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Cannabinoids in the treatment of cancer anorexia and cachexia: where have we been, where are we going?

Cachexia-anorexia cancer syndrome remains an unmet clinical need with a dearth of treatment and no standard of care. Acting through the endocannabinoid system, cannabinoids are one potential cancer cachexia treatment. Herein the potential mechanisms for cannabinoids for cancer cachexia are discussed as are previous and ongoing clinical trials.

Could cannabinoids provide a new hope for ovarian cancer patients?

It is known that gynecological cancers remain a worldwide problem and as shown by the statistics, there is a need for new gynecological cancer treatments. Cannabinoids, the pharmacologically active compounds of the Cannabis sativa plant, have been used for many centuries by individuals as a symptomatic treatment to alleviate pain, nausea, vomiting, and to help stimulate appetite. Research has revealed that cannabinoids also exert anti-cancer activity such as anti-proliferative and pro-apoptotic effects through a variety of mechanisms. There is significant value in the development of these com- pounds as anti-cancer therapies in clinical practice as they do not produce the typi- cal toxic side effects that exist with conventional therapies and recent clinical trials have shown their great tolerability by patients at high doses. Cannabinoids can induce psychoactive effects that could limit their progression. Therefore, non-psychoactive cannabinoids are attracting pharmacological interest due to their inability to produce psychological effects. Recent studies have focussed on non-psychoactive cannabi- noids in ovarian cancer and have revealed promising pre-clinical results that indicate that these compounds may have potential benefits in the treatment of these cancers. However, there are still unanswered questions and research gaps that need to be addressed. This review summarizes the current understanding of this topic and iden- tifies the current gaps in knowledge that provide a useful direction for future work.

Unveiling the angiogenic effects of cannabinoids: Enhancers or inhibitors?

Cannabinoids are compounds found in the cannabis sativa plant. Cannabinoids, such as delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have potential therapeutic benefits in various medical conditions. Some can activate the cannabinoid receptors type-1 and -2 (CB1 and CB2), that are part of the endocannabinoid system (ECS), alongside the endocannabinoids and their metabolic enzymes. The ECS regulates physiological and cognitive processes and is a potential therapeutic target for a wide range of health conditions like chronic pain, anxiety, and neurodegenerative diseases. Synthetic cannabinoids, are associated with serious health risks, including addiction, psychosis, and death. Nonetheless, some of these molecules are also being explored for pharmacological applications.

Cannabidiol and Intestinal Motility: a Systematic Review

Cannabidiol (CBD) is a nonintoxicating cannabinoid extracted from the cannabis plant that is used for medicinal purposes. Ingestion of CBD is claimed to address several pathologies, including gastrointestinal disorders, although limited evidence has been generated thus far to substantiate many of its health claims. Nevertheless, CBD usage as an over-the-counter treatment for gastrointestinal disorders is likely to expand in response to increasing commercial availability, permissive legal status, and acceptance by consumers. This systematic review critically evaluates the knowledge boundaries of the published research on CBD, intestinal motility, and intestinal motility disorders. Research on CBD and intestinal motility is currently limited but does support the safety and efficacy of CBD for several therapeutic applications, including seizure disorders, inflammatory responses, and upper gastrointestinal dysfunction (ie, nausea and vomiting). CBD, therefore, may have therapeutic potential for addressing functional gastrointestinal disorders. The results of this review show promising in vitro and preclinical data supporting a role of CBD in intestinal motility. This includes improved gastrointestinal-related outcomes in murine models of colitis. These studies, however, vary by dose, delivery method, and CBD-extract composition. Clinical trials have yet to find a conclusive benefit of CBD on intestinal motility disorders, but these trials have been limited in scope. In addition, critical factors such as CBD dosing parameters have not yet been established. Further research will establish the efficacy of CBD in applications to address intestinal motility.

