Whack-a-mole Drugs

CNR: Whack-a-mole Drugs

New psychoactive substances like Tianeptine or “gas station heroin” are popping up in North Carolina, and our Legislature is struggling with the problem.  https://www.wbtv.com/2024/02/14/nc-lawmakers-working-ban-gas-station-drug-that-mimics-effects-opioids/

But as soon as the Legislature bans substances, copycat drugs pop up, maybe with a molecule in a complex organic compound changed here or there.

To go beyond listing dangerous drugs that are out there already, I’m trying to find catch-all language that would list or cover “whack-a-mole” new drugs that people would discover or invent.

It took me years to get up to speed on marijuana taxation, so I don’t imagine I can grasp new psychoactive substances very readily.  Here’s what I’ve found so far, mainly to show how little I know.  There is language from New Zealand and from the United Kingdom that may be helpful.

New Zealand has this language:

Broadly speaking, a psychoactive substance is anything:

·  that is capable of producing a psychoactive effect in an individual who uses the substance (ie, affects the mind of the user in any way) AND

·  whose primary purpose is to induce a psychoactive effect in an individual who uses the substance or product AND

·  that is not a medicine, controlled drug, precursor substance, herbal remedy, food, dietary supplement, tobacco product or alcohol.

https://www.health.govt.nz/our-work/regulation-health-and-disability-system/psychoactive-substances-regulation/definitions-and-history-psychoactive-substances

New Zealand’s effort is not getting glowing reviews, but I wonder if it’s better than nothing.  

https://www.health.govt.nz/publication/review-psychoactive-substances-act-2013

The UK has a similar approach:

Meaning of “psychoactive substance” etc

(1)In this Act “psychoactive substance” means any substance which—

(a)is capable of producing a psychoactive effect in a person who consumes it, and

(b)is not an exempted substance (see section 3).

(2)For the purposes of this Act a substance produces a psychoactive effect in a person if, by stimulating or depressing the person’s central nervous system, it affects the person’s mental functioning or emotional state; and references to a substance’s psychoactive effects are to be read accordingly.

https://www.cps.gov.uk/legal-guidance/psychoactive-substances#:~:text=The%20Psychoactive%20Substances%20Act%202016,is%20seven%20years%27%20imprisonment).

I don’t know how the UK system is working.  There are criticisms (and details) at  https://en.wikipedia.org/wiki/Psychoactive_Substances_Act_2016.

A friend from CANN-RA, the Cannabis Regulators Association,writes:

ASTM has a standard defining “intoxicating cannabinoids” out for balloting. It starts by categorizing all cannabinoids as “potentially intoxicating” until there’s evidence on which to make a determination. But the standard focuses only on CB1-mediated intoxication (effects like THC), so if something is intoxicating by a different mechanism, it counts as “non-intoxicating.” It also doesn’t necessarily account for human metabolism: If test tube studies show that the substance doesn’t activate human CB1 receptors, it’s non-intoxicating… even if enzymes in the liver or blood convert the substance into an intoxicating derivative when a person ingests it. And it has a very narrow definition of cannabinoid that doesn’t include a lot of synthetic cannabinoids. This is in the “too narrow” category.

The New Zealand standard looks like it may go the other direction, being too broad. Or maybe it’s really broad on the surface, but in practice the exceptions make it hard to navigate. Regulation of psychoactive substances is really not coherent, because the regulatory approach to each emerges out of the historical and cultural context that gave rise to the regulation. Caffeine is a popular drug, but is not a “psychoactive substance” under this definition because it is widely accepted and has been folded into regulation as a food, dietary supplement, and medicine. Tobacco and alcohol each have their own unique regulatory structures because of their long history of use in America. On the other hand, I’m not at all clear where betel (areca nut) falls under America’s regulatory system because it wasn’t historically widely used or noticed here, despite being the fourth most commonly used drug worldwide (behind caffeine, alcohol, and tobacco). Kava happened to be present in the dietary supplement market prior to 1994, so it’s grandfathered into that regulatory scheme, although I suspect it would not be allowed as a new dietary ingredient if it didn’t pre-date DSHEA and was submitted as a new dietary ingredient for consideration today. Under New Zealand’s scheme, I’m not sure where something like nitrous oxide would fall: It’s definitely psychoactive, but is it’s primary purpose to induce psychoactive effects or as a propellant for whipped cream? Or is it exempt anyway because it’s a medicine (used as an anaesthetic), despite the psychoactive use being outside of the medical context.

