“Chronic stress impairs radial neural stem cell (rNSC) differentiation and adult hippocampal neurogenesis (AHN), whereas promoting AHN can increase stress resilience against depression. Therefore, investigating the mechanism of neural differentiation and AHN is of great importance for developing antidepressant drugs. The nonpsychoactive phytocannabinoid cannabidiol (CBD) has been shown to be effective against depression. However, whether CBD can modulate rNSC differentiation and hippocampal neurogenesis is unknown. Here, by using the chronic restraint stress (CRS) mouse model, we showed that hippocampal rNSCs mostly differentiated into astrocytes under stress conditions. Moreover, transcriptome analysis revealed that the FoxO signaling pathway was involved in the regulation of this process. The administration of CBD rescued depressive-like symptoms in CRS mice and prevented rNSCs overactivation and differentiation into astrocyte, which was partly mediated by the modulation of the FoxO signaling pathway. These results revealed a previously unknown neural mechanism for neural differentiation and AHN in depression and provided mechanistic insights into the antidepressive effects of CBD.”
Cannabis terpenes display variable protective and anti-aggregatory actions against neurotoxic β amyloid in vitro: highlighting the protective bioactivity of α-bisabolol in motorneuronal-like NSC-34 cells
“Background: Terpenes form a diverse class of naturally occurring chemicals ascribed various biological activities. Cannabis contains over 400 different terpenes of varying chemical complexity which may add to the known biological activities of phytocannabinoids of relevance to the increasing use of medical cannabis; however, to date have been incompletely characterized. We assessed three terpenes predominant in cannabis: α-bisabolol, myrcene and β-caryophyllene for neuroprotective and anti-aggregative properties in both undifferentiated and differentiated NSC-34 motorneuronal-like cells as a sensitive model for neurotoxicity to oxidative stress and amyloid β (Aβ1-42) protein exposure.
Methods: Cell viability was assessed biochemically using the MTT assay in the presence of either α-bisabolol, myrcene and β-caryophyllene (1-1000 µM) for 48 hr. Sub-toxic threshold test concentrations of each terpene were then applied to cells, alone or with concomitant incubation with the lipid peroxidant tert-butyl hyrdroperoxide (t-BHP) or amyloid β (Aβ1-42; 0-1 µM) to assess neuroprotective effects. Direct effects of each terpene on Aβ fibril formation and aggregation were also evaluated using the Thioflavin T (ThT) fluorometric kinetic assay, circular dichroism and transmission electron microscopy (TEM) to visualise fibril and aggregate morphology.
Results: Terpenes were intrinsically benign to NSC-34 cells up to 100 µM. No significant antioxidant effects were observed following t-BHP administration with myrcene and β-caryophyllene, however α-bisabolol provided a modest but significant increase in cell viability in undifferentiated cells. α-bisabolol also demonstrated a significant neuroprotective effect against amyloid β exposure, with β-caryophyllene also providing a lesser, but significant increase in cell viability. Protective effects of terpenes were more pronounced in undifferentiated versus differentiated cells, attributable more so to an attenuated loss of cell viability in response to Aβ1-42 following NSC-34 cell differentiation. Neuroprotection was associated with a direct inhibition of Aβ1-42 fibril and aggregate density, evidenced by both attenuated ThT fluorescence kinetics and both spectral and microscopic evidence of altered and diminished density of Aβ aggregates. While myrcene and β-caryophyllene also elicited reductions in ThT fluorescence and alterations in Aβ aggregation, these were less well associated with neuroprotective capacity.
Conclusions: These findings highlight a neuroprotective role of α-bisabolol against Aβ-mediated neurotoxicity associated with an inhibition of Aβ fibrillization and modest antioxidant effect against lipid peroxidation, while β-caryophyllene also provided a small but significant measure of protection to Aβ-mediated neurotoxicity. Anti-aggregatory effects were not directly correlated with neuroprotective efficacy. This demonstrates that bioactivity of selected terpenes should be a consideration in the emergent use of medicinal cannabis formulations for the treatment of neurodegenerative diseases.”
Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles
“Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is an urgent need for new treatment protocols that can also target biofilm-embedded bacteria. Many secondary metabolites of plants possess anti-bacterial activities, and especially the phytocannabinoids of the Cannabis sativa L. varieties have reached a renaissance and attracted much attention for their anti-microbial and anti-biofilm activities at concentrations below the cytotoxic threshold on normal mammalian cells. Accordingly, many synthetic cannabinoids have been designed with the intention to increase the specificity and selectivity of the compounds. The structurally unrelated endocannabinoids have also been found to have anti-microbial and anti-biofilm activities. Recent data suggest for a mutual communication between the endocannabinoid system and the gut microbiota. The present review focuses on the anti-microbial activities of phytocannabinoids and endocannabinoids integrated with some selected issues of their many physiological and pharmacological activities.”
