“Background: Thirty-six states, including Florida, have legalized marijuana for medical and/or recreational use, yet how it is used and perceived by persons with cancer is not well understood.
Objectives: The purpose of this study was to identify patterns of use, perceived benefits, and side effects of medical marijuana (MMJ) among cancer patients in Florida.
Methods: For this descriptive, cross-sectional study, anyone residing within the state of Florida who was diagnosed or treated for a malignancy within the last five years and had used MMJ was eligible. An online survey containing questions about dosing, side effects, perceived benefits, and barriers to use was used. Descriptive statistics including frequencies, percentages, means, and standard deviations were used to analyze quantitative data. Responses to open-ended questions were coded and categorized.
Results: Sleep (n = 112), pain (n = 96), and anxiety (n = 82) were the most common symptoms participants used MMJ to relieve and overall felt it was highly effective. MMJ was well tolerated with a minority (10.3%) reporting any adverse effects. Cost was the most frequent barrier reported by participants (42.8%). A variety of legal, bureaucratic, and system-related barriers were described.
Conclusion: Participants perceived MMJ to be helpful in alleviating cancer symptoms. They held negative perceptions of the way MMJ is implemented and integrated into their oncology treatment plan. Enhanced communication and patient/provider education on MMJ are needed to inform patient decision making.”
“Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns.
Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors.
In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9, SEC61G, TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways.
Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed.”
“The antineoplastic role of cannabinoids in malignancy of the immune system, as well as in many other tumors, i.e., osteosarcoma, is well documented. Cannabinoids derive from the Cannabis plant, and interact with the cannabinoid receptors CB1 and CB2, principally expressed in the central nervous system and in peripheral and immune cells, respectively. These receptors, together with their specific ligands (endocannabinoids) and the enzymes involved in their own synthesis and degradation, constitute the endocannabinoid system (ECS). ECS is involved in many biological functions, such as pain management, regulation of appetite, control of bone metabolism, and, noteworthily, it modulates both inflammatory processes and immune response. Several authors proposed ECS as anticancer target for different neoplasms; in particular, a proper stimulation of CB2 receptors is responsible for counteracting tumor growth and progression. We demonstrate the involvement of ECS in this neoplasm and highlight the possibility to target it to arrest growth and progression of B-ALL
Our findings describe the involvement of CB2 receptors in the pathogenesis of B-ALL, and also propose its stimulation as an innovative and effective anticancer strategy. In particular, this approach is a “molecular target therapy approach”, since the selective triggering of cannabinoid modulates both gene and protein expression. We identified a specific anti-tumoral signature playing a key role in the development and maintenance of tumors, speculating a protective effect of CB2 selective stimulation. Certainly, further investigations are needed to better understand the molecular and biochemical mechanisms underlying the observed interactions, but our study seems to already highlight a good and beneficial therapeutic perspective to ameliorate the outcome for high-risk B-ALL patients.”
“Mesothelioma is an aggressive cancer with limited treatment options and a poor prognosis. Phytocannabinoids possess anti-tumour and palliative properties in multiple cancers, however their effects in mesothelioma are unknown. We investigated the anti-cancer effects and potential mechanisms of action for several phytocannabinoids in mesothelioma cell lines.
A panel of 13 phytocannabinoids inhibited growth of human (MSTO and H2452) and rat (II-45) mesothelioma cells in vitro, and cannabidiol (CBD) and cannabigerol (CBG) were the most potent compounds. Treatment with CBD or CBG resulted in G0/G1 arrest, delayed entry into S phase and induced apoptosis. CBD and CBG also significantly reduced mesothelioma cell migration and invasion. These effects were supported by changes in the expression of genes associated with the cell cycle, proliferation, and cell movement following CBD or CBG treatment. Gene expression levels of CNR1, GPR55, and 5HT1A also increased with CBD or CBG treatment. However, treatment with CBD or CBG in a syngeneic orthotopic rat mesothelioma model was unable to increase survival.
Our data show that cannabinoids have anti-cancer effects on mesothelioma cells in vitro and alternatives of drug delivery may be needed to enhance their effects in vivo.”
