Tag Archives: tetrahydrocannabinol

Role of marijuana components on the regenerative ability of stem cells

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“Stem cell therapy promotes tissue regeneration and wound healing. Efforts have been made to prime stem cells to enhance their regenerative abilities.

Certain marijuana components, namely the non-psychoactive cannabidiol (CBD) and psychoactive tetrahydrocannabinol (THC), are defined as immunomodulators.9 We test whether two sources of stem cells, primed with CBD or THC, would demonstrate improved regenerative abilities.

Human adipose-derived stem cells (ASCs) and bone marrow-derived stem cells (BMDSCs), not obtained from the same individual, were treated with low (300 nM) or high (3 μM) concentration CBD. Porcine ASCs and BMDSCs were isolated from a single pig, and treated with either low or high concentrations of CBD or THC. Transwell migration and MTT proliferation assays were performed on the human ASCs and BMDSCs. Also, transwell migration assay was performed on the porcine ASCs and BMDSCs. Finally, a wound healing scratch assay in porcine primary fibroblasts (PFs) was performed, co-cultured with the cannabinoid-treated ASCs.

CBD priming at low concentration induces migration by 180% (P < .01) in porcine ASCs, and by only 93% (P < .02) in porcine BMDSCs. In porcine stem cells, THC priming at low concentration induces migration by 91.6% (P < .01) in ASCs but by only 44.3% (P < .03) in BMDSCs. Compared to PFs co-cultured with untreated ASCs, PFs co-cultured with low CBD-primed ASCs had 75% faster wound closure at 18 hours (P < .01).

CBD and THC priming of ASCs and BMDSCs, particularly at lower doses, enhances a number of regenerative parameters, suggesting that these major marijuana components may improve stem cell-based therapies.

SIGNIFICANCE OF THE STUDY: Our study demonstrates that cannabinoids can enhance the regenerative capacity of two major sources of stem cells, adipose- and bone marrow-derived, from human and porcine donors. Stem cell isolation and expansion is invasive, costly and time consuming. Stem cells with improved regenerative properties may be effective in the treatment of acute or chronic wounds. This is the first study to compare the priming potential of two sources of stem cells from the same animal, with the same genetic and epigenetic profile, as well as the first to prime with THC.”

https://pubmed.ncbi.nlm.nih.gov/33349985/

https://onlinelibrary.wiley.com/doi/10.1002/cbf.3609

Assessment of antiviral potencies of cannabinoids against SARS-CoV-2 using computational and in vitro approaches

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International Journal of Biological Macromolecules“Effective treatment choices to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are limited because of the absence of effective target-based therapeutics. The main object of the current research was to estimate the antiviral activity of cannabinoids (CBDs) against the human coronavirus SARS-CoV-2.

In the presented research work, we performed in silico and in vitro experiments to aid the sighting of lead CBDs for treating the viral infections of SARS-CoV-2. Virtual screening was carried out for interactions between 32 CBDs and the SARS-CoV-2 Mpro enzyme. Afterward, in vitro antiviral activity was carried out of five CBDs molecules against SARS-CoV-2.

Interestingly, among them, two CBDs molecules namely Δ (Yu et al., 2020 [9])-tetrahydrocannabinol (IC50 = 10.25 μM) and cannabidiol (IC50 = 7.91 μM) were observed to be more potent antiviral molecules against SARS-CoV-2 compared to the reference drugs lopinavir, chloroquine, and remdesivir (IC50 ranges of 8.16-13.15 μM). These molecules were found to have stable conformations with the active binding pocket of the SARS-CoV-2 Mpro by molecular dynamic simulation and density functional theory.

Our findings suggest cannabidiol and Δ (Yu et al., 2020 [9])-tetrahydrocannabinol are possible drugs against human coronavirus that might be used in combination or with other drug molecules to treat COVID-19 patients.”

https://pubmed.ncbi.nlm.nih.gov/33290767/

“In summary, this report demonstrates the antiviral potencies of CBD and Δ9-THC against SARS-CoV-2. Based on privileged safety index CBD and Δ9-THC in human and their current in vitro potencies against SARS-CoV-2, it can be concluded that these compounds are potential antiviral molecules towards SARS-CoV-2 and may have worked as dual-acting against SARS-CoV-2, not only block the viral translation procedure by inhibiting SARS-CoV-2 Mpro but also reduce pro-inflammatory cytokines levels in lung cells by acting as agonists of CB-2 receptor. The successful in vitro work here of CBD and Δ9-THC lays the framework for their application in human clinical trials for the treatment of human coronavirus infections. Thus, CBD and Δ9-THC may be used in combination or with other drugs to treat COVID-19 patients.”

https://www.sciencedirect.com/science/article/pii/S0141813020351783?via%3Dihub

Fig. 1

L-Theanine Prevents Long-Term Affective and Cognitive Side-Effects of Adolescent Δ-9-Tetrahydrocannabinol Exposure and Blocks Associated Molecular and Neuronal Abnormalities in the Mesocorticolimbic Circuitry

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Journal of Neuroscience“Chronic adolescent exposure to Δ-9-Tetrahydrocannabinol (THC) is linked to elevated neuropsychiatric risk and induces neuronal, molecular and behavioural abnormalities resembling neuropsychiatric endophenotypes. Previous evidence has revealed that the mesocorticolimbic circuitry, including the prefrontal cortex (PFC) and mesolimbic dopamine (DA) pathway are particularly susceptible to THC-induced pathological alterations, including dysregulation of DAergic activity states, loss of PFC GABAergic inhibitory control and affective and cognitive abnormalities. There are currently limited pharmacological intervention strategies capable of preventing THC-induced neuropathological adaptations.

L-theanine is an amino acid analogue of L-glutamate and L-glutamine derived from various plant sources, including green tea leaves. L-theanine has previously been shown to modulate levels of GABA, DA and glutamate in various neural regions and to possess neuroprotective properties.

Using a pre-clinical model of adolescent THC exposure in male rats, we report that L-theanine pre-treatment prior to adolescent THC exposure is capable of preventing long-term, THC-induced dysregulation of both PFC and VTA DAergic activity states, a neuroprotective effect which persists into adulthood. In addition, pre-treatment with L-theanine blocked THC-induced downregulation of local GSK-3 and Akt signaling pathways directly in the PFC, two biomarkers previously associated with cannabis-related psychiatric risk and sub-cortical DAergic dysregulation.

Finally, L-theanine powerfully blocked the development of both affective and cognitive abnormalities commonly associated with adolescent THC exposure, further demonstrating functional and long-term neuroprotective effects of L-theanine in the mesocorticolimbic system.

SIGNIFICANCE STATEMENT With the increasing trend of cannabis legalization and consumption during adolescence, it is essential to expand knowledge on the potential effects of adolescent cannabis exposure on brain development and identify potential pharmacological strategies to minimize THC-induced neuropathology. Previous evidence demonstrates that adolescent THC exposure induces long-lasting affective and cognitive abnormalities, mesocorticolimbic dysregulation and schizophrenia-like molecular biomarkers that persist into adulthood.

We demonstrate for the first time that L-theanine, an amino acid analogue of L-glutamate and L-glutamine, is capable of preventing long-term THC side-effects. L-theanine prevented development of THC-induced behavioral aberrations, blocked cortical downregulation of local GSK-3 and Akt signaling pathways and normalized dysregulation of both PFC and VTA DAergic activity, demonstrating powerful and functional neuroprotective effects against THC-induced developmental neuropathology.”

https://pubmed.ncbi.nlm.nih.gov/33268546/

https://www.jneurosci.org/content/early/2020/11/24/JNEUROSCI.1050-20.2020

Medicinal Applications of Cannabinoids Extracted from Cannabis sativa (L.): A new Route to Fight against COVID-19?

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 “Cannabis sativa is a well-known plant which has been of benefit since ancient times in several medicinal systems, including Chinese, Indian, Greek and Egyptian ones.

Although C. sativa is one of the most investigated medicinal plants in the world, it faces the most controversial of issues for its legalization as a medication. C. sativa contains several hundreds of phytoconstituents including the infamous «cannabinoid.” It is necessary to properly understand the medicinal importance of these phytochemicals and spread awareness among the countries where it’s still facing legal complexities.

The current review is focusing on most recent literature pertaining to the various applications of cannabinoids with a special focus on medicinal aspect of the phytochemicals. Peer reviewed articles focusing on the importance of cannabis and cannabinoids were the target of this review. Articles were selected based on the relevance to the general scope of the work i.e. application of cannabinoids.

Cannabinoids can truly be regarded as wonder drug keeping their immense diversity of usage but unfortunately, many of the mares never researched biologically or pharmacologically due to their low yield in the plant. However, the approval of some cannabinoids by the FDA (along with other recognized national medical health systems) has opened the horizons for the explicit use of these natural drugs in medicines such as Epidiolex® (cannabidiol used for the treatment of severe forms of epilepsy) and Sativex®(‘Δ9 -tetrahydrocannabinol and cannabidiol’ used for the treatment of spasticity caused by multiple sclerosis, aka: MS.)

Many pharmacological properties of C. sativa are attributed to cannabidiol (CBD), a non-psychoactive component, along with Δ9 -tetrahydrocannabinol (Δ9 -THC), a psychoactive component. This review addresses the most important application or current utilization of cannabinoids in a variety of treatments such as: chronic pain, cancer, emesis, anorexia, irritable bowel syndrome, communicative diseases, glaucoma and central nervous system disorders. The biosynthetic pathway of cannabinoids is also discussed. In short, this plant has a myriad of bioactive compounds which have the potential to increase the list of approved cannabinoids suitable for therapy.”

https://pubmed.ncbi.nlm.nih.gov/33267756/

https://www.eurekaselect.com/188617/article

The effect of cannabidiol on canine neoplastic cell proliferation and MAP Kinase activation during autophagy and apoptosis

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“Low tetrahydrocannabinol Cannabis sativa products, also known as hemp products, have become widely available and their use in veterinary patients has become increasingly popular. Despite prevalence of use, the veterinary literature is lacking and evidence-based resource for cannabinoid efficacy.

The most prevailing cannabinoid found in hemp is cannabidiolic acid (CBDA) and becomes cannabidiol (CBD) during heat extraction; CBD has been studied for its direct anti-neoplastic properties alone and in combination with standard cancer therapies, yielding encouraging results.

The objectives of our study were to explore the anti-proliferative and cell death response associated with in vitro treatment of canine cancer cell lines with CBD alone and combination with common chemotherapeutics, as well as investigation into major proliferative pathways (e.g. p38, JNK, AKT, mTOR) potentially involved in the response to treatment with CBD.

CBD significantly reduced canine cancer cell proliferation far better than cannabidiolic acid (CBDA) across five canine neoplastic cell lines when treated with concentrations ranging from 2.5-10 μg/mL. Combinatory treatment with CBD and vincristine reduced cell proliferation in a synergistic or additive manner at anti-proliferative concentrations with less clear results using doxorubicin in combination with CBD. The cellular signaling effects of CBD treatment, showed that autophagy supervened induction of apoptosis and may be related to prompt induction of ERK and JNK phosphorylation prior to autophagy.

In conclusion, CBD is effective at hindering cell proliferation and induction of autophagy and apoptosis rapidly across neoplastic cell lines and further clinical trials are needed to understand its efficacy and interactions with traditional chemotherapy.”

https://pubmed.ncbi.nlm.nih.gov/33247539/

https://onlinelibrary.wiley.com/doi/10.1111/vco.12669

Cannabis and its Constituents for Cancer: History, Biogenesis, Chemistry and Pharmacological Activities

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Pharmacological Research “Cannabis has long been used for healing and recreation in several regions of the world. Over 400 bioactive constituents, including more than 100 phytocannabinoids, have been isolated from this plant. The non-psychoactive cannabidiol (CBD) and the psychoactive Δ9-tetrahydrocannabinol (Δ9-THC) are the major and widely studied constituents from this plant.

