“Historical relevance: Cannabis sativa L. (C. sativa) is a plant whose use as a therapeutic agent shares its origins with the first Far East’s human societies. Cannabis has been used not only for recreational purposes, but as a food to obtain textile fibers, to produce hemp paper, to treat many physical and mental disorders.
This review aims to provide a complete assessment of the deep knowledge of the cannabis psychoactive effects and medicinal properties in the course of history covering i.) the empirical use of the seeds and the inflorescences to treat many physical ailments by the ancient Oriental physicians ii.) the current use of cannabis as a therapeutic agent after the discovery of its key psychoactive constituent and the human endogenous endocannabinoid system.
Results and conclusion: Through a detailed analysis of the available resources about the origins of C. sativa we found that its use by ancient civilizations as a source of food and textile fibers dates back over 10,000 years, while its therapeutic applications have been improved over the centuries, from the ancient East medicine of the 2nd and 1st millennium B.C. to the more recent introduction in the Western world after the 1st century A.D. In the 20th and 21th centuries, Cannabis and its derivatives have been considered as a menace and banned throughout the world, but nowadays they are still the most widely consumed illicit drugs all over the world. Its legalization in some jurisdictions has been accompanied by new lines of research to investigate its possible applications for medical and therapeutic purposes.”
“Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘
“The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of 
“While natural Δ9-tetrahidrocannabinol (Δ9THC), 
“The inhibitor of DNA binding (Id) proteins are regulators of cell cycle and cell differentiation. Of all Id family proteins, Id1 is mostly linked to tumorigenesis, cellular senescence as well as cell proliferation and survival.
“HIV infection affects an estimated 38 million people. Approximately 50% of HIV patients exhibit neurocognitive dysfunction termed HIV-Associated Neurocognitive Disorder (HAND). HAND is a consequence of chronic low-level neuroinflammation due to HIV entry into the brain. Initially, monocytes become activated in circulation and traffic to the brain. Monocytes, when activated, become susceptible to infection by HIV and can then carry the virus across the blood brain barrier. Once in the brain, activated monocytes secrete chemokines, which recruit virus-specific CD8+ T cells into the brain to further promote neuroinflammation. HAND is closely linked to systemic inflammation driven, in part, by HIV but is also due to persistent translocation of microorganisms across the GI tract. Persistent anti-viral responses in the GI tract compromise microbial barrier integrity. Indeed, HIV patients can exhibit remarkably high levels of activated (CD16+) monocytes in circulation.
“Modern day research, in an attempt to determine the potential therapeutic and adverse effects of illicit substances, is a growing field, but one that faces many regulatory challenges. Due to the potential abuse of illicit substances such as 
“The therapeutic effect of the Cannabis plant largely depends on the presence and specific ratio of a spectrum of phytocannabinoids. While prescription of medicinal Cannabis for various conditions constantly grows, its consumption is mostly limited to oral or respiratory pathways, impeding its duration of action, bioavailability and efficacy. Herein, a long-acting formulation in the form of melt-printed polymeric microdepots for full-spectrum 
“The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality.
“The demonstrated expression of endocannabinoid receptors in myofascial tissue suggested the role of fascia as a source and modulator of pain.