We showed that several phytocannabinoids inhibited growth of mesothelioma cells, with two phytocannabinoids, cannabidiol (CBD) and cannabigerol (CBG), being the most potent. CBD and CBG also inhibited mesothelioma cell migration and invasion. Gene expression analysis highlighted signalling pathways that play a role in how CBD and CBG may exert their anti-cancer effects. CBD and CBG were unable to increase survival in a rat model of mesothelioma but this may be due to limitations in the drug delivery method.
Our data present the first report that plant cannabinoids have anti-proliferative effects on mesothelioma cells, that was associated with apoptosis, rather than autophagy or production of ROS. CBD and CBG were the most potent cannabinoids and also inhibited mesothelioma cell migration and invasion.”
“Identifying effective anti-aging compounds is a cornerstone of modern longevity, aging, and skin-health research. There is considerable evidence of the effectiveness of nutrient signaling regulators such as metformin, resveratrol, and rapamycin in longevity and anti-aging studies; however, their potential protective role in skin aging is controversial.
In light of the increasing appearance of phytocannabinoids in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of phytocannabinoids in combination with nutrient signaling regulators in skin rejuvenation. Utilizing CCD-1064Sk skin fibroblasts, the effect of metformin, triacetylresveratrol, and rapamycin combined with phytocannabinoids on cellular viability, functional activity, metabolic function, and nuclear architecture was tested.
We found triacetylresveratrol combined with cannabidiol increased the viability of skin fibroblasts (p < 0.0001), restored wound-healing functional activity (p < 0.001), reduced metabolic dysfunction, and ameliorated nuclear eccentricity and circularity in senescent fibroblasts (p < 0.01). Conversely, metformin with or without phytocannabinoids did not show any beneficial effects on functional activity, while rapamycin inhibited cell viability (p < 0.01) and the speed of wound healing (p < 0.001).
Therefore, triacetylresveratrol and cannabidiol can be a valuable source of biologically active substances used in aging and more studies using animals to confirm the efficacy of cannabidiol combined with triacetylresveratrol should be performed.”
“We, for the first time, show that application of TRSV in combination with CBD constitutes a very promising anti-aging and regenerative regimen that can potentially be used for treatment or/and prevention of appearance of aging spots and treating cutaneous wounds. Moreover, we found pCBs alone appeared to be highly efficacious as an anti-aging treatment. Further work should study and test pCBs alone, as well as TRSV in combination with CBD as anti-aging remedies.”
“Seeds from non-drug varieties of hemp (Cannabis sativa L.) have been used for traditional medicine, food, and fiber production. Our study shows that phytol obtained from hemp seed oil (HSO) exerts anti-inflammatory activity in human monocyte-macrophages.
Fresh human monocytes and human macrophages derived from circulating monocytes were used to evaluate both plasticity and anti-inflammatory effects of phytol from HSO at 10-100 mM using FACS analysis, ELISA, and RT-qPCR methods. The quantitative study of the acyclic alcohol fraction isolated from HSO shows that phytol is the most abundant component (167.59 ± 1.81 mg/Kg of HSO).
Phytol was able to skew monocyte-macrophage plasticity toward the anti-inflammatory non-classical CD14+CD16++ monocyte phenotype and toward macrophage M2 (CD200Rhigh and MRC-1high), as well as to reduce the production of IL-1β, IL-6, and TNF-α, diminishing the inflammatory competence of mature human macrophages after lipopolysaccharide (LPS) treatment.
These findings point out for the first time the reprogramming and anti-inflammatory activity of phytol in human monocyte-macrophages. In addition, our study may help to understand the mechanisms by which phytol from HSO contributes to the constant and progressive plasticity of the human monocyte-macrophage linage.”
“These results showed that phytol, which was isolated and identified for the first time in HSO, can help to better understand the specific mechanism by which this acyclic diterpene exerts beneficial effects on monocyte-macrophage plasticity. So far, HSO has already been demonstrated to include healthy polyunsaturated fatty acids, as well as antioxidant tocopherols and anti-inflammatory phytosterols in its unsaponifiable fraction. In recent years, inflammation has emerged as a leading pathophysiologic mechanism in atherosclerosis and other diseases, so the effects of phytol on different hallmarks of the inflammatory response contribute to the recommendation of HSO as an interesting source of functional compounds.”
