Prenatal broad-spectrum cannabidiol administration prevents an autism-like phenotype in male offspring from a maternal stress/terbutaline rat model

Posted on August 23, 2024 by David

“Recently, the diagnosis of autism spectrum disorder (ASD) has increased from 1 in 150 to every 1 in 36 children in the United States, warranting a need for novel prevention and therapeutic strategies.

Broad-spectrum cannabidiol oil, free from delta-9-tetrahydrocannabinol, the psychoactive component of cannabis, may be one such therapeutic. It has a high safety profile and is frequently used as a complementary and integrative intervention by persons experiencing symptoms of anxiety, stress, and inflammation.

Using a neurodevelopmental rat model of ASD (based on neuroinflammation induced by stress and terbutaline exposure during pre- and postnatal development), we sought to prevent the development of ASD-like behaviors in male offspring by administering broad-spectrum cannabidiol oil to dams throughout pregnancy (10 mg/kg, i.p., daily, embryonic days 3-16). To assess an ASD-like phenotype in the offspring, we used three behavioral measures relevant to three core ASD symptoms: 1) social communication (time spent vocalizing when alone); 2) repetitive behavior (marbles buried during a marble burying test); and 3) social interaction (time spent interacting with a novel conspecific during the three-chamber social interaction test).

Broad-spectrum cannabidiol oil given during pregnancy decreased scores for all three ASD-related behavioral responses, resulting in an overall significant prevention of the ASD-like phenotype. These findings highlight the potential of broad-spectrum cannabidiol oil as a complementary and integrative approach for prevention of stressor-induced sequelae relevant to development of an ASD-like phenotype.”

https://pubmed.ncbi.nlm.nih.gov/39170798/

“•CBD prevented an overall autistic-like phenotype from developing in male rats.
•CBD may be an appropriate complementary prenatal neuroinflammatory preventative.”

https://www.sciencedirect.com/science/article/pii/S2666354624001066?via%3Dihub

Effects of a cannabidiol/terpene formulation on sleep in individuals with insomnia: a double-blind, placebo-controlled, randomized, crossover study

Posted on August 23, 2024 by David

“Study objectives: Cannabidiol (CBD) is increasingly used as a health supplement, though few clinical studies have demonstrated benefits. The primary objective of this study was to evaluate the effects of an oral CBD-terpene formulation on sleep physiology in individuals with insomnia.

Methods: In this double-blind, placebo-controlled, randomized clinical trial, 125 individuals with insomnia received an oral administration of CBD (300 mg) and terpenes (1 mg each of linalool, myrcene, phytol, limonene, α-terpinene, α-terpineol, α-pinene, and β-caryophyllene) for ≥ 4 days/week over 4 weeks using a crossover design. The study medication was devoid of Δ⁹-tetrahydrocannabinol (Δ⁹-THC). The primary outcome measure was the percentage of time participants spent in the combination of slow wave sleep (SWS) and rapid eye movement (REM) sleep stages, as measured by a wrist-worn sleep-tracking device.

Results: This CBD-terpene regimen marginally increased the mean nightly percentage of time participants spent in SWS + REM sleep compared to the placebo [mean (SEM), 1.3% (0.60%), 95% C.I. 0.1 to 2.5%, P = 0.03]. More robust increases were observed in participants with low baseline SWS + REM sleep, as well as in day sleepers. For select participants, the increase in SWS + REM sleep averaged as much as 48 minutes/night over a four-week treatment period. This treatment had no effect on total sleep time (TST), resting heart rate or heart rate variability, and no adverse events were reported.

Conclusions: Select CBD-terpene ratios may increase SWS + REM sleep in some individuals with insomnia, and may have the potential to provide a safe and efficacious alternative to over-the-counter (OTC) sleep aids and commonly prescribed sleep medications.”

https://pubmed.ncbi.nlm.nih.gov/39167421/

https://jcsm.aasm.org/doi/10.5664/jcsm.11324

Bidirectional Effect of Long-Term Δ9-Tetrahydrocannabinol Treatment on mTOR Activity and Metabolome

Posted on August 22, 2024 by David

Go to ACS Pharmacology & Translational Science

“Brain aging is associated with cognitive decline, reduced synaptic plasticity, and altered metabolism. The activity of mechanistic target of rapamycin (mTOR) has a major impact on aging by regulating cellular metabolism. Although reduced mTOR signaling has a general antiaging effect, it can negatively affect the aging brain by reducing synaptogenesis and thus cognitive functions.

