Acute nicotine vapor normalizes sensorimotor gating and reduces locomotor activity deficits in HIV-1 transgenic rats.

Rationale: Despite improved life expectancy of people with HIV (PWH), HIV-associated neurocognitive impairment (NCI) persists, alongside deficits in sensorimotor gating and neuroinflammation. PWH exhibit high smoking rates, possibly due to neuroprotective, anti-inflammatory, and cognitive-enhancing effects of nicotine, suggesting potential self-medication. Objectives: Here, we tested the effects of acute nicotine vapor exposure on translatable measures of sensorimotor gating and exploratory behavior in the HIV-1 transgenic (HIV-1Tg) rat model of HIV. Methods: Male and female HIV-1Tg and F344 control rats (n=57) were exposed to acute nicotine or vehicle vapor. Sensorimotor gating was assessed using prepulse inhibition (PPI) of the acoustic startle response, and exploratory behavior was evaluated using the behavioral pattern monitor (BPM). Results: Vehicle-treated HIV-1Tg rats exhibited PPI deficits at low prepulse intensities compared to F344 controls, as seen previously. No PPI deficits were observed in nicotine-treated HIV1-Tg rats, however. HIV-1Tg rats were hypoactive in the BPM relative to controls, whilst nicotine vapor increased activity and exploratory behavior across genotypes. Cotinine analyses confirmed comparable levels of the primary metabolite of nicotine across genotypes. Conclusions: Previous findings of PPI deficits in HIV-1Tg rats were replicated and, importantly, attenuated by acute nicotine vapor. Evidence for similar cotinine levels suggest a nicotine-specific effect in HIV-1Tg rats. HIV-1Tg rats had reduced exploratory behavior compared to controls, attenuated by acute nicotine vapor. Therefore, acute nicotine may be beneficial for remediating sensorimotor and locomotor activity deficits in PWH. Future studies should determine the long-term effects of nicotine vapor on similar HIV/NCI-relevant behaviors.

The Impact of Cannabis Use on Cognition in People with HIV: Evidence of Function-Dependent Effects and Mechanisms from Clinical and Preclinical Studies.

PURPOSE OF REVIEW: Cannabis may have beneficial anti-inflammatory effects in people with HIV (PWH); however, given this population's high burden of persisting neurocognitive impairment (NCI), clinicians are concerned they may be particularly vulnerable to the deleterious effects of cannabis on cognition. Here, we present a systematic scoping review of clinical and preclinical studies evaluating the effects of cannabinoid exposure on cognition in HIV. RECENT FINDINGS: Results revealed little evidence to support a harmful impact of cannabis use on cognition in HIV, with few eligible preclinical data existing. Furthermore, the beneficial/harmful effects of cannabis use observed on cognition were function-dependent and confounded by several factors (e.g., age, frequency of use). Results are discussed alongside potential mechanisms of cannabis effects on cognition in HIV (e.g., anti-inflammatory), and considerations are outlined for screening PWH that may benefit from cannabis interventions. We further highlight the value of accelerating research discoveries in this area by utilizing translatable cross-species tasks to facilitate comparisons across human and animal work.

The Role of Cannabis and The Endocannabinoid System in Sleep Regulation and Cognition: A Review of Human and Animal Studies.

OBJECTIVES: Both sleep and cognition are partially modulated by the endocannabinoid (ECB) system. Cannabis has been reported to have effects on sleep and cognition. This review aims to summarize the recent literature on the ECB system, the role of cannabis and the ECB system on sleep regulation and cognition. Further, this review will identify existing gaps in knowledge and suggest potential targets for future research. METHODS: We performed this review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Reports were identified by searching PubMed/MEDLINE, Embase, CINAHL, Web of Science, and PsycINFO for articles published through September 2021 for studies with data available on aspects of cognition, cannabis, or the ECB system, and sleep or circadian rhythms (CRs). RESULTS: We identified 6 human and 6 animal studies to be eligible for inclusion in this review. Several human studies found that cannabis use is not associated with changes in sleep quality or cognitive function. However, individual cannabinoids appeared to have independent effects on cognition and sleep; THC alone decreased cognitive performance and increased daytime sleepiness, whereas CBD alone had no effect on sleep or cognition. Animal studies demonstrated that manipulation of the ECB system altered activity and cognitive function, some of which appeared to be dependent on the light/dark cycle. CONCLUSION: The sleep-wake cycle and CRs are both likely modulated by the ECB system, potentially resulting in effects on cognition, however this area is critically understudied.