“Background: The psychoactive and non-psychoactive constituents of cannabis, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), synergistically reduce allodynia in various animal models of neuropathic pain. Unfortunately, THC-containing drugs also produce substantial side-effects when administered systemically. We examined the effectiveness of targeted spinal delivery of these cannabis constituents, alone and in combination.
Methods: The effect of acute intrathecal drug delivery on allodynia and common cannabinoid-like side-effects was examined in a mouse chronic constriction injury (CCI) model of neuropathic pain.
Results: intrathecal THC and CBD produced dose-dependent reductions in mechanical and cold allodynia. In a 1:1 combination, they synergistically reduced mechanical and cold allodynia, with a two-fold increase in potency compared to their predicted additive effect. Neither THC, CBD nor combination THC:CBD produced any cannabis-like side-effects at equivalent doses. The anti-allodynic effects of THC were abolished and partly reduced by cannabinoid CB1 and CB2 receptor antagonists AM281 and AM630, respectively. The anti-allodynic effects of CBD were partly reduced by AM630.
Conclusions: these findings indicate that intrathecal THC and CBD, individually and in combination, could provide a safe and effective treatment for nerve injury induced neuropathic pain.”
“The present findings indicate that intrathecal delivery of the phytocannabinoids THC and CBD reduces the mechanical and cold allodynia associated with a nerve injury induced model of neuropathic pain. Interestingly, THC and CBD acted synergistically to reduce allodynia, leading to a substantial increase in their anti-allodynic potency. In addition, both THC and CBD were devoid of the cannabis-like side-effects associated with the systemic delivery of THC-containing cannabinoids. These findings indicate that spinal delivery of the primary phytocannabinoids of the plant Cannabis sativa has potential in the treatment of chronic neuropathic pain.”
“The lack of effective treatment for neurological disorders has encouraged the search for novel therapeutic strategies. Remarkably, neuroinflammation provoked by the activated microglia is emerging as an important therapeutic target for neurological dysfunction in the central nervous system. In the pathological context, the hyperactivation of microglia leads to neuroinflammation through the release of neurotoxic molecules, such as reactive oxygen species, proteinases, proinflammatory cytokines and chemokines.
Cannabidiol (CBD) is a major pharmacologically active phytocannabinoids derived from Cannabis sativa L. CBD has promising therapeutic effects based on mounting clinical and preclinical studies of neurological disorders, such as epilepsy, multiple sclerosis, ischemic brain injuries, neuropathic pain, schizophrenia and Alzheimer’s disease.
A number of preclinical studies suggested that CBD exhibited potent inhibitory effects of neurotoxic molecules and inflammatory modulators, highlighting its remarkable therapeutic potential for the treatment of numerous neurological disorders. However, the molecular mechanisms of action underpinning CBD’s effects on neuroinflammation appear to be complex and are poorly understood.
This review summarises the anti-neuroinflammatory activities of CBD against various neurological disorders with a particular focus on their main molecular mechanisms of action, which were related to the downregulation of NADPH oxidase-mediated ROS, TLR4-NFκB and IFN-β-JAK-STAT pathways. We also illustrate the pharmacological action of CBD’s derivatives focusing on their anti-neuroinflammatory and neuroprotective effects for neurological disorders. We included the studies that demonstrated synergistic enhanced anti-neuroinflammatory activity using CBD and other biomolecules.
The studies that are summarised in the review shed light on the development of CBD, including its derivatives and combination preparations as novel therapeutic options for the prevention and/or treatment of neurological disorders where neuroinflammation plays an important role in the pathological components.”
“Cannabinoids are a group of terpenophenolic compounds derived from the Cannabis sativa L. plant. The preclinical studies summarised in this review supported the therapeutic use of CBD in treating neurological disorders from its action in addressing microglia-mediated neuroinflammation. The findings of this review shed light on the development of CBD and relevant compounds as novel and more advantageous therapeutics to prevent or treat neurological disorders by targeting microglia-mediated neuroinflammation.”
