“These data support the notion that CBD and CBDV act as functional partial agonists on dopamine D2-like receptors in vivo.
The discovery that dopamine receptor is involved in the actions of phytocannabinoids moves a significant step toward our understanding of the mechanisms for medical uses of cannabis in the treatment of neurological and psychiatric disorders.”
https://pubmed.ncbi.nlm.nih.gov/33097185/
https://www.sciencedirect.com/science/article/abs/pii/S0006291X20319306?via%3Dihub
“In this proof-of-concept study, the antioxidant activity of phytocannabinoids, namely cannabidiol (CBD) and Δ9- tetrahydrocannabinol (THC), were investigated using an in vitro system of differentiated human neuronal SY-SH5Y cells.
We showed that THC had a high potency to combat oxidative stress in both in vitro models, while CBD did not show a remarkable antioxidant activity. The cannabis extracts also exhibited a significant antioxidant activity, which depended on the ratio of the THC and CBD. However, our results did not suggest any antagonist effect of the CBD on the antioxidant activity of THC. The effect of cannabis extracts on the cell viability of differentiated human neuronal SY-SH5Y cells was also investigated, which emphasized the differences between the bioactivity of cannabis extracts due to their composition.
Our preliminary results demonstrated that cannabis extracts and phytocannabinoids have a promising potential as antioxidants, which can be further investigated to develop novel pharmaceuticals targeting oxidative stress therapy.”
https://pubmed.ncbi.nlm.nih.gov/33105840/
https://www.mdpi.com/1424-8247/13/11/328
“UV phototherapy used in chronic skin diseases causes redox imbalance and pro-inflammatory reactions, especially in the case of unchanged skin cells.
To prevent the harmful effects of UV radiation, cannabidiol (CBD) has been used, which has antioxidant and anti-inflammatory properties. Therefore, the aim of this study was to evaluate the effect of CBD on the metabolism of skin keratinocytes in nude rats exposed to UVA/UVB radiation using a proteomic approach.
The results obtained with SDS-PAGE/nanoHPLC/QexactiveOrbiTrap show that exposure of rat’s skin to UVA/UVB radiation, as well as the action of CBD, significantly modified the expression of proteins involved in inflammation, redox balance and apoptosis.
UVA/UVB radiation significantly increased the expression and biological effectiveness of the nuclear factor associated with erythroid factor 2 (Nrf2) and cytoprotective proteins being products of its transcriptional activity, including superoxide dismutase (Cu,Zn-SOD) and the inflammatory response (nuclear receptor coactivator-3 and paralemmin-3), while CBD treatment counteracted and partially eliminated these changes.
Moreover, cannabidiol reversed changes in the UV-induced apoptotic pathways by modifying anti-apoptotic and pro-apoptotic factors (apoptosis regulator Bcl-2 and transforming growth factor-β).
The results show that CBD maintains keratinocyte proteostasis and therefore could be suggested as a protective measure in the prevention of UV-induced metabolic changes in epidermal keratinocytes.”
https://pubmed.ncbi.nlm.nih.gov/33086172/
“In summary, UVA and UVB radiation affect the proteomic profile of keratinocytes of healthy rat skin in different ways. Both types of radiation change the level of proteins involved in the regulation of cellular redox balance, inflammation, and apoptosis. In contrast, topical application of CBD to rat skin, when exposed to UV radiation, helps normalize the expression of keratinocyte proteins that are metabolically relevant by modeling their biosynthesis and degradation. Thus, CBD can maintain the proteostasis of keratinocytes. Because UV therapy is a part of the treatment of skin diseases, e.g. psoriasis, the use of CBD on unchanged skin may be suggested as a protective factor to reduce the metabolic changes caused by UV radiation in unchanged keratinocytes. This suggestion is particularly important when the beneficial effect of cannabidiol on psoriasis-induced skin lesions has recently also been confirmed.”
https://www.sciencedirect.com/science/article/pii/S0731708520315429?via%3Dihub
“This study evaluated the synergistic anti-cancer potential of cannabinoid combinations across the MDA-MB-231 and MCF-7 human breast cancer cell lines. Cannabinoids were combined and their synergistic interactions were evaluated using median effect analysis.
The most promising cannabinoid combination (C6) consisted of tetrahydrocannabinol, cannabigerol (CBG), cannabinol (CBN), and cannabidiol (CBD), and displayed favorable dose reduction indices and limited cytotoxicity against the non-cancerous breast cell line, MCF-10A. C6 exerted its effects in the MCF-7 cell line by inducing cell cycle arrest in the G2 phase, followed by the induction of apoptosis.