Non-psychotropic Cannabis sativa L. phytocomplex modulates microglial inflammatory response through CB2 receptors-, endocannabinoids-, and NF-κB-mediated signaling
“Cannabis sativa L. is increasingly emerging for its protective role in modulating neuroinflammation, a complex process orchestrated among others by microglia, the resident immune cells of the central nervous system. Phytocannabinoids, especially cannabidiol (CBD), terpenes, and other constituents trigger several upstream and downstream microglial intracellular pathways. Here, we investigated the molecular mechanisms of a CBD- and terpenes-enriched C. sativa extract (CSE) in an in vitro model of neuroinflammation. We evaluated the effect of CSE on the inflammatory response induced by exposure to lipopolysaccharide (LPS) in BV-2 microglial cells, compared with CBD and β-caryophyllene (CAR), CB2 receptors (CB2r) inverse and full agonist, respectively. The LPS-induced upregulation of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α was significantly attenuated by CSE and only partially by CBD, whereas CAR was ineffective. In BV-2 cells, these anti-inflammatory effects exerted by CSE phytocomplex were only partially dependent on CB2r modulation and they were mediated by the regulation of enzymes responsible for the endocannabinoids metabolism, by the inhibition of reactive oxygen species release and the modulation of JNK/p38 cascade with consequent NF-κB p65 nuclear translocation suppression. Our data suggest that C. sativa phytocomplex and its multitarget mechanism could represent a novel therapeutic strategy for neuroinflammatory-related diseases.”
Cannabis use among patients with cutaneous lymphoma: A cross-sectional survey
“Objective: To evaluate patterns of cannabis use in patients with cutaneous lymphoma (CL), as well as the association between cannabis use and itch specifically.
Design: Cross-sectional survey created in partnership with the Cutaneous Lymphoma Foundation (CLF).
Setting: The online survey was distributed electronically via email to the CLF listserv and links posted to social media over a 2-week period. Main Outcome Measures Respondents were classified as current cannabis users, prior users, and never users. A visual analog scale (VAS) was used to assess itching severity, improvement of itch, and interest in learning about cannabis.
Results: A total of 119 patient responses (61% female, mean age 59y) were included in analysis. The majority had mycosis fungoides or Sézary syndrome (74%; 88/119) and early stage (IA-IIA) disease (56%; 48/86). Mean VAS itch score was 3.2 + 2.8 for the cohort. Over half (55%; 60/110) reported ever having used cannabis, with 22% (24/110) endorsing current cannabis use. Common methods of cannabis use were smoking (54%) and vaporizing (46%). 25% (6/24) of current users reported using cannabis specifically to treat itch; these respondents noted that cannabis resulted in moderate improvement of itching (mean 6.6/10). There was strong interest in learning more about cannabis and cancer, and most desired this information from their CL doctor/nurse.
Conclusions: Cannabis use is common among patients with CL, and patients report improvement of itching as a result of using cannabis. Further studies are needed to elucidate the risks and benefits of cannabis use in this patient population.”
Measuring the Change in Health-Related Quality of Life in Patients Using Marijuana for Pain Relief
“Current evidence suggests that cannabinoids are safe with minimal side effects and are effective in managing chronic pain. Data also show that medical marijuana (MM) may improve quality of life (QoL) among patients. However, there are little data showing the health-related QoL (HRQoL) benefit in MM patients using it for pain. The purpose of this study was to determine if there is a relationship between HRQol and MM use in patients using it to relieve pain.
Results
1,762 people responded to the screening request, and 1,393 (79%) met screening criteria. Of those, 353 (25.3%) agreed to participate and 51% completed all 4 surveys, for a final sample of 181 with 85 male and 95 female and one nonbinary subject. The average age was 41.21 (SD = 12.9) years, with no difference between genders. The adjusted HRQoL score improved from 0.722 to 0.747 (p = 0.011) from survey 2 to survey 4, as did the self-reported pain and health scores. The EQ-5D subscales revealed no change in mobility or usual activities, significant improvement in anxiety and pain, and a significant worsening in self-care.
Conclusion
The results show a significant improvement in HRQoL among patients using MM for pain. The EQ-5D subscales validated the pain improvement and also showed an improvement in anxiety. However, the decline in the self-care subscale may have tempered the overall improvement in HRQoL, and further research into which aspects of self-care are impacted by MM use in this population is warranted. Overall, there is a positive relationship between MM use and HRQoL in patients using it for pain.”