“Introduction: Medicinal cannabis is prescribed in Australia for patients with chronic refractory pain conditions. However, measures of safety and effectiveness of different cannabinoids are lacking. We designed an observational study to capture effectiveness, adverse events (AEs), and health-related quality of life (HRQoL) measures in patients prescribed an oral medicinal cannabis formulation at Cannabis Access Clinics through the Cannabis Access Clinics Observational study (CACOS).
Objectives: We aimed to evaluate effectiveness, reported AEs, and change in patient-reported outcomes in individuals prescribed a cannabinoid oil formulation for management of chronic pain.
Methods: A cross-sectional analysis was conducted on patients prescribed an oil formulation of Δ9-tetrahydrocannabinol and cannabidiol for pain symptoms of at least 3-month duration. Clinician-reported AEs were organized by system, organ, class, and frequency. Analysis of patient-reported responses to a questionnaire was conducted using published minimal clinically important differences to determine meaningful change in HRQoL over time.
Results: More than half (n = 91/151, 60.3%) of the participants experienced at least one AE during the observation period (mean 133 ± 116 days). No serious AEs were reported. Patient-reported pain impact scores were significantly reduced across the cohort (p = 0.034), and pain intensity scores verged on significance (p = 0.053). The majority of patients saw meaningful improvements in sleep (49.3%) and fatigue (35.6%).
Conclusion: This analysis presents real-world data collected as part of standard of care. More than one-third of patients benefited from oral medicinal cannabis, which is impactful given the refractory nature of their pain. Amelioration of the impact of pain confirms continued prescribing of this formulation and validates our observational methodology as a tool to determine the therapeutic potency of medicinal cannabinoids.”
“This is a clinically relevant finding considering that this patient cohort comprises refractory cases where relief has not been obtained with existing medications, including opioids, NSAIDs, and steroids.”
“Small molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the cause of the COVID-19 pandemic.
To expedite the discovery of lead compounds for development, assays have been developed based on affinity selection-mass spectrometry (AS-MS), which enables the rapid screening of mixtures such as combinatorial libraries and extracts of botanicals or other sources of natural products. AS-MS assays have been used to find ligands to the SARS-CoV-2 spike protein for inhibition of cell entry as well as to the 3-chymotrypsin-like cysteine protease (3CLpro) and the RNA-dependent RNA polymerase complex constituent Nsp9, which are targets for inhibition of viral replication.
The AS-MS approach of magnetic microbead affinity selection screening has been used to discover high-affinity peptide ligands to the spike protein as well as the hemp cannabinoids cannabidiolic acid and cannabigerolic acid, which can prevent cell infection by SARS-CoV-2.
Another AS-MS method, native mass spectrometry, has been used to discover that the flavonoids baicalein, scutellarein, and ganhuangenin, can inhibit the SARS-CoV-2 protease 3CLpro. Native mass spectrometry has also been used to find an ent-kaurane natural product, oridonin, that can bind to the viral protein Nsp9 and interfere with RNA replication.
These natural lead compounds are under investigation for the development of therapeutic agents to prevent or treat SARS-CoV-2 infection.”
“Background: The synthetic tetrahydrocannabinol analogue nabilone improved overall non-motor symptom (NMS) burden in Parkinson’s disease (PD) patients in comparison to placebo.
Objectives: To characterize the effects of nabilone on different sleep outcomes in PD patients.
Methods: We performed a post-hoc analysis of the controlled, double-blind, enriched enrollment randomized withdrawal NMS-Nab study to assess the effects of nabilone on sleep outcomes in study participants who reported clinically-relevant sleep problems (MDS-UPDRS-1.7 ≥ 2 points).
Results: After open-label nabilone administration, 77.4% reported no relevant sleep problem. In the withdrawal phase of the trial, the MDS-UPDRS-1.7. and the NMS-Scale Domain 2 (i.e., Sleep/Fatigue) significantly worsened only in PD patients in the placebo group, which was mostly driven by a significant worsening of insomnia (question 5 of the NMS-Scale Domain 2).
Conclusions: This post-hoc analysis of the NMS-Nab trial suggests that nabilone has beneficial effects on sleep outcomes in PD patients experiencing sleep problems at baseline.”
