Tag Archives: cannabinoid

Spinal astroglial cannabinoid receptors control pathological tremor

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Nature Neuroscience“Cannabinoids reduce tremor associated with motor disorders induced by injuries and neurodegenerative disease. Here we show that this effect is mediated by cannabinoid receptors on astrocytes in the ventral horn of the spinal cord, where alternating limb movements are initiated. We first demonstrate that tremor is reduced in a mouse model of essential tremor after intrathecal injection of the cannabinoid analog WIN55,212-2. We investigate the underlying mechanism using electrophysiological recordings in spinal cord slices and show that endocannabinoids released from depolarized interneurons activate astrocytic cannabinoid receptors, causing an increase in intracellular Ca2+, subsequent release of purines and inhibition of excitatory neurotransmission. Finally, we show that the anti-tremor action of WIN55,212-2 in the spinal cords of mice is suppressed after knocking out CB1 receptors in astrocytes. Our data suggest that cannabinoids reduce tremor via their action on spinal astrocytes.”

https://pubmed.ncbi.nlm.nih.gov/33737752/

https://www.nature.com/articles/s41593-021-00818-4

“Medical cannabis can reduce essential tremor: Turns on overlooked cells in central nervous system”  https://www.sciencedaily.com/releases/2021/03/210319125519.htm

Cannabis, a Miracle Drug with Polyvalent Therapeutic Utility: Preclinical and Clinical-Based Evidence

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/WebMaterial/ShowPic/1319420“Cannabis sativa L. is an annual herbaceous dioecious plant which was first cultivated by agricultural human societies in Asia. Over the period of time, various parts of the plant like leaf, flower, and seed were used for recreational as well as therapeutic purposes. The main chemical components of Cannabis sativa are termed as cannabinoids, among them the key psychoactive constituent is Δ-9-tetrahydrocannabinol and cannabidiol (CBD) as active nonpsychotic constituent. Upon doing extensive literature review, it was found that cannabis has been widely studied for a number of disorders. Very recently, a pure CBD formulation, named Epidiolex, got a green flag from both United States Food and Drug Administration and Drug Enforcement Administration for 2 rare types of epilepsies. This laid a milestone in medical cannabis research.

This review intends to give a basic and extensive assessment, from past till present, of the ethnological, plant, chemical, pharmacological, and legal aspects of C. sativa. Further, this review contemplates the evidence the studies obtained of cannabis components on Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis, multiple sclerosis, emesis, epilepsy, chronic pain, and cancer as a cytotoxic agent as well as a palliative therapy. The assessment in this study was done by reviewing in extensive details from studies on historical importance, ethnopharmacological aspects, and legal grounds of C. sativa from extensive literature available on the scientific databases, with a vision for elevating further pharmaceutical research to investigate its total potential as a therapeutic agent.”

https://pubmed.ncbi.nlm.nih.gov/34676349/

“This study has analyzed and reviewed the historical, botanical, chemical, ethnopharmacological, and legal aspects of C. sativa from the first human use to the present medical applications with an analysis of its multiple therapeutic applications for various diseased conditions in the contemporary scientific context. There is an abundance of support for its several medicative uses as well as a possible benefit in various diseased conditions. Extensive pharmacological examination is still needed to better understand the clinical significance and uses of active cannabinoids in the treatment and prevention of chronic diseases. Also, cannabis can be chemically standardized and under prescription can be used. With the majority of the United States currently legalizing medicinal cannabis and/or restricted CBD-only use, physicians need to be educated on the history and correct clinical use of cannabis, as a result of which patients can know more and more about possible treatment utilizing cannabis. Medical cannabis has shown to have clinical efficacy in our past, and in present, data show its therapeutic effects. Extensive research in the field of cannabis can be very fruitful for the medicine world.”

https://www.karger.com/Article/FullText/515042

Cannabinoids and Neurogenesis: The Promised Solution for Neurodegeneration?

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molecules-logo“The concept of neurons as irreplaceable cells does not hold true today. Experiments and evidence of neurogenesis, also, in the adult brain give hope that some compounds or drugs can enhance this process, helping to reverse the outcomes of diseases or traumas that once were thought to be everlasting.

Cannabinoids, both from natural and artificial origins, already proved to have several beneficial effects (e.g., anti-inflammatory, anti-oxidants and analgesic action), but also capacity to increase neuronal population, by replacing the cells that were lost and/or regenerate a damaged nerve cell.