Increased mTOR activity facilitates aging and is responsible for the amnestic effect of the cannabinoid receptor 1 agonist Δ⁹-tetrahydrocannabinol (THC) in higher doses. Long-term low-dose Δ⁹-THC had an antiaging effect on the brain by restoring cognitive abilities and synapse densities in old mice. Whether changes in mTOR signaling and metabolome are associated with its positive effects on the aging brain is an open question.

Here, we show that Δ⁹-THC treatment has a tissue-dependent and dual effect on mTOR signaling and the metabolome. In the brain, Δ⁹-THC treatment induced a transient increase in mTOR activity and in the levels of amino acids and metabolites involved in energy production, followed by an increased synthesis of synaptic proteins. Unexpectedly, we found a similar reduction in the mTOR activity in adipose tissue and in the level of amino acids and carbohydrate metabolites in blood plasma as in animals on a low-calorie diet.

Thus, long-term Δ⁹-THC treatment first increases the level of energy and synaptic protein production in the brain, followed by a reduction in mTOR activity and metabolic processes in the periphery. Our study suggests that a dual effect on mTOR activity and the metabolome could be the basis for an effective antiaging and pro-cognitive medication.”

https://pubs.acs.org/doi/10.1021/acsptsci.4c00002

“Low-dose long-term administration of cannabis compound reverses brain aging”

Low-dose long-term administration of cannabis compound reverses brain aging

“Anti-ageing and increased mental capacity through cannabis”

https://www.uni-bonn.de/en/news/164-2024#:~:text=%22We%20concluded%20that%20long%2Dterm,%2C%22%20says%20Bilkei%2DGorzo.

Cannabis for Refractory Chemotherapy-Induced Nausea and Vomiting

Posted on August 22, 2024 by David

“Chemotherapy-induced nausea and vomiting (CINV) is a dreaded side effect of chemotherapy that remains common despite substantial advances in antiemetic treatments. Cannabis products have long had a role in the treatment of refractory CINV, but evidence supporting their use is outdated. In the article that accompanies this editorial, Grimison et al⁴ present results from a trial of a novel cannabis product that may be of benefit for CINV refractory to treatment with currently recommended antiemetics.

In conclusion, the trial by Grimison et al⁴ represents the first large trial of THC:CBD for CINV and demonstrates encouraging results for secondary prevention of refractory CINV. For patients receiving moderate- or high-emetic-risk chemotherapy, THC:CBD may be considered as an option for secondary prophylaxis of CINV for patients who had refractory nausea in a previous cycle despite guideline-concordant treatment. However, the applicability and generalizability of the evidence is limited by heterogeneity in the patient population, changes in antiemetic guidelines since the conception of the trial, and availability of THC:CBD. Additional trials should compare THC:CBD to other antiemetics, particularly to olanzapine, both in chemotherapy-naïve patients and in those with CINV refractory to standard antiemetic regimens. Further research is also warranted regarding optimal THC:CBD ratios to alleviate nausea while preventing adverse effects associated with THC.”

https://ascopubs.org/doi/10.1200/JCO.24.00438

Cannabis therapy in rheumatological diseases: A systematic review

Posted on August 22, 2024 by David

“Cannabis has been used in rheumatic diseases as therapy for chronic pain or inflammatory conditions. Herein, the authors systematically review the rheumatological diseases in which cannabis has been studied: systemic sclerosis, fibromyalgia, osteoarthritis, rheumatoid arthritis, osteoporosis, polymyalgia rheumatica, gout, dermatomyositis, and psoriatic arthritis. We systematically searched PubMed for articles on cannabis and rheumatic diseases between 1966 and March 2023. Twenty-eight articles have been selected for review.