A Pilot Assessment of the Effects of HIV and Methamphetamine Dependence on Socially Dysregulated Behavior in the Human Behavioral Pattern Monitor.

Deficits in social cognition are seen in both people living with HIV (PWH) and people with a history of methamphetamine (METH) dependence. Dually affected individuals may experience additive negative effects on social cognition due to these conditions. We evaluated social cognition in 4 diagnostic groups (HIV-/METH-, HIV-/METH+, HIV+/METH-, HIV+/METH+). First, we used traditional social-emotional functioning assessments, the Difficulties in Emotion Regulation Scale and the Faux Pas Task, to determine any significant effects of METH dependence and HIV on social cognition. Next, we quantified social cognition using the Human Behavioral Pattern Monitor by evaluating social behavior represented by interaction with novel objects. METH dependence significantly affected social-emotional functions and HIV significantly affected on object interactions, however no significant additive effects were observed using these methods. The nuanced relationship between HIV and METH dependence suggests that other factors (i.e., adaptive life skills) likely mediate social cognition-related behaviors.

RESUMEN: Los déficits en la cognición social se observan tanto en las personas que viven con el VIH (PWH) como en las personas con antecedentes de dependencia de la metanfetamina (METH). Las personas con ambas condiciones pueden experimentar efectos negativos aditivos en la cognición social. Evaluamos la cognición social en 4 grupos de diagnóstico (VIH−/METH−, VIH−/METH+, VIH+/METH−, VIH+/METH+). En primer lugar, utilizamos evaluaciones tradicionales del funcionamiento socioemocional, la Escala de Dificultades en la Regulación Emocional y la Prueba de Faux Pas, para determinar efecto significativo debido a la dependencia de METH y el VIH en la cognición social. Entonces, cuantificamos la cognición social utilizando el Monitor de Patrones de comportamiento humano mediante la evaluación del comportamiento social representado por la interacción con objetos novedosos. La dependencia de METH afectó significativamente las funciones socioemocionales y el VIH afectó significativamente las interacciones con los objetos, sin embargo, no se observaron efectos aditivos significativos al usar estos métodos. La relación compleja entre el VIH y la dependencia de METH sugiere que otros factores (i.e., habilidades adaptativas) probablemente regulan los comportamientos relacionados con la cognición social.

Mitigating the health effects of systemic racism: Evaluation of the Race-Based Stress and Trauma Empowerment intervention.

BACKGROUND: Disparities in physical and mental health among Black, Indigenous, and People of Color (BIPOC) are well-documented and mirrored in the Veteran population. Chronic stress due to racism and discrimination is one possible mechanism driving these negative health outcomes. The Race-Based Stress and Trauma Empowerment (RBSTE) group is a novel, manualized, health promotion intervention designed to address the direct and indirect impacts of racism among Veterans of Color. This paper describes the protocol of the first pilot randomized controlled trial (RCT) of RBSTE. This study will examine the feasibility, acceptability, and appropriateness of RBSTE compared to an active control (an adaptation of Present-Centered Therapy; PCT) in a Veterans Affairs (VA) healthcare setting. A secondary aim is to identify and optimize strategies for holistic evaluation. METHODS: Veterans of Color (N = 48) endorsing perceived discrimination and stress will be randomized to RBSTE or PCT; both groups will be delivered in 8 weekly, 90-min virtual group sessions. Outcomes will include measures of psychological distress, discrimination and ethnoracial identity, holistic wellness, and allostatic load. Measures will be administered at baseline and post-intervention. CONCLUSION: This study will inform future interventions targeting identity-based stressors and represents an important step in advancing equity for BIPOC in medicine and research. CLINICAL TRIAL REGISTRATION NUMBER: NCT05422638.

iTat transgenic mice exhibit hyper-locomotion in the behavioral pattern monitor after chronic exposure to methamphetamine but are unaffected by Tat expression.

