<div> <p>Historically, natural products from plants, fungi, bacteria and animals have played an important role in the discovery of new drugs. In fact, it has been found that 34% of new FDA-approved drugs over the last 30 years were derived from natural products or their derivatives. Because of the chemical and structural diversity of natural products, they continue to be one of the best options for discovering novel compounds and scaffolds; this is especially true for compounds targeting the µ-, δ-, and κ- opioid receptors. However, traditional opioids such as morphine cause many therapeutically limiting side effects. Therefore, there have been immense efforts to develop opioids that avoid these side effects, with “signal-biased” compounds being an intense area of interest. The research presented here investigates of the biased mechanisms of compounds found in and derived from <i>Mitragyna speciosa</i>, also known as kratom, and <i>Picralima nitida</i>, also known as akuamma. Kratom and akuamma compounds are examined for their therapeutic potential in treating alcohol abuse and pain, respectively, two prevalent conditions with extreme societal and economic costs.</p> </div> <br>

No description available.

Thesis (M.Ph.)--Chinese University of Hongkong. / Bibliography: leaves 53-58.

BACKGROUND: Naloxone, an opioid antagonist, offers a powerful tool for preventing opioid overdose deaths. Because studies have shown opioid overdose education and naloxone distribution (OEND) programs to be a safe, feasible, and effective intervention, several policymakers and public health agencies have advocated for broader access to this life-saving medication. Community health centers (CHCs) are a promising location for expanding naloxone access. This investigation examined the experience of CHC-based HIV primary care teams with a variety of overdose education and naloxone access (OENA) strategies in order to inform future dissemination efforts. METHODS: A mixed methods study was conducted with eight CHCs located in Massachusetts communities experiencing high opioid overdose fatality rates. Individual and group interviews with 29 clinic staff members; clinic and participant surveys; and document review were used to elucidate the OENA strategies. The Consolidated Framework for Implementation Research guided the data collection process and subsequent analysis, which revealed several factors supporting or hindering implementation of OENA activities in CHC primary care settings. RESULTS: Operating in a facilitative state policy environment, the CHCs utilized a mix of approaches to OENA: providing clinic-based services, issuing prescriptions, utilizing pharmacy standing orders, and making referrals to existing community-based OEND programs. With prescribers having limited time and competing priorities, nurses, health educators, and other staff played a prominent role in OENA. Pharmacies also served as important access points for patients and community residents. Several strategies were used to engage patients, including active outreach, partnerships with external organizations, and efforts to destigmatize substance use disorders. Clinic staff participation was enhanced through leadership support for harm reduction approaches, ongoing training, peer modeling, and information sharing. CONCLUSIONS: This study demonstrated that OENA can be integrated into CHC primary care services, adapted to the clinic context, and modified as needed. Successful implementation required a systems-level response, grounded in a team-based care model and a consideration of patient needs. The process for naloxone reimbursement needs to be determined to minimize CHC or patient barriers and ensure sustainability. Clinic training and technical assistance plans should be customized according to the staff members’ potential roles and their stage of readiness.

Aims and objectives Substance misuse is a chronic relapsing condition associated with high morbidity and mortality. Treatment attempts to reduce harms associated with drug use and to promote recovery and has developed considerably in the last 30 years. Opioid substitution therapy using methadone (OST-M) is an effective treatment for opioid dependency. Though the effectiveness of OST-M in delivering harm-reduction is well evidenced, evidence demonstrating recovery is limited as is understanding of those factors influencing progress. In this context, national policy makers and stakeholders have repeatedly questioned the value of OST-M as a substance misuse treatment and, at times, have sought to limit its use. Rigorous, long term outcome studies of UK subjects are required to improve clinical outcomes in OST-M subjects and to ensure ongoing availability of evidence-based treatments. In this context, the study had two main objectives: to demonstrate that standard clinical information systems can deliver rich, valid datasets to support outcome research; to use these data to explore the relationships between a selection of baseline variables (patient characteristics, comorbid conditions, the nature of substance misuse and the treatment received), the clinical process and long term outcomes achieved in a large cohort of OST-M patients in a standard NHS treatment setting. Methods and materials Standard clinical information, collected over 7 years, was linked with validated data from a range of databases. A large representative sample (76% of the OST-M treatment population in a region) was described in detail. Follow-up data were retrieved from clinical casenotes (4 years) and linked datasets (4-7 years) and collated to create a database for analysis. Variables for analysis were selected following a review of the published literature. Univariate analyses were undertaken to demonstrate statistically significant associations between baseline and follow-up variables. Significant variables were then entered into multiple regression analyses to develop predictive models for selected outcomes. Any predictive models were then subjected to cross-validation to determine their predictive power in novel datasets. Key results Many highly significant associations were shown. Significant personal (demographic) factors included: age, gender, having children, having conflict in personal relationships, educational level achieved and being in employment. It was notable that the area lived in (of three districts) was strongly associated with a wide variation in clinical process and outcomes achieved. Whether treated in primary care or specialist services, the medical treatments received, the level of non-NHS support and patient satisfaction showed strong associations with outcome. Baseline illicit drug use was also strongly associated with outcome. Multiple regression analyses found that despite these highly significant associations, strong predictive models of long terms outcome could not be demonstrated. Where weak models were created - predicting drug use (by self - report); drug use (positive tests); family stability - cross validation showed these had no predictive value in novel datasets. Conclusions Standard clinical information, linked with relevant NHS datasets can give rich and comprehensive data suitable for research of large representative samples over long time periods. This study represents one of the largest OST-M populations ever described in the UK with longer follow-up periods than most of the published literature. In this study strong associations were found between a range of independent and dependent variables over 4-7 years. These findings broadly reflected the evidence base. However, the associated variables could not generate strong useful predictive models of long term outcome. This could reflect issues of study design or data quality. This type of approach should be further developed in the field of substance misuse research. Issues of data quality would require to be addressed to maximize the value of these datasets. Further research is required to develop better understanding into key factors influencing long term outcomes of treatment in substance misuse.