Cannabinoids exert their effects through the endocannabinoid system (ECS) that comprises cannabinoid receptors (CB1, CB2), endogenous ligands, and metabolizing enzymes. Several preclinical studies have demonstrated the potential of cannabinoids against leukemia, lymphoma, glioblastoma, and cancers of the breast, colorectum, pancreas, cervix and prostate.

Cannabis and its constituents can modulate multiple cancer related pathways such as PKB, AMPK, CAMKK-β, mTOR, PDHK, HIF-1α, and PPAR-γ. Cannabinoids can block cell growth, progression of cell cycle and induce apoptosis selectively in tumour cells. Cannabinoids can also enhance the efficacy of cancer therapeutics. These compounds have been used for the management of anorexia, queasiness, and pain in cancer patients.

Cannabinoid based products such as dronabinol, nabilone, nabiximols, and epidyolex are now approved for medical use in cancer patients. Cannabinoids are reported to produce a favourable safety profile. However, psychoactive properties and poor bioavailability limit the use of some cannabinoids. The Academic Institutions across the globe are offering training courses on cannabis. How cannabis and its constituents exert anticancer activities is discussed in this article. We also discuss areas that require attention and more extensive research.”

https://pubmed.ncbi.nlm.nih.gov/33246167/

https://www.sciencedirect.com/science/article/abs/pii/S1043661820316108?via%3Dihub

The Effects of Cannabis Use on Cognitive Function in Healthy Aging: A Systematic Scoping Review

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Archives of Clinical Neuropsychology“Background: Older adults (≥50 years) represent the fastest-growing population of people who use cannabis, potentially due to the increasing promotion of cannabis as medicine by dispensaries and cannabis websites. Given healthy aging and cannabis use are both associated with cognitive decline, it is important to establish the effects of cannabis on cognition in healthy aging.

Objective: This systematic scoping review used preferred reporting items for systematic reviews and meta-analyses guidelines to critically examine the extent of literature on this topic and highlight areas for future research.

Results: Six articles reported findings for older populations (three human and three rodent studies), highlighting the paucity of research in this area. Human studies revealed largely null results, likely due to several methodological limitations. Better-controlled rodent studies indicate that the relationship between ∆9-tetrahydrocannabinol (THC) and cognitive function in healthy aging depends on age and level of THC exposure. Extremely low doses of THC improved cognition in very old rodents. Somewhat higher chronic doses improved cognition in moderately aged rodents. No studies examined the effects of cannabidiol (CBD) or high-CBD cannabis on cognition.

Conclusions: This systematic scoping review provides crucial, timely direction for future research on this emerging issue. Future research that combines neuroimaging and cognitive assessment would serve to advance understanding of the effects of age and quantity of THC and CBD on cognition in healthy aging.”

https://pubmed.ncbi.nlm.nih.gov/33159510/

“THC; the main psychoactive cannabis compound; exerted pro-cognitive effects on memory and learning in older populations.”

https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acaa105/5960018

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

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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

Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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Issue Cover “Objective: To determine the benefit of a tetrahydrocannabinol (THC)-rich cannabis oil on symptoms and quality of life of fibromyalgia patients.

Conclusions: Phytocannabinoids can be a low-cost and well-tolerated therapy to reduce symptoms and increase the quality of life of patients with fibromyalgia. Future studies are still needed to assess long-term benefits, and studies with different varieties of cannabinoids associated with a washout period must be done to enhance our knowledge of cannabis action in this health condition.”

https://pubmed.ncbi.nlm.nih.gov/33118602/

“To our knowledge, this is the first randomized controlled trial to demonstrate the benefit of cannabis oil—a THC-rich whole plant extract—on symptoms and on quality of life of people with fibromyalgia. We conclude that phytocannabinoids can be a low-cost and well-tolerated therapy for symptom relief and quality of life improvement in these patients, and we suggest that this therapy could be included as an herbal medicine option for the treatment of this condition”

https://academic.oup.com/painmedicine/article/21/10/2212/5942556

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

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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