Morphological observations indicated the induction of cytoplasmic vacuolation, with further investigation suggesting that the vacuole membrane was derived from the endoplasmic reticulum. In addition, lipid accumulation, increased lysosome size, and significant increases in the endoplasmic reticulum chaperone protein glucose-regulated protein 78 (GRP78) expression were also observed.
The selectivity and ability of cannabinoids to halt cancer cell proliferation via pathways resembling apoptosis, autophagy, and paraptosis shows promise for cannabinoid use in standardized breast cancer treatment.”
“Considering lack of target-specific antiviral treatment and vaccination for COVID-19, it is absolutely exigent to have an effective therapeutic modality to reduce hospitalization and mortality rate as well as to improve COVID-19-infected patient outcomes.
In a follow-up study to our recent findings indicating the potential of Cannabidiol (CBD) in the treatment of acute respiratory distress syndrome (ARDS), here we show for the first time that CBD may ameliorate the symptoms of ARDS through up-regulation of apelin, a peptide with significant role in the central and peripheral regulation of immunity, CNS, metabolic and cardiovascular system.
CBD treatment was able to reverse the symptoms of ARDS towards a normal level. Importantly, CBD treatment increased the apelin expression significantly, suggesting a potential crosstalk between apelinergic system and CBD may be the therapeutic target in the treatment of inflammatory diseases such as COVID-19 and many other pathologic conditions.”
https://pubmed.ncbi.nlm.nih.gov/33058425/
“Cannabidiol (CBD) is a non‐psychotropic phytocannabinoid that regulates immune responses in multiple experimental disease models, including work by our laboratory showing a benefit following ARDS‐like injury in mice. Consistent with our findings, a recent commentary, based on anecdotal reports, supports the therapeutic use of CBD in COVID‐19‐infected patients. Our data demonstrate that CBD improves lung structure and exerts a potent anti‐inflammatory effect following experimental ARDS.”
“Hemp (Cannabis sativa L.) is currently one of the most controversial and promising crops. This study compared nine wild hemp (C. sativa spp. spontanea V.) accessions with 13 registered cultivars, eight breeding lines, and one cannabidiol (CBD) hemp strain belonging to C. sativa L.
The first three groups had similar main essential oil (EO) constituents, but in different concentrations; the CBD hemp had a different EO profile. The concentration of the four major constituents in the industrial hemp lines and wild hemp accessions varied as follows: β-caryophyllene 11-22% and 15.4-29.6%; α-humulene 4.4-7.6% and 5.3-11.9%; caryophyllene oxide 8.6-13.7% and 0.2-31.2%; and humulene epoxide 2, 2.3-5.6% and 1.2-9.5%, respectively.
The concentration of CBD in the EO of wild hemp varied from 6.9 to 52.4% of the total oil while CBD in the EO of the registered cultivars varied from 7.1 to 25%; CBD in the EO of the breeding lines and in the CBD strain varied from 6.4 to 25% and 7.4 to 8.8%, respectively. The concentrations of δ9-tetrahydrocannabinol (THC) in the EO of the three groups of hemp were significantly different, with the highest concentration being 3.5%.
The EO of wild hemp had greater antimicrobial activity compared with the EO of registered cultivars.
This is the first report to show that significant amounts of CBD could be accumulated in the EO of wild and registered cultivars of hemp following hydro-distillation. The amount of CBD in the EO can be greater than that in the EO of the USA strain used for commercial production of CBD. Furthermore, this is among the first reports that show greater antimicrobial activity of the EO of wild hemp vs. the EO of registered cultivars.
The results suggest that wild hemp may offer an excellent opportunity for future breeding and the selection of cultivars with a desirable composition of the EO and possibly CBD-rich EO production.”
“Epilepsy is a chronic neurological disease characterized by recurrent epileptic seizures. Studies have shown the complexity of epileptogenesis and ictogenesis, in which immunological processes and epigenetic and structural changes in neuronal tissues have been identified as triggering epilepsy.
Cannabidiol (CBD) is a major active component of the Cannabis plant and the source of CBD-enriched products for the treatment of epilepsy and associated diseases.
In this review, we provide an up-to-date discussion on cellular and molecular mechanisms triggered during epilepsy crises, and the phytochemical characteristics of CBD that make it an attractive candidate for controlling rare syndromes, with excellent therapeutic properties. We also discuss possible CBD anticonvulsant mechanisms and molecular targets in neurodegenerative disorders and epilepsy.