Cannabis (Marijuana) has multiple effects on the human body, such as analgesia, euphoria and memory impairment. Delta-9 tetrahydrocannabinol (D9-THC), the active ingredient in cannabis, binds to cannabinoid receptors, seven-transmembrane G protein-coupled receptors (GPCRs) that mediate a variety of physiological functions. GPCRs were believed to function only in homomeric forms, however, recent findings show that different GPCRs can also form heteromeric complexes that may expand their signaling properties. In this study, we focused on Cannabinoid CB1 receptor (CB1R) heteromers with the mu-opioid receptor (MOR) and the Dopamine type 2 receptor (D2R), respectively. We utilized a variety of techniques, such as the calcium mobilization assay, a luciferase complementation assay and an electrophysiology assay to study the pharmacology of the CB1R-MOR and CB1R-D2R heteromers. Our data demonstrate that co-expression of CB1R enhances the Gi signaling through MOR and inhibits the beta-arrestin recruitment to MOR. We also show that co-application of CB1R ligands can further accentuate the MOR signaling modulation. Co-expression of a CB1R transmembrane domain 5 (TM5), but not a TM1, mini-gene abrogated the signaling change suggesting that it is likely due to heteromerization of MOR and CB1R. Utilizing this herteromeric signaling could provide a novel therapeutic approach that may yield potent analgesic effects with reduced side effects. We have also found that CB1R switched its signaling specificity from Gi to Gs upon its heteromerizaiton with D2R. In conclusion, our data show that CB1R expands its signaling repertory and modulates the partner receptor signaling upon heteromerization.

Prevention, social work, and community awareness programs have not led to the successful reduction of opioid overdose deaths nationwide, and particularly in Ohio. This study explored social work perspectives about trauma-€informed care (TIC) for persons with opioid use disorder in Ohio. The research questions for this study examined how social workers in Ohio implemented TIC when providing outpatient treatment to opioid users and what challenges they faced when providing TIC. Using an action research methodology, data were collected through individual semistructured interviews with 5 social work professionals, selected through purposive sampling based on experience in the field of substance use in Ohio and the use of TIC. Contemporary trauma theory and TIC were chosen to frame the research project. Three themes emerged through thematic analysis of the data: appreciation for trauma-€informed opioid use disorder treatment, organizational and professional challenges to the use of trauma-€informed opioid use disorder treatment, and environmental barriers to successful trauma-€informed outpatient opioid use disorder programming. The study aligned with the social work core values of competence and principles of harm reduction. The findings from the study might bring about social change by igniting dialogue among treatment providers about how TIC interventions could support integrated treatment and holistic approaches to combatting opioid addiction in Ohio.

Policy-makers, funding bodies and treatment providers need current, comparable and accurate information on the activities and outcomes of alcohol and other drug (AOD) treatment services to respond to the needs of the sector. If meaningful comparisons are to be made at the jurisdictional level, a standardised treatment outcome monitoring system must be developed and implemented, that takes into account differences in client characteristics, treatment settings and modes of service provision. A brief, multi-dimensional instrument, the Brief Treatment Outcome Measure (BTOM) has been developed for routine, ongoing treatment outcome monitoring with clients receiving opioid maintenance pharmacotherapy (OMP) services in New South Wales (NSW), and for use in treatment evaluation research. This is the first time in Australia that an attempt has been made to integrate outcome monitoring into routine clinical practice across an AOD treatment sector. The BTOM contains thirty-three items across the domains of dependence, blood-borne virus exposure risk, drug use, health/psychological functioning and social functioning. The internal reliability of the BTOM is satisfactory; retest reliabilities for the measures are good to excellent and concurrent validation of BTOM scales yielded acceptable agreement. Average completion times of the BTOM were 14.5 minutes when administered by researchers and 21 minutes by clinicians. A 30-month feasibility trial was conducted in selected NSW OMP treatment agencies to determine the practicability of implementing an OMS; to identify issues that would impact on the quality of the data; and identify administrative processes that could facilitate implementation whilst minimising the burden on agency staff. In addition, clinicians who had administered the BTOM were surveyed 18 months into the trial to ascertain their attitudes towards the clinical utility, acceptability of content and the level of support given to them to administer the BTOM as part of routine clinical practice. Results from the trial indicate that the BTOM measures are sensitive to change over time; that the change observed is consistent with that reported in the OMP treatment outcome literature; and that clinicians, whilst generally being positively predisposed towards using the instrument, express concerns relating to the burden of administering and the clinical utility of conducting outcome monitoring.

Objectives: Electro-acupuncture (EA) has been demonstrated to be effective in reducing post-operative acute consumption of opioid-like medications (OLM) by previous studies. This effect has not been examined in patients with chronic pain. In this thesis, a randomised, double-blind, sham acupuncture-controlled study was reported. The trial aimed to evaluate the effect of EA in reducing OLM consumption in patients with chronic non-malignant pain. Methods: Thirty-five patients were recruited from a multidisciplinary pain management clinic in Melbourne. After a two-week baseline assessment, participants were randomly assigned to one of the two groups by a computer generated randomisation sequence: real EA (REA, n = 17) or sham EA (SEA, n = 18). The REA group received 2/100 Hz EA stimulation on two pairs of acupoints (Zusanli ST36 and Fenglong ST40 on one leg and Hegu LI4 and Quchi LI11 on one arm) and manual acupuncture on an additional five chosen acupoints for 30 minutes. The SEA group received superficial needling on non-acupoints without Deqi sensation or electrical stimulation. Both groups received treatment twice a week for six weeks. Participants were followed up for 12 weeks at intervals of four weeks. During the trial, participants were given clear instructions on how to reduce their OLM usage. A researcher telephoned the participants three times during the trial to encourage them to reduce OLM intake. The assessor, researcher and participants were blinded to treatment allocation. Outcome measures: The primary outcome measures included OLM consumption, related side effects, dosage of non-opioid analgesics and the intensity and unpleasantness of pain. These measures were recorded daily for two weeks before the intervention, six weeks during the treatment period and three times during the follow up period. Secondary outcome measures were depression and quality of life as assessed by the Beck Depression Inventory-II (BDI-II) and the Medical Outcome Study 36-Item Short Form (SF-36), respectively. Data were analysed with independent t-tests or analysis of variance (ANOVA) where appropriate and per protocol analysis was employed. Results: Nine participants withdrew from the study. At baseline, the two groups were comparable on all demographic characteristics and major outcome variables except for the average intensity of pain. During the treatment period, the reduction of OLM consumption was more rapid in the REA group (64%) than in the SEA (46%) (ANOVA, p less than 0.05). The effect was maintained for four weeks in the REA group. There were no differences in the improvement of all other measures between the two groups. The incidence of EA-related adverse events (AEs) per treatment was 21% and 10% in the REA and SEA groups, respectively. All AEs were minor. Over 90% of the participants were satisfied with the treatments given and would recommend EA to others. The blinding was successful. Conclusions: EA could be an effective and safe treatment for reducing OLM consumption for patients with chronic pain, and may be used as an adjunct therapy in chronic pain management. Further studies with larger sample sizes are warranted.

Opioid dependence is a chronic relapsing condition resulting in significant individual and community harms, for which the most effective treatment is long term opioid pharmacotherapy (OP). In contrast to other Australian states and territories, in Victoria, 80-85 % of OP prescribing is undertaken by GPs, and while demand for this treatment is difficult to estimate, all evidence indicates that the current and future GP workforce is inadequate to meet projected need. / GPs have shown a reluctance to become actively involved in the treatment of patients with drug dependence, especially where illicit drugs are involved. In order to prescribe OP, Australian medical practitioners are required to complete a specific training program. Little is known of the reasons why GPs decline to undertake this training, and why the majority who complete training, subsequently prescribe to very few or no patients. / Using in-depth interviews and an analysis of existing data from the Victorian Department of Human Services, this thesis not only explores why GPs are unwilling to complete OP training, and why many subsequently fail to prescribe, but also identifies both barriers and facilitators which influence GPs in their decisions regarding these issues. The results have not only provided new information on the reasons GPs decline the offer of training but also supported existing research.