Cannabis-Based Products for the Treatment of Skin Inflammatory Diseases: A Timely Review
“The use of natural products in dermatology is increasingly being pursued due to sustainability and ecological issues, and as a possible way to improve the therapeutic outcome of chronic skin diseases, relieving the burden for both patients and healthcare systems. The legalization of cannabis by a growing number of countries has opened the way for researching the use of cannabinoids in therapeutic topical formulations. Cannabinoids are a diverse class of pharmacologically active compounds produced by Cannabis sativa (phytocannabinoids) and similar molecules (endocannabinoids, synthetic cannabinoids). Humans possess an endocannabinoid system involved in the regulation of several physiological processes, which includes naturally-produced endocannabinoids, and proteins involved in their transport, synthesis and degradation. The modulation of the endocannabinoid system is a promising therapeutic target for multiple diseases, including vascular, mental and neurodegenerative disorders. However, due to the complex nature of this system and its crosstalk with other biological systems, the development of novel target drugs is an ongoing challenging task. The discovery of a skin endocannabinoid system and its role in maintaining skin homeostasis, alongside the anti-inflammatory actions of cannabinoids, has raised interest in their use for the treatment of skin inflammatory diseases, which is the focus of this review. Oral treatments are only effective at high doses, having considerable adverse effects; thus, research into plant-based or synthetic cannabinoids that can be incorporated into high-quality, safe topical products for the treatment of inflammatory skin conditions is timely. Previous studies revealed that such products are usually well tolerated and showed promising results for example in the treatment of atopic dermatitis, psoriasis, and contact dermatitis. However, further controlled human clinical trials are needed to fully unravel the potential of these compounds, and the possible side effects associated with their topical use.”
Overview of Cannabis including Kampo Medicine and Therapy for Treatment of Dementia: A Review
“Cannabis sativa L. is an annual herb oldest cultivated plants as a source of fiber since about 5000 B.C. On the other hand, the cannabis flower and seed are listed in Shennong’s classic Materia Medica approximately 2000 years ago. The formulas prescribed with cannabis in Kampo medicine have been summarized. Cannabidiol (CBD) and tetrahydrocannabinol (THC) are the major neurological and psychiatric cannabinoids, and develop to drugs. It becomes evident that the therapeutic CBD and/or THC are the important candidate of anti-dementia drugs having different mechanism for Alzheimer’s patients. Two receptors and endocannabinoids are also discussed for underlying mechanism of action. In order to promote the breeding of cannabis plant containing higher concentration of target cannabinoid the biosynthetic enzymes were isolated, cloning and the tertiary structure of THCA synthase determined by x-ray analysis resulting in the possibility of molecular breeding for cannabinoids.”
Autism and associated disorders: cannabis as a potential therapy
“Autism spectrum disorder (ASD) is a group of disabilities with impairments in physical, verbal, and behavior areas. Regardless the growing frequency of autism, no medicine has been formed for the management of the ASD primary symptoms. The most frequently prescribed drugs are off-label. Therefore, there is necessity for an advance tactic for the treatment of autism. The endocannabinoid system has a central role in ruling emotion and social behaviors. Dysfunctions of the system donate to the behavioral deficits in autism. Therefore, the endocannabinoid system represents a potential target for the development of a novel autism therapy. Cannabis and associated compounds have produced substantial research attention as a capable therapy in neurobehavioral and neurological syndromes. In this review we examine the potential benefits of medical cannabis and related compounds in the treatment of ASD and concurrent disorders.”
Effect of Cannabidiol on the Neural Glyoxalase Pathway Function and Longevity of Several C. elegans Strains Including a C. elegans Alzheimer’s Disease Model
“Cannabidiol is a nonpsychoactive phytocannabinoid produced by the Cannabis sativa plant and possesses a wide range of pharmacological activities, including anti-inflammatory, antioxidant, and neuroprotective activities. Cannabidiol functions in a neuroprotective manner, in part through the activation of cellular antioxidant pathways. The glyoxalase pathway detoxifies methylglyoxal, a highly reactive metabolic byproduct that can accumulate in the brain, and contributes to the severity of neurodegenerative diseases, including Alzheimer’s disease. While cannabidiol’s antioxidant properties have been investigated, it is currently unknown how it may modulate the glyoxalase pathway. In this research paper, we examine the effects of Cannabidiol on cerebellar neurons and in several Caenorhabditis elegans strains. We determined that a limited amount of Cannabidiol can prevent methylglyoxal-mediated cellular damage through enhancement of the neural glyoxalase pathway and extend the lifespan and survival of C. elegans, including a transgenic C. elegans strain modeling Alzheimer’s disease.”