Although antiretroviral therapy (ART) has increased the quality of life and lifespan in people living with HIV (PWH), millions continue to suffer from the neurobehavioral effects of the virus. Additionally, the abuse of illicit drugs (methamphetamine in particular) is significantly higher in PWH compared to the general population, which may further impact their neurological functions. The HIV regulatory protein, Tat, has been implicated in the neurobehavioral impacts of HIV and is purported to inhibit dopamine transporter (DAT) function in a way similar to methamphetamine. Thus, we hypothesized that a combination of Tat expression and methamphetamine would exert synergistic deleterious effects on behavior and DAT expression. We examined the impact of chronic methamphetamine exposure on exploration in transgenic mice expressing human Tat (iTat) vs. their wildtype littermates using the behavioral pattern monitor (BPM). During baseline, mice exhibited sex-dependent differences in BPM behavior, which persisted through methamphetamine exposure, and Tat activation with doxycycline. We observed a main effect of methamphetamine, wherein exposure, irrespective of genotype, increased locomotor activity and decreased specific exploration. After doxycycline treatment, mice continued to exhibit drug-dependent alterations in locomotion, with no effect of Tat, or methamphetamine interactions. DAT levels were higher in wildtype, saline-exposed males compared to all other groups. These data support stimulant-induced changes of locomotor activity and exploration, and suggest that viral Tat and methamphetamine do not synergistically interact to alter these behaviors in mice. These findings are important for future studies attempting to disentangle the effect of substances that impact DAT on HAND-relevant behaviors using such transgenic animals.

Chronic methamphetamine exposure exerts few effects on the iTat mouse model of HIV, but blocks Tat expression-induced slowed reward retrieval.

Human immunodeficiency virus (HIV) continues to infect millions worldwide, negatively impacting neurobehavioral function. Further understanding of the combined effects of HIV and methamphetamine use is crucial, as methamphetamine use is prevalent in people with HIV. The HIV-associated protein Tat may contribute to cognitive dysfunction, modeled preclinically in mice using doxycycline (DOX)-inducible Tat expression (iTat). Tat may exert its effects on cognitive function via disruption of the dopamine transporter, similar to the action of methamphetamine. Additionally, Tat and methamphetamine both decrease interneuron populations, including those expressing calbindin. It is important to understand the combined effects of Tat and methamphetamine in preclinical models of HIV infection. Here, we used iTat transgenic mice and a chronic binge regimen of methamphetamine exposure to determine their combined impact on reward learning and motivation. We also measured calbindin expression in behavior-relevant brain regions. Before induction with DOX, iTat mice exhibited no differences in behavior. Chronic methamphetamine exposure before Tat induction impaired initial reward learning but did not affect motivation. Furthermore, DOX-induced Tat expression did not alter behavior, but slowed latencies to retrieve rewards. This effect of Tat, however, was not observed in methamphetamine-treated mice, indicative of a potential protective effect. Finally, Tat expression was associated with an increase in calbindin-expressing cells in the VTA, while methamphetamine exposure did not alter calbindin numbers. These findings may indicate a protective role of methamphetamine in HIV neuropathology, which in turn may help in our understanding of why people with HIV use methamphetamine at disproportionately higher rates.

The relationship between novelty-seeking traits and behavior: Establishing construct validity for the human Behavioral Pattern Monitor.

Novelty seeking is a tendency to approach new situations, putatively driven by the brain's catecholaminergic system. It is traditionally measured via self-report, but a laboratory-based paradigm, the human Behavioral Pattern Monitor (hBPM), quantifies behavior in a novel environment and has utility in cross-species studies of neuropsychiatric disorders. Our primary aim assessed whether self-reported novelty-seeking traits were associated with novelty-seeking behavior in the hBPM. An existing sample of 106 volunteers were categorized as high vs. low novelty seekers using the Temperament and Character Inventory (TCI). Subjects had been randomized to one dose of amphetamine (10 or 20 mg) or modafinil (200 or 400 mg), allowing us to explore whether a pharmacological catecholamine challenge further enhanced novelty-seeking behavior. High TCI novelty-seekers had more hBPM motor activity and novel object interactions. The exploratory analyses, although limited by low power, suggested that amphetamine and modafinil did not markedly moderate novelty-seeking traits. The hBPM demonstrates construct validity as a lab-based measure of novelty seeking and thus useful in translational studies of neuropsychiatric conditions and treatment options. Further research may illuminate whether a biological predisposition towards higher catecholaminergic activity, combined with the novelty-seeking trait, may increase propensity for risky and addictive behaviors.

