I summarized the clinical cannabis research published between 2016 and 2020, translating the information to make it understandable for laypeople. Below is a small sample of the work I did.
137. Cannabinoids and Hormone Receptor-Positive Breast Cancer Treatment
Name of the publication: Cancers
Publication date: February 3, 2020
List of scientists’ names: Luka Dobovišek, Fran Krstanović, Simona Borštnar, Nataša Debeljak
Nature of the research:
1. Basic research
2. Human and animal studies
3. Vivo and Vitro
Tag: THC, CBD
Outcome:
Mounting evidence shows that cannabinoids may have anti-tumor behavior, inhibiting the proliferation of breast estrogen receptor-positive breast cancer cell lines; however, this information mostly comes from preclinical and animal studies, and clinical evidence is needed before this data can be confirmed.
Explanation:
The most common cancer in women globally is breast cancer. Between 70 and 80 percent of breast cancers are hormone receptor-positive (HR+) because they express estrogen receptors. An additional 65 percent of breast cancers are also progesterone receptor-positive. Progesterone receptor expression is considered a biomarker of estrogen-receptor signaling, and estrogen-receptor expression predicts the effectiveness of endocrine therapy, which is one of the primary ways to manage HR+ breast cancer.
Activating estrogen-receptors is considered important for treating HR+ breast cancer. Recent studies have shown that cannabinoids, which are mostly known to activate the body’s cannabinoid receptors CB1 and CB2, also activate other receptors. In addition, it has been shown that cannabinoids, such as THC and CBD, have contributed to the anti-proliferative effect of HR+ breast cancer treatment, making it more effective.
Furthermore, THC has been noted in animal models of breast cancers, including HR+ breast cancer, to increase the anti-tumor responses of botanical drug preparations. However, no clinical evidence has evaluated the role of cannabinoids on breast cancer treatment outcomes of any subtype of breast cancer.
Still, clinical evidence does exist for CB2 expression in HER2-positive tumors. HER2 is a gene that can impact breast cancer development. CB2 expression in HER2-positive tumors has been associated with reduced survival rates, increased recurrence rates, and distant metastases development.
This means that CB2 antagonists, including some cannabinoids, could potentially increase HR+ breast cancer outcomes. Clinical trials are needed to test this hypothesis, as the complexity of the interactions between HR+ breast cancer and cannabinoids that make their clinical significance hard to predict.
All of this data is promising for HR+ breast cancer treatment. Future clinical trials will help to establish the safety and efficacy of the use of cannabinoids in treating HR+ breast cancer and breast cancer in general.
Name of the publication: International Journal of Molecular Sciences
Publication date: January 25, 2020
List of scientists’ names: Laura Pietrovito, Marta Iozzo, Marina Bacci, Elisa Giannoni, Paola Chiarugi
Nature of the research:
1. Basic research
2. Human study
3. Vitro
Tag: THC, CBD
Outcome:
This data shows that the use of cannabinoids, specifically ones with high affinity for CB1 and CB2 receptors like WIN 55-212.2, a synthetic cannabinoid that produces similar effects to THC, are promising as anti-cancer drugs for treating prostate cancer thanks to their ability to strike cancer and stromal cells at the same time.
Explanation:
There are three kinds of cannabinoids. Endocannabinoids are endogenous ligands, or proteins that are produced by the body. Phytocannabinoids are derived from the cannabis plant. Synthetic cannabinoids are man-made to mimic the effects of other cannabinoids. There is evidence showing that cannabinoids of all kinds (endo-, phyto-, and synthetic) have potential as anticancer agents because of their ability to damage cancer cells without affecting non-cancer cells.
Still, treating cancer also depends on stromal cells, which are connection tissues in any organ. Stomal cells evolve alongside cancer and assist in the progression of tumors. Mounting evidence over the last few decades has shown that cannabinoids may be able to impair cancer progression by modulating the anti-tumor immune response, inhibiting the proliferation and migration of cancer cells, and impairing the formation of blood vessels in tumor tissue.
