Tag Archives: Hemp

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

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ijms-logo“Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols.

Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases.

Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed.

Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor.

Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.”

https://pubmed.ncbi.nlm.nih.gov/32443623/

https://www.mdpi.com/1422-0067/21/10/3575

CBD Suppression of EAE Is Correlated With Early Inhibition of Splenic IFN-γ + CD8+ T Cells and Modest Inhibition of Neuroinflammation

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SpringerLink “In this study cannabidiol (CBD) was administered orally to determine its effects and mechanisms in the experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis (MS). We hypothesized that 75 mg/kg of oral CBD given for 5 days after initiation of disease would reduce EAE severity through suppression of either the early peripheral immune or late neuroimmune response.

EAE was induced in C57BL/6 mice at two different magnitudes, and peripheral inflammatory and neuroinflammatory responses were measured at days 3, 10, and 18. Th1, Th17, Tc1, Tc17, Tregs, and myeloid derived suppressor cells (MDSC) were identified from the lymph nodes and spleens of each mouse to determine if CBD altered the suppressor cell or inflammatory cell populations in secondary lymphoid tissues. Additionally, neuroinflammation was identified in brain and spinal cord tissues using various immunohistochemical techniques and flow cytometry.

Early treatment of EAE with oral CBD reduced clinical disease at the day 18 timepoint which correlated with a significant decrease in the percentage of MOG35-55 specific IFN-γ producing CD8+ T cells in the spleen at day 10. Analysis of both T cell infiltration and lesion size within the spinal cord also showed a moderate reduction in neuroinflammation within the central nervous system (CNS).

These results provide evidence that oral CBD suppressed the peripheral immune response that precedes neuroinflammation; however, analysis of the neuroinflammatory endpoints also suggest that the modest reduction in neuroinflammation was only partially responsible for CBD’s neuroprotective capability. Graphical Abstract CBD was administered orally for the first 5 days following initiation of EAE. CBD attenuated clinical disease, and we found that CBD suppressed IFN-γ producing CD8+ T cells in the spleen at day 10. There was also modest suppression of neuroinflammation.

Together these data demonstrate that early, oral administration of CBD protected mice from disease, but the modest effects on neuroinflammation suggest other mechanisms participate in CBD’s neuroprotective effect in EAE.”

https://pubmed.ncbi.nlm.nih.gov/32440886/

https://link.springer.com/article/10.1007%2Fs11481-020-09917-8

Cannabidiol Prevents the Expression of the Locomotor Sensitization and the Metabolic Changes in the Nucleus Accumbens and Prefrontal Cortex Elicited by the Combined Administration of Cocaine and Caffeine in Rats

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 SpringerLink“In the last years, clinical and preclinical researchers have increased their interest in non-psychotomimetic cannabinoids, like cannabidiol (CBD), as a strategy for treating psychostimulant use disorders. However, there are discrepancies in the pharmacological effects and brain targets of CBD.

We evaluated if CBD was able to prevent the locomotor sensitization elicited by cocaine and caffeine co-administration. The effect of CBD on putative alterations in the metabolic activity of the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc), and its respective subregions (cingulated, prelimbic, and infralimbic cortices, and NAc core and shell) associated to the behavioral response, was also investigated.

Rats were intraperitoneally and repeatedly treated with CBD (20 mg/kg) or its vehicle, followed by the combination of cocaine and caffeine (Coc+Caf; 5 mg/kg and 2.5 mg/kg, respectively) or saline for 3 days. After 5 days of withdrawal, all animals were challenged with Coc+Caf (day 9). Locomotor activity was automatically recorded and analyzed by a video-tracking software.

The metabolic activity was determined by measuring cytochrome oxidase-I (CO-I) staining. Locomotion was significantly and similarly increased both in Veh-Coc+Caf- and CBD-Coc+Caf-treated animals during the pretreatment period (3 days); however, on day 9, the expression of the sensitization was blunted in CBD-treated animals. A hypoactive metabolic response and a hyperactive metabolic response in mPFC and NAc subregions respectively were observed after the behavioral sensitization.

CBD prevented almost all these changes.

Our findings substantially contribute to the understanding of the functional changes associated with cocaine- and caffeine-induced sensitization and the effect of CBD on this process.”

https://pubmed.ncbi.nlm.nih.gov/32415526/

https://link.springer.com/article/10.1007%2Fs12640-020-00218-9

A Balanced Approach for Cannabidiol Use in Chronic Pain

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Frontiers in Pharmacology (@FrontPharmacol) | Twitter “Cannabidiol (CBD), the major non-psychoactive constituent of Cannabis sativa L., has gained traction as a potential treatment for intractable chronic pain in many conditions. Clinical evidence suggests that CBD provides therapeutic benefit in certain forms of epilepsy and imparts analgesia in certain conditions, and improves quality of life.