Combined prior chronic methamphetamine treatment and gp120 expression reduce PPI in aged male but not female mice.

Methamphetamine (METH) use disorder is highly prevalent among people with HIV and is a significant public health problem. Furthermore, people with HIV are living longer and using drugs such as METH even into old age, making it important to understand the effects of METH use and aging in this population. HIV, METH, and aging negatively impact a variety of brain functions, including sensorimotor gating (i.e. - automatic, pre-conscious information processing). Sensorimotor gating is often measured using prepulse inhibition (PPI), a paradigm that can be conducted in animals, thereby allowing for preclinical studies. Little is known about how HIV, METH, and aging interact to affect PPI. The goal of this study was therefore to examine how METH affects PPI in aged gp120 mice, a mouse model of HIV. PPI was measured at 8, 14, and 22 months in male and female wild type (WT) and gp120 mice. PPI was also measured during and after METH treatment at 23-24 months. Aging was associated with decreased PPI in both sexes and genotypes. Combined prior METH treatment and gp120 expression caused the greatest reduction in PPI in aged male mice. Prior METH treatment decreased PPI in aged WT female mice, but not aged gp120 female mice. Overall, these results suggest the effects of HIV and METH on information processing seem to be influenced by age and sex. Combined HIV and METH may impair information processing in older men, but not older women.

Deriving psychiatric symptom-based biomarkers from multivariate relationships between psychophysiological and biochemical measures.

Identification of biomarkers for psychiatric disorders remains very challenging due to substantial symptom heterogeneity and diagnostic comorbidity, limiting the ability to map symptoms to underlying neurobiology. Dimensional symptom clusters, such as anhedonia, hyperarousal, etc., are complex and arise due to interactions of a multitude of complex biological relationships. The primary aim of the current investigation was to use multi-set canonical correlation analysis (mCCA) to derive biomarkers (biochemical, physiological) linked to dimensional symptoms across the anxiety and depressive spectrum. Active-duty service members (N = 2,592) completed standardized depression, anxiety and posttraumatic stress questionnaires and several psychophysiological and biochemical assays. Using this approach, we identified two phenotype associations between distinct physiological and biological phenotypes. One was characterized by symptoms of dysphoric arousal (anhedonia, anxiety, hypervigilance) which was associated with low blood pressure and startle reactivity. This finding is in line with previous studies suggesting blunted physiological reactivity is associated with subpopulations endorsing anxiety with comorbid depressive features. A second phenotype of anxious fatigue (high anxiety and reexperiencing/avoidance symptoms coupled with fatigue) was associated with elevated blood levels of norepinephrine and the inflammatory marker C-reactive protein in conjunction with high blood pressure. This second phenotype may describe populations in which inflammation and high sympathetic outflow might contribute to anxious fatigue. Overall, these findings support the growing consensus that distinct neuropsychiatric symptom patterns are associated with differential physiological and blood-based biological profiles and highlight the potential of mCCA to reveal important psychiatric symptom biomarkers from several psychophysiological and biochemical measures.

MicroPET evidence for a hypersensitive neuroinflammatory profile of gp120 mouse model of HIV.

Despite increased survivability for people living with HIV (PLWH), HIV-related cognitive deficits persist. Determining biological mechanism(s) underlying abnormalities is critical to minimize the long-term impact of HIV. Positron emission tomography (PET) studies reveal that PLWH exhibit elevated neuroinflammation, potentially contributing to these problems. PLWH are hypersensitive to environmental insults that drive elevated inflammatory profiles. Gp120 is an envelope glycoprotein exposed on the surface of the HIV envelope which enables HIV entry into a cell contributing to HIV-related neurotoxicity. In vivo evidence for mice overexpressing gp120 (transgenic) mice exhibiting neuroinflammation remains unclear. Here, we conducted microPET imaging in gp120 transgenic and wildtype mice, using the radiotracer [(18)F]FEPPA (binds to the translocator protein expressed by activated microglial serving as a neuroinflammatory marker). Imaging was performed at baseline and 24 h after lipopolysaccharide (LPS; 5 mg/kg) treatment (endotoxin that triggers an immune response). Gp120 transgenic mice exhibited elevated [(18F)]FEPPA in response to LPS vs. wildtype mice throughout the brain including dorsal and ventral striata, hypothalamus, and hippocampus. Gp120 transgenic mice are hypersensitive to environmental inflammatory insults, consistent with PLWH, measurable in vivo. It remains to-be-determined whether this heightened sensitivity is connected to the behavioral abnormalities of these mice or sensitive to any treatments.

