The Antioxidant and Neuroprotective Potential of Leaves and Inflorescences Extracts of Selected Hemp Varieties Obtained with scCO2

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“Cannabis sativa, a versatile plant with numerous varieties, holds promising potential for a wide range of biological activity. As raw materials for research, we chose leaves and inflorescences of hemp varieties such as Białobrzeskie, Henola, and Tygra, which are cultivated mainly for their fibers or seeds. The choice of extraction is a key step in obtaining the selected compositions of active compounds from plant material. Bearing in mind the lipophilic nature of cannabinoids, we performed supercritical carbon dioxide (scCO2) extraction at 50 °C under 2000 (a) and 6000 PSI (b). The cannabinoid contents were determined with the use of the HPLC-DAD method. The antioxidant capabilities were assessed through a series of procedures, including the DPPH, ABTS, CUPRAC, and FRAP methods. The capacity to inhibit enzymes that play a role in the progression of neurodegenerative diseases, such as acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and tyrosinase was also studied. The dominant cannabinoids in the extracts were cannabidiol (CBD) and cannabidiolic acid (CBDA). The highest concentration of eight cannabinoids was detected in the Tygra inflorescences extract (b). The most notable antioxidant properties were provided by the Tygra inflorescences extract (b). Nonetheless, it was the Henola inflorescences extract (b) that demonstrated the most efficient inhibition of AChE and BChE, and tyrosinase was inhibited the most significantly by the Białobrzeskie inflorescences extract (b). Multidimensional comparative analysis enrolled all assays and revealed that the Henola inflorescences extract (b) showed the most substantial neuroprotective potential.”

https://pubmed.ncbi.nlm.nih.gov/37891906/

https://www.mdpi.com/2076-3921/12/10/1827

Protective Actions of Cannabidiol on Aging-Related Inflammation, Oxidative Stress and Apoptosis Alterations in Liver and Lung of Long Evans Rats

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“Background: Aging is characterised by the progressive accumulation of oxidative damage which leads to inflammation and apoptosis in cells. This affects all tissues in the body causing the deterioration of several organs. Previous studies observed that cannabidiol (CBD) could extend lifespan and health span by its antioxidant, anti-inflammatory and autophagy properties. However, research on the anti-aging effect of CBD is still in the beginning stages. This study aimed to investigate the role of cannabidiol (CBD) in the prevention of age-related alterations in liver and lung using a murine model.

Methods: 15-month-old Long Evans rats were treated with 10 mg/kg b.w./day of CBD for 10 weeks and compared to animals of the same age as old control and 2-month-old animals as young control. Gene and/or protein expressions, by RT-qPCR and Western blotting, respectively, were assessed in terms of molecules related to oxidative stress (GST, GPx, GR and HO-1d), inflammation (NFκB, IL-1β and TNF-α) and apoptosis (BAX, Bcl-2, AIF, and CASP-1). In addition, MDA and MPO levels were measured by colorimetric assay. Results were analysed by ANOVA followed by Tukey-Kramer test, considering statistically significant a p < 0.05.

Results: GST, GPx and GR expressions were significantly reduced (p < 0.01) in liver samples from old animals compared to young ones and CBD treatment was able to revert it. A significant increase was observed in old animals compared to young ones in relation to oxidative stress markers (MDA and HO-1d), proinflammatory molecules (NFκB, IL-1β and TNF-α), MPO levels and proapoptotic molecules (BAX, AIF and CASP-1), while no significant alterations were observed in the antiapoptotic molecules (Bcl-2). All these changes were more noticeable in the liver, while the lung seemed to be less affected. In almost all the measured parameters, CBD treatment was able to revert the alterations caused by age restoring the levels to those observed in the group of young animals.