THC and CBD are the two primary phytocannabinoids in cannabis; they are its best-characterized cannabinoids to date. THC has a high affinity for binding to the body’s cannabinoid receptors CB1 and CB2, which have been found to be up-regulated in malignant tissues. The high expression of CB1 and CB2 seems to be connected to poor prognosis for human tumors. Cannabinoids like THC that limit CB1 and CB2 expression may lead to better cancer outcomes.
The research here shows that cannabinoid treatment reduces stromal cell activation and reactivity. Specifically, the synthetic cannabinoid and full agonist of CB1 and CB2 WIN 55-212.2 mesylate has significant anti-cancer activity in prostate cancer patients. WIN 55-212.2 has an even higher affinity for CB1 and CB2 than THC.
Overall, this data presents strong support for using cannabinoids to treat prostate cancer, as they appear to be anti-tumor agents that target both cancer and stromal cells. Further studies are needed to better understand the role of endocannabinoids in tumor progression as well as the role of phyto- and synthetic cannabinoids in counteracting it.
139. Urine Endocannabinoids as Novel Non-Invasive Biomarkers for Bladder Cancer at Early Stage
Name of the publication: Cancers
Publication date: February 18, 2020
List of scientists’ names: Riccardo Vago, Alessandro Ravelli, Arianna Bettiga, Silvana Casati, Giovanni Lavorgna, Fabio Benigni, Andrea Salonia, Francesco Montorsi, Marica Orioli, Pierangela Ciuffreda, Roberta Ottria
Nature of the research:
1. Controlled study
2. Human study
3. Vitro
Tag: Endocannabinoid
Outcome:
Four hundred and four bladder cancer samples were analyzed suggests that endocannabinoids and N-acylethanolamides (specifically arachidonoylethanolamide and stearoylethanoamide) are early biomarkers for bladder cancer, supporting the hypothesis that activating the endocannabinoid system could counteract bladder cancer.
Explanation:
Bladder cancer is among the top ten diagnosed cancers globally. It also has the highest lifetime treatment cost of any cancer. While there have been great improvements in bladder cancer prevention and progression over the years that have improved survival rates, it still has a high rate of tumor recurrence and progression, even with treatment by surgery, chemotherapy, or immunotherapy.
For these reasons, new, less invasive methods for diagnostic and prognostic bladder cancer surveillance are a necessity. Research into the human endocannabinoid system (ECS) has provided a lot of evidence for the role of the ECS in cancer development. Endocannabinoids produces by the body may be able to inhibit cell proliferation, migration, and progression, inhibit angiogenesis, and promote apoptosis and cell cycle arrest.
Specifically, endocannabinoids, which are part of the group called N-acylethanolamides (NAEs), and other NAEs, seem to be involved in bladder cancer proliferation and progression, according to studies of cellular models. This means that a modification in endocannabinoid and NAE levels in urine in bladder cancer patients could potentially be hypothesized.
This report analyzed seven different endocannabinoids and NAEs in 404 urine samples of bladder cancer patients compared to those endocannabinoid and NAE levels in healthy patients’ urine. The control group of healthy patients had no current or previous cancer diagnosis or urinary tract pathologies.
The results strongly suggest that endocannabinoids and NAEs, especially arachidonoylethanolamide and stearoylethanoamide, are early biomarkers of bladder cancer. In addition, variations in some endocannabinoid metabolic enzymes were statistically significant, linking them to bladder cancer.
This data supports the theory that activating the ECS can counteract bladder cancer. Additional experiments analyzing a larger group of patients are necessary to confirm promoting endocannabinoids and NAEs as bladder cancer biomarkers.