Neurogenesis is a process which is not highly represented in literature as neuroprotection, though it is as important as prevention of nervous system damage, because it can represent a possible solution when neuronal death is already present, such as in neurodegenerative diseases.

The aim of this review is to resume the experimental evidence of phyto- and synthetic cannabinoids effects on neurogenesis, both in vitro and in vivo, in order to elucidate if they possess also neurogenetic and neurorepairing properties.”

https://pubmed.ncbi.nlm.nih.gov/34684894/

“The current results of cannabinoids effects on neurogenesis are encouraging, and it is expectable that the amount of evidence continues to increase in the future with other experiments.”

https://www.mdpi.com/1420-3049/26/20/6313/htm

Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms

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Ostovari, Yu research published in PLOS ONE - Healthcare Ergonomics Analytics Lab - Purdue University“Background: The use of cannabis for symptoms of endometriosis was investigated utilising retrospective archival data from Strainprint Technologies Ltd., a Canadian data technology company with a mobile phone application that tracks a range of data including dose, mode of administration, chemovar and their effects on various self-reported outcomes, including pelvic pain.

Results: A total number of 252 participants identifying as suffering endometriosis recorded 16193 sessions using cannabis between April 2017 and February 2020. The most common method of ingestion was inhalation (n = 10914, 67.4%), with pain as the most common reported symptom being treated by cannabis (n = 9281, 57.3%). Gastrointestinal symptoms, though a less common reason for cannabis usage (15.2%), had the greatest self-reported improvement after use. Inhaled forms had higher efficacy for pain, while oral forms were superior for mood and gastrointestinal symptoms. Dosage varied across ingestion methods, with a median dose of 9 inhalations (IQR 5 to 11) for inhaled dosage forms and 1 mg/mL (IQR 0.5 to 2) for other ingested dosage forms. The ratio of THC to CBD had a statistically significant, yet clinically small, differential effect on efficacy, depending on method of ingestion.

Conclusions: Cannabis appears to be effective for pelvic pain, gastrointestinal issues and mood, with effectiveness differing based on method of ingestion. The greater propensity for use of an inhaled dosage delivery may be due to the rapid onset of pain-relieving effects versus the slower onset of oral products. Oral forms appeared to be superior compared to inhaled forms in the less commonly reported mood or gastrointestinal categories. Clinical trials investigating the tolerability and effectiveness of cannabis for endometriosis pain and associated symptoms are urgently required.”

“Recent studies have suggested that a dysfunction in the endocannabinoid system (ECS) is present in endometriosis patients, and that aspects of endometriosis-associated pain may be targeted by modulating the ECS .Previous research on the use of illicit cannabis in women with endometriosis has shown promise in the treatment of endometriosis pain and co-morbid symptoms such as poor sleep, gastrointestinal upset and mood disorders.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0258940

Perspectives of pediatric oncologists and palliative care physicians on the therapeutic use of cannabis in children with cancer

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Cancer Reports“Background: Children with cancer are increasingly using cannabis therapeutically.

Aim: The purpose of this study was to determine the perspectives and practices of pediatric oncologists and palliative care physicians regarding the use of cannabis for medical purposes among children with cancer.

Methods: A self-administered, voluntary, cross-sectional, deidentified online survey was sent to all pediatric oncologists and palliative care physicians in Canada between June and August 2020. Survey domains included education, knowledge, and concerns about cannabis, views on its effectiveness, and the importance of cannabis-related research. Data were analyzed using descriptive statistics.

Results: In total, 122/259 (47.1%) physicians completed the survey. Although 62.2% of the physicians completed some form of training about medical cannabis, nearly all (95.8%) desired to know more about the dosing, side effects, and safety of cannabis. Physicians identified a potential role of cannabis in the management of nausea and vomiting (85.7%), chronic pain (72.3%), cachexia/poor appetite (67.2%), and anxiety or depression (42.9%). Only four (0.3%) physicians recognized cannabis to be potentially useful as an anticancer agent. Nearly all physicians reported that cannabis-related research for symptom relief is essential (91.5%) in pediatric oncology, whereas 51.7% expressed that future studies are necessary to determine the anticancer effects of cannabis.