Conclusions: Chronic treatment with CBD in 15-month-old rats showed beneficial effects in lung and more significantly in liver by reducing the levels of inflammatory, oxidative and apoptotic mediators, and hence the cell damage associated with these three processes inherent to aging.”

https://pubmed.ncbi.nlm.nih.gov/37891916/

“This study’s results suggest that chronic treatment with CBD in 15-month-old rats could have beneficial effects in the lung and more significantly in the liver by reducing the levels of inflammatory, oxidative, and apoptotic mediators, and hence the cell damage associated with these three processes inherent to aging.”

https://www.mdpi.com/2076-3921/12/10/1837

Computational Study on the Enzyme-Ligand Relationship between Cannabis Phytochemicals and Human Acetylcholinesterase: Implications in Alzheimer’s Disease

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“Cannabis has shown promise in treating various neurological disorders, including Alzheimer’s disease (AD). AD is a devastating neurodegenerative disorder that affects millions of people worldwide. Current treatments for AD are limited and are not very effective.

This study investigated the enzyme-ligand relationship between nine active components of cannabis and human acetylcholinesterase (HuAChE) enzyme, which is significant in AD. Specifically, computational methods such as quantum mechanics, molecular docking, molecular dynamics, and free energy calculations were used to identify the cannabis phytochemicals with the highest HuAChE affinity and to understand the specific binding mechanisms involved.

Our results showed that cannabichromene and cannabigerol were the cannabis phytochemicals with the highest affinity for HuAChE, with cannabichromene exhibiting the greatest binding energy. However, both substances showed lower affinity than that of the pharmaceutical drug donepezil.

This study suggests that cannabichromene has a specific affinity for the peripheral anionic site (PAS) and acyl-binding pocket (ABP), while cannabigerol predominantly binds to PAS. Also, it was found that cannabichromene has a specific affinity for PAS and ABP, while cannabigerol predominantly binds to PAS.

Our findings suggest that cannabichromene and cannabigerol are potential therapeutic agents, but further research is needed to validate their effectiveness. The specific binding mechanisms identified may also provide helpful information for the design of more effective cannabis-based drugs.

Overall, this study provides valuable insights into the potential of cannabis-based drugs for treating neurological diseases.”

https://pubmed.ncbi.nlm.nih.gov/37815196/

https://pubs.acs.org/doi/10.1021/acs.jpcb.3c04315

The Use of Dispensary-Obtained Tetrahydrocannabinol as a Treatment for Neuropsychiatric Symptoms of Dementia

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“Objective: Neuropsychiatric symptoms (NPS) of dementia represent a large driver of health care costs, caregiver burden, and institutionalization of people with dementia. Management options are limited, and antipsychotics are often used, although they carry a significant side effect profile. One novel option is tetrahydrocannabinol (THC); however, in the US, to obtain THC for patients with dementia, caregivers have to go to a commercial dispensary. We evaluated the effectiveness of dispensary-obtained THC for patients with dementia and NPS.

Methods: Two independent reviewers reviewed charts of patients with diagnosed dementia (N = 50) seen in geriatric psychiatry between 2017 and 2021 for whom dispensary-obtained THC was recommended. The primary outcome was effectiveness in treating NPS; secondary outcomes were the proportion of caregivers who obtained and administered THC (uptake), post-THC antipsychotic use, and adverse reactions leading to treatment discontinuation.

Results: Caregiver uptake of dispensary-obtained THC was high (38/50, 76%). The majority of patients (30/38, 79%) who took THC had an improvement in NPS according to their caregivers. THC was recommended most often for the NPS of agitation, aggression, irritability, lability, anxiety, and insomnia. Among the 20 patients who were taking antipsychotics at baseline and took THC, over half (12/20, 60%) were able to decrease or discontinue the antipsychotic. Adverse reactions to THC included dizziness, worsening of agitation, and worsening of paranoia; two caregivers of patients who took THC reported adverse reactions that led to treatment discontinuation.

Conclusions: Our results suggest that dispensary-obtained THC can be effective in managing a subset of NPS in patients with dementia and may decrease the requirement for antipsychotics.”

https://pubmed.ncbi.nlm.nih.gov/37728481/

https://www.psychiatrist.com/jcp/neurologic/dementia/dispensary-obtained-tetrahydrocannabinol-treatment-neuropsychiatric-symptoms-dementia/

Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy

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“In this review article, we embark on a thorough exploration of cannabinoids, compounds that have garnered considerable attention for their potential therapeutic applications. Initially, this article delves into the fundamental background of cannabinoids, emphasizing the role of endogenous cannabinoids in the human body and outlining their significance in studying neurodegenerative diseases and cancer. Building on this foundation, this article categorizes cannabinoids into three main types: phytocannabinoids (plant-derived cannabinoids), endocannabinoids (naturally occurring in the body), and synthetic cannabinoids (laboratory-produced cannabinoids). The intricate mechanisms through which these compounds interact with cannabinoid receptors and signaling pathways are elucidated. A comprehensive overview of cannabinoid pharmacology follows, highlighting their absorption, distribution, metabolism, and excretion, as well as their pharmacokinetic and pharmacodynamic properties. Special emphasis is placed on the role of cannabinoids in neurodegenerative diseases, showcasing their potential benefits in conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. The potential antitumor properties of cannabinoids are also investigated, exploring their potential therapeutic applications in cancer treatment and the mechanisms underlying their anticancer effects. Clinical aspects are thoroughly discussed, from the viability of cannabinoids as therapeutic agents to current clinical trials, safety considerations, and the adverse effects observed. This review culminates in a discussion of promising future research avenues and the broader implications for cannabinoid-based therapies, concluding with a reflection on the immense potential of cannabinoids in modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/37759788/

https://www.mdpi.com/2218-273X/13/9/1388

Synergetic effect of β-asarone and cannabidiol against Aβ aggregation in vitro and in vivo

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“Alzheimer’s disease (AD) is a complex and multifactorial neurodegenerative disorder, and it is unlikely that any single drug or intervention will be very successful. The pathophysiology of Alzheimer’s disease involves a range of complicated biological processes, including the accumulation of beta-amyloid protein and tau protein. Given the complexity of AD and amyloid accumulation, a combination of interventions remains to be further explored. Here, we investigated the potential of combining β-asarone and cannabidiol (CBD) as a treatment for AD. The study analyzed the combined effects of these two phytochemicals on beta-amyloid (Aβ) protein aggregation and toxicity in bulk solution, in cells as well as in C.elegans. We detailed the morphological and size changes of Aβ40 aggregates in the presence of β-asarone and cannabidiol. More importantly, the presence of both compounds synergistically inhibited apoptosis and downregulated relative gene expression in cells, and that it may also slow aging, decrease the rate of paralysis, enhance learning capacity, and boost autophagy activity in C.elegans. Our studies suggest that multiple drugs, like β-asarone and CBD, may be potentially developed as a medicinal adjunct in the treatment of AD, although further clinical trials are needed to determine the efficacy and safety of this combination treatment in humans.”

https://pubmed.ncbi.nlm.nih.gov/37602231/

https://www.csbj.org/article/S2001-0370(23)00262-3/fulltext

Cannabis reduces anxiety in dementia

MMW - Advances in Medicine 14/2023

“Neuropsychiatric symptoms occur in almost 90% of people with dementia. Agitated and aggressive behavior significantly reduces the quality of life of those affected and those around them, but it is difficult to access therapy. One option could be medicinal cannabis. The results of a double-blind, placebo-controlled study indicate that a full-spectrum cannabis extract with a high content of cannabidiol (CBD) can reduce dementia-related agitation [1]. In the study, 60 patients with severe neurocognitive disorder and associated behavioral disorders received a full-spectrum cannabis extract with 1% tetrahydrocannabinol (THC) and 30% CBD (Re:cannis) or a placebo oil. After 16 weeks, sleep disturbances, Agitation and aggression significantly improved compared to the placebo group. Since the effects only became apparent in the 14th week, patience is required.”

https://www.springermedizin.de/agitiertheit/demenz/cannabis-daempft-die-unruhe-bei-demenz/25883850?fulltextView=true&doi=10.1007%2Fs15006-023-2867-2

Hippocampal differential expression underlying the neuroprotective effect of delta-9-tetrahydrocannabinol microdose on old mice