140. A Case Report of the Benefit of Cannabidiol (Cannabidiol (CBD)-Predominant Medical Cannabis Preparation) in the Management of Refractory Skin Graft Vs Host Disease (GVHD)
Name of the publication: Biology of Blood and Marrow Transplantation
Publication date: March 2020
List of scientists’ names: Tsiporah B. Shore, MD; Jessy Ryan; Michael Samuel, MD
Nature of the research:
1. Case report
2. Human study
3. Vivo
Tag: CBD, THC, Cannabis
Outcome:
This case report on a 35-year-old woman with graft-versus-host disease (GVHD) showed that an oral medical cannabis solution with a high 19:1 CBD:THC ratio at a daily dose of 6 ml resolved her GVHD with only mild flakiness and itching, with a sustained dosage and response one year after starting CBD; this case report adds to the evidence regarding the anti-inflammatory and immunosuppressive effects of medical cannabis related to GVHD treatment.
Explanation:
The cannabis plant contains many cannabinoids. Its two primary cannabinoids are THC and CBD, which research shows have potent anti-inflammatory and immunosuppressive actions. However, THC also has notable psychoactive properties.
A phase 2 study of CBD added on to standard GVHD treatment showed a better patient outcome than the use of standard GVHD treatment alone. Another phase 2a study of CBD for treating GVHD showed most of the patients involved having complete remission.
This case report of a steroid refractory eczematous GVHD studied the use of a CBD-predominant medical cannabis product as an add on to traditional GVHD treatment for a 35-year-old patient. The patient was a woman with T-cell Acute Lymphoblastic Leukemia with central nervous system involvement in complete remission. She underwent matched related donor stem cell transplant (SCT) and developed GVHD.
A rash on her face and scalp began 126 days after her transplant, and within a week involved 100 percent of her body surface area, with itching, facial and orbital swelling, and feet and ankle swelling.
Her skin biopsy showed a variant of GVHD involving eczema that was well-known as being aggressive and hard to manage with immunosuppression typically carrying a poor prognosis. All treatment attempts with phototherapy, steroid ointment, systemic steroids, photopheresis, ruxolitinib, and ibrutinib did not provide very effective or lasting improvement. The patient experienced several infectious complications that required hospitalizations.
Sixteen months after SCT, the patient started using a medical cannabis product with a high 19:1 CBD:THC ratio. The oral solution contained 47.5 mg CBD and 2.5 mg THC. Her daily dose of 6 ml containing 285 mg CBD and 15 mg THC was taken at night because it causes sleepiness.
After three months, the patient saw significant improvement and discontinued use of ibrutinib and photopheresis. At two years post SCT, the patient’s GVHD was resolved with only mild residual itching and flakiness. This response has been sustained after one year of beginning this CBD treatment remaining at six ml daily.
This case report adds medical cannabis’ anti-inflammatory and immunosuppressive profiles in the treatment of GVHD. Additional research is warranted based on the current data to investigate the role and optimal dosage of cannabis in managing GVHD.
141. The Highs and Lows of Cannabis in Cancer Treatment and Bone Marrow Transplantation
Name of the publication: Rambam Maimonides Medical Journal
Publication date: January 2020
List of scientists’ names: Osnat Almogi-Hazan, Ph.D.; Iman Khuja, M.Sc.; Sivan Ritter, D.V.M., B.A.; Reuven Or, M.D.
Nature of the research:
1. Basic research
2. Human and animal studies
3. Vivo and Vitro
Tag: Cannabis, THC, CBD
Outcome:
Cannabinoids have been shown to be beneficial in treating cancer patients’ symptoms and may also have anti-tumor effects in certain types of cancer; still, more research is needed to confirm the direct anti-tumor effects of cannabinoids and their impact on the immune system.
Explanation:
Cancer is one of the most common diseases in the world, and it’s often fatal. Current cancer treatments, including both curative and palliative care, in their attempt to destroy harmful cells and tissues in the body also end up hurting healthy tissues and leading to strong negative side effects, including nausea, vomiting, pain, and loss of appetite. This leads to a reduced quality of life, and sometimes the treatment strategies for dealing with the symptoms are ineffective.