HIV Transgenic Rats Demonstrate Impaired Sensorimotor Gating But Are Insensitive to Cannabinoid (Δ9-Tetrahydrocannabinol)-Induced Deficits.

BACKGROUND: HIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals. METHODS: PPI was measured in male and female HIVtg rats and wild-type controls following acute, nonconcurrent treatment with the primary constituents of cannabis: Δ 9-tetrahydrocannabinol (THC; 1 and 3 mg/kg, s.c.) and cannabidiol (1, 10, and 30 mg/kg, i.p.). RESULTS: HIVtg rats exhibited a significant PPI deficit relative to wild-type controls. THC reduced PPI in controls but not HIVtg rats. Cannabidiol exerted only minor, genotype-independent effects on PPI. CONCLUSIONS: HIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use among PWH.

The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid.

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = -0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.

HIV Transgenic Rats Demonstrate Superior Task Acquisition and Intact Reversal Learning in the Within-Session Probabilistic Reversal Learning Task.

The HIV transgenic (HIVtg) rat is a commonly used animal model of chronic HIV infection that exhibits a wide range of cognitive deficits. To date, relatively little work has been conducted on these rats' capacity for reversal learning, an assay of executive function and cognitive flexibility used in humans. The present study sought to determine the impact of HIV genotype on probabilistic reversal learning, effortful motivation, and spontaneous locomotion/exploration in rats. Male (n = 8) and female (n = 8) HIVtg rats and wildtype (WT) controls were utilized. Cognitive flexibility was assessed via the Probabilistic Reversal Learning Task (PRLT), which reinforced responses to two stimuli on differential probabilistic schedules that periodically reversed. Effortful motivation and locomotor/exploratory behavior were assessed via the Progressive Ratio Breakpoint Task (PRBT) and the Behavioral Pattern Monitor (BPM), respectively. Regardless of sex, HIVtg rats required fewer trials to ascertain initial PRLT reward schedules than WT rats, and completed the same number of reversals. Secondary behaviors suggested that HIVtg PRLT performance was facilitated by a speed-accuracy tradeoff strategy. No main or interactive effects of genotype were observed in the PRBT or BPM. Relative to WT controls, HIVtg rats exhibited superior probabilistic reinforcement learning. Reversal learning was unaffected by HIV genotype, as was effortful motivation and exploratory behavior. These findings contrast with previous characterizations of the HIVtg rat, thus indicating a nuanced cognitive profile that is dependent upon such task specifications as within- versus between-session assessment and probabilistic versus deterministic reward schedules.

The relationship between cannabis use and cognition in people with bipolar disorder: A systematic scoping review.

Bipolar disorder (BD) and cannabis use are highly comorbid and are each associated with cognitive impairment.  Given the prevalence of cannabis use in people with BD, it is important to understand whether the two interact to impact cognitive function. We performed a systematic scoping review to determine what is currently known in this field. We systematically searched PubMed, Embase, CINAHL, Web of Science, and PsycINFO for studies on the relationship between cannabis use and cognition in people with BD or relevant animal models. Six observational human studies and no animal studies met inclusion criteria. Two studies found cannabis use in BD was associated with better performance in some cognitive domains, while three studies found no association. One study found cannabis use in BD was associated with worse overall cognition. Overall, most identified studies suggest cannabis use is not associated with significant cognitive impairment in BD; however, the scope of knowledge in this field is limited, and more systematic studies are clearly required. Future studies should focus on longitudinal and experimental trials, and well-controlled observational studies with rigorous quantification of the onset, frequency, quantity, duration, and type of cannabis use, as well as BD illness features.

Chronic antipsychotic treatment exerts limited effects on the mania-like behavior of dopamine transporter knockdown mice.