+++

I suppose there would need to be a body or agency of some kind that makes ongoing determinations very quickly as new drugs pop up.  

The DEA handled fentanyl:  “When a new analog appeared on the streets, the DEA would list it as illegal, and the illicit labs would respond by creating a new, legal analog. This deadly game of ‘Whack-A-Mole’  . . . continued until 2018 when the DEA listed all drugs related to fentanyl as illegal — a move referred to as class-wide scheduling.”    

https://nij.ojp.gov/topics/articles/fighting-uphill-war-against-illicit-drugs-and-overdose-deaths-detecting-emerging

But the DEA hasn’t acted on tianeptine or other drugs that are problematic.


#CBD #Hemp

Whack-a-mole Drugs


March 1, 2024 6:55 pm

PubMed: Easy and Accessible Synthesis of Cannabinoids from CBD

PubMed: Easy and Accessible Synthesis of Cannabinoids from CBD

J Nat Prod. 2024 Mar 1. doi: 10.1021/acs.jnatprod.3c01117. Online ahead of print.

ABSTRACT

Cannabidiol (CBD), a prominent phytocannabinoid found in various Cannabis chemotypes, is under extensive investigation for its therapeutic potential. Moreover, because it is nonpsychoactive, it can also be utilized as a functional ingredient in foods and supplements in certain countries, depending on its legal status. From a chemical reactivity point of view, CBD can undergo conversion into different structurally related compounds both during storage and after the consumption of CBD-based products. The analytical determination of these compounds is of paramount concern due to potential toxicity and the risk of losing the active ingredient (CBD) title. Consequently, the complete stereoselective total synthesis of representative CBD-derived compounds has become a matter of great interest. The synthesis of pure CBD-derived compounds, achievable in a few synthetic steps, is essential for preparing analytical standards and facilitating biological studies. This paper details the transformation of the readily available CBD into Δ8-THC, Δ9-THC, Δ8iso-THC, CBE, HCDN, CBDQ, Δ6iso-CBD, and 1,8-cineol cannabinoid (CCB). The described protocols were executed without the extensive use of protecting groups, avoiding tedious purifications, and ensuring complete control over the structural features.

PMID:38427968 | DOI:10.1021/acs.jnatprod.3c01117

https://pubmed.ncbi.nlm.nih.gov/38427968/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240301192127&v=2.18.0.post9+e462414 March 1, 2024 11:00 am

PubMed: Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia

PubMed: Exploring the therapeutic potential of cannabidiol for sleep deprivation-induced hyperalgesia

Neuropharmacology. 2024 Feb 28:109893. doi: 10.1016/j.neuropharm.2024.109893. Online ahead of print.

ABSTRACT

Hyperalgesia resulting from sleep deprivation (SD) poses a significant a global public health challenge with limited treatment options. The nucleus accumbens (NAc) plays a crucial role in the modulation of pain and sleep, with its activity regulated by two distinct types of medium spiny neurons (MSNs) expressing dopamine 1 or dopamine 2 (D1-or D2) receptors (referred to as D1-MSNs and D2-MSNs, respectively). However, the specific involvement of the NAc in SD-induced hyperalgesia remains uncertain. Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has demonstrated analgesic effects in clinical and preclinical studies. Nevertheless, its potentcy in addressing this particular issue remains to be determined. Here, we report that SD induced a pronounced pronociceptive effect attributed to the heightened intrinsic excitability of D2-MSNs within the NAc in Male C57BL/6N mice. CBD (30 mg/kg, i.p.) exhibited an anti-hyperalgesic effect. CBD significantly improved the thresholds for thermal and mechanical pain and increased wakefulness by reducing delta power. Additionally, CBD inhibited the intrinsic excitability of D2-MSNs both in vitro and in vivo. Bilateral microinjection of the selective D2 receptor antagonist raclopride into the NAc partially reversed the antinociceptive effect of CBD. Thus, these findings strongly suggested that SD activates NAc D2-MSNs, contributing heightened to pain sensitivity. CBD exhibits antinociceptive effects by activating D2R, thereby inhibiting the excitability of D2-MSNs and promoting wakefulness under SD conditions.