Cannabis and its derivative cannabinoids, the active compounds in the cannabis plant, may have anti-emetic and analgesic effects. Therefore, they have applications for cancer patients to treat chemotherapy-induced nausea, vomiting, and chronic pain. They may also have curative, anti-cancer effects.
Recent research has shown some anti-tumor actions of cannabinoid-based treatments, modulating cancer cell proliferation and survival. These were in vitro studies on animal models, however, which does not always translate to human patients.
Human immune cells have the ability to get rid of cancer, but cancer patients’ anti-tumor response is not enough on its own. This is why immunotherapy has become a crucial cancer therapy, restoring immune deficiencies caused by cancer to better fight it off.
Cannabinoid-based treatments have demonstrated immune-regulatory properties in both preclinical and clinical research. As such, cannabinoid-based treatments could be beneficial for cancer patients to strengthen their immunity as well as other immunotherapies.
Most of the research into the anti-cancer effects of cannabinoids has investigated THC and CBD, the two primary active cannabinoids in the cannabis plant. Animal models, retrospective observational studies, and a modest number of clinical trials show THC and CBD to be promising in treating breast cancer, lung cancer, kidney cancer, melanoma, graft-versus-host disease.
Additional studies have suggested the potential that THC and CBD (as well as other cannabinoids) work better together than individually because of their synergistic effects. This would mean that finding medical ways to use the whole plant would be more effective in treating cancer than using isolated cannabinoids.
Cannabinoid-based treatments have palliative benefits for treating cancer, though their anti-cancer activities are still unclear. More research into the direct anti-tumor effects of cannabinoids in terms of their interaction with the immune system is necessary to better understand cannabinoids’ potential curative role in cancer.
Name of the publication: Journal of Cannabis Research
Publication date: March 26, 2020
List of scientists’ names: Offir Ben-Ishay, Ortal Bar-On, Yoram Kluger
Nature of the research:
1. Uncontrolled study
2. Human study
3. Vivo
Tag: THC, Cannabis
Outcome:
The results of this study indicate that using Kite-Systems CannaHaler smokeless inhalation device could be a feasible pharmaceutical dosing administrator based on its efficiency and minimal variation.
Explanation:
Postoperative pain management continues to need improvement, as many of the commonly used drugs, such as opiates and non-opiate analgesics, are either not effective or come with severe side effects.
Cannabis-based drugs seem to offer a feasible alternative. The two primary cannabinoids in cannabis, THC and CBD, have been shown to possess effective analgesic, anti-inflammatory, and muscle spasm relief actions in addition to reducing nausea and vomiting and stimulating appetite. Also, adverse effects appear to be minimal and not serious. These effects support the case for cannabinoid-based medicines for postoperative recovery.
This study evaluates the use of the CannaHaler, a smokeless, metered-dose inhaler by Kite-Systems, on 12 healthy adults in terms of pharmacokinetics and safety. The 12 adults were divided into four groups, receiving 10, 15, 20, or 25 mg of THC in a single dose. THC levels in the blood were measured at baseline and then 30 minutes after receiving a dose. Adverse effects and pharmacokinetic profiles were also monitored.
The results found that the maximum concentration received in each participant matched the product with no change in time needed to get to that dose regardless of dose quantity. No adverse effects were noted in any participant and very modest cognitive impairment that faded quickly and was reversible. Blood pressure, heart rate, and blood oxygen saturation did not clinically change during the time frame of the study.
Compared to smoking cannabis or taking it orally, the CannaHaler was more effective at reaching its potential pharmaceutical grade. With only 12 participants, this study is limited by its small size. Still, it provides a basis and framework for further study to evaluate the potential uses of the CannaHaler for postoperative pain.
Overall, this trial showed the feasibility and efficiency of the CannaHaler in doses up to 25 mg, as it was able to provide precise dosage and minimal adverse events.
Name of the publication: Oncotarget
Publication date: March 31, 2020
List of scientists’ names: Moran Mazuz, Amir Tiroler, Lilach Moyal, Emmilia Hodak, Stalin Nadarajan, Ajjampura C. Vinayaka, Batia Gorovitz-Haris, Ido Lubin, Avi Drori, Guy Drori, Owen Van Cauwenberghe, Adi Faigenboim, Dvora Namdar, Iris Amitay-Laish, Hinanit Koltai
Nature of the research:
1. Basic research
2. Human studies
3. Vitro and Ex Vivo
Tag: CBD, THC
Outcome:
This research demonstrates that cannabis extracts as well as their synergistic combinations caused cytotoxic effects to cutaneous T-cell lymphoma (CTCL) cell lines in vivo and to Sézary syndrome (SPBL) ex vivo, and specific formations of synergistic cannabinoids caused apoptosis and cell cycle arrest, impacting several biological pathways, some of which are linked to cancer.
Explanation:
While the cannabis plant has been used by human for thousands of years, interest has shifted from its psychotropic effects to its medicinal effects over time. Cannabis’ psychotropic effects primarily come from THC, its most prominent cannabinoid. However, the plant has over 200 known cannabinoids, another of which is CBD, which is the second most prominent after THC. There are also more than 160 known terpenophenolic compounds in cannabis, as well as lots of other compounds.
THC seems to activate the body’s endocannabinoid receptors CB1 and CB2, which are present in many kinds of cells in the skin and T-lymphocytes, which are white blood cells in the immune system that develop from bone marrow stem cells.
Cutaneous T-cell lymphomas (CTCLs) are part of a heterogeneous group of non-Hodgkin lymphomas, including the most common mycosis fungoides (MF) and the rare Sézary syndrome (SPBL). Treating MF and SPBL is meant to preserve quality of life and limit disease progression and symptomatic morbidity, such as skin lesions, tumors that can cover more than 80 percent of skin surface that can spread to the blood, lymph nodes, and internal organs.
Cannabinoids and cannabinoid combinations working synergistically have exhibited anti-tumor effects in animal models. Specifically, THC and CBD seem to cause cell death on T-cell leukemia lines both in combination and when used alone.
This research into cannabinoids and synergistic cannabinoid combinations found certain synergistic combinations to have strong cytotoxic activity in MF and SPBL cell lines and against SPBL in in vitro and ex vivo studies. High-CBD cannabis strains also showed cytotoxic activity against cells related to MF.
Fractionation of the whole cannabis plant extract demonstrated much higher cytotoxic activity than the whole extract, as when fractioned a specific way, synergistic activity on MF and SPBL was significantly increased. This suggests that fractionation could be more effective in general than using the whole extract.
Overall, this preclinical data suggests that specific combinations of cannabinoids have the most synergistic effect may be developed. However, human clinical trials are necessary to accurately determine the synergistic effectiveness of these cannabinoid combinations in treating CTCL.
Name of the publication: Cureus
Publication date: January 2020
List of scientists’ names: Veronica Stahl, Kumar Vasudevan
Nature of the research:
1. Uncontrolled study
2. Human study
3. Vivo
Tag: Cannabis, CBD, CBG, CBC
Outcome:
This study of the effect of cannabinoids on the dental plaques on 60 adults found that cannabinoids may be effective antibacterial agents against bacteria associated with dental plaque, providing a safer and more effective treatment than synthetic antibiotics that will reduce drug resistance development.
Explanation:
Dental plaque is the soft deposits that adhere to the surface of teeth or other hard surfaces in the oral cavity. It comes from food, saliva, and other fluids on the tooth surface, accounting for thousands of bacteria that eventually convert to acids and can cause dental diseases like gingivitis, periodontal diseases, and cavities. The most concerning of these issues is periodontal disease, a gum infection, the most common cause of tooth loss for adults.
With dental plaque being the cause of these dental issues, it should be regularly removed to avoid them. Regular teeth brushing, flossing, chemical aids, and mouthwashes can help to remove dental plaque. An effective addition to these practices to avoid periodontal disease is antimicrobial treatment.
Cannabis has gained a lot of recent attention in the medical world for all of its potential therapeutic benefits. The active compounds found in the cannabis plant are called cannabinoids, and they include THC, CBD, CBG, and CBC, among many others. Research has shown that cannabinoids have antibacterial properties.
This is the first study of its kind, evaluating the effectiveness of cannabinoids used in oral care products to prevent dental bacteria and reduce dental plaque as a result. It is a preliminary observatory study on 60 adults between the ages of 18 and 45.
The dental plaque of these 60 participants was divided into six groups based on the Dutch periodontal screening index regarding their periodontal status. The dental plaques of each participant were put into two Petri dishes. The first Petri dish contained four sections: CBD, CBC, CBN, and CBG. The second Petri dish contained four sections as well: CBGA (the acid form of CBG), Oral B, Colgate, and Cannabite F (a pomegranate and algae toothpaste).
The results showed that cannabinoids were significantly effective in reducing bacteria in dental plaque, more than synthetic oral care products like Oral B and Colgate. While cannabinoid efficiency may vary from person to person, cannabinoids may be an effective antibacterial agent against bacteria associated with dental plaque. Additional studies of larger size are needed to confirm this data.
145. Cannabidiol in sport: Ergogenic or else?
Name of the publication: Pharmacological Research
Publication date: June 2020
List of scientists’ names: François-Xavier Gamelina, Gregory Cuvelierb, Antoine Mendesa, Julien Aucouturiera, Serge Berthoina, Vincenzo Di Marzoc, Elsa Heyman
Nature of the research:
1. Basic research
2. Human and animal studies
3. Vivo and Vitro
Tag: CBD
Outcome:
Preclinical studies indicate that CBD has anti-inflammatory, anxiolytic, analgesic, and neuroprotective actions in addition to influencing the sleep-wake cycle, meaning that CBD could be an effective therapeutic compound in the realm of sport to help athletes manage injuries, stress, anxiety, and sleep issues.
Cannabis is a prohibited substance according to the World AntiDoping Agency (WADA), meaning its use is prohibited in the world of sports. While athletes are free to use cannabis outside of competition, THC, the primary compound in cannabis, has been known to have negative effects on sport performance, mostly due to its psychoactive effects. As such, many athletes steer clear of it.
However, cannabis research has revealed that CBD, another primary compound in cannabis that is non-intoxicating, may have therapeutic properties. In 2018, WADA removed CBD from its list of prohibited substances as a result. CBD’s medical possibilities in the sports world have thus been opened up.
While there are not many clinical studies of CBD, preclinical research shows that it has anti-inflammatory and analgesic properties. Athletes could benefit from CBD use to manage inflammation, pain, and swelling connected to injuries as an alternative to the commonly used anti-inflammatory drugs, opioids, and corticosteroids that often come with the potential, serious adverse effects.
Several studies have shown that CBD is also effective at reducing anxiety and improving fear memory processes (often linked to post-traumatic stress disorder). As many athletes deal with anxiety disorders and unjustified fear, CBD could be useful in this regard. Avoiding anxiety can also mean better performance and improved recovery after injuries.
Many athletes experience concussions related to their sport. Concussions are considered a kind of mild traumatic brain injury, as they can cause fatigue, headache, dizziness, irritability memory impairment, and difficulty concentrating that may or may not resolve from rest. Studies have indicated that CBD has helped treat behavioral dysfunctions associated with mild traumatic brain injury. CBD could help avoid subsequent progressive neurodegeneration that can cause progressive cognition and memory decline, depression, dementia, and other related behavioral issues.
CBD has been reported to improve the sleep-wake cycle as well to facilitate better sleep. Sleep loss in athletes is common due to performance-related anxiety and can subsequently decrease sport performance.
Overall, preclinical studies suggest that CBD has a lot of promise to help athletes manage injury, stress, anxiety, and sleep disorders. However, human clinical trials are needed to confirm these results. Additionally, the lack of regulation and control on CBD products could make some unsafe to use. As such, CBD clinical trials in athletes are urgently needed.
Jess Lakritz 