Based on these arguments, we conclude that CBD presents a biotecnological potential in the anticonvulsant process, including decreasing dependence on health care in hospitals, and could make the patient’s life more stable, with regard to neurological conditions.”
https://pubmed.ncbi.nlm.nih.gov/33031814/
“Therapeutic properties of cannabidiol in the treatment of epilepsy”
https://www.sciencedirect.com/science/article/abs/pii/S0149763420305832?via%3Dihub
“Anxiety disorders in young people are frequently comorbid with other mental disorders and respond unsatisfactorily to first-line treatment in many cases.
Here, we report the case of a 20-year-old man with severe social anxiety disorder, major depressive disorder, insomnia and attenuated psychotic symptoms despite ongoing treatment with cognitive behavioural therapy and mirtazapine who was treated with adjunctive cannabidiol (CBD) in doses between 200 and 800 mg/day for 6 months.
During treatment with CBD, he experienced subjective benefits to his anxiety, depression and positive symptoms during treatment that were confirmed by clinicians and by standardised research instruments.
Findings from this case study add to existing evidence in support of the safety of CBD and suggest that it may be useful for young people with treatment refractory anxiety and for attenuated psychotic symptoms.”
“Pharmaceutically purified oral cannabidiol (CBD) has been recently approved by the US Food and Drug Administration and European Medicines Agency as treatment of seizures associated with Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS), which are severe and difficult-to-treat developmental and epileptic encephalopathies with onset in early childhood.
Areas covered: This review will critically review the pharmacokinetic properties of CBD, the interactions with antiseizure and non-antiseizure medications, and the main tolerability and safety issues to provide guidance for its use in everyday practice.
Expert opinion: CBD is metabolized in the liver and can influence the activity of enzymes involved in drug metabolism. The best characterized drug-drug interaction is between CBD and clobazam. The most common adverse events include somnolence, gastrointestinal discomfort and increase in serum transaminases.
High-grade purified CBD oral solution represents an effective therapeutic option in patients with DS and LGS.
The findings cannot be extrapolated to other cannabis-based products, synthetic cannabinoids for medicinal use and non-medicinal cannabis and CBD derivatives.”
https://pubmed.ncbi.nlm.nih.gov/33026899/
“Pharmaceutically purified oral cannabidiol (CBD) is approved for treatment of seizures associated with Dravet syndrome and Lennox-Gastaut syndrome.”
https://www.tandfonline.com/doi/abs/10.1080/14737175.2021.1834383?journalCode=iern20
“Fibromyalgia is a complex disease process that is as prevalent as it is poorly understood. Research into the pathophysiology is ongoing, and findings will likely assist in identifying new therapeutic options to augment those in existence today that are still insufficient for the care of a large population of patients.
Recent evidence describes the use of cannabinoids in the treatment of fibromyalgia.
This study provides a systematic, thorough review of the evidence alongside a review of the seminal data regarding the pathophysiology, diagnosis, and current treatment options.
Fibromyalgia is characterized by widespread chronic pain, fatigue, and depressive episodes without an organic diagnosis, which may be prevalent in up to 10% of the population and carries a significant cost in healthcare utilization, morbidity, a reduced quality of life, and productivity. It is frequently associated with psychiatric comorbidities. The diagnosis is clinical and usually prolonged, and diagnostic criteria continue to evolve. Some therapies have been previously described, including neuropathic medications, milnacipran, and antidepressants. Despite some level of efficacy, only physical exercise has strong evidence to support it.
Cannabis has been used historically to treat different pain conditions since ancient times.
Recent advances allowed for the isolation of the active substances in cannabis and the production of cannabinoid products that are nearly devoid of psychoactive influence and provide pain relief and alleviation of other symptoms. Many of these, as well as cannabis itself, are approved for use in chronic pain conditions.
Evidence supporting cannabis in chronic pain conditions is plentiful; however, in fibromyalgia, they are mostly limited. Only a handful of randomized trials exists, and their objectivity has been questioned. However, many retrospective trials and patient surveys suggest the significant alleviation of pain, improvement in sleep, and abatement of associated symptoms.
Evidence supporting the use of cannabis in chronic pain and specifically in fibromyalgia is being gathered as the use of cannabis increases with current global trends. While the current evidence is still limited, emerging data do suggest a positive effect of cannabis in fibromyalgia.
Cannabis use is not without risks, including psychiatric, cognitive, and developmental as well as the risks of addiction. As such, clinical judgment is warranted to weigh these risks and prescribe to patients who are more likely to benefit from this treatment. Further research is required to define appropriate patient selection and treatment regimens.”
https://pubmed.ncbi.nlm.nih.gov/33004171/
https://www.sciencedirect.com/science/article/pii/S1521689620300781?via%3Dihub