Marijuana use and HIV treatment outcomes among PWH receiving care at an urban HIV clinic.

Journal of Substance Abuse Treatment

“While marijuana use is prevalent among persons with HIV (PWH), few studies have examined the relationship between marijuana use and HIV treatment outcomes independent of alcohol and other drug use.

METHODS:

We conducted a prospective cohort study to examine the relationships between frequency of marijuana use and antiretroviral therapy (ART) adherence and viral suppression in patients enrolled in the Johns Hopkins HIV Clinical Cohort between September 2013 through November 2015 (N=1377). We categorized marijuana use as no use, none in the last 3months, monthly use or less, weekly/daily. Our outcomes of interest were use of ART, ≥90 ART adherence, and viral suppression (HIV1-RNA<200 copies). We conducted multivariable analyses to examine associations between the frequency of marijuana use and our treatment outcomes, using generalized estimating equations to account for repeated measures. Other independent variables of interest included alcohol use, other drug use, and depressive symptoms. Analyses were adjusted for age, race, sex and HIV acquisition risk factor.

RESULTS:

In multivariable analyses we found no statistically significant association between frequency of marijuana use and our treatment outcomes. Alcohol use, other drug use and depressive symptoms were associated with lower odds of ART adherence and viral suppression.

CONCLUSIONS:

In this sample of PWH in care, frequency of marijuana use independent of other substance use does not appear to be associated with negative HIV treatment outcomes. Our results indicate that unlike alcohol, other substances and depression, marijuana use may not be a barrier to the effective treatment of HIV.”

https://www.ncbi.nlm.nih.gov/pubmed/29021107

http://www.journalofsubstanceabusetreatment.com/article/S0740-5472(17)30225-8/fulltext

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Daily cannabis and reduced risk of steatosis in human immunodeficiency virus and hepatitis C virus co-infected patients (ANRS CO13-HEPAVIH).

Journal of Viral Hepatitis

“Liver steatosis is common in Human Immunodeficiency Virus (HIV) – Hepatitis C Virus (HCV) co-infected patients. Some recent studies have found that cannabis use is negatively associated with insulin resistance in the general population and in HIV-HCV co-infected patients.

Given the causal link between insulin resistance and steatosis, we hypothesized that cannabis use has a positive impact on steatosis.

Therefore, we aimed to study whether cannabis use in this population was associated with a reduced risk of steatosis, measured by ultrasound examination.

The ANRS CO13-HEPAVIH cohort is a French nationwide multicenter of HIV-HCV co-infected patients. Medical and socio-behavioral data from clinical follow-up visits and annual self-administered questionnaires were prospectively collected. A cross-sectional analysis was conducted using data from the first visit where both ultrasound examination data for steatosis (positive or negative diagnosis) and data on cannabis use were available. A logistic regression model was used to evaluate the association between cannabis use and steatosis. Among study sample patients (n=838), 40.1% had steatosis. Fourteen percent reported daily cannabis use, 11.7% regular use, and 74.7% no use or occasional use (“never or sometimes”).

Daily cannabisuse was independently associated with a reduced prevalence of steatosis (adjusted odds ratio [95%]=0.64 [0.42;0.99]; p=0.046), after adjusting for body mass index, hazardous alcohol consumption and current or lifetime use of lamivudine/zidovudine. Daily cannabisuse may be a protective factor against steatosis in HIV-HCV co-infected patients. These findings confirm the need for a clinical evaluation of cannabis-based pharmacotherapies in this population.”

https://www.ncbi.nlm.nih.gov/pubmed/28984055

http://onlinelibrary.wiley.com/doi/10.1111/jvh.12797/abstract

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Association of Cannabis, Stimulant, and Alcohol use with Mortality Prognosis Among HIV-Infected Men.

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“Questionnaires over a 9-year study period (2002-2010) were used to characterize cannabis, stimulant, and alcohol use among 3099 HIV-infected men participating in the Veterans Aging Cohort Study (VACS) to determine whether use of these substances is associated with changes in the VACS Index, a validated prognostic indicator for all-cause mortality.

At baseline, 18% of participants reported no substance use in the past year, 24% lower risk alcohol use only, 18% unhealthy alcohol use only, 15% cannabis use (with or without alcohol), and 24% stimulant use (with or without alcohol or cannabis).

In adjusted longitudinal analyses, cannabis use [β = -0.97 (95% CI -1.93, 0.00), p = 0.048] was not associated with mortality risk, while stimulant use [1.08 (0.16, 2.00), p = 0.021] was associated with an increased mortality risk, compared to lower risk alcohol use.

Our findings show no evidence of a negative effect of cannabis use on mortality risk, while stimulant use was associated with increased mortality risk among HIV-infected men. Interventions to reduce stimulant use in this patient population may reduce mortality.”

