Category Archives: Uncategorized

Cannabinoids in Integumentary Wound Care: A Systematic Review of Emerging Preclinical and Clinical Evidence

Posted on by
Reply
pubmed logo

“This systematic review critically evaluates preclinical and clinical data on the antibacterial and wound healing properties of cannabinoids in integument wounds.

Comprehensive searches were conducted across multiple databases, including CINAHL, Cochrane library, Medline, Embase, PubMed, Web of Science, and LILACS, encompassing records up to May 22, 2024. Eighteen studies met the inclusion criteria. Eleven were animal studies, predominantly utilizing murine models (n = 10) and one equine model, involving 437 animals. The seven human studies ranged from case reports to randomized controlled trials, encompassing 92 participants aged six months to ninety years, with sample sizes varying from 1 to 69 patients. The studies examined the effects of various cannabinoid formulations, including combinations with other plant extracts, crude extracts, and purified and synthetic cannabis-based medications administered topically, intraperitoneally, orally, or sublingually.

Four animal and three human studies reported complete wound closure. Hemp fruit oil extract, cannabidiol (CBD), and GP1a resulted in complete wound closure in twenty-three (range: 5-84) days with a healing rate of 66-86% within ten days in animal studies. One human study documented a wound healing rate of 3.3 cm2 over 30 days, while three studies on chronic, non-healing wounds reported an average healing time of 54 (21-150) days for 17 patients by oral oils with tetrahydrocannabinol (THC) and CBD and topical gels with THC, CBD, and terpenes. CBD and tetrahydrocannabidiol demonstrated significant potential in reducing bacterial loads in murine models. However, further high-quality research is imperative to fully elucidate the therapeutic potential of cannabinoids in the treatment of bacterial skin infections and wounds. Additionally, it is crucial to delineate the impact of medicinal cannabis on the various phases of wound healing.”

https://pubmed.ncbi.nlm.nih.gov/39204426/

“This systematic review methodically evaluates the current evidence on the wound healing and antibacterial properties of medicinal cannabis (MC) in treating integumentary wounds and infections, whether used alone or in combination with other agents. The findings demonstrate that MC possesses significant antibacterial properties and promotes wound healing, showing promising results in both animal models and human studies.”

https://www.mdpi.com/1999-4923/16/8/1081

Chronic Cannabidiol Administration Mitigates Excessive Daytime Sleepiness and Fatigue in Patients with Primary Hypertension: Insights from a Randomized Crossover Trial

Posted on by
Reply
pubmed logo

“Background: The chronic effects of cannabidiol (CBD) supplementation on factors that could impact the quality of life (anxiety, sleeping quality, memory, etc.) are poorly explored. Hence, the aim of this study was to establish whether chronic CBD supplementation will improve self-reported outcomes related to quality of life. 

Methods: In this randomized crossover trial, 64 patients with primary hypertension were assigned to receive CBD (225-450 mg) for 5 weeks followed by 5 weeks of placebo or vice versa, with a 2-week washout in-between the two. Self-reported outcomes were assessed using short form-36 (SF-36), Pittsburgh sleep quality index (PSQI), Epworth sleepiness scale (ESS), memory complaint questionnaire (MAC-Q), and state-trait anxiety inventory (STAI). 

Results: Five-week administration of CBD, but not of placebo, resulted in improvement of ESS score (F = 6.738, p = 0.011), as well as fatigue/vitality (ΔCBD = 5.0, p < 0.001) and psychological well-being dimensions of SF-36 (ΔCBD = 7.4, p = 0.039). No overall benefit of CBD on quality of life was noted (p = 0.674). No changes were seen in total scores of MAC-Q, PSQI, or STAI (p = 0.151, p = 0.862, p = 0.702, respectively). No significant correlations were found between plasma CBD concentrations and any of the scores. 

Conclusions: Chronic CBD administration reduced excessive daytime sleepiness, despite the fact that no change was observed in self-reported quality of sleep. Furthermore, self-reported fatigue and psychological well-being dimensions of quality of life also improved following chronic CBD use.”

https://pubmed.ncbi.nlm.nih.gov/39187263/

https://www.liebertpub.com/doi/10.1089/can.2024.0028

Successful use of cannabidiol in nonconvulsive status epilepticus in Angelman syndrome

Posted on by
Reply

“Angelman syndrome (AS) is a rare neurogenetic disorder characterized by developmental delay, epileptic seizures, cognitive impairment, electroencephalographic epileptiform and slow interictal abnormalities, and motor dysfunction.1

In AS, nonconvulsive status epilepticus (NCSE) is frequent, is characterized by period of decreased responsiveness which may last hours to days, and it occur in about 20% of patients.2 Treatment of NCSE in AS is challenging and no specific drugs are approved with this purpose.

Epidyolex® is approved by EMA up to a dose of 20 mg/kg/d for individuals >2 years with Lennox–Gastaut Syndrome (LGS) or Dravet Syndrome (DS), and with a higher maximum dose of 25 mg/kg/d in those with tuberous sclerosis complex (TSC) (EMA).3

We recently treated an 8-year-old boy with AS expressing deletion of 15q11.2q13 (6.23 Mb). At the age of 2 years, he started to present with asynchronous bilateral upper limbs myoclonia. He was treated with clonazepam and ethosuximide with good effects, being almost seizure-free until the age of 5 years, when myoclonia associated with poor responsiveness reappeared consistently.

