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Objective: Neuropsychiatric symptoms (NPS) of dementia represent a large driver of health care costs, caregiver burden, and institutionalization of people with dementia. Management options are limited, and antipsychotics are often used, although they carry a significant side effect profile. One novel option is tetrahydrocannabinol (THC); however, in the US, to obtain THC for patients with dementia, caregivers have to go to a commercial dispensary. We evaluated the effectiveness of dispensary-obtained THC for patients with dementia and NPS., Methods: Two independent reviewers reviewed charts of patients with diagnosed dementia (N = 50) seen in geriatric psychiatry between 2017 and 2021 for whom dispensary-obtained THC was recommended. The primary outcome was effectiveness in treating NPS; secondary outcomes were the proportion of caregivers who obtained and administered THC (uptake), post-THC antipsychotic use, and adverse reactions leading to treatment discontinuation., Results: Caregiver uptake of dispensary-obtained THC was high (38/50, 76%). The majority of patients (30/38, 79%) who took THC had an improvement in NPS according to their caregivers. THC was recommended most often for the NPS of agitation, aggression, irritability, lability, anxiety, and insomnia. Among the 20 patients who were taking antipsychotics at baseline and took THC, over half (12/20, 60%) were able to decrease or discontinue the antipsychotic. Adverse reactions to THC included dizziness, worsening of agitation, and worsening of paranoia; two caregivers of patients who took THC reported adverse reactions that led to treatment discontinuation., Conclusions: Our results suggest that dispensary-obtained THC can be effective in managing a subset of NPS in patients with dementia and may decrease the requirement for antipsychotics., (© Copyright 2023 Physicians Postgraduate Press, Inc.)

1. Explain the detrimental effects of under-treated behavioral symptoms of dementia on patients and caregivers, and list the pros and cons of the current standard treatment of behavioral symptoms of dementia. 2. Understand current research supporting THC use for behavioral symptoms of dementia. THC from cannabis dispensaries shows promise in effectively managing neuropsychiatric symptoms (NPS) in dementia patients. Our preliminary study demonstrated high caregiver acceptance, substantial NPS improvement, and potential for reduced antipsychotic use. Ongoing research explores factors influencing THC efficacy, offering hope for better NPS management in dementia care. Neuropsychiatric symptoms (NPS) in dementia patients significantly contribute to poor quality of life, increased healthcare costs, and caregiver burden.1 Current management options primarily rely on nonpharmacologic strategies, including environmental modifications, as first-line interventions for NPS.2 However, these strategies often prove insufficient or logistically challenging, resulting in the utilization of antipsychotics with their associated substantial side effect profiles.3 One innovative avenue showing promise is the use of tetrahydrocannabinol (THC).4 In the preliminary phase of our study, we conducted a retrospective cohort study encompassing 50 patients diagnosed with dementia, all of whom were offered treatment with THC edibles obtained from cannabis dispensaries. Our results revealed substantial caregiver acceptance of dispensary-sourced THC (38/50, 76%) and subsequent high caregiver-reported improvements in NPS (30/38, 79%). Notably, very few adverse reactions (5/38, 13%) were reported in association with THC use, and a significant number of patients achieved reductions in or discontinuation of antipsychotic medications following THC treatment. Expanding upon these initial findings, the subsequent phase of our investigation seeks to explore the multifactorial aspects associated with THC's efficacy in managing NPS. Preliminary analyses have already identified a significant association (r = 0.014) between the type of dementia diagnosis and the determined efficacy of THC, with vascular dementia emerging as the most prevalent specific diagnosis. An ongoing open-label prospective study is currently utilizing quantitative measures to assess THC's effectiveness for agitation, aggression, and sleep cycle regulation, as well as investigating factors related to caregiver/patient acceptance of perceived 'natural treatments' like cannabis. These findings promise to provide a comprehensive understanding of THC's potential utility in addressing NPS in dementia patients, offering hope for improved quality of life for both patients and their caregivers. Disease specific management / Integrative Medicine [ABSTRACT FROM AUTHOR]

The major barrier to cure HIV infection is the early generation and extended survival of HIV reservoirs in the circulation and tissues. Currently, the techniques used to detect and quantify HIV reservoirs are mostly based on blood-based assays; however, it has become evident that viral reservoirs remain in tissues. Our study describes a novel multi-component imaging method (HIV DNA, mRNA, and viral proteins in the same assay) to identify, quantify, and characterize viral reservoirs in tissues and blood products obtained from HIV-infected individuals even when systemic replication is undetectable. In the human brains of HIV-infected individuals under ART, we identified that microglia/macrophages and a small population of astrocytes are the main cells with integrated HIV DNA. Only half of the cells with integrated HIV DNA expressed viral mRNA, and one-third expressed viral proteins. Surprisingly, we identified residual HIV-p24, gp120, nef, vpr, and tat protein expression and accumulation in uninfected cells around HIV-infected cells suggesting local synthesis, secretion, and bystander uptake. In conclusion, our data show that ART reduces the size of the brain's HIV reservoirs; however, local/chronic viral protein secretion still occurs, indicating that the brain is still a major anatomical target to cure HIV infection. [ABSTRACT FROM AUTHOR]

The human immunodeficiency virus-1 (HIV) enters the brain shortly after infection, leading to long-term neurological complications in half of the HIV-infected population, even in the current anti-retroviral therapy (ART) era. Despite decades of research, no biomarkers can objectively measure and, more importantly, predict the onset of HIV-associated neurocognitive disorders. Several biomarkers have been proposed; however, most of them only reflect late events of neuronal damage. Our laboratory recently identified that ATP and PGE2, inflammatory molecules released through Pannexin-1 channels, are elevated in the serum of HIV-infected individuals compared to uninfected individuals and other inflammatory diseases. More importantly, high circulating ATP levels, but not PGE2, can predict a decline in cognition, suggesting that HIV-infected individuals have impaired ATP metabolism and associated signaling. We identified that Pannexin-1 channel opening contributes to the high serological ATP levels, and ATP in the circulation could be used as a biomarker of HIV-associated cognitive impairment. In addition, we believe that ATP is a major contributor to chronic inflammation in the HIV-infected population, even in the anti-retroviral era. Here, we discuss the mechanisms associated with Pannexin-1 channel opening within the circulation, as well as within the resident viral reservoirs, ATP dysregulation, and cognitive disease observed in the HIV-infected population. [ABSTRACT FROM AUTHOR]