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Δ9-Tetrahydrocannabinol Suppresses Secretion of IFNα by Plasmacytoid Dendritic Cells From Healthy and HIV-Infected Individuals.

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“Plasmacytoid dendritic cells (pDCs) play a crucial role in host antiviral immune response through secretion of type I interferon. Interferon alpha (IFNα), a type I IFN, is critical for mounting the initial response to viral pathogens. A consequence of Human Immunodeficiency Virus-1 (HIV) infection is a decrease in both pDC number and function, but prolonged pDC activity has been linked with progression from HIV infection to the development of AIDS. Patients with HIV in the United States routinely use cannabinoid-based therapies to combat the side effects of HIV infection and antiretroviral therapy. However, cannabinoids, including Δ-tetrahydrocannabinol (THC), are well-characterized immunosuppressants. Here, we report that THC suppressed secretion of IFNα by pDC from both healthy and HIV+ donors through a mechanism involving impaired phosphorylation of interferon regulatory factor 7. These results suggest that THC can suppress pDC function during the early host antiviral response by dampening pDC activation.”

“Study: THC May Help Prevent HIV from Becoming AIDS”  https://thejointblog.com/study-thc-may-help-prevent-hiv-becoming-aids/

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Confirmed marijuana use and lymphocyte count in black people living with HIV

Drug and Alcohol Dependence Home

“Marijuana is a commonly used recreational substance with purported analgesic and mood enhancing properties. Many people living with HIV identify marijuana as a palliative substance.

However, through its main psychoactive component, tetrahydrocannabinol (THC), is known to influence the immune system. The effects of marijuana use in people with HIV are still controversial, with very scant literature in Black adults.

The current study determined the differences in the lymphocyte count, specifically the number cluster differentiation 4 and 8 (CD4+ and CD8+), among patients who urine drug tested negative for THC (n = 70) and those who tested positive for THC (n = 25).”  HTTP://WWW.SCIENCEDIRECT.COM/SCIENCE/ARTICLE/PII/S037687161730412X

“After adjusting for demographic and HIV-related covariates, THC-positive patients had significantly higher CD4+ and CD8+ counts than their THC-negative counterparts.”  http://www.drugandalcoholdependence.com/article/S0376-8716(17)30412-X/fulltext

“These results extend previous HIV-related immunity findings in an underrepresented group, and suggest that THC use does not reduce immune function as measured by CD count. Further research is warranted on the overall effects of THC on immune function in HIV positive patients.”  https://www.ncbi.nlm.nih.gov/pubmed/28850903

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Cannabinoid receptor 2-63 RR variant is independently associated with severe necroinflammation in HIV/HCV coinfected patients.

 

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“This is the first study to analyze the impact of the rs35761398 variant of the CNR2 gene leading to the substitution of GLN (Q) of codon 63 of the cannabinoid receptor 2 (CB2) with ARG (R) on the clinical presentation of chronic hepatitis in HIV/HCV coinfected patients.

This study shows interesting interplay between the CB2-RR variant and liver necroinflammation in chronic hepatitis patients with HIV/HCV coinfection, an observation of clinical value that coincides with the interest in the use of the CB2 agonists and antagonists in clinical practice emerging from the literature.”

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Endocannabinoids exert CB1 receptor-mediated neuroprotective effects in models of neuronal damage induced by HIV-1 Tat protein.

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“In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND). Endocannabinoids (eCBs) elicit neuroprotective and anti-inflammatory actions in several central nervous system (CNS) disease models, but their effects in HAND remain unknown. HIV-1 does not infect neurons, but produces viral toxins, such as transactivator of transcription (Tat), that disrupt neuronal calcium equilibrium and give rise to synaptodendritic injuries and cell death, the former being highly correlated with HAND. Consequently, we tested whether the eCBs N-arachidonoyl ethanolamine (anandamide/AEA) and 2-arachidonoyl-glycerol (2-AG) offer neuroprotective actions in a neuronal culture model. Specifically, we examined the neuroprotective actions of these eCBs on Tat excitotoxicity in primary cultures of prefrontal cortex neurons (PFC), and whether cannabinoid receptors mediate this neuroprotection. Tat-induced excitotoxicity was reflected by increased intracellular calcium levels, synaptodendritic damage, neuronal excitability, and neuronal death. Further, upregulation of cannabinoid 1 receptor (CB1R) protein levels was noted in the presence of HIV-1 Tat. The direct application of AEA and 2-AG reduced excitotoxic levels of intracellular calcium and promoted neuronal survival following Tat exposure, which was prevented by the CB1R antagonist rimonabant, but not by the CB2R antagonist AM630. Overall, our findings indicate that eCBs protect PFC neurons from Tat excitotoxicity in vitro via a CB1R-related mechanism. Thus, the eCB system possesses promising targets for treatment of neurodegenerative disorders associated with HIV-1 infection.”