Most of them (n=13) were on fibromyalgia and all of them but one showed important reduction in pain; sleep and mood also improved. On rheumatoid arthritis, two papers displayed decrease in pain and in one of them a reduction in inflammatory parameters was found. In scleroderma there was a case description with good results, one study on local use for digital ulcers also with good outcomes and a third one, that disclosed good results for skin fibrosis. In dermatomyositis a single study showed improvement of skin manifestations and in osteoarthritis (3 studies) this drug has demonstrated a good analgesic effect. Several surveys (n=5) on the general use of cannabis showed that rheumatological patients (mixed diseases) do use this drug even without medical supervision. The reported side effects were mild.

In conclusion, cannabis treatment is an interesting option for the treatment of rheumatological diseases that should be further explored with more studies.”

https://pubmed.ncbi.nlm.nih.gov/39165706/

https://northclinist.com/jvi.aspx?un=NCI-43669&volume=11&issue=4

Cannabinoid Therapy in Athletics: A Review of Current Cannabis Research to Evaluate Potential Real-World Cannabinoid Applications in Sport

Posted on August 22, 2024 by David

“The increasing legalization of Cannabis sativa plant products has sparked growing interest in their therapeutic applications.

Prohibition laws established in 1937 hindered formal research on cannabis, a plant with cultural and medicinal roots dating back to 2700 BC in Chinese history.

Despite regulatory hurdles, published research on cannabis has emerged; yet elite athletes remain an underrepresented population in these studies. Athletes, known for exploring diverse substances to optimize performance, are drawn to the potential benefits of cannabinoid therapy, with anecdotal reports suggesting positive effects on issues ranging from anxiety to brain injuries.

This review aims to evaluate empirical published cannabis research with a specific focus on its potential applications in athletics. The changing legal landscape, especially the removal of cannabis from drug testing programs in leagues such as the National Basketball Association (NBA), and endorsements by Major League Baseball (MLB) for cannabinoid products and the National Football League (NFL) for cannabis research, reflects a shift in the acceptability of such substances in sports. However, stigma, confusion, and a lack of education persist, hindering a cohesive understanding among sports organizations, including business professionals, policymakers, coaches, and medical/training staff, in addition to athletes themselves. Adding to the confusion is the lack of consistency with cannabinoid regulations from sport to sport, within or out of competition, and with cannabis bioactive compounds.

The need for this review is underscored by the evolving attitudes toward cannabinoids in professional sports and the potential therapeutic benefits or harms they may offer. By synthesizing current cannabis research, this review aims to provide a comprehensive understanding of the applications and implications of cannabinoid use in the realm of athletics.”

https://pubmed.ncbi.nlm.nih.gov/39168949/

FDA-approved cannabidiol [Epidiolex®] alleviates Gulf War Illness-linked cognitive and mood dysfunction, hyperalgesia, neuroinflammatory signaling, and declined neurogenesis

Posted on August 22, 2024 by David

“Background: Chronic Gulf War Illness (GWI) is characterized by cognitive and mood impairments, as well as persistent neuroinflammation and oxidative stress. This study aimed to investigate the efficacy of Epidiolex^®, a Food and Drug Administration (FDA)-approved cannabidiol (CBD), in improving brain function in a rat model of chronic GWI.

Methods: Six months after exposure to low doses of GWI-related chemicals [pyridostigmine bromide, N,N-diethyl-meta-toluamide (DEET), and permethrin (PER)] along with moderate stress, rats with chronic GWI were administered either vehicle (VEH) or CBD (20 mg/kg, oral) for 16 weeks. Neurobehavioral tests were conducted on 11 weeks after treatment initiation to evaluate the performance of rats in tasks related to associative recognition memory, object location memory, pattern separation, and sucrose preference. The effect of CBD on hyperalgesia was also examined. The brain tissues were processed for immunohistochemical and molecular studies following behavioral tests.

Results: GWI rats treated with VEH exhibited impairments in all cognitive tasks and anhedonia, whereas CBD-treated GWI rats showed improvements in all cognitive tasks and no anhedonia. Additionally, CBD treatment alleviated hyperalgesia in GWI rats. Analysis of hippocampal tissues from VEH-treated rats revealed astrocyte hypertrophy and increased percentages of activated microglia presenting NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) complexes as well as elevated levels of proteins involved in NLRP3 inflammasome activation and Janus kinase/signal transducers and activators of the transcription (JAK/STAT) signaling. Furthermore, there were increased concentrations of proinflammatory and oxidative stress markers along with decreased neurogenesis. In contrast, the hippocampus from CBD-treated GWI rats displayed reduced levels of proteins mediating the activation of NLRP3 inflammasomes and JAK/STAT signaling, normalized concentrations of proinflammatory cytokines and oxidative stress markers, and improved neurogenesis. Notably, CBD treatment did not alter the concentration of endogenous cannabinoid anandamide in the hippocampus.

