Protective Effects of ( E)-β-Caryophyllene (BCP) in Chronic Inflammation

nutrients-logo“(E)-β-caryophyllene (BCP) is a bicyclic sesquiterpene widely distributed in the plant kingdom, where it contributes a unique aroma to essential oils and has a pivotal role in the survival and evolution of higher plants.

Recent studies provided evidence for protective roles of BCP in animal cells, highlighting its possible use as a novel therapeutic tool.

Experimental results show the ability of BCP to reduce pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress, in particular metabolic and neurological diseases.

Through the binding to CB2 cannabinoid receptors and the interaction with members of the family of peroxisome proliferator-activated receptors (PPARs), BCP shows beneficial effects on obesity, non-alcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) liver diseases, diabetes, cardiovascular diseases, pain and other nervous system disorders.

This review describes the current knowledge on the biosynthesis and natural sources of BCP, and reviews its role and mechanisms of action in different inflammation-related metabolic and neurologic disorders.”

https://pubmed.ncbi.nlm.nih.gov/33114564/

https://www.mdpi.com/2072-6643/12/11/3273

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”   http://www.ncbi.nlm.nih.gov/pubmed/23138934

“Beta-caryophyllene is a dietary cannabinoid.”   https://www.ncbi.nlm.nih.gov/pubmed/18574142

Evaluating the Suitability and Potential Efficiency of Cannabis sativa Oil for Patients with Primary Burning Mouth Syndrome: A Prospective, Open-Label, Single-Arm Pilot Study

Pain Medicine“Objective: To evaluate the use of a Cannabis sativa oil in the management of patients diagnosed with primary burning mouth syndrome (BMS).

Results: Subjects showed a statistically significant improvement over time in terms of a clinical remission of the oral symptoms. Levels of anxiety and depression also changed statistically, displaying a favorable improvement. No serious reactions were detailed. None of the patients had to stop the treatment due to adverse events.

Conclusions: In this pilot evaluation, the C. sativa oil provided was effective and well tolerated in patients with primary BMS. Further bigger and properly defined randomized controlled trials, with different therapeutic approaches or placebo control, are needed, however.”

https://pubmed.ncbi.nlm.nih.gov/33123730/

https://academic.oup.com/painmedicine/advance-article-abstract/doi/10.1093/pm/pnaa318/5943271?redirectedFrom=fulltext

Cannabinoids Inhibited Pancreatic Cancer via P-21 Activated Kinase 1 Mediated Pathway

ijms-logo“The anti-cancer effects of cannabinoids including CBD (Cannabidiol) and THC ((-)-trans-∆9-tetrahydrocannabinol) have been reported in the case of pancreatic cancer (PC).

The connection of these cannabinoids to KRas oncogenes that mutate in more than 90% of PC, and their effects on PD-L1, a key target of immune checkpoint blockade, have not been thoroughly investigated. Using cell lines and mouse models of PC, the effects of CBD and THC on cancer growth, the interaction between PC cells and a stromal cell, namely pancreatic stellate cells (PSCs), and the mechanism(s) involved were determined by cell-based assays and mouse study in vivo.

CBD and THC inhibited the proliferation of PC, PSC, and PSC-stimulated PC cells. They also suppressed pancreatic tumour growth in mice. Furthermore, CBD and/or THC reduced the expression of PD-L1 by either PC or PSC cells. Knockout of p-21 activated kinase 1 (PAK1, activated by KRas) in PC and PSC cells and, in mice, dramatically decreased or blocked these inhibitory effects of CBD and/or THC.

These results indicated that CBD and THC exerted their inhibitions on PC and PSC via a p-21 activated kinase 1 (PAK1)-dependent pathway, suggesting that CBD and THC suppress Kras activated pathway by targeting PAK1. The inhibition by CBD and THC of PD-L1 expression will enhance the immune checkpoint blockade of PC.”

https://pubmed.ncbi.nlm.nih.gov/33126623/

https://www.mdpi.com/1422-0067/21/21/8035

Cannabidiol (CBD) reduces cocaine-environment memory in mice

Pharmacology Biochemistry and Behavior “Cocaine addiction is a global health problem with no approved pharmacotherapies.

Preclinical research indicates the non-intoxicating phytocannabinoid, cannabidiol (CBD), can reduce addiction-relevant behaviour for several drug classes (e.g. ethanol, opiates, psychostimulants) in rodents. However, research into the effects of CBD on cocaine addiction-like behaviours is limited, and the acute effects of CBD on cocaine reward are unknown.