PMID:38428482 | DOI:10.1016/j.neuropharm.2024.109893

https://pubmed.ncbi.nlm.nih.gov/38428482/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240302112153&v=2.18.0.post9+e462414 March 1, 2024 11:00 am

PubMed: Cannabidiol induces systemic analgesia through activation of the PI3Kgamma/nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism

PubMed: Cannabidiol induces systemic analgesia through activation of the PI3Kgamma/nNOS/NO/KATP signaling pathway in neuropathic mice. A KATP channel S-nitrosylation-dependent mechanism

Nitric Oxide. 2024 Feb 28:S1089-8603(24)00028-4. doi: 10.1016/j.niox.2024.02.005. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) is the second most abundant pharmacologically active component present in Cannabis sp. Unlike Δ-9-tetrahydrocannabinol (THC), it has no psychotomimetic effects and has recently received significant interest from the scientific community due to its potential to treat anxiety and epilepsy. CBD has excellent anti-inflammatory potential and can be used to treat some types of inflammatory and neuropathic pain. In this context, the present study aimed to evaluate the analgesic mechanism of cannabidiol administered systemically for the treatment of neuropathic pain and determine the endogenous mechanisms involved with this analgesia.

METHODS: Neuropathic pain was induced by sciatic nerve constriction surgery, and the nociceptive threshold was measured using the paw compression test in mice.

RESULTS: CBD produced dose-dependent antinociception after intraperitoneal injection. Selective inhibition of PI3Kγ dose-dependently reversed CBD-induced antinociception. Selective inhibition of nNOS enzymes reversed the antinociception induced by CBD, while selective inhibition of iNOS and eNOS did not alter this antinociception. However, the inhibition of cGMP production by guanylyl cyclase did not alter CBD-mediated antinociception, but selective blockade of ATP-sensitive K+ channels dose-dependently reversed CBD-induced antinociception. Inhibition of S-nitrosylation dose-dependently and completely reversed CBD-mediated antinociception.

CONCLUSION: Cannabidiol has an antinociceptive effect when administered systemically and this effect is mediated by the activation of PI3Kγ as well as by nitric oxide and subsequent direct S-nitrosylation of KATP channels on peripheral nociceptors.

PMID:38428514 | DOI:10.1016/j.niox.2024.02.005

https://pubmed.ncbi.nlm.nih.gov/38428514/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240302112153&v=2.18.0.post9+e462414 March 1, 2024 11:00 am

Colorado hemp seed supplier sues Oregon, California companies for $1.4 million

HempToday®: Colorado hemp seed supplier sues Oregon, California companies for $1.4 million
A Colorado hemp company has gone to court to try to collect $1.4 million from an Oregon farming operation in a cultivation seed deal that went sour. MH Consulting LLC, […]

#CBD #Hemp

Colorado hemp seed supplier sues Oregon, California companies for $1.4 million


March 1, 2024 8:00 am

EU-Italian funded project aims to develop hemp supply chains in Sicily

HempToday®: EU-Italian funded project aims to develop hemp supply chains in Sicily
Sicilian officials say they will launch a broad-based program aimed at developing local supply chains for industrial hemp. The initiative, “Canapa New Tech” (“New Tech Hemp”), is under the Sicily […]

#CBD #Hemp

EU-Italian funded project aims to develop hemp supply chains in Sicily


February 29, 2024 8:59 am

South Dakota law aimed at hemp intoxicants is likely to wipe out CBD market

HempToday®: South Dakota law aimed at hemp intoxicants is likely to wipe out CBD market
A proposed South Dakota law intended to crack down on products that contain high concentrations of intoxicating delta-8 THC and other cannabinoids also threatens the CBD market in one of […]

#CBD #Hemp
https://hemptoday.net/south-dakota-law-against-hemp-intoxicants-is-likely-to-wipe-out-cbd-market/
February 28, 2024 6:53 am

PubMed: Therapeutic Polymer-Based Cannabidiol Formulation: Tackling Neuroinflammation Associated with Ischemic Events in the Brain

PubMed: Therapeutic Polymer-Based Cannabidiol Formulation: Tackling Neuroinflammation Associated with Ischemic Events in the Brain

Mol Pharm. 2024 Feb 27. doi: 10.1021/acs.molpharmaceut.3c00244. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is the most relevant nonpsychostimulant phytocompound found in Cannabis sativa. CBD has been extensively studied and has been proposed as a therapeutic candidate for neuroinflammation-related conditions. However, being a highly lipophilic drug, it has several drawbacks for pharmaceutical use, including low solubility and high permeability. Synthetic polymers can be used as drug delivery systems to improve CBD’s stability, half-life, and biodistribution. Here, we propose using a synthetic polymer as a nanoparticulate vehicle for CBD (NPCBD) to overcome the pharmacological drawbacks of free drugs. We tested the NPCBD-engineered system in the context of ischemic events in a relevant oxygen and glucose deprivation (OGD) model in primary cortical cells (PCC). Moreover, we have characterized the inflammatory response of relevant cell types, such as THP-1 (human monocytes), HMC3 (human microglia), and PCC, to NPCBD and observed a shift in the inflammatory state of the treated cells after the ischemic event. In addition, NPCBD exhibited a promising ability to restore mitochondrial function after OGD insult in both HMC3 and PCC cells at low doses of 1 and 0.2 μM CBD. Taken together, these results suggest the potential for preclinical use.

PMID:38412451 | DOI:10.1021/acs.molpharmaceut.3c00244

https://pubmed.ncbi.nlm.nih.gov/38412451/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240227193131&v=2.18.0.post9+e462414 February 27, 2024 11:00 am

Proposed law to raise THC limit for hemp to 1.0% is nixed by lawmakers in Virginia

HempToday®: Proposed law to raise THC limit for hemp to 1.0% is nixed by lawmakers in Virginia
Virginia lawmakers have turned back a bill that sought to increase the legal limit for THC in industrial hemp plants to 1.0% and ease state licensing requirements. The proposed measure, […]

#CBD #Hemp

Proposed law to raise THC limit for hemp to 1.0% is nixed by lawmakers in Virginia


February 27, 2024 9:54 am

PubMed: Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress

PubMed: Cannabidiol protects C2C12 myotubes against cisplatin-induced atrophy by regulating oxidative stress

Am J Physiol Cell Physiol. 2024 Feb 26. doi: 10.1152/ajpcell.00622.2023. Online ahead of print.

ABSTRACT

Cancer and chemotherapy can both cause cachexia, a complex multi-organ syndrome characterized by body weight loss, due to adipose tissue and skeletal muscle wasting. Changes in body weight and muscle mass are predictive of response to chemotherapy, incidence of treatment-related complications and, ultimately, patient survival, but there are currently still no clear therapeutic strategies to counteract cachexia. Cannabidiol (CBD) is a bioactive phytocannabinoid produced from a plant named Cannabis sativa. In recent years, CBD has demonstrated beneficial effects on maintaining skeletal muscle mass, function and metabolism in models of muscular dystrophy or diet-induced obesity. Here, we used a model of myotubes in culture to evaluate the potential beneficial effects of CBD on cisplatin-induced skeletal muscle wasting. 24-h cisplatin treatment resulted in a ≈30% reduction in myotube diameter, driven by a drastic reduction in protein synthesis rate and a twofold increase in proteolysis. 24-h cisplatin treatment also significantly increased myotube TBARS content, catalase activity and antioxidant system mRNA levels (GPX1, SOD1, SOD2 and CAT) indicating increased oxidative stress. 24-h cisplatin treatment also increased the mitochondrial protein content of NDUFB8, UQCRC2, COX4 and VDAC1, which are involved in mitochondrial respiration and control of apoptosis. Importantly, CBD was found to antagonize chemotherapy-induced C2C12 myotube atrophy by promoting protein homeostasis and reducing oxidative stress. Our results show that CBD could be used as an adjuvant in the treatment of cancer cachexia to help maintain muscle mass and improve patient quality of life.

PMID:38406827 | DOI:10.1152/ajpcell.00622.2023

https://pubmed.ncbi.nlm.nih.gov/38406827/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240226072257&v=2.18.0.post9+e462414 February 26, 2024 11:00 am

PubMed: Enhancing massed prolonged exposure with cannabidiol to improve posttraumatic stress disorder: Design and methodology of a pilot randomized clinical trial

PubMed: Enhancing massed prolonged exposure with cannabidiol to improve posttraumatic stress disorder: Design and methodology of a pilot randomized clinical trial

Contemp Clin Trials Commun. 2024 Feb 15;38:101270. doi: 10.1016/j.conctc.2024.101270. eCollection 2024 Apr.

ABSTRACT

BACKGROUND: The impact of posttraumatic stress disorder (PTSD) is substantial and often results in pervasive functional impairments. Although evidence-based treatments for PTSD are established, there remains room for improvement as many individuals continue to meet diagnostic criteria even after successful treatment completion. Cannabidiol (CBD) has attracted considerable attention based on its potential to treat a myriad of health conditions. CBD may decrease anxiety and facilitate extinction learning processes, two critical targets of trauma-focused psychotherapies. We present the design and methods for a pilot randomized clinical trial to examine the combination of CBD and prolonged exposure for PTSD.

METHODS: Participants (n = 24) will be randomized to CBD or placebo for 18 days delivered in combination with ten daily prolonged exposure sessions over two weeks. The study medication will be Epidiolex® (250 mg BID). The PTSD Checklist for DSM-5 will be the primary outcome to assess PTSD severity at baseline, during treatment, and at 1-month follow-up. Blood, saliva, and heart rate will be collected during treatment to assess intervention effects on biological outcomes related to PTSD and the endocannabinoid system.

RESULTS: Consistent with the purpose of a pilot, our goals are to evaluate the feasibility of study procedures, safety of the intervention, and the preliminary effect of CBD to inform a larger trial. Descriptive and inferential statistics will be used to address study aims.

CONCLUSION: Findings will inform decision making on combining CBD with behavioral interventions for PTSD to enhance outcomes and mitigate the morbidity of this debilitating condition.

PMID:38404650 | PMC:PMC10884801 | DOI:10.1016/j.conctc.2024.101270

https://pubmed.ncbi.nlm.nih.gov/38404650/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240226072257&v=2.18.0.post9+e462414 February 26, 2024 11:00 am

PubMed: Phytochemical Characterization and TRPA1/TRPM8 Modulation Profile of the Cannabigerol-Rich Cannabis sativa L. Chemotype IV

PubMed: Phytochemical Characterization and TRPA1/TRPM8 Modulation Profile of the Cannabigerol-Rich Cannabis sativa L. Chemotype IV

J Nat Prod. 2024 Feb 26. doi: 10.1021/acs.jnatprod.3c00831. Online ahead of print.

ABSTRACT

The first detailed phytochemical analysis of the cannabigerol (CBG)-rich chemotype IV of Cannabis sativa L. resulted in the isolation of the expected cannabigerolic acid/cannabigerol (CBGA/CBG) and cannabidiolic acid/cannabidiol (CBDA/CBD) and of nine new phytocannabinoids (513), which were fully characterized by HR-ESIMS and 1D and 2D NMR. These included mono- or dihydroxylated CBGA/CBG analogues, a congener with a truncated side chain (10), cyclocannabigerol B (11), and the CBD derivatives named cannabifuranols (12 and 13). Cyclocannabigerol B and cannabifuranols are characterized by a novel phytocannabinoid structural architecture. The isolated phytocannabinoids were assayed on the receptor channels TRPA1 and TRPM8, unveiling a potent dual TRPA1 agonist/TRPM8 antagonist profile for compounds 6, 7, and 14. Chiral separation of the two enantiomers of 5 resulted in the discovery of a synergistic effect of the two enantiomers on TRPA1.

PMID:38408345 | DOI:10.1021/acs.jnatprod.3c00831

https://pubmed.ncbi.nlm.nih.gov/38408345/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240226192203&v=2.18.0.post9+e462414 February 26, 2024 11:00 am

Opponents say Florida laws aimed at intoxicating hemp would effectively ban CBD

HempToday®: Opponents say Florida laws aimed at intoxicating hemp would effectively ban CBD
A proposed Florida law that would ban intoxicating hemp compounds and impose tight restrictions on CBD products is expected to get a vote in the House of Representatives soon, after its […]

#CBD #Hemp

Opponents say Florida laws aimed at intoxicating hemp would effectively ban CBD


February 26, 2024 8:45 am

PubMed: Cutaneous Delivery and Biodistribution of Cannabidiol in Human Skin after Topical Application of Colloidal Formulations

PubMed: Cutaneous Delivery and Biodistribution of Cannabidiol in Human Skin after Topical Application of Colloidal Formulations

Pharmaceutics. 2024 Jan 30;16(2):202. doi: 10.3390/pharmaceutics16020202.

ABSTRACT

The objective of this study was to investigate the cutaneous delivery of cannabidiol (CBD) from aqueous formulations developed for the targeted local treatment of dermatological conditions. CBD was formulated using a proprietary colloidal drug delivery system (VESIsorb®) into an aqueous colloidal solution at 2% (ACS 2%) and two colloidal gels (CG 1% and CG 2%, which contained 1% and 2% CBD, respectively). Two basic formulations containing CBD (5% in propylene glycol (PG 5%) and a 6.6% oil solution (OS 6.6%)) and two marketed CBD products (RP1 and RP2, containing 1% CBD) were used as comparators. Cutaneous delivery and cutaneous biodistribution experiments were performed using human abdominal skin (500-700 µm) under infinite- and finite-dose conditions with 0.5% Tween 80 in the PBS receiver phase. The quantification of CBD in the skin samples was performed using a validated UHPLC-MS/MS method and an internal standard (CBD-d3). The cutaneous deposition of CBD under finite-dose conditions demonstrated the superiority of CG 1%, CG 2%, and ACS 2% over the marketed products; CG 1% had the highest delivery efficiency (5.25%). Cutaneous biodistribution studies showed the superiority of the colloidal systems in delivering CBD to the viable epidermis, and the upper and lower papillary dermis, which are the target sites for the treatment of several dermatological conditions.

PMID:38399256 | DOI:10.3390/pharmaceutics16020202

https://pubmed.ncbi.nlm.nih.gov/38399256/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240224122351&v=2.18.0.post9+e462414 February 24, 2024 11:00 am

PubMed: Physicochemical Characterisation of Seeds, Oil and Defatted Cake of Three Hempseed Varieties Cultivated in Spain

PubMed: Physicochemical Characterisation of Seeds, Oil and Defatted Cake of Three Hempseed Varieties Cultivated in Spain

Foods. 2024 Feb 9;13(4):531. doi: 10.3390/foods13040531.

ABSTRACT

The increasing use of hempseed in food products highlights the need for a comprehensive database for scientific research and industrial applications. In food development, information about the techno-functional properties of raw materials plays a crucial role in determining the suitability of each product for specific applications. Thus, this study aims to characterise three hempseed varieties (Ferimon, Henola and Uso-31), comparing their physicochemical and nutritional compositions. Moreover, the study investigates the impact of hempseed varieties on the techno-functional, physical and thermal properties of the partially defatted hempseed flours (PDHFs) obtained from single screw pressing (SSP) oil extraction. The fatty acid and tocopherol profiles of the dehulled seeds and oil were also analysed. Significant variations in yield and physical properties were observed among hempseed varieties, influenced by genetics, adaptation to agro-climatic conditions and cultivation systems. Despite its lower yield (kg/ha), Uso-31 exhibited superior 1000-seed weight, dehulling yield and larger mean seed size (1.79 ± 0.02 mm). Hempseed oil was rich in unsaturated fatty acids, particularly linoleic (51.2-53.4 g/100 g oil) and α-linolenic (14.88-18.97 g/100 oil) acids, showing variations in γ- and α-tocopherols depending on the variety. The variety also influenced the least gelation concentration (LGC) and techno-functional properties such as water absorption capacity (WAC), emulsifying activity (EA) and emulsion stability (ES). SDS-PAGE and DSC measurements indicated the presence of 11S and 7S globulin proteins with denaturation temperatures above 87.8 °C. These findings confirm that the studied hempseed flours are valuable techno-functional and nutritional ingredients suitable for sustainable food formulations.

PMID:38397508 | DOI:10.3390/foods13040531

https://pubmed.ncbi.nlm.nih.gov/38397508/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240224122351&v=2.18.0.post9+e462414 February 24, 2024 11:00 am

PubMed: The Role of Cannabidiol in Liver Disease: A Systemic Review

PubMed: The Role of Cannabidiol in Liver Disease: A Systemic Review

Int J Mol Sci. 2024 Feb 17;25(4):2370. doi: 10.3390/ijms25042370.

ABSTRACT

Cannabidiol (CBD), a non-psychoactive phytocannabinoid abundant in Cannabis sativa, has gained considerable attention for its anti-inflammatory, antioxidant, analgesic, and neuroprotective properties. It exhibits the potential to prevent or slow the progression of various diseases, ranging from malignant tumors and viral infections to neurodegenerative disorders and ischemic diseases. Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), alcoholic liver disease, and viral hepatitis stand as prominent causes of morbidity and mortality in chronic liver diseases globally. The literature has substantiated CBD’s potential therapeutic effects across diverse liver diseases in in vivo and in vitro models. However, the precise mechanism of action remains elusive, and an absence of evidence hinders its translation into clinical practice. This comprehensive review emphasizes the wealth of data linking CBD to liver diseases. Importantly, we delve into a detailed discussion of the receptors through which CBD might exert its effects, including cannabinoid receptors, CB1 and CB2, peroxisome proliferator-activated receptors (PPARs), G protein-coupled receptor 55 (GPR55), transient receptor potential channels (TRPs), and their intricate connections with liver diseases. In conclusion, we address new questions that warrant further investigation in this evolving field.

PMID:38397045 | DOI:10.3390/ijms25042370

https://pubmed.ncbi.nlm.nih.gov/38397045/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240224122351&v=2.18.0.post9+e462414 February 24, 2024 11:00 am

PubMed: Strategies to Improve Cannabidiol Bioavailability and Drug Delivery

PubMed: Strategies to Improve Cannabidiol Bioavailability and Drug Delivery

Pharmaceuticals (Basel). 2024 Feb 13;17(2):244. doi: 10.3390/ph17020244.

ABSTRACT

The poor physicochemical properties of cannabidiol (CBD) hamper its clinical development. The aim of this review was to examine the literature to identify novel oral products and delivery strategies for CBD, while assessing their clinical implications and translatability. Evaluation of the published literature revealed that oral CBD strategies are primarily focused on lipid-based and emulsion solutions or encapsulations, which improve the overall pharmacokinetics (PK) of CBD. Some emulsion formulations demonstrate more rapid systemic delivery. Variability in the PK effects of different oral CBD products is apparent across species. Several novel administration routes exist for CBD delivery that may offer promise for specific indications. For example, intranasal administration and inhalation allow quick delivery of CBD to the plasma and the brain, whereas transdermal and transmucosal administration routes deliver CBD systemically more slowly. There are limited but promising data on novel delivery routes such as intramuscular and subcutaneous. Very limited data show that CBD is generally well distributed across tissues and that some CBD products enable increased delivery of CBD to different brain regions. However, evidence is limited regarding whether changes in CBD PK profiles and tissue distribution equate to superior therapeutic efficacy across indications and whether specific CBD products might be suited to particular indications.

PMID:38399459 | DOI:10.3390/ph17020244

https://pubmed.ncbi.nlm.nih.gov/38399459/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240224122351&v=2.18.0.post9+e462414 February 24, 2024 11:00 am

PubMed: Impact of Using Oilseed Industry Byproducts Rich in Linoleic and Alpha-Linolenic Acid in Ruminant Nutrition on Milk Production and Milk Fatty Acid Profile

PubMed: Impact of Using Oilseed Industry Byproducts Rich in Linoleic and Alpha-Linolenic Acid in Ruminant Nutrition on Milk Production and Milk Fatty Acid Profile

Animals (Basel). 2024 Feb 6;14(4):539. doi: 10.3390/ani14040539.

ABSTRACT

Milk contains more than 400 different fatty acids, some of which play a positive role in promoting human health. The profile of fatty acids in milk can be enhanced by providing animals with plant-based resources that possess feeding characteristics adequate for favorable changes in the fatty acid composition and increasing healthy fatty acids in milk. This review summarizes the available 41 research studies on the utilization of oilseed industry byproducts rich in linoleic acid (hemp, pumpkin, sunflower) and alpha-linolenic acid (camelina and linseed) in dairy cow, sheep, and goat nutrition; their impact on milk production characteristics; and potential to improve fatty acid composition of milk through the diet. This review illustrates that incorporating byproducts into the diet for dairy ruminants generally does not have any adverse effects on both milk production and composition. A similar trend of improvement in milk fatty acid profile was observed when ruminants were fed diets supplemented with camelina, linseed, and sunflower byproducts, while no significant changes were noted with pumpkin byproducts. Hempseed byproducts showed potential for use as an alternative ingredient in dairy ruminant diets. Nevertheless, more in-depth research investigating the inclusion of selected byproducts is required before valid conclusions can be drawn regarding their value.

PMID:38396507 | DOI:10.3390/ani14040539

https://pubmed.ncbi.nlm.nih.gov/38396507/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240224122351&v=2.18.0.post9+e462414 February 24, 2024 11:00 am

PubMed: Repeated cannabidiol treatment affects neuroplasticity and endocannabinoid signaling in the prefrontal cortex of the Flinders Sensitive Line (FSL) rat model of depression

PubMed: Repeated cannabidiol treatment affects neuroplasticity and endocