The Anti-Inflammatory Effects of Cannabidiol (CBD) on Acne.

Acne is the most common skin condition in the United States and affects approximately 85% of people ages 12-24. As a multifactorial disease, the pathogenesis of acne involves overproduction of sebum, irregular shedding of the cutaneous cells, accretion of Cutibacterium acnes at the pilosebaceous unit, and inflammation. To date, conventional therapies for acne include topical retinoids, over-the-counter bactericidal agents, and systematic treatments, such as oral antibiotics and isotretinoin. However, the potential for significant side effects and risk of antibiotic resistance remain limitations in these therapies, in turn reducing patient compliance and adherence to acne treatment regimens. Therefore, the use of natural plant-derived treatments or phytotherapeutics as an alternative or adjuvant to conventional treatments is attractive to patients due to their safety and minimal risk for side effects. Cannabidiol (CBD) is a non-psychoactive phytocannabinoid of the Cannabis sativa (hemp) plant. The therapeutic use of CBD has been implicated in many diseases with an inflammatory aspect, including cancers, neurodegeneration, immunological disorders, and dermatological diseases. However, the use of CBD for acne treatment remains a novel window of opportunity. Herein, we summarize the available and relevant data, highlighting the potential use of CBD in acne for its anti-inflammatory properties. To that extent, CBD and other cannabis constituents such as cannabis seeds were found to reduce inflammation and expression of inflammatory cytokines including TNF-α and IL-1ß when evaluated in acne-like conditions. Treatment with these cannabis extracts was also found to be safe and well tolerated, further strengthening the prospect of CBD as an anti-inflammatory therapeutic for acne.

Opioid Antagonist Nanodrugs Successfully Attenuate the Severity of Ischemic Stroke.

The United States is in the midst of an opioid epidemic that is linked to a number of serious health issues, including an increase in cerebrovascular events, namely, stroke. Chronic prescription opioid use exacerbates the risk and severity of ischemic stroke, contributing to stroke as the fifth overall cause of death in the United States and costing the US health care system over $30 billion annually. Pathologically, opioids challenge the integrity of the blood-brain barrier (BBB), resulting in a dysregulation of tight junction (TJ) proteins that are crucial in maintaining barrier homeostasis. Despite this, treatment options for ischemic stroke are limited, and there are no pharmacological options to attenuate TJ damage, including in incidents that are linked to opioid use. Herein, we have generated carrier-free, pure "nanodrugs" or nanoparticles of naloxone and naltrexone with enhanced therapeutic properties compared to the original (parent) drugs. The generated nanoformulations of both opioid antagonists exhibited successful attenuation of morphine- or oxycodone-induced alterations of TJ protein expression and reduced oxidative stress to a greater extent than the parent drugs (non-nano). As a proof of concept, we then proceeded to evaluate the therapeutic effectiveness of the generated nanodrugs in an ischemic stroke model of mice exposed to morphine or oxycodone. Our results demonstrate that the opioid antagonist nanoformulations reduced stroke severity in mice. Overall, this research implements advances in nanotechnology-based repurposing of FDA-approved therapeutics, and the obtained results also suggest underlying pharmacological mechanisms of opioid antagonists, further supporting these opioid antagonists and their respective nanoformulations as potential therapeutic agents for ischemic stroke.

The Inflammatory Aspect of Male and Female Pattern Hair Loss.

Male and female pattern hair loss (MPHL and FPHL, respectively), is the most common cause of hair loss affecting nearly 80 million people in the US, yet treatment options remain limited and lacking. As the need for more effective therapeutics remains unmet, this perspective offers a unique angle by directing attention to the inflammatory aspect of MPHL and FPHL. Evidence and implications of inflammation as a characteristic feature of MPHL and FPHL are highlighted through evaluation of clinical and quantitative data. Comparable results suggest the presence of significant perifollicular inflammatory infiltrates, such as lymphocytes and histiocytes, as well as the involvement of inflammatory genes, such as CASP7 and TNF, in the presentation of MPHL and FPHL. Resurfacing of the inflammatory aspect in MPHL and FPHL pathogenesis will advance future developments in MPHL and FPHL therapeutic options.

Cannabidiol as a Novel Therapeutic for Immune Modulation.

The immune-suppressive effects of cannabidiol (CBD) are attributed to the modulation of essential immunological signaling pathways and receptors. Mechanistic understanding of the pharmacological effects of CBD emphasizes the therapeutic potential of CBD as a novel immune modulator. Studies have observed that the antagonists of CB1 and CB2 receptors and transient receptor potential vanilloid 1 reverse the immunomodulatory effects of CBD. CBD also inhibits critical activators of the Janus kinase/signal transducer and activator of transcription signaling pathway, as well as the nucleotide-binding oligomerization domain-like receptor signaling pathway, in turn decreasing pro-inflammatory cytokine production. Furthermore, CBD protects against cellular damage incurred during immune responses by modulating adenosine signaling. Ultimately, the data overwhelmingly support the immunosuppressive effects of CBD and this timely review draws attention to the prospective development of CBD as an effective immune modulatory therapeutic.

The Paradox of HIV Blood-Brain Barrier Penetrance and Antiretroviral Drug Delivery Deficiencies.

HIV attacks the body's immune cells, frequently compromises the integrity of the blood-brain barrier (BBB), and infects the CNS in the early stages of infection. Dysfunction of the BBB further potentiates viral replication within the CNS, which can lead to HIV-associated neuropathology. Antiretroviral therapy (ART) significantly improves HIV patient outcomes and reduces mortality rates. However, there has been limited progress in targeting latent viral reservoirs within the CNS, which may eventually lead to rebound viremia. While ART drugs are shown to be effective in attenuating HIV replication in the periphery, the protection of the brain by the BBB offers an isolated sanctuary to harbor HIV and maintains chronic and persistent replication within the CNS. In this review, we elucidate the pathology of the BBB, its ability to potentiate viral replication, as well as current therapies and insufficiencies in treating HIV-infected individuals.

Opioid antagonists as potential therapeutics for ischemic stroke.

Chronic use of prescription opioids exacerbates risk and severity of ischemic stroke. Annually, 6 million people die from stroke worldwide and there are no neuroprotective or neurorestorative agents to improve stroke outcomes and promote recovery. Prescribed opioids such as morphine have been shown to alter tight junction protein expression, resulting in the disruption of the blood brain barrier (BBB), ultimately leading to stroke pathogenesis. Consequently, protection of the BBB has been proposed as a therapeutic strategy for ischemic stroke. This perspective addresses the deficiency in stroke pharmacological options and examines a novel application and repurposing of FDA-approved opioid antagonists as a prospective neuroprotective therapeutic strategy to minimize BBB damage, reduce stroke severity, and promote neural recovery. Future directions discuss potential drug design and delivery methods to enhance these novel therapeutic targets.