics, and 13% of that variance was shared via the externalizing spectrum. Findings highlight shared risk among illicit substance use disorders and among other disorders on the externalizing spectrum. These findings suggest externalizing and illicit substance use as transdiagnostic targets for treatments aimed at individuals with comorbid substance use disorders, pathological gambling, and other externalizing disorders.

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Traumatic brain injury (TBI) is a prominent healthcare concern in the U.S. as millions of TBI-related emergency department visits occur annually. Recent reports estimate more than 5 million Americans currently suffer from life-long disabilities and psychiatric complications associated with TBI. While the risk of TBI has conventionally been considered to be male dominated, analyses of sex-comparable sports indicate that rates of concussions are higher and recovery time is longer following brain injury in females. Following anxiety and depression, substance use disorder (SUD) is the third most common de-novo neuropsychiatric condition diagnosed in both male and female TBI patients. Importantly, during adolescence the primary neuronal networks that regulate reward behaviors and perception of drug-induced euphoria are not fully developed, corroborating epidemiological studies identifying TBI sustained during adolescence as a risk factor for problematic drug use. Yet, to date, little is known about how TBI-induced molecular changes affect brain structures essential for the perception of reward and processing drug-induced euphoria. The following experiments were designed to test the hypothesis that adolescent TBI-induced neuroinflammation in areas such as prefrontal cortex (PFC) and nucleus accumbens (NAc) results in remodeling of neuronal reward networks and affect how the rewarding effects of cocaine shift as a consequence of TBI. Notably, the extent of sex differences in SUD susceptibility in TBI has not be investigated. Therefore, we also investigated whether the immune response stimulated by early-life TBI alters maturation of reward neurocircuits, leading to increased SUD vulnerability in a sex-dependent manner. Following the induction of TBI using the controlled cortical impact (CCI) model of brain injury, we utilized a biased, three-phased cocaine conditioned place preference (CPP) assay to assess the behavioral response to the rewarding effects of cocaine following adolescent injury in male and female C57BL6 mice. Furthermore, we characterized the effect of CCI-TBI on the stimulation of neuroinflammation within the PFC and NAc, comprising the reward pathway. Specifically, our studies revealed a sex-specific increase in 1) sensitivity to the rewarding efficacy of a subthreshold doses of cocaine interpreted from significantly higher cocaine CPP shifts, 2) the activation and phagocytosis of microglia observed by the positive expression of neuronal synaptic proteins in microglia sorted using flow cytometry, 3) increase in permeability of the blood-brain barrier indicated by discontinuous and depleted expression of tight junction proteins that line microvasculature isolated from reward nuclei, 4) decreased neuronal complexity, arborization, and spine density quantified from Golgi-cox stained NAc neurons, 5) changes in expression of genes related to the dopamine system analyzed by qRT-PCR in only male mice injured during adolescence. Additionally, our results imply that high levels of female hormones can promote neuroprotection against increased sensitivity to the rewarding properties of cocaine following injury, associated with decreased neuroinflammatory profiles after TBI in adolescent females. The studies herein aimed to elucidate underlying neuropathological outcomes following TBI in the reward circuitry that could be contributing to increased risk of addiction-like behavior observed clinically. Our findings suggest that TBI during adolescence may enhance the abuse liability of cocaine in adulthood and vulnerability to the rewarding effects of cocaine could be higher as a result of brain injury. Key pathological findings in the NAc such as activated microglial phagocytosis, BBB changes, reduced neuronal complexity, and changes in dopamine gene expression in areas of the reward pathways support the notion that neuroinflammation may contribute to how the rewarding efficacy of cocaine are affected post-TBI during adolescence. The ultimate goal of this research is to 1) advance TBI and SUD literature with the potential to increase awareness and help health care providers inform TBI patients about the increased risk for SUDs, and 2) to translate identified correlated mechanisms into novel targeted therapies that would provide a launching point for the treatment of patients with TBI-related SUD. / Biomedical Sciences