Category Archives: Cancer

Biological Effects of Cannabidiol on Human Cancer Cells: Systematic Review of the Literature

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Pharmacological Research


“This systematic review examine the biological effects of CBD, a major component of therapeutic Cannabis, on human pathological and cancer cell populations of integumentary, gastro-intestinal, genital and breast, respiratory, nervous, haematopoietic and skeletal districts in terms of cell viability, proliferation, migration, apoptosis, inflammation, metastasis, and CBD receptor expression. The included studies were in English, on human cell lines and primary culture from non-healthy donors with CBD exposure as variable and no CBD exposure as control. Quality assessment was based on ToxRtool with a reliability score ranging from 15 to 18. Following the PRISMA statement 4 independent reviewers performed an electronic search using MEDLINE via PubMed, Scopus and Web of Science. From 3974 articles, 83 studies have been selected. Data showed conflicting results due to different concentration exposure, administrations and time points. CBD inhibited cell viability and proliferation in most cellular districts except the integumentary apparatus. Also a significant inhibition of migration was observed in all cell types, while an increase in apoptosis at both high and low doses (greater and less than 10μM respectively). Considering inflammation, CBD caused an anti-inflammatory effect on nervous cells at low doses and on gastro-intestinal cells at high doses, while metastatic power was reduced even at low doses, but in a skeletal cell line there was an increased angiogenesis. CB1 receptor has been related to viability effects, CB2 to apoptosis and TRPV1 to inflammation and invasiveness. A detailed insight into these aspects would allow therapeutic use of this substance without possible side effects.”

https://pubmed.ncbi.nlm.nih.gov/35643249/

https://www.sciencedirect.com/science/article/abs/pii/S1043661822002122?via%3Dihub


Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR

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Cell Death Discovery

“Cannabinoid receptors, CB1 and CB2, have been implicated as emerging targets for cancer therapy. Herein, we investigated the potential regulation mechanism of CB1 and its implications in colorectal cancer. CB1 and EGFR expression were examined in colorectal cancer cell lines. The effects of CB1 agonist ACEA and its antagonist AM251 on the proliferation, migration and invasion of colorectal cancer cells and the expression of M1 and M2 macrophage markers were examined. EGFR overexpression was performed with plasmids containing EGFR gene. Tumor xenografts were constructed to explore the effects of CB1 activation on tumorigenesis. We showed that CB1 was downregulated while EGFR was upregulated in colorectal cancer cells. The activation of CB1 suppressed the proliferation, migration and invasion of colorectal cancer cells and the differentiation of M2 macrophages, while CB1 inhibition had opposite effects. Moreover, the alterations in tumorigenesis and M2 macrophage activation induced by CB1 activation were counteracted by EGFR overexpression. Besides, CB1 silencing promoted tumor cell proliferation and M2 polarization which was counteracted by EGFR knockdown. In vivo, CB1 activation also repressed tumorigenesis and M2 macrophage activation. The present study demonstrated that CB1 activation suppressed M2 macrophage through EGFR downregulation in colorectal cancers. These findings first unveiled the potential avenue of CB1 as a targeted therapy for colorectal cancer.”

https://pubmed.ncbi.nlm.nih.gov/35641479/

“In conclusion, our study showed that CB1 activation suppressed tumor growth and M2 macrophage activation in colorectal cancer by downregulating EGFR. Our study provided the first evidence that CB1 activation was capable to suppress M2 macrophage activation. Since M2 macrophage are linked with immune evasion in various cancers, CB1 might be a promising target for cancer treatment.”

https://www.nature.com/articles/s41420-022-01064-8

“The use of THC, or selective targeting of the CB1 receptor, may represent a novel strategy for colorectal cancer therapy.”

https://pubmed.ncbi.nlm.nih.gov/17583570/

The Effectiveness and Safety of Medical Cannabis for Treating Cancer Related Symptoms in Oncology Patients

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Frontiers in Pain Research (@FrontPain) / Twitter

“The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment.

Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients’ disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups.

Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment.

The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects.