Objectives: The present experiments sought to clarify the effects of CBD (10 mg/kg) on the acquisition, consolidation, reconsolidation, extinction and drug-primed reinstatement of cocaine (15 mg/kg) conditioned place preference (CPP) in adult male C57BL6/J mice.

Results: CBD treatment reduced preference for the cocaine-context 20 days after CBD cessation. CBD also reduced consolidation of cocaine memory, and this was evident 1 day after cessation of CBD treatment. Interestingly, CBD treatment also modified cocaine-induced locomotion. CBD did not affect reconsolidation of cocaine-induced place preference, the rate of extinction of cocaine memory, or drug-primed reinstatement of cocaine CPP.

Conclusions: These findings indicate specific effects of acute 10 mg/kg CBD on cocaine memory processes, suggesting delayed effects on cocaine preference and consolidation of cocaine memory, and support the therapeutic utility of CBD for targeting some drug-associated memory processes.”

https://pubmed.ncbi.nlm.nih.gov/33127382/

https://www.sciencedirect.com/science/article/pii/S009130572030527X?via%3Dihub

Cannabis sativa extracts protect LDL from Cu 2+-mediated oxidation

See the source image“Multiple therapeutic properties have been attributed to Cannabis sativa. However, further research is required to unveil the medicinal potential of Cannabis and the relationship between biological activity and chemical profile.

Objectives: The primary objective of this study was to characterize the chemical profile and antioxidant properties of three varieties of Cannabis sativa available in Uruguay during progressive stages of maturation.

Results: The main cannabinoids in the youngest inflorescences were tetrahydrocannabinolic acid (THC-A, 242 ± 62 mg/g) and tetrahydrocannabinol (THC, 7.3 ± 6.5 mg/g). Cannabinoid levels increased more than twice in two of the mature samples. A third sample showed a lower and constant concentration of THC-A and THC (177 ± 25 and 1 ± 1, respectively). The THC-A/THC rich cannabis extracts increased the latency phase of LDL oxidation by a factor of 1.2-3.5 per μg, and slowed down the propagation phase of lipoperoxidation (IC50 1.7-4.6 μg/mL). Hemp, a cannabidiol (CBD, 198 mg/g) and cannabidiolic acid (CBD-A, 92 mg/g) rich variety, also prevented the formation of conjugated dienes during LDL oxidation. In fact, 1 μg of extract was able to stretch the latency phase 3.7 times and also to significantly reduce the steepness of the propagation phase (IC50 of 8 μg/mL). Synthetic THC lengthened the duration of the lag phase by a factor of 21 per μg, while for the propagation phase showed an IC50 ≤ 1 μg/mL. Conversely, THC-A was unable to improve any parameter. Meanwhile, the presence of 1 μg of pure CBD and CBD-A increased the initial latency phase 4.8 and 9.4 times, respectively, but did not have an effect on the propagation phase.

Conclusion: Cannabis whole extracts acted on both phases of lipid oxidation in copper challenged LDL. Those effects were just partially related with the content of cannabinoids and partially recapitulated by isolated pure cannabinoids. Our results support the potentially beneficial effects of cannabis sativa whole extracts on the initial phase of atherosclerosis.”

https://pubmed.ncbi.nlm.nih.gov/33123676/

“Our findings support the beneficial effects of Cannabis sativa extracts on the initial phase of atherosclerosis. Since isolated cannabinoids were less effective preventing the oxidation of LDL, a synergistic effect between the diverse arrange of phytochemicals present in complex extracts is supported, reinforcing the entourage hypothesis and the use of whole medicinal cannabis extracts for therapeutic purposes.”

https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-020-00042-0

A Critical Review of the Role of the Cannabinoid Compounds Δ 9-Tetrahydrocannabinol (Δ 9-THC) and Cannabidiol (CBD) and their Combination in Multiple Sclerosis Treatment

molecules-logo“Many people with MS (pwMS) use unregulated cannabis or cannabis products to treat the symptoms associated with the disease. In line with this, Sativex, a synthetic combination of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) has been approved to treat symptoms of spasticity.

In animals, CBD is effective in reducing the amounts of T-cell infiltrates in the spinal cord, suggesting CBD has anti-inflammatory properties. By doing this, CBD has shown to delay symptom onset in animal models of multiple sclerosis and slow disease progression. Importantly, combinations of CBD and Δ9-THC appear more effective in treating animal models of multiple sclerosis.