Conclusions: The use of an FDA-approved CBD (Epidiolex^®) has been shown to effectively alleviate cognitive and mood impairments as well as hyperalgesia associated with chronic GWI. Importantly, the improvements observed in rats with chronic GWI in this study were attributed to the ability of CBD to significantly suppress signaling pathways that perpetuate chronic neuroinflammation.”

https://pubmed.ncbi.nlm.nih.gov/39169440/

CBD oil by-product (Hemp flakes): Evaluation for nutritional composition, heavy metals and functionality as a food ingredient

Posted on August 22, 2024 by David

“Background: The recent interest among consumers in industrial hemp due to health and wellness benefits has led to several products from industrial hemp, including cannabidiol (CBD) oil. CBD oil extraction from hemp buds and flowers generates by-product biomass (hemp flakes), often posing disposal challenges and with little or no applications. We hypothesized that hemp flakes possess residual compounds with nutritional and health value that could be used to improve utilization.

Methods: Locally sourced hemp flakes were compared to three commercial hemp protein products. The nutritional composition (proximate analysis), heavy metals (Al, Cu, As, Pb, Co, Cd), and functional composition (phenolic and antioxidant properties-total phenolic compounds (TPC), total flavonoid compounds (TFC), ferric reducing antioxidant potential (FRAP), 1,1-diphenyl-1-picrylhydrazyl (DPPH), Trolox equivalent antioxidant capacity (TEAC)), (CBD, cannabiodiolic acid-CBDA, cannabichromene-CBC, cannabigerol-CBG, and cannabinol-CBN) contents were determined and compared.

Findings: Hemp flakes had a similar nutritional composition to commercial hemp protein products, with heavy metal levels within FDA allowed limits. The by-product had significantly higher CBDA levels than commercial products. Overall, hemp flakes had comparable nutrient composition and antioxidant capabilities. Based on the protein composition of hemp flakes (31.62 %) versus the highest commercial product (43 %), hemp flakes are an acceptable functional food ingredient.”

https://pubmed.ncbi.nlm.nih.gov/39165951/

“It is predicted that by 2050, the world’s population will reach 9 billion, and a sustained food supply will be a concern; therefore, it is appropriate to examine alternatives, including the exploration of agricultural waste materials. Hemp flakes as a by-product from CBD oil extraction could be utilized due to their nutritional and functional value. The hemp flake used in this work demonstrated to hold nutritional and health components comparable to related commercial products. The antioxidant levels showed variations attributed to the source of hemp material and solvent extraction method. Hemp flakes exhibited high and similar antioxidant properties as measured by TPC, TFC, FRAP, and TEAC and possessed comparable radical scavenging properties as measured by DPPH. The hemp by-product showed comparative amounts of cannabinoids with the highest content of cannabidiolic acid, which is known to break down to cannabidiol and possess functional benefits. Further, the results of this work have exemplified that hemp flakes generated from CBD oil extraction have a considerable nutritional and functional value that supports its potential to be incorporated in food preparations as an ingredient. It was also established that the hemp flakes contained levels below the permissible levels of heavy metals in foods, according to health and environmental agencies. It is concluded that the by-product from CBD oil extraction could be utilized as an ingredient in food processing, such as a composite with other ingredients to complement nutrition and health functionality for consumers.”

https://www.cell.com/heliyon/fulltext/S2405-8440(24)11217-0?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2405844024112170%3Fshowall%3Dtrue

Cannabidiol Enhances the Anticancer Activity of Etoposide on Prostate Cancer Cells