CBD continues to be Schedule I or V on the list of controlled substances of the Drug Enforcement Agency of the United States. However, preparations labeled CBD are available publicly in stores and on the streets. However, use of CBD does not always resolve pain. CBD purchased freely entails the risk of adulteration by potentially hazardous chemicals. As well, CBD use by pregnant women is rising and poses a major health-hazard for future generations.

In this mini-review, we present balanced and unbiased pre-clinical and clinical findings for the beneficial effects of CBD treatment on chronic pain and its deleterious effects on prenatal development.”

https://pubmed.ncbi.nlm.nih.gov/32425793/

https://www.frontiersin.org/articles/10.3389/fphar.2020.00561/full

www.frontiersin.org

The Cannabis Spread Throughout the Continents and Its Therapeutic Use in History

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“Historical relevance: Cannabis sativa L. (C. sativa) is a plant whose use as a therapeutic agent shares its origins with the first Far East’s human societies. Cannabis has been used not only for recreational purposes, but as a food to obtain textile fibers, to produce hemp paper, to treat many physical and mental disorders.

This review aims to provide a complete assessment of the deep knowledge of the cannabis psychoactive effects and medicinal properties in the course of history covering i.) the empirical use of the seeds and the inflorescences to treat many physical ailments by the ancient Oriental physicians ii.) the current use of cannabis as a therapeutic agent after the discovery of its key psychoactive constituent and the human endogenous endocannabinoid system.

Results and conclusion: Through a detailed analysis of the available resources about the origins of C. sativa we found that its use by ancient civilizations as a source of food and textile fibers dates back over 10,000 years, while its therapeutic applications have been improved over the centuries, from the ancient East medicine of the 2nd and 1st millennium B.C. to the more recent introduction in the Western world after the 1st century A.D. In the 20th and 21th centuries, Cannabis and its derivatives have been considered as a menace and banned throughout the world, but nowadays they are still the most widely consumed illicit drugs all over the world. Its legalization in some jurisdictions has been accompanied by new lines of research to investigate its possible applications for medical and therapeutic purposes.”

https://pubmed.ncbi.nlm.nih.gov/32433013/?from_term=cannabinoid&from_sort=date&from_size=200&from_pos=6

http://www.eurekaselect.com/182145/article

The Therapeutic Effectiveness of Full Spectrum Hemp Oil Using a Chronic Neuropathic Pain Model

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life-logo“Few models exist that can control for placebo and expectancy effects commonly observed in clinical trials measuring ‘Cannabis’ pharmacodynamics. We used the Foramen Rotundum Inflammatory Constriction Trigeminal Infraorbital Nerve injury (FRICT-ION) model to measure the effect of “full-spectrum” whole plant extracted hemp oil on chronic neuropathic pain sensitivity in mice.

Results: Mechanical allodynia was alleviated within 1 h (d = 2.50, p < 0.001) with a peak reversal effect at 4 h (d = 7.21, p < 0.001) and remained significant throughout the 6 h observation window. There was no threshold change on contralateral whisker pad after hemp oil administration, demonstrating the localization of anesthetic response to affected areas.

Conclusion: Future research should focus on how whole plant extracted hemp oil affects multi-sensory and cognitive-attentional systems that process pain.

The present study shows for the first time that common, commercially available, and easily reproducible full-spectrum hemp oil induces significant anti-allodynic effects with a bell-shaped pain sensitivity effect peeking between 2 and 4 h and lasting over 6 h. The study provides evidence that phytochemical extracts of the Cannabis plant, even with relatively low levels of THC, can significantly improve mechanical pressure pain in animals with established chronic neuropathic hypersensitivity.”

https://www.mdpi.com/2075-1729/10/5/69/htm

“Legal Cannabis hemp oil effectively treats chronic neuropathic pain: study”   https://medicalxpress.com/news/2020-05-legal-cannabis-hemp-oil-effectively.html

Investigation of cannabidiol gastro retentive tablets based on regional absorption of cannabinoids in rats.