While CBD reduces the amounts of cell infiltrates in the spinal cord, Δ9-THC reduces scores of spasticity. In human studies, the results are less encouraging and conflict with the findings in animals. Drugs which deliver a combination of Δ9-THC and CBD in a 1:1 ratio appear to be only moderately effective in reducing spasticity scores, but appear to be almost as effective as current front-line treatments and cause less severe side effects than other treatments, such as baclofen (a GABA-B receptor agonist) and tizanidine (an α2 adrenergic receptor agonist).

The findings of the studies reviewed suggest that cannabinoids may help treat neuropathic pain in pwMS as an add-on therapy to already established pain treatments.

Long term double-blind placebo studies are greatly needed to further our understanding of the role of cannabinoids in multiple sclerosis treatment.”

https://pubmed.ncbi.nlm.nih.gov/33113776/

https://www.mdpi.com/1420-3049/25/21/4930

Cannabidiol (CBD) enhanced the hippocampal immune response and autophagy of APP/PS1 Alzheimer’s mice uncovered by RNA-seq

 Life Sciences“Alzheimer’s disease (AD) is a central nervous system disease characterized by dementia, which has now become a major threat to global health.

Cannabidiol (CBD) is a natural component extracted from the hemp plant and exhibits multiple mechanisms to improve the pathological process of AD in vitro and in vivo. However, its underlying molecular mechanism is still unclear.

This study attempts to reveal its common mechanism through transcriptome sequence.

This study illustrated that CBD may improve the pathological process of AD by enhancing immune system response and autophagy pathway.”

https://pubmed.ncbi.nlm.nih.gov/33096116/

https://www.sciencedirect.com/science/article/abs/pii/S0024320520313771?via%3Dihub

Update on cannabis and cannabinoids for cancer pain

Current Issue Cover Image “The prevalence of cancer pain will continue to rise as pain is common among the survivorship and general cancer population. As interest in cannabis and cannabinoids for medicinal use including pain management continues to rise, there is growing need to update and review the current state of evidence for their use. The literature was searched for articles in English with key words cannabis, cannabinoids, and cancer pain. The sources of articles were PubMed, Embase, and open Google search.

Recent findings: In a double-blind randomized placebo-controlled trial including a 3-week treatment period of nabiximol for advanced cancer patients with pain refractory to optimized opiate therapy, improvements in average pain were seen in the intention to treat population (P = 0.0854) and per- protocol population (P = 0.0378).

Summary: To date, preclinical data has demonstrated evidence to suggest promising potential for cancer pain and the urgent need to translate this into clinical practice. Unfortunately, due to limited data, for adults with advanced cancer being treated with opiate therapy, the addition of cannabis or cannabinoids is not currently supported to address cancer pain effectively.”

https://pubmed.ncbi.nlm.nih.gov/33110020/

https://journals.lww.com/co-anesthesiology/Abstract/2020/12000/Update_on_cannabis_and_cannabinoids_for_cancer.19.aspx

Cannabidiol interactions with voltage-gated sodium channels

eLife logo “Voltage-gated sodium channels are targets for a range of pharmaceutical drugs developed for treatment of neurological diseases.

Cannabidiol (CBD), the non-psychoactive compound isolated from cannabis plants, was recently approved for treatment of two types of epilepsy associated with sodium channel mutations.

This study used high resolution X-ray crystallography to demonstrate the detailed nature of the interactions between CBD and the NavMs voltage-gated sodium channel, and electrophysiology to show the functional effects of binding CBD to these channels.

CBD binds at a novel site at the interface of the fenestrations and the central hydrophobic cavity of the channel. Binding at this site blocks the transmembrane-spanning sodium ion translocation pathway, providing a molecular mechanism for channel inhibition. Modelling studies suggest why the closely-related psychoactive compound tetrahydrocannabinol may not have the same effects on these channels. Finally, comparisons are made with the TRPV2 channel, also recently proposed as a target site for CBD.

In summary, this study provides novel insight into a possible mechanism for CBD interactions with sodium channels.”

https://pubmed.ncbi.nlm.nih.gov/33089780/

https://elifesciences.org/articles/58593

Involvement of dopamine receptor in the actions of non-psychoactive phytocannabinoids

Biochemical and Biophysical Research Communications “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