Posted on August 20, 2024 by David

“Introduction: Cannabis sativa extract has been used as an herbal medicine since ancient times. It is one of the most researched extracts, especially among supportive treatments against cancer. Prostate cancer is one of the most frequently diagnosed cancer types in men worldwide and an estimated 288,300 new cases were diagnosed in 2023. Today, many advanced therapeutic approaches are used for prostate cancer, such as immunotherapy and chemotherapy, but acquired drug resistance, long-term drug usage and differentiation of cancer cells mostly restricted the efficiency of therapies. Therefore, it is thought that the use of natural products to overcome these limitations and improve the effectiveness of existing therapies may offer promising approaches. The present study focused on the investigation of the possible enhancer role of cannabidiol (CBD), which is a potent ingredient compound of Cannabis, on the chemotherapeutic agent etoposide in prostate cancer cells.

Methods: Herein, we tested the potentiator role of CBD on etoposide in prostate cancer cells by testing the cytotoxic effect, morphological alterations, apoptotic effects, autophagy, unfolded protein response (UPR) signaling, endoplasmic reticulum-associated degradation mechanism (ERAD), angiogenic and androgenic factors, and epithelial-mesenchymal transition (EMT). In addition, we examined the combined treatment of CBD and etoposide on colonial growth, migrative, invasive capability, 3D tumor formation, and cellular senescence.

Results: Our findings demonstrated that cotreatment of etoposide with CBD importantly suppressed autophagic flux and induced ERAD and UPR signaling in LNCaP cells. Also, CBD strongly enhanced the etoposide-mediated suppression of androgenic signaling, angiogenic factor VEGF-A, protooncogene c-Myc, EMT, and also induced apoptosis through activation caspase-3 and PARP-1. Moreover, coadministration markedly decreased tumorigenic properties, such as proliferative capacity, colonial growth, migration, and 3D tumor formation and also induced senescence. Altogether, our data revealed that CBD has a potent enhancer effect on etoposide-associated anticancer activities.

Conclusion: The present study suggests that the use of CBD as a supportive therapy in existing chemotherapeutic approaches may be a promising option, but this effectiveness needs to be investigated on a large scale.”

https://pubmed.ncbi.nlm.nih.gov/39161998/

https://www.liebertpub.com/doi/10.1089/can.2023.0284

A National Survey of Marijuana Use Among U.S. Adults According to Obesity Status, 2016-2022

Posted on August 20, 2024 by David

“Background and Objective: Research has linked marijuana use with lower body mass index (BMI). The current study explores the correlation between marijuana use on BMI in the general U.S. population. It reports the prevalence of marijuana in adults in relation to BMI, overall and across the levels of important variables.

Materials and Methods: This study used a probability sample of U.S. adults 18 years of age and older from the 2016 through 2022 Behavioral Risk Factor Surveillance System, a telephone-administered survey. The survey collects data from a representative sample regarding health-related risk behaviors, chronic health conditions, and use of preventive services. The primary outcome variables are current (at least once in the last 30 days) and daily (at least 20 of the last 30 days) marijuana use.

Results: The study sample consists of 735,921 participants in the surveys that completed the optional module on marijuana use. Prevalence of marijuana use in adults doubled during the study period (7.48% to 14.91%). The increase directly corresponds with a shift toward legalization of medical and recreational marijuana. On average, the prevalence of use is 9% higher when medical marijuana is legal and 81% higher when recreational marijuana is legal (vs. not legal). For obese individuals, prevalence of current marijuana use is 35% lower than for nonobese individuals on average. Lower prevalence of marijuana use in obese individuals is consistently observed across the levels of certain demographic variables, employment status, tobacco smoking history, marijuana legalization status, and certain medical conditions (asthma, arthritis, and depression). In 2022, the adjusted odds of current or daily marijuana use are significantly lower and similar among obese (vs. non-obese) (0.68, 0.69, respectively), such that reduced obesity does not require daily use. Similarly, the adjusted odds of current marijuana use decrease in similar fashion to daily marijuana use with higher BMI weight classification.

Conclusion: Marijuana use is correlated with lower BMI. As legalization and prevalence of the drug in the U.S. increases, the prevalence of obesity may decline. However, clinicians should view this outcome along with the known health risks associated with marijuana use.”

https://pubmed.ncbi.nlm.nih.gov/39158998/

https://www.liebertpub.com/doi/10.1089/can.2024.0069