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“Delta-9-tetrahydrocannabinol (THC) is the primary psychoactive compound of the cannabis plant and an exogenous ligand of the endocannabinoid system. In previous studies, we demonstrated that a single microdose of THC (0.002 mg/kg, 3-4 orders of magnitude lower than the standard dose for rodents) exerts distinct, long-term neuroprotection in model mice subjected to acute neurological insults. When administered to old, healthy mice, the THC microdose induced remarkable long-lasting (weeks) improvement in a wide range of cognitive functions, including significant morphological and biochemical brain alterations. To elucidate the mechanisms underlying these effects, we analyzed the gene expression of hippocampal samples from the model mice. Samples taken 5 days after THC treatment showed significant differential expression of genes associated with neurogenesis and brain development. In samples taken 5 weeks after treatment, the transcriptional signature was shifted to that of neuronal differentiation and survival. This study demonstrated the use of hippocampal transcriptome profiling in uncovering the molecular basis of the atypical, anti-aging effects of THC microdose treatment in old mice.”

https://pubmed.ncbi.nlm.nih.gov/37534036/

“Our findings imply that the THC microdose treatment alleviates age-dependent cognitive deficits by modulating multiple hallmarks of brain aging, supporting past hypotheses regarding the relation between aging and the endocannabinoid system.”

https://www.frontiersin.org/articles/10.3389/fnins.2023.1182932/full

The role of cannabidiol in aging

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“Aging is usually considered a key risk factor associated with multiple diseases, such as neurodegenerative diseases, cardiovascular diseases and cancer. Furthermore, the burden of age-related diseases has become a global challenge. It is of great significance to search for drugs to extend lifespan and healthspan. Cannabidiol (CBD), a natural nontoxic phytocannabinoid, has been regarded as a potential candidate drug for antiaging. An increasing number of studies have suggested that CBD could benefit healthy longevity. Herein, we summarized the effect of CBD on aging and analyzed the possible mechanism. All these conclusions may provide a perspective for further study of CBD on aging.”

https://pubmed.ncbi.nlm.nih.gov/37418976/

“CBD is a potential antiaging candidate. CBD possesses antioxidant, anti-inflammatory and autophagy-inducing properties. CBD has potentially beneficial therapeutic effects for several age-related diseases.”

https://www.sciencedirect.com/science/article/pii/S075333222300865X?via%3Dihub


Under the umbrella of depression and Alzheimer’s disease physiopathology: can cannabinoids be a dual-pleiotropic therapy?

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“Depression and Alzheimer´s disease (AD) are two disorders highly prevalent worldwide. Depression affects more than 300 million people worldwide while AD affects 60% to 80% of the 55 million cases of dementia. Both diseases are affected by aging with high prevalence in elderly and share not only the main brain affected areas but also several physiopathological mechanisms. Depression disease is already ascribed as a risk factor to the development of AD. Despite the wide diversity of pharmacological treatments currently available in clinical practice for depression management, they remain associated to a slow recovery process and to treatment-resistant depression. On the other hand, AD treatment is essentially based in symptomatology relieve. Thus, the need for new multi-target treatments arises.

Herein, we discuss the current state-of-art regarding the contribution of the endocannabinoid system (ECS) in synaptic transmission processes, synapses plasticity and neurogenesis and consequently the use of exogenous cannabinoids in the treatment of depression and on delaying the progression of AD. Besides the well-known imbalance of neurotransmitter levels, including serotonin, noradrenaline, dopamine and glutamate, recent scientific evidence highlights aberrant spine density, neuroinflammation, dysregulation of neurotrophic factor levels and formation of amyloid beta (Aβ) peptides, as the main physiopathological mechanisms compromised in depression and AD. The contribution of the ECS in these mechanisms is herein specified as well as the pleiotropic effects of phytocannabinoids.

At the end, it became evident that Cannabinol, Cannabidiol, Cannabigerol, Cannabidivarin and Cannabichromene may act in novel therapeutic targets, presenting high potential in the pharmacotherapy of both diseases.”

https://pubmed.ncbi.nlm.nih.gov/37414155/

“Endocannabinoid system is dysregulated in depression and AD.

Cannabinoids have potential to modulate the physiopathological mechanisms common in both diseases.”

https://www.sciencedirect.com/science/article/pii/S1568163723001575?via%3Dihub