Conclusions: Our findings indicate that most pediatric oncologists and palliative care physicians recognize a potential role for cannabis in symptom control in children with cancer. Well-conducted studies are required to create evidence for cannabis use and promote shared decision making with pediatric oncology patients and their caregivers.”

https://pubmed.ncbi.nlm.nih.gov/34672127/

“Several important implications from our findings include an urgent call for research and the development of clinical practice guidelines to support families and health care providers advising on the use of cannabis products in pediatric oncology. Funding agencies would be wise to provide direct funding opportunities for cannabis research in cancer, particularly among pediatric oncology populations where interest and use are rapidly outpacing the generation of rigorous evidence on dosing, efficacy, and safety.”

https://onlinelibrary.wiley.com/doi/10.1002/cnr2.1551

Health Outcomes among Adults Initiating Medical Cannabis for Chronic Pain: A 3-month Prospective Study Incorporating Ecological Momentary Assessment (EMA)

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“In response to the need of more rigorous data on medical cannabis and chronic pain, we conducted a 3-month prospective study incorporating ecological momentary assessment (EMA) to examine the effects of medical cannabis on pain, anxiety/depression, sleep, and quality of life.

Data were collected from 46 adults (Mean age=55.7±11.9, 52.2% male) newly initiating medical cannabis treatment for chronic pain. Participants completed a baseline survey, EMA for approximately 1 week pre- and up to 3 weeks post- medical cannabis treatment, and a 3-month follow-up survey.

The self-reported EMA data (2535 random and 705 daily assessments) indicated significant reductions in momentary pain intensity (b = -16.5, p < .001, 16.5 points reduction on 0-100 visual analog) and anxiety (b = -0.89, p < .05), and significant increase in daily sleep duration (b = 0.34, p < .01) and sleep quality (b = 0.32, p <.001) after participants initiated medical cannabis for a few weeks.

At 3 months, self-reported survey data showed significantly lower levels of worst pain (t = -2.38, p < .05), pain interference (t = -3.82, p < .05), and depression (t = -3.43, p < .01), as well as increased sleep duration (t = 3.95, p < .001), sleep quality (t = -3.04, p < .01), and quality of life (t = 4.48, p < .001) compared to baseline.

In our sample of primarily middle-aged and older adults with chronic pain, medical cannabis was associated with reduced pain intensity/inference, lower anxiety/depression, and improved sleep and quality of life.”

https://pubmed.ncbi.nlm.nih.gov/34671723/

https://publications.sciences.ucf.edu/cannabis/index.php/Cannabis/article/view/97

Inflammaging and Cannabinoids

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Ageing Research Reviews“Aging is a complex phenomenon associated with a wide spectrum of physical and physiological changes affecting every part of all metazoans, if they escape death prior to reaching maturity. Critical to survival, the immune system evolved as the principal component of response to injury and defense against pathogen invasions. Because how significantly immune system affects and is affected by aging, several neologisms now appear to encapsulate these reciprocal relationships, such as Immunosenescence. The central part of Immunosenescence is Inflammaging -a sustained, low-grade, sterile inflammation occurring after reaching reproductive prime. Once initiated, the impact of Inflammaging and its adverse effects determine the direction and magnitudes of further Inflammaging. In this article, we review the nature of this vicious cycle, we will propose that phytocannabinoids as immune regulators may possess the potential as effective adjunctive therapies to slow and, in certain cases, reverse the pathologic senescence to permit a more healthy aging.”

https://pubmed.ncbi.nlm.nih.gov/34662745/

“The beneficial effects of cannabinoids may be considered as alternative therapy in treating age-related diseases.”

https://www.sciencedirect.com/science/article/pii/S1568163721002348?via%3Dihub

Hepatic Cannabinoid Signaling in the Regulation of Alcohol-Associated Liver Disease

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Logo of arcr“Purpose: The endocannabinoid system has emerged as a key regulatory signaling pathway in the pathophysiology of alcohol-associated liver disease (ALD). More than 30 years of research have established different roles of endocannabinoids and their receptors in various aspects of liver diseases, such as steatosis, inflammation, and fibrosis. However, pharmacological applications of the endocannabinoid system for the treatment of ALD have not been successful because of psychoactive side effects, despite some beneficial effects. Thus, a more delicate and detailed elucidation of the mechanism linking the endocannabinoid system and ALD may be of paramount significance in efforts to apply the system to the treatment of ALD.

Search results: According to the inclusion and exclusion criteria, the authors selected 47 eligible full-text articles out of 2,691 searched initially. Studies in the past 3 decades revealed the opposite effects of cannabinoid receptors CB1R and CB2R on steatosis, inflammation, and fibrosis in ALD.

Discussion and conclusions: This review summarizes the endocannabinoid signaling in the general physiology of the liver, the pathogenesis of ALD, and some of the potential therapeutic implications of cannabinoid-based treatments for ALD.”

https://pubmed.ncbi.nlm.nih.gov/34646717/

“Over the past 30 years, it has been found that the endocannabinoid system is involved in a variety of pathways associated with the onset, or the progression, of several diseases, including ALD. The endocannabinoid system has been observed in both the hepatocytes and various nonparenchymal cells in the liver, in which the endocannabinoid production and its receptor activation may contribute to the development of a spectrum of ALD, ranging from simple alcoholic steatosis to more severe forms such as steatohepatitis and fibrosis. Therefore, understanding the precise physiology of the endocannabinoid system in the liver and unveiling the mechanism underlying the association between ALD progression and hepatic endocannabinoid signaling seem to bear a paramount significance for the advancement of ALD treatment, as well as for the treatment of other chronic liver diseases (e.g., NAFLD, viral hepatitis). Moreover, developing efficacious and highly selective cannabinoid receptor–modulating drugs could be a major breakthrough in the treatment of ALD.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8496755/

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Cannabis Use Is Inversely Associated with Overweight and Obesity in Hepatitis B Virus-Infected Patients (ANRS CO22 Hepather Cohort)

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View details for Cannabis and Cannabinoid Research cover image“Chronic hepatitis B virus (HBV) infection may evolve into cirrhosis and hepatocellular carcinoma, and this progression may be accelerated by specific risk factors, including overweight and obesity. Although evidence for a protective effect of cannabis use on elevated body weight has been found for other populations, no data are available for HBV-infected patients. 

Aims: We aimed to identify risk factors (including cannabis use) for overweight and obesity in patients with HBV chronic infection. 

Methods: Using baseline data from the French ANRS CO22 Hepather cohort, we performed two separate analyses, one using “central obesity” (based on waist circumference) and the other “overweight” and “obesity” (based on body mass index) as outcomes. Logistic and multinomial regressions were used to model central obesity and overweight/obesity, respectively. 

Results: Among the 3706 patients in the study population, 50.8% had central obesity, 34.7% overweight, and 14.4% obesity. After multivariable adjustment, current cannabis use was associated with a 59% lower risk of central obesity compared with no lifetime use (adjusted odds ratio [95% CI]: 0.41 [0.24 to 0.70]). It was also associated with a 54% and 84% lower risk of overweight (adjusted relative risk ratio [95% CI]: 0.46 [0.27 to 0.76]) and obesity (0.16 [0.04 to 0.67]), respectively. 

Conclusions: Cannabis use was associated with lower risks of overweight and obesity in patients with HBV chronic infection. Future studies should test whether these potential benefits of cannabis and cannabinoid use translate into reduced liver disease progression in this high-risk population.”

https://pubmed.ncbi.nlm.nih.gov/34648718/

https://www.liebertpub.com/doi/10.1089/can.2021.0094

Novel CBG Derivatives Can Reduce Inflammation, Pain and Obesity

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molecules-logo“Interest in CBG (cannabigerol) has been growing in the past few years, due to its anti-inflammatory properties and other therapeutic benefits.

Here we report the synthesis of three new CBG derivatives (HUM-223, HUM-233 and HUM-234) and show them to possess anti-inflammatory and analgesic properties.

In addition, HUM-234 also prevents obesity in mice fed a high-fat diet (HFD). The metabolic state of the treated mice on HFD is significantly better than that of vehicle-treated mice, and their liver slices show significantly less steatosis than untreated HFD or CBG-treated ones from HFD mice.

We believe that HUM-223, HUM-233 and HUM-234 have the potential for development as novel drug candidates for the treatment of inflammatory conditions, and in the case of HUM-234, potentially for obesity where there is a huge unmet need.”

https://pubmed.ncbi.nlm.nih.gov/34577072/

https://www.mdpi.com/1420-3049/26/18/5601