“∆ 9 -Tetrahydrocannabinol (∆9 -THC), the active phytocannabinoid in cannabis, is virtually an adjunct to the endogenous endocannabinoid signaling system.
By interacting with G-protein-coupled receptors CB1 and CB2, ∆9 -THC affects peripheral and central circulation by lowering sympathetic activity, altering gene expression, cell proliferation, and differentiation, decreasing leukocyte migration, modulating neurotransmitter release thereby modulating cardiovascular functioning, tumorigenesis, immune responses, behavioral and locomotory activities respectively.
∆ 9 -THC is effective in suppressing chemotherapy-induced vomiting, retards malignant tumor growth, inhibits metastasis, and promotes apoptosis. Other mechanisms involved are targeting cell cycle at the G2-M phase in human breast cancer, downregulation of E2F transcription factor 1 (E2F1) in human glioblastoma multiforme, and stimulation of ER stress-induced autophagy.
∆ 9 -THC also plays a role in ameliorating neuroinflammation, excitotoxicity, neuroplasticity, trauma, and stroke and is associated with reliving childhood epilepsy, brain trauma, and neurodegenerative diseases.
∆9 -THC via CB1 receptors affects nociception, emotion, memory, and reduces neuronal excitability and excitotoxicity in epilepsy. It also increases renal blood flow, reduces intraocular pressure via a sympathetic pathway, and modulates hormonal release, thereby decreasing the reproductive function and increasing glucose metabolism.
Versatile medical marijuana has stimulated abundant research demonstrating substantial therapeutic promise, suggesting the possibilities of first-in-class drugs in diverse therapeutic segments. In this review, we represent the current pharmacological status of the phytocannabinoid, ∆ 9 -THC, and synthetic analogs in cancer, cardiovascular, and neurodegenerative disorders.”
“While activation of cannabinoid (CB2) receptors has been shown to be neuroprotective, no studies have examined whether this neuroprotection is directed at cerebral arterioles and no studies have examined whether activation of CB2 receptors can rescue cerebrovascular dysfunction during a chronic disease state such as type 1 diabetes (T1D).
“Non-Uremic Calciphylaxis (NUC) is a rare condition that often manifests as intractable and painful integumentary wounds, afflicting patients with a high burden of co-morbidity.
“There is no argument with regard to the physical and psychological stress-related nature of neuropsychiatric disorders. Yet, the mechanisms that facilitate disease onset starting from molecular stress responses are elusive.
“The endocannabinoid signaling system (ECSS) is altered by exposure to stress and mediates and modulates the effects of stress on the brain.
“Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (-)-trans-Δ9-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain.
“Coronavirus disease 2019 (COVID-19) is spreading fast all around the world with more than fourteen millions of detected infected cases and more than 600.000 deaths by 20th July 2020. While scientist are working to find a vaccine, current epidemiological data shows that the most common comorbidities for patients with the worst prognosis, hypertension and diabetes, are often treated with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).
“Alzheimer’s disease (AD) is an irreversible chronic neurodegenerative disorder that occurs when neurons in the brain degenerate and die. Pain frequently arises in older patients with neurodegenerative diseases including AD. However, the presence of pain in older people is usually overlooked with cognitive dysfunctions. Most of the times dementia patients experience moderate to severe pain but the development of severe cognitive dysfunctions tremendously affects their capability to express the presence of pain. Currently, there are no effective treatments against AD that emphasize the necessity for increasing research to develop novel drugs for treating or preventing the disease process. Furthermore, the prospective therapeutic use of cannabinoids in AD has been studied for the past few years. In this regard, targeting the endocannabinoid system has considered as a probable therapeutic strategy to control several associated pathological pathways, such as mitochondrial dysfunction, excitotoxicity, oxidative stress, and neuroinflammation for the management of AD. In this review, we focus on recent studies about the role of cannabinoids for the treatment of pain and related neuropathological changes in AD.”
“Cannabinoid receptors type 1 (CB1) and 2 (CB2) are widely expressed in the human body, and are attractive drug targets in the prevention and management of central nervous system (CNS) and immune system dysfunction, respectively. Recent breakthroughs in the structural elucidation of cannabinoid receptors and their signaling complexes with G proteins, provide the important molecular basis of ligand-receptor interactions, activation and signaling mechanism, which will facilitate the next-generation drug design and the precise modulation of the endocannabinoid system. Here, we provide an overview on the structural features of cannabinoid receptors in different functional states and the diverse ligand binding modes. The major challenges and new strategies for future therapeutic applications targeting the endocannabinoid system (ECS) are also discussed.”