BACKGROUND: Bipolar disorder is a life-threatening disorder linked to dopamine transporter (DAT) polymorphisms, with reduced DAT levels seen in positron emission tomography and postmortem brains. AIMS: The purpose of this study was to examine the effects of approved antipsychotics on DAT dysfunction-mediated mania behavior in mice. METHODS: DAT knockdown mice received either D2-family receptor antagonist risperidone or asenapine and mania-related behaviors were assessed in the clinically-relevant behavioral pattern monitor to assess spontaneous exploration. RESULTS: Chronic risperidone did not reverse mania-like behavior in DAT knockdown mice. Chronic asenapine reduced mania behavior but this effect was more pronounced in wild-type littermates than in DAT knockdown mice. CONCLUSION: Taken together, these findings suggest that while acute antipsychotic treatment may be beneficial in management of bipolar mania, more targeted therapeutics may be necessary for long-term treatment. Specific investigation into DAT-targeting drugs could improve future treatment of bipolar mania.

The Effects of Cannabis Use on Cognitive Function in Healthy Aging: A Systematic Scoping Review.

BACKGROUND: Older adults (≥50 years) represent the fastest-growing population of people who use cannabis, potentially due to the increasing promotion of cannabis as medicine by dispensaries and cannabis websites. Given healthy aging and cannabis use are both associated with cognitive decline, it is important to establish the effects of cannabis on cognition in healthy aging. OBJECTIVE: This systematic scoping review used preferred reporting items for systematic reviews and meta-analyses guidelines to critically examine the extent of literature on this topic and highlight areas for future research. METHOD: A search of six databases (PubMed, EMBASE, PsycINFO, Web of Science, Family and Society Studies Worldwide, and CINAHL) for articles published by September 2019, yielded 1,014 unique results. RESULTS: Six articles reported findings for older populations (three human and three rodent studies), highlighting the paucity of research in this area. Human studies revealed largely null results, likely due to several methodological limitations. Better-controlled rodent studies indicate that the relationship between ∆9-tetrahydrocannabinol (THC) and cognitive function in healthy aging depends on age and level of THC exposure. Extremely low doses of THC improved cognition in very old rodents. Somewhat higher chronic doses improved cognition in moderately aged rodents. No studies examined the effects of cannabidiol (CBD) or high-CBD cannabis on cognition. CONCLUSIONS: This systematic scoping review provides crucial, timely direction for future research on this emerging issue. Future research that combines neuroimaging and cognitive assessment would serve to advance understanding of the effects of age and quantity of THC and CBD on cognition in healthy aging.

Both HIV and Tat expression decrease prepulse inhibition with further impairment by methamphetamine.

HIV infection and methamphetamine (METH) use are highly comorbid and represent a significant public health problem. Both conditions are known to negatively impact a variety of brain functions. One brain function that may be affected by HIV and METH use is sensorimotor gating, an automatic, pre-conscious filtering of sensory information that is thought to contribute to higher order cognitive processes. Sensorimotor gating is often measured using prepulse inhibition (PPI), a paradigm that can be conducted in both humans and animals, thereby enabling cross-species translational studies. While previous studies suggest HIV and METH may individually impair PPI, little research has been conducted on the effects of combined HIV and METH on PPI. The goal of this cross-species study was to determine the effects of METH on PPI in the inducible Tat (iTat) mouse model of HIV and in people with HIV. PPI was measured in the iTat mouse model before, during, and after chronic METH treatment and after Tat induction. Chronic METH treatment decreased PPI in male but not female mice. PPI normalized with cessation of METH. Inducing Tat expression decreased PPI in male but not in female mice. No interactions between chronic METH treatment and Tat expression were observed in mice. In humans, HIV was associated with decreased PPI in both men and women. Furthermore, PPI was lowest in people with HIV who also had a history of METH dependence. Overall, these results suggest HIV and METH may additively impair early information processing in humans, potentially affecting downstream cognitive function.

Sustained attention and vigilance deficits associated with HIV and a history of methamphetamine dependence.

BACKGROUND: Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy. One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, antiretroviral therapy initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; <50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the main and interactive (additive versus synergistic) effects of HIV and history of METH on the sustained attention and vigilance cognitive domain, while controlling for VLS. METHODS: Participants included 205 (median age = 44 years; 77% males; HIV-/METH- n = 67; HIV+/METH - n = 49; HIV-/METH+ n = 36; HIV+/METH+ n = 53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners' and the 5-Choice continuous performance tests (CPTs). RESULTS: METH participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV- participants. There was no HIV x METH interaction on sustained attention and vigilance. CONCLUSIONS: Recent methamphetamine use among METH people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of antiretroviral therapy, and METH use interventions.