https://www.ncbi.nlm.nih.gov/pubmed/28733129

http://www.sciencedirect.com/science/article/pii/S1044743117300830

 

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Medicinal Uses of Marijuana and Cannabinoids

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“In the past two decades, there has been increasing interest in the therapeutic potential of cannabis and single cannabinoids, mainly cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC). THC and cannabis products rich in THC exert their effects mainly through the activation of cannabinoid receptors (CB1 and CB2). Since 1975, 140 controlled clinical trials using different cannabinoids or whole-plant preparations for the treatment of a large number of disorders and symptoms have been conducted. Results have led to the approval of cannabis-based medicines [dronabinol, nabilone, and the cannabis extract nabiximols (Sativex®, THC:CBD = 1:1)] as well as cannabis flowers in several countries. Controlled clinical studies provide substantial evidence for the use of cannabinoid receptor agonists in cancer chemotherapy induced nausea and vomiting, appetite loss and cachexia in cancer and HIV patients, neuropathic and chronic pain, and in spasticity in multiple sclerosis. In addition, there is also some evidence suggesting a therapeutic potential of cannabis-based medicines in other indications including Tourette syndrome, spinal cord injury, Crohn’s disease, irritable bowel syndrome, and glaucoma. In several other indications, small uncontrolled and single-case studies reporting beneficial effects are available, for example in posttraumatic stress disorder, attention deficit hyperactivity disorder, and migraine. The most common side effects of THC and cannabis-based medicines rich in THC are sedation and dizziness (in more than 10% of patients), psychological effects, and dry mouth. Tolerance to these side effects nearly always develops within a short time. Withdrawal symptoms are hardly ever a problem in the therapeutic setting. In recent years there is an increasing interest in the medical use of CBD, which exerts no intoxicating side effects and is usually well-tolerated. Preliminary data suggest promising effects in the treatment of anxiety disorders, schizophrenia, dystonia, and some forms of epilepsy. This review gives an overview on clinical studies which have been published over the past 40 years.”

http://www.tandfonline.com/doi/abs/10.1080/07352689.2016.1265360?needAccess=true&journalCode=bpts20

“Review Identifies 140 Controlled Clinical Trials Related to Cannabis”  http://blog.norml.org/2017/06/04/review-identifies-140-controlled-clinical-trials-related-to-cannabis/

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Cannabis Use, Medication Management and Adherence Among Persons Living with HIV.

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“Cannabis is used to relieve nausea, trigger weight gain, and reduce pain among adults living with HIV; however, the relationship between its use and medication adherence and management is unclear. Participants (N = 107) were from an ongoing cohort study of community-dwelling HIV+ adults, stratified by cannabis (CB) use: HIV+/CB+ (n = 41) and HIV+/CB- (n = 66). CB+ participants either tested positive in a urine toxicology screen for THC or had a self-reported history of regular and recent use. HIV-status was provided by physician results and/or biomarker assessment. Adherence was measured via the Morisky scale and medication management was assessed via the Medication Management Test-Revised. After adjusting for gender, we found no association between cannabis use group and adherence nor medication management. The amount of cannabis used was also not associated with measures of adherence and management. Preliminary findings suggest that cannabis use may not adversely influence medication adherence/management among adults living with HIV.”

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Antihyperalgesic Activities of Endocannabinoids in a Mouse Model of Antiretroviral-Induced Neuropathic Pain.

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“Nucleoside reverse transcriptase inhibitors (NRTIs) are the cornerstone of the antiretroviral therapy for human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). However, their use is sometimes limited by the development of a painful sensory neuropathy, which does not respond well to drugs.

Smoked cannabis has been reported in clinical trials to have efficacy in relieving painful HIV-associated sensory neuropathy.

The aim of this study was to evaluate whether the expression of endocannabinoid system molecules is altered during NRTI-induced painful neuropathy, and also whether endocannabinoids can attenuate NRTI-induced painful neuropathy.

Conclusion: These data show that ddC induces thermal hyperalgesia, which is associated with dysregulation of the mRNA expression of some endocannabinoid system molecules. The endocannabinoids AEA and 2-AG have antihyperalgesic activity, which is dependent on cannabinoid receptor and GPR55 activation. Thus, agonists of cannabinoid receptors and GPR55 could be useful therapeutic agents for the management of NRTI-induced painful sensory neuropathy.”

https://www.ncbi.nlm.nih.gov/pubmed/28373843

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