The main finding of the current study is that most cancer comorbid symptoms improved significantly during 6 months of MC treatment.

Additionally, we found that MC treatment in cancer patients was well tolerated and safe.”

https://pubmed.ncbi.nlm.nih.gov/35669038/

https://www.frontiersin.org/articles/10.3389/fpain.2022.861037/full?utm_source=fweb

“Cancer Pain Treatment Using Marijuana Safe and Effective, Large Study Finds”

https://www.newsweek.com/cannabis-medicinal-cancer-patient-symptoms-pain-relief-1711981


Cannabidiol exerts anti-proliferative activity via a cannabinoid receptor 2-dependent mechanism in human colorectal cancer cells

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International Immunopharmacology

“Colorectal cancer is the third leading cause of cancer incidence and mortality in the United States. Cannabidiol (CBD), the second most abundant phytocannabinoid in Cannabis sativa, has potential use in cancer treatment on the basis of many studies showing its anti-cancer activity in diverse types of cancer, including colon cancer. However, its mechanism of action is not yet fully understood.

In the current study, we observed CBD to repress viability of different human colorectal cancer cells in a dose-dependent manner. CBD treatment led to G1-phase cell cycle arrest and an increased sub-G1 population (apoptotic cells); it also downregulated protein expression of cyclin D1, cyclin D3, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6. CBD further increased caspase 3/7 activity and cleaved poly(ADP-ribose) polymerase, and elevated expression of endoplasmic reticulum (ER) stress proteins including binding immunoglobulin protein (BiP), inositol-requiring enzyme 1α (IRE1α), phosphorylated eukaryotic initiation factor 2α (eIF2α), activating transcription factor 3 (ATF3), and ATF4.

We found that CBD repressed cell viability and induced apoptotic cell death through a mechanism dependent on cannabinoid receptor type 2 (CB2), but not on CB1, transient receptor potential vanilloid, or peroxisome proliferator-activated receptor gamma. Anti-proliferative activity was also observed for other non-psychoactive cannabinoid derivatives including cannabidivarin (CBDV), cannabigerol (CBG), cannabicyclol (CBL), and cannabigerovarin (CBGV). Our data indicate that CBD and its derivatives could be promising agents for the prevention of human colorectal cancer.”

https://pubmed.ncbi.nlm.nih.gov/35598400/

“CBD represses viability of human colorectal cancer cells.•

CBD induces cell cycle arrest and increases apoptosis and ER stress in human colorectal cancer cells.•

CBD represses cell viability and induces apoptotic cell death via a CB2-dependent mechanism.”

https://www.sciencedirect.com/science/article/pii/S1567576922003496?via%3Dihub


Management of chronic pain with Jalaprakshalana (water-wash) Shodhita (processed) Bhanga ( Cannabis sativa L.) in cancer patients with deprived quality of life: An open-label single arm clinical trial

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“Introduction: Pain is a common and complex symptom of cancer having physical, social, spiritual and psychological aspects. Approximately 70%-80% of cancer patients experiences pain, as reported in India. Ayurveda recommends use of Shodhita (Processed) Bhanga (Cannabis) for the management of pain but no research yet carried out on its clinical effectiveness.

Objective: To assess the analgesic potential of Jala-Prakshalana (Water-wash) processed Cannabis sativa L. leaves powder in cancer patients with deprived quality of life (QOL) through openlabel single arm clinical trial.

Materials and methods: Waterwash processed Cannabis leaves powder filled in capsule, was administered in 24 cancer patients with deprived QOL presenting complaints of pain, anxiety or depression; for a period of 4 weeks; in a dose of 250 mg thrice a day; along with 50 ml of cow’s milk and 4 g of crystal sugar. Primary outcome i.e. pain was measured by Wong-Bakers FACES Pain Scale (FACES), Objective Pain Assessment (OPA) scale and Neuropathic Pain Scale (NPS). Secondary outcome namely anxiety was quantified by Hospital Anxiety and Depression Scale (HADS), QOL by FACT-G scale, performance score by Eastern Cooperative Oncology Group (ECOG) and Karnofsky score.

Results: Significant reduction in pain was found on FACES Pain Scale (P < 0.05), OPA (P < 0.05), NPS (P < 0.001), HADS (P < 0.001), FACT-G scale (P < 0.001), performance status score like ECOG (P < 0.05) and Karnofsky score (P < 0.01).

Conclusion: Jalaprakshalana Shodhita Bhanga powder in a dose of 250 mg thrice per day; relieves cancerinduced pain, anxiety and depression significantly and does not cause any major adverse effect and withdrawal symptoms during trial period.”

https://pubmed.ncbi.nlm.nih.gov/31831967/

“Administration of Jalaprakshalana Shodhita Bhanga (water-wash processed Cannabis) leaves powder in dose of 250 mg thrice a day with 50 ml of cow’s milk and 4 g sugar as an adjuvant, for a period of 1 month; significantly relieves pain, anxiety and depression of cancer patients without creating any major side effects, dependency and withdrawal symptoms. Processed Cannabis is significantly effective for improvement in QOL of a cancer patient.”

https://www.ayujournal.org/article.asp?issn=0974-8520;year=2019;volume=40;issue=1;spage=34;epage=43;aulast=Tavhare

The Role of Cannabidiol (CBD) in a Cisplatin-Induced Model of Chronic Neuropathic Pain

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“Cannabinoid-based therapies offer a safer, non-opioid alternative for the management of chronic pain. While most studies focus on the analgesic potential of the main psychoactive component of marijuana, Δ9-tetrahydrocannabinol, fewer studies have investigated the role of the non-psychoactive component, cannabidiol (CBD). CBD has been purported to have analgesic, anti-inflammatory, anticonvulsant, and anxiolytic effects. In addition to having actions at both cannabinoid receptors (CB1 and CB2 ), CBD has been shown to interact with both the transient receptor potential vanilloid-1 (TRPV1) and serotonergic (5-HT) receptors. Clinically, CBD’s lack of psychoactivity and decreased abuse liability make it an appealing pharmacotherapeutic for the management of chronic pain. Therefore, the purpose of the current study was to determine whether CBD sex- or dose-dependently reverses antinociception in an acute model of thermal pain and/or mechanical allodynia in a model of cisplatin-induced chronic neuropathic pain. Furthermore, we observed the degree to which CB1 , CB2 , 5-HT, and TRPV1 receptors may be mediating these anti-allodynic responses. Male and female wild-type mice were assessed for either the anti-allodynic effects of 0, 1, 3, 10, and 30 mg/kg CBD in a cisplatin-induced model of neuropathic pain or the antinociceptive effects of 0, 1, 3, 10, 30, and 100 mg/kg CBD in a model of acute thermal (tail-flick) pain 60 minutes following CBD administration. To determine the relative contributions of each receptor subtype in mediating the anti-allodynic effects of CBD, male and female mice were pretreated with either: vehicle, the CB1 inverse agonist SR141716A (10 mg/kg), the CB2 antagonist SR144528 (10 mg/kg), the TRPV1 antagonist capsazepine (10 mg/kg), or the 5-HT2 antagonist methysergide (4 mg/kg) 30 minutes prior to treatment with CBD. Mice were assessed for the effects of the pretreatment alone and in combination with CBD. CBD at a dose of 3 mg/kg was able to partially reverse cisplatin-induced allodynia in male and female mice, while doses of 10 and 30 mg/kg resulted in nearly complete reversal. Our preliminary findings showed that the anti-allodynic effects of 30 mg/kg CBD were completely blocked following pretreatment with SR141716A and SR144528, and partially blocked by capsazepine in both male and female mice. Interestingly, pretreatment with methysergide partially attenuated the anti-allodynic effects of CBD in females alone. In contrast, CBD (0-100 mg/kg) failed to induce antinociception on the tail-flick assay. CBD did induce mild hypothermia with males showing a greater degree of CBD-mediated hypothermia than female mice. Taken together, these findings suggest that CBD may be a more effective treatment option for the management of chronic pain. This study highlights the therapeutic potential of CBD in a model of neuropathic pain and suggests that these effects may have clinical implications for the use of cannabinoids in chronic pain management.”

https://pubmed.ncbi.nlm.nih.gov/35560789/

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.R5197

Synthesis and In Vitro Characterization of Selective Cannabinoid CB2 Receptor Agonists: Biological Evaluation against Neuroblastoma Cancer Cells

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molecules-logo

“1,8-naphthyridine-3-carboxamide structures were previously identified as a promising scaffold from which to obtain CB2R agonists with anticancer and anti-inflammatory activity. This work describes the synthesis and functional characterization of new 1,8-naphthyridin-2(1H)-one-3-carboxamides with high affinity and selectivity for CB2R. The new compounds were able to pharmacologically modulate the cAMP response without modulating CB2R-dependent β-arrestin2 recruitment. These structures were also evaluated for their anti-cancer activity against SH-SY5Y and SK-N-BE cells. They were able to reduce the cell viability of both neuroblastoma cancer cell lines with micromolar potency (IC50 of FG158a = 11.8 μM and FG160a = 13.2 μM in SH-SY5Y cells) by a CB2R-mediated mechanism. Finally, in SH-SY5Y cells one of the newly synthesized compounds, FG158a, was able to modulate ERK1/2 expression by a CB2R-mediated effect, thus suggesting that this signaling pathway might be involved in its potential anti-cancer effect.”

https://pubmed.ncbi.nlm.nih.gov/35566369/

https://www.mdpi.com/1420-3049/27/9/3019


The Role of Nutritional Status, Gastrointestinal Peptides, and Endocannabinoids in the Prognosis and Treatment of Children with Cancer

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ijms-logo

“Neoplastic diseases in children are the second most frequent cause of death among the young. It is estimated that 400,000 children worldwide will be diagnosed with cancer each year. The nutritional status at diagnosis is a prognostic indicator and influences the treatment tolerance. Both malnutrition and obesity increase the risk of mortality and complications during treatment. It is necessary to constantly search for new factors that impair the nutritional status.

The endocannabinoid system (ECS) is a signaling system whose best-known function is regulating energy balance and food intake, but it also plays a role in pain control, embryogenesis, neurogenesis, learning, and the regulation of lipid and glucose metabolism. Its action is multidirectional, and its role is being discovered in an increasing number of diseases.

In adults, cannabinoids have been shown to have anti-cancer properties against breast and pancreatic cancer, melanoma, lymphoma, and brain tumors. Data on the importance of both the endocannabinoid system and synthetic cannabinoids are lacking in children with cancer.

This review highlights the role of nutritional status in the oncological treatment process, and describes the role of ECS and gastrointestinal peptides in regulating appetite. We also point to the need for research to evaluate the role of the endocannabinoid system in children with cancer, together with a prospective assessment of nutritional status during oncological treatment.”

https://pubmed.ncbi.nlm.nih.gov/35563548/

https://www.mdpi.com/1422-0067/23/9/5159


Synthesis of A Tetrahydrocannabinol (THC) Analog For Analyzing Cellular Proliferation in Concert With Epigallocatechin Gallate (EGCG) on A Bone-like Cancer Cell Line (UMR 106-01 BSP)

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“Cannabinoids have been extensively studied in the field of cancer research. Tetrahydrocannabinol (THC) has shown promising results in influencing cellular proliferation when in association with other cannabinoids. This traditional entourage effect solely focuses on the study of THC with other cannabinoids. However, not many studies have been done to explore the synergistic effect of THC analogs when used with non-cannabinoid compounds. THC in its isolate form for experimentation is very strictly regulated. Therefore, this study was conducted in the pursuit of synthesizing and experimenting with analogs of THC to observe a potential entourage effect with epigallocatechin gallate (EGCG), a compound known for its efficacy to reduce proliferation at higher concentrations in UMR cells. It was hypothesized that active analogs of THC can be synthesized and used in concert with EGCG to potentiate decreased proliferation in the bone-like cancer cell line UMR 106-01 BSP (UMR cells). Briefly, a Knoevenagel condensation and a Diels-Alder reaction using 1,3-cyclohexanediol dissolved in methanol (MeOH) and citronellal with ethylenediamine diacetic acid (EDDA) at a temperature of 60℃ was used to synthesize a novel THC analog, 3,10,10-Trimethyl-1,2,3,4,4a,6,7,8,10,10a-decahydro-9-oxa-5-phenanthrenone (TDP). UMR cells were routinely passaged, counted, plated in six-well culture plates at 480,00 cells/mL, then treated with 10-fold dilutions of TDP. The plates were incubated for 72 hours in a humidified incubator at 37 degrees Celsius with 5% carbon dioxide infusion. At the end of the experiment, the cells were routinely washed with HANKS buffered saline solution (HBSS), then routinely counted using the Luna Automated Cell Counter. In another experiment, designated cells were co-treated with TDP+EGCG, following the protocol above. F test ANOVA was used to compare variances and all values in the results were expressed as means ± SD. The results from the attempted cannabinoid analog synthesis yielded a novel active THC analog, TDP. Serial dilutions treatment of the UMR cells with TDP alone showed its ability to decrease cell count in a concentration dependent manner. However, when coupled with higher concentrations of EGCG, the co-treatment increased cell count rather than potentiating the effect of decreasing cellular proliferation. The F Test ANOVA showed robust statistical significance (p values <0.05) with regard to TDP’s effect of decreasing cell proliferation in UMR cells in a concentration-dependent manner. Overall, the outcomes of this study suggest that active forms of THC analogs can be synthesized and tested in concert with other non-cannabinoid compounds like EGCG. This study opens the door to explore the entourage effect of TDP with other non-cannabinoid compounds that may provide another tool in the therapeutic treatment of bone cancer cells.”

https://pubmed.ncbi.nlm.nih.gov/35555816/

https://faseb.onlinelibrary.wiley.com/doi/10.1096/fasebj.2022.36.S1.L8061

Cutaneous Squamous Cell Carcinoma and Lichen Simplex Chronicus Successfully Treated with Topical Cannabinoid Oil: A Case Report and Summary of Cannabinoids in Dermatology

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“Cannabidiol is a member of the cannabinoids, consisting of a diverse class of compounds derived from Cannabis sativa. There are three types of cannabinoids based on origin: endocannabinoids (endogenous), phytocannabinoids (plant-derived), and synthetic cannabinoids (synthesized). The endocannabinoid system plays a key role in skin homeostasis, such as proliferation, differentiation, and inflammatory signaling. A 64-year-old woman with a history of multiple squamous cell carcinomas who presented with skin lesions on her bilateral dorsal hands is reported. Her skin biopsies showed lichen simplex chronicus on her left hand and squamous cell carcinoma on her right hand; both lesions resolved with topical application of 20% cannabidiol. Cutaneous adverse events associated with cannabinoid use and potential therapeutic uses of cannabinoids in inflammatory skin diseases and skin cancer are also summarized.”

https://pubmed.ncbi.nlm.nih.gov/35530920/

“Cannabinoids are a class of drugs that are found in animals, humans, and plants; they are also synthesized. They are useful in the management of several systemic diseases. Indeed, cannabinoids have also been observed to be potentially effective in the treatment of cosmetic skin conditions and cutaneous diseases. In addition, they may be therapeutic in the management of not only non-melanoma skin cancer, such as squamous cell carcinoma, but also melanoma and Kaposi sarcoma. Our patient had successful treatment of a benign skin condition (lichen simplex chronicus); in addition, she had complete regression of several biopsy-confirmed squamous cell carcinomas. Therefore, the possibility of treating non-melanoma skin cancer, such as squamous cell carcinoma, with topical cannabinoids may warrant further investigation.”

https://www.cureus.com/articles/91630-cutaneous-squamous-cell-carcinoma-and-lichen-simplex-chronicus-successfully-treated-with-topical-cannabinoid-oil-a-case-report-and-summary-of-cannabinoids-in-dermatology