The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems. In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development. The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development. The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases. This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.

Since the first reports of AIDS, skin involvement has become a burdensome stigma for seropositive patients and a challenging task for dermatologist and infectious disease specialists due to the severe and recalcitrant nature of the conditions. Dermatologic manifestations in AIDS patients act as markers of disease progression, a fact that enhances the importance of understanding their pathogenesis.Broadly, cutaneous disorders associated with HIV type‐1 infection can be classified as primary and secondary. While the pathogenesis of secondary complications, such as opportunistic infections and skin tumours, is directly correlated with a decline in the CD4⁺ T cell count, the origin of the certain manifestations primarily associated with the retroviral infection itself still remains under investigation.The focus of this review is to highlight the immunological phenomena that occur in the skin of HIV‐1‐seropositive patients, which ultimately lead to skin disorders, such as seborrhoeic dermatitis, atopic dermatitis, psoriasis and eosinophilic folliculitis. Furthermore, we compile the latest data on how shifts in the cytokines milieu, impairments of the innate immune compartment, reactions to xenobiotics and autoimmunity are causative agents in HIV‐1‐driven skin diseases. Additionally, we provide a thorough analysis of the small animal models currently used to study HIV‐1‐associated skin complications, centering on transgenic rodent models, which unfortunately, have not been able to fully unveil the role of HIV‐1 genes in the pathogenesis of their primarily associated dermatological manifestations.

The cannabis plant (Cannabis sativa L.) produces an estimated 545 chemical compounds of different biogenetic classes. In addition to economic value, many of these phytochemicals have medicinal and physiological activity. The plant is most popularly known for its two most-prominent and most-studied secondary metabolites—Δ⁹-tetrahydrocannabinol (Δ⁹-THC) and cannabidiol (CBD). Both Δ⁹-THC and CBD have a wide therapeutic window across many ailments and form part of a class of secondary metabolites called cannabinoids—of which approximately over 104 exist. This review will focus on non-cannabinoid metabolites of Cannabis sativa that also have therapeutic potential, some of which share medicinal properties similar to those of cannabinoids. The most notable of these non-cannabinoid phytochemicals are flavonoids and terpenes. We will also discuss future directions in cannabis research and development of cannabis-based pharmaceuticals. Caflanone, a flavonoid molecule with selective activity against the human viruses including the coronavirus OC43 (HCov-OC43) that is responsible for COVID-19, and certain cancers, is one of the most promising non-cannabinoid molecules that is being advanced into clinical trials. As validated by thousands of years of the use of cannabis for medicinal purposes, vast anecdotal evidence abounds on the medicinal benefits of the plant. These benefits are attributed to the many phytochemicals in this plant, including non-cannabinoids. The most promising non-cannabinoids with potential to alleviate global disease burdens are discussed.

Background: Lassa hemorrhagic fever (LHF) is a rodent-borne viral disease that can be fatal for human beings. In this study, an attenuated Lassa vaccine candidate, ML29, was tested in SIV-infected rhesus macaques for its ability to elicit immune responses without instigating signs pathognomonic for arenavirus disease. ML29 is a reassortant between Lassa and Mopeia viruses that causes a transient infection in non-human primates and confers sterilizing protection from lethal Lassa viral challenge. However, since the LHF endemic area of West Africa also has high HIV seroprevalence, it is important to determine whether vaccination could be safe in the context of HIV infection. Results: SIV-infected and uninfected rhesus macaques were vaccinated with the ML29 virus and monitored for specific humoral and cellular immune responses, as well as for classical and non-classical signs of arenavirus disease. Classical disease signs included viremia, rash, respiratory distress, malaise, high liver enzyme levels, and virus invasion of the central nervous system. Non-classical signs, derived from profiling the blood transcriptome of virulent and non-virulent arenavirus infections, included increased expression of interferon-stimulated genes (ISG) and decreased expression of COX2, IL-1β, coagulation intermediates and nuclear receptors needed for stress signaling. All vaccinated monkeys showed ML29-specific antibody responses and ML29-specific cell-mediated immunity. Conclusion: SIV-infected and uninfected rhesus macaques responded similarly to ML29 vaccination, and none developed chronic arenavirus infection. Importantly, none of the macaques developed signs, classical or non-classical, of arenavirus disease.

Oral and dental diseases are a major global burden, the most common non-communicable diseases (NCDs), and may even affect an individual’s general quality of life and health. The most prevalent dental and oral health conditions are tooth decay (otherwise referred to as dental caries/cavities), oral cancers, gingivitis, periodontitis, periodontal (gum) disease, Noma, oro-dental trauma, oral manifestations of HIV, sensitive teeth, cracked teeth, broken teeth, and congenital anomalies such as cleft lip and palate. Herbs have been utilized for hundreds of years in traditional Chinese, African and Indian medicine and even in some Western countries, for the treatment of oral and dental conditions including but not limited to dental caries, gingivitis and toothaches, dental pulpitis, halitosis (bad breath), mucositis, sore throat, oral wound infections, and periodontal abscesses. Herbs have also been used as plaque removers (chew sticks), antimicrobials, analgesics, anti-inflammatory agents, and antiseptics. Cannabis sativa L. in particular has been utilized in traditional Asian medicine for tooth-pain management, prevention of dental caries and reduction in gum inflammation. The distribution of cannabinoid (CB) receptors in the mouth suggest that the endocannabinoid system may be a target for the treatment of oral and dental diseases. Most recently, interest has been geared toward the use of Cannabidiol (CBD), one of several secondary metabolites produced by C. sativa L. CBD is a known anti-inflammatory, analgesic, anxiolytic, anti-microbial and anti-cancer agent, and as a result, may have therapeutic potential against conditions such burning mouth syndrome, dental anxiety, gingivitis, and possible oral cancer. Other major secondary metabolites of C. sativa L. such as terpenes and flavonoids also share anti-inflammatory, analgesic, anxiolytic and anti-microbial properties and may also have dental and oral applications. This review will investigate the potential of secondary metabolites of C. sativa L. in the treatment of dental and oral diseases.

Physical exercise is well known to benefit human health at every age. However, the exact mechanism through which physical exercise improves health remains unknown. Recent studies into exercise-induced myokine FNDC5/irisin, a newly discovered hormone, have begun to shed light on this mystery. Exercise-induced myokine FNDC5/irisin have been shown to be protective against cardiovascular damage post ischemic event, improve function in the neurons of Alzheimer’s disease patients, and have been implicated in macrophage and adipocyte regulation. Elegantly designed experiments have shown FNDC5/irisin to promote Nkx2.5+ cardiac progenitor cell dependent cardiac regeneration, neovascularization, and reduce cardiac fibrosis. It has also been shown to improve macrophage function, which may protect against injuries to the cardiac conduction system. Similarly, FNDC5/irisin knockout mice have been shown to have reduced memory performance, while peripheral overexpression of FNDC5/irisin has been shown to improve memory impairment in a murine Alzheimer’s disease model. Finally, FNDC5/irisin has been linked to regulation of osteocytes and adipocytes by signaling through the cytoplasmic membrane integrated protein aV/b5 integrin, the first known receptor for this newly discovered hormone. Although these recent discoveries have cemented the importance of FNDC5/irisin, many details regarding how FNDC5/irisin fits into the physiology of exercise benefits remain unknown and are deserving of future inquiry.