At the age of 8 years, he was receiving ethosuximide (20.5 mg/kg/d) and clonazepam (0.08 mg/kg/d), he presented with marked drowsiness and an increase of myoclonia (Figure 1A). He was admitted in our Department of Neurology (Bambino Gesù Children Hospital – Rome, Italy). Long-term EEG monitoring showed a NCSE pattern (Figure 1A,B), clinically characterized by a reduction in motor initiative and an increase in tremor. This pattern resolved only intermittently during intravenous Midazolam administration. Intravenous valproate (bolus at 30 mg/kg/d and then continuous infusion at 2 mg/kg/d) (Figure 1C) and levetiracetam (bolus at 60 mg/kg/d) (Figure 1D), were ineffective and therefore stopped.

We added Epidyolex® CBD, with a faster titration than usual, starting with 10 mg/kg/d up to 20 mg/kg/d in 8 days. After 1 week, he became more responsive (Figure 1E,F), and after 1 month, he was seizure-free, and the EEG was significantly improved (Figure 1G,H). Epidyolex® was added to ethosuximide and clobazam which were not effective alone. After 4 months of follow-up, no clinical-EEG modifications were observed. The patients did not present adverse events both in the acute phase of administration and during the follow-up.

This case has shown the potential benefits given by Epidyolex® CBD for the treatment of NCSE in a patient with AS. The faster titration was well tolerated.

Given the need for innovative treatments, especially for drug-resistant epilepsies, Epidyolex® CBD may be a promising anti-seizure medication and has been given “off label” to people with epilepsy syndromes outside LGS, DS, and TSC.4 Interestingly, acute CBD (100 mg/kg) treatment attenuated hyperthermia- and acoustically induced seizures in a mouse model of AS supporting the hypothesis that CBD may alleviate seizures and EEG abnormalities in AS, putting the basis for a rational development of CBD as treatment for epilepsy in AS.5 The use of CBD in refractory status epilepticus has been recently reviewed, and in 9 out of 11 treated patients the outcome was favorable.6

We believe this is the first report of the use of CBD in the acute treatment of NCSE in patients with AS. Although anecdotal, this observation ought to encourage further trials and confirmation from future studies.”

https://onlinelibrary.wiley.com/doi/10.1002/epi4.12948

Bioelectronic sensing platform emulating the human endocannabinoid system for assessing and modulating of cannabinoid activity

Posted on by
Reply
pubmed logo

“Cannabinoids are involved in physiological and neuromodulatory processes through their interactions with the human cannabinoid receptor-based endocannabinoid system. Their association with neurodegenerative diseases and brain reward pathways underscores the importance of evaluating and modulating cannabinoid activity for both understanding physiological mechanisms and developing therapeutic drugs. The use of agonists and antagonists could be strategic approaches for modulation.

In this study, we introduce a bioelectronic sensor designed to monitor cannabinoid binding to receptors and assess their agonistic and antagonistic properties. We produced human cannabinoid receptor 1 (hCB1R) via an Escherichia coli expression system and incorporated it into nanodiscs (NDs). These hCB1R-NDs were then immobilized on a single-walled carbon nanotube field-effect transistor (swCNT-FET) to construct a bioelectronic sensing platform. This novel system can sensitively detect the cannabinoid ligand anandamide (AEA) at concentrations as low as 1 fM, demonstrating high selectivity and real-time response. It also successfully identified the hCB1R agonist Δ9-tetrahydrocannabinol and observed that the hCB1R antagonist rimonabant diminished the sensor signal upon AEA binding, indicating the antagonism-based modulation of ligand interaction. Consequently, our bioelectronic sensing platform holds potential for ligand detection and analysis of agonism and antagonism.”

https://pubmed.ncbi.nlm.nih.gov/39173339/

https://www.sciencedirect.com/science/article/abs/pii/S0956566324006924?via%3Dihub

Unveiling Colombia’s medicinal Cannabis sativa treasure trove: Phenotypic and Chemotypic diversity in legal cultivation

Posted on by
Reply
pubmed logo

“Introduction: Cannabis sativa is a highly versatile plant with a long history of cultivation and domestication. It produces multiple compounds that exert distinct and valuable therapeutic effects by modulating diverse biological systems, including the endocannabinoid system (ECS). Access to standardized, metabolically diverse, and reproducible C. sativa chemotypes and chemovars is essential for physicians to optimize individualized patient treatment and for industries to conduct drug-discovery campaigns.

Objective: This study aimed to characterize and assess the phytochemical diversity of C. sativa chemotypes in diverse ecological regions of Colombia, South America.

Methodology: Ten cannabinoids and 23 terpenes were measured using liquid and gas chromatography, in addition to other phenotypic traits, in 156 C. sativa plants that were grown in diverse ecological regions in Colombia, a hotspot for global biodiversity.

Results: Our results reveal significant phytochemical diversity in Colombian-grown C. sativa plants, with four distinct chemotypes based on cannabinoid profile. The significant amount of usually uncommon terpenes suggests that Colombia’s environments may have unique capabilities that allow the plant to express these compounds. Colombia’s diverse climates offer enormous cultivation potential, making it a key player in both domestic and international medicinal and recreational C. sativa trade.

Conclusion: These findings underscore Colombia’s capacity to pioneer global C. sativa production diversification, particularly in South America with new emerging markets.”

https://pubmed.ncbi.nlm.nih.gov/39169651/

https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/10.1002/pca.3436

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

Posted on by
Reply
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.

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

Posted on by
Reply
pubmed logo

“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 by
Reply
pubmed logo

“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 by
Reply
pubmed logo

“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


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

Posted on by
Reply
pubmed logo

“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