Abstract Objective To establish the prevalence of long-term and serious harms of medical cannabis for chronic pain. Design Systematic review and meta-analysis. Data sources MEDLINE, EMBASE, PsycINFO and CENTRAL from inception to 1 April 2020. Study selection Non-randomised studies reporting on harms of medical cannabis or cannabinoids in adults or children living with chronic pain with ≥4 weeks of follow-up. Data extraction and synthesis A parallel guideline panel provided input on the design and interpretation of the systematic review, including selection of adverse events for consideration. Two reviewers, working independently and in duplicate, screened the search results, extracted data and assessed risk of bias. We used random-effects models for...

Abstract Cannabinoids and their endogenous and synthetic analogs impact blood pressure and contribute to the incidence of hypertension. It was previously reported that the endocannabinoid system plays an important role in developing hypertension; however, it was also shown that cannabinoids elicit profound hypotension associated with hemorrhagic, cardiogenic, and endotoxic shock. This study aimed to test acute and chronic effects of an endogenous ligand of cannabinoid receptor anandamide (AEA) on blood pressure and kidney injury in vivo in conscious Dahl salt-sensitive (SS) rats. We demonstrated that acute i.v. bolus administration of a low or a high doses (0.05 or 3 mg/kg) of AEA did not affect blood pressure for 2 h...

Abstract Cannabinoids, mainly cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), are the most studied group of compounds obtained from Cannabis sativa because of their several pharmaceutical properties. Current evidence suggests a crucial role of cannabinoids as potent anti-inflammatory agents for the treatment of chronic inflammatory diseases; however, the mechanisms remain largely unclear. Cytokine storm, a dysregulated severe inflammatory response by our immune system, is involved in the pathogenesis of numerous chronic inflammatory disorders, including coronavirus disease 2019 (COVID-19), which results in the accumulation of pro-inflammatory cytokines. Therefore, we hypothesized that CBD and THC reduce the levels of pro-inflammatory cytokines by inhibiting key inflammatory signaling pathways. The nucleotide-binding and...

Abstract Characterised by chronic widespread musculoskeletal pain, generalised hyperalgesia, and psychological distress, fibromyalgia (FM) is a significant unmet clinical need. The endogenous cannabinoid system plays an important role in modulating both pain and the stress response. Here, we appraise the evidence, from preclinical and clinical studies, for a role of the endocannabinoid system in FM and the therapeutic potential of targeting the endocannabinoid system. While many animal models have been used to study FM, the reserpine-induced myalgia model has emerged as perhaps the most translatable to the clinical phenotype. Inhibition of fatty acid amide hydrolase (FAAH) has shown promise in preclinical studies, ameliorating pain- and anxiety-related behaviour . Clinically, there is evidence for alterations in...

Abstract Two major cannabinoids of cannabis, namely cannabidiol (CBD) and tetrahydrocannabinol (THC) have been reportedly used as alternative medicine for diabetes treatment in both pre-clinical and clinical research. However, their mechanisms of action still remain unclear. Therefore, this study aimed to evaluate the α-glucosidase inhibitory activity of THC, CBD and the standardized cannabinoid extracts. Based on in silico studies, THC generated hydrogen bonding and Van der Waals interactions, while CBD exhibited only Van der Waals interactions with functional residues of target α-glucosidase protein, with good binding energies of −7.5 and −6.9 kcal/mol, respectively. In addition, both of them showed excellent pharmacokinetic profiles with minor toxicity in terms of tumorigenic and reproductive effects. In addition, the enzyme based in...

Please use this link to access this publication. Abstract Medical marijuana has been approved by the FDA for treating chemotherapy-induced nausea and vomiting. However, less is known about its direct effects on tumor cells and the tumor microenvironment. In this study, RNA-sequencing datasets in the NCBI GEO repository were first analyzed; upregulation of cannabinoid receptors was observed in both primary and metastatic colorectal cancer (CRC) tumor tissues. An increase of cannabinoid receptors was also found in patients with CRC, azoxymethane/dextran sulfate sodium-induced CRC and CRC metastatic mouse models. Δ9-Tetrahydrocannabinol (Δ9-THC)-induced tumor progression in both primary and metastatic mouse models and also increased angiogenesis. A...

Abstract Cannabis sativa is one of the first medicinal plants used by humans. Its medical use remains controversial because it is a psychotropic drug whose use has been banned. Recently, however, some countries have approved its use, including for recreational and medical purposes, and have allowed the scientific study of its compounds. Cannabis is characterized by the production of special types of natural products called phytocannabinoids that are synthesized exclusively by this genus. Phytocannabinoids and endocannabinoids are chemically different, but both pharmacologically modulate CB1, CB2, GRP55, GRP119 and TRPV1 receptor activities, involving activities such as memory, sleep, mood, appetite and motor regulation, pain sensation, neuroinflammation, neurogenesis and...

Abstract The use of cannabinoids as therapeutic drugs has increased among aging populations recently. Age-related changes in the endogenous cannabinoid system could influence the effects of therapies that target the cannabinoid system. At the preclinical level, cannabidiol (CBD) induces anti-amyloidogenic, antioxidative, anti-apoptotic, anti-inflammatory, and neuroprotective effects. These findings suggest a potential therapeutic role of cannabinoids to neurodegenerative disorders such as Parkinson’s disease (PD) and Alzheimer. Emerging evidence suggests that CBD and tetrahydrocannabinol have neuroprotective therapeutic-like effects on dementias. In clinical practice, cannabinoids are being used off-label to relieve symptoms of PD and AD. In fact, patients are using cannabis compounds for the treatment of...

Abstract Chronic pain is a complex sensory, cognitive, and emotional experience that imposes a great personal, psychological, and socioeconomic burden on patients. An estimated 1.5 billion people worldwide are afflicted with chronic pain, which is often difficult to treat and may be resistant to the potent pain-relieving effects of opioid analgesics. Attention has therefore focused on advancing new pain therapies directed at the cannabinoid system because of its key role in pain modulation. Endocannabinoids and exogenous cannabinoids exert their actions primarily through Gi/o-protein coupled cannabinoid CB1 and CB2 receptors expressed throughout the nervous system. CB1 receptors are found at key nodes along the pain...

Abstract Purpose Dry eye disease (DED) is a multifactorial disease, with limitations regarding efficacy and tolerability of applied substances. Among several candidates, the endocannabinoid system with its receptors (CB1R and CB2R) were reported to modulate inflammation, wound healing and pain, which are also core DED pathomechanisms. This study is to investigate the therapeutic responses of Δ-9 tetrahydrocannabinol (a non-selective agonist) and two selective antagonists, SR141716A (CB1R antagonist) and SR144528 (CB2R antagonist), as a topical application using a DED mouse model. Method Experimental DED was induced in naïve C57BL/6 mice. Expression of CBR at the ocular surface of naïve and DED mice was determined by qPCR and in-situ hybridization. Either THC or CBR antagonists were compounded in an aqueous solution...