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European Journal of Pharmaceutics and Biopharmaceutics“The cannabis plant has been widely researched for many therapeutic indications and found to be effective in many chronic conditions such as epilepsy, neuropathic or chronic pain and more. However, biased opinion against compounds of the plant, regulatory as well as compounding challenges have led to very few approved medicinal products. Those formulations which are approved are dosed several times a day, creating an unmet need for controlled release (CR) formulations of cannabinoids. Conventional CR formulations rely on prolonged absorption including the colon. The purpose of this work is to investigate regional absorption of major cannabinoids THC and CBD from the colon and develop a suitable CR formulation. As hypothesized by researchers, THC and CBD have poor absorption from the colon compared to small intestine, suggesting that these compounds have a narrow absorption window. The suggested formulation examined in-vitro was a floating gastro retentive tablet based on egg albumin matrix, gas generating agents and surfactants. In-vivo investigation of CBD containing formulation in the freely moving rat model proved a prolonged absorption phase with a substantial increase in bioavailability compared to CBD solution. The findings of this paper answer a crucial question regarding potential application of CR dosage forms for cannabinoids and shed light on the regional intestinal absorption of these compounds. Ultimately, these results cement the way for future development of cannabinoid gastro retentive dosage forms.”

https://www.ncbi.nlm.nih.gov/pubmed/32422168

https://www.sciencedirect.com/science/article/abs/pii/S0939641120301375?via%3Dihub

Cannabidiol (CBD) as a treatment of acute and chronic back pain: A case series and literature review.

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 Journal of opioid management (in SafetyLit)“Two patient case reports are presented describing the use of cannabidiol (CBD) for the symptomatic relief of a lumbar compression fracture and in the mitigation of thoracic discomfort and dysesthesia secondary to a surgically resected meningioma.

DISCUSSION:

CBD appears to have antisnociceptive and anti-inflammatory effects on opioid-naive patients with neuro-pathic and radicular pain. Of note, the patients in this case series used the same CBD cream: Baskin Essentials Body Wellness Cream (400 mg CBD per two oz.) Conclusion: Hemp-derived CBD in a transdermal cream provided significant symptom and pain relief for the patients described in this case series. Based on these results, we believe further investigation is warranted to see if CBD-containing products should have a more prominent role in the treatment of acute and chronic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/32421842

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with CNR1 rs806368 and ACHE rs17228602.

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biomolecules-logo“The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (AChE). Molecular docking and LogP determination were performed to predict the AChE inhibitory effect and lipophilicity. AChE enzyme activity was measured in the blood of cannabis addicted human subjects. Further, genetic predisposition to cannabis addiction was investigated by association analysis of cannabinoid receptor 1 (CNR1) single nucleotide polymorphism (SNP) rs806368 and ACHE rs17228602 using restriction fragment length polymorphism (RFLP) method. All the understudied cannabis constituents showed promising binding affinities with AChE and are lipophilic in nature. The AChE activity was observed to be indifferent in cannabis addicted and non-addicted healthy controls. There was no significant association with CNR1 SNP rs806368 and ACHE rs17228602. The study concludes that in silico prediction for individual biomolecules of cannabis is different from in vivo physiological action in human subjects when all are present together. However, for a deeper mechanistic insight into these interactions and association, multi-population studies are suggested. Further studies to explore the inhibitory potential of different cannabis constituents for intended AChE inhibitor-based drug are warranted.”

https://www.ncbi.nlm.nih.gov/pubmed/32414087

https://www.mdpi.com/2218-273X/10/5/758

“Characterization of Lignanamides from Hemp (Cannabis sativa L.) Seed and Their Antioxidant and Acetylcholinesterase Inhibitory Activities.”  https://www.ncbi.nlm.nih.gov/pubmed/26585089

Cannabis Phytomolecule ‘Entourage’: From Domestication to Medical Use.

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Trends in Plant Science: Special issue: Specifi...“Cannabis has been used as a medicine for millennia.

Crude extracts of cannabis inflorescence contain numerous phytomolecules, including phytocannabinoids, terpenes, and flavonoids. Combinations of phytomolecules have been recently established as superior to the use of single molecules in medical treatment owing to the ‘entourage effect’.

Two types of entourage effects are defined: ‘intra-entourage’, resulting from interactions among phytocannabinoids or terpenes, and ‘inter-entourage’, attributed to interactions between phytocannabinoids and terpenes. It is suggested that the phytomolecule assemblages found in cannabis chemovars today derive from selective breeding during ancient cultivation.

We propose that the current cannabis chemotaxonomy should be redefined according to chemical content and medicinal activity. In parallel, combinations of phytomolecules that exhibit entourage activity should be explored further for future drug development.”

https://www.ncbi.nlm.nih.gov/pubmed/32417167

“Cannabis has been used for millennia by humanity for social, ritual, and medical purposes. Humans bred and selected for cannabis strains based on their needs.”

https://www.cell.com/trends/plant-science/pdf/S1360-1385(20)30122-9.pdf?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1360138520301229%3Fshowall%3Dtrue