Cannabinoid contents in hemp teas and estimation of their transfer into tea infusions

This study focused on the investigation of cannabinoid profiles and contents of 23 different
hemp teas and on the individual transfer of 16 cannabinoids from hemp teas into their tea
infusions. The total cannabinoid content in the dry products averaged 14,960mg kg1, with
CBD&CBDA (sum of cannabidiol (CBD) and cannabidiolic acid (CBDA)) being the major compo-
nent, accounting for 87% of the total cannabinoid content. The D9-tetrahydrocannabinol (D9- 11 1
THC) content ranged from 16mg kg to 935mg kg and was on average 221mg kg . For each hemp tea, an infusion was prepared according to a standardized protocol issued by the German Standardisation body DIN and transfer rates per cannabinoid were estimated by com- paring the contents in the dry material with the concentrations in the aqueous infusion. The limited water solubility of cannabinoids results in limited extraction efficiency for cannabinoids using boiling water to prepare a tea infusion and the average transfer rate of the psychoactive D9-THC was only 0.5%.

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

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.

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

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.

Long-term safety of medical cannabis in Parkinson’s disease: A retrospective case-control study

Whole-plant medical cannabis (MC) products are widely used for controlling symptoms associated with Parkinson’s disease (PD). Despite its widespread use, few studies have investigated the long-term impact of MC on the progression of PD or its safety profile. This study examined the effects of MC on PD in a real-life setting. A retrospective case-control study of 152 idiopathic PD patients (mean age 69.1 ± 9.0 years), followed at the Sheba Medical Center Movement Disorders Institute (SMDI) from 2008 to 2022 was conducted. Seventy-six patients who used licensed whole-plant medical cannabis (MC) for at least a year were compared to a matched group who did not receive MC in terms of their Levodopa Equivalent Daily Dose (LEDD), Hoehn and Yahr (H&Y) stage, and cognitive, depressive, and psychotic symptoms.

The Effect of Cannabidiol 3% on Neuropsychiatric Symptoms in Dementia – Six-Month Follow-Up

To investigate the beneficial outcomes of giving cannabidiol (CBD) 3% over a six-month period in the BPSD, the management of which is a crucial issue for everyday clinical praxis and to compare the progress in BPSD of patients who receive Cannabidiol 3% with those who follow usual medical treatment (UMT) in everyday clinical praxis. A total of 20 PwD with severe BPSD were recruited from the database of Alzheimer Hellas with NPI score >30. Ten of them were assigned to UMT, while ten were assigned to a six-month treatment with CBD drops. The follow-up assessment was performed with NPI, both clinically and by structured telephone interview.

Disorders of cancer metabolism: The therapeutic potential of cannabinoids

Abnormal energy metabolism, as one of the important hallmarks of cancer, was induced by multiple carcinogenic factors and tumor-specific microenvironments. It comprises aerobic glycolysis, de novo lipid biosynthesis, and glutamine-dependent anaplerosis. Considering that metabolic reprogramming provides various nutrients for tumor survival and development, it has been considered a potential target for cancer therapy. Cannabinoids have been shown to exhibit a variety of anticancer activities by unclear mechanisms. This paper first reviews the recent progress of related signaling pathways (reactive oxygen species (ROS), AMP-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPK), phosphoinositide 3-kinase (PI3K), hypoxia-inducible factor-1alpha (HIF-1α), and p53) mediating the reprogramming of cancer metabolism (including glucose metabolism, lipid metabolism, and amino acid metabolism). Then we comprehensively explore the latest discoveries and possible mechanisms of the anticancer effects of cannabinoids through the regulation of the above-mentioned related signaling pathways, to provide new targets and insights for cancer prevention and treatment.

Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis

Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds.

Phytocannabinoids in Triple Negative Breast Cancer Treatment: Current Knowledge and Future Insights

Triple negative breast cancer (TNBC) represents an aggressive subtype of breast cancer, which is deficient in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Thus, TNBC cells are unable to respond to the conventional hormonal therapies, making chemotherapy the only therapeutic choice. Patients with TNBC develop metastasis and recurrence over time and have reduced survival compared to patients with other subtypes of breast cancer. Therefore, there is a need for innovative therapies. Data emerged from pre-clinical studies, highlighted various antitumor activities of plant-derived Cannabis sativa and synthetic cannabinoids (CBs), including delta-9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD). On the contrary, some studies indicated that CBs might also promote tumor progression. At present, clinical studies on the effects of CBs from Cannabis sativa in cancer patients are few. In the present study, we reviewed known and possible interactions between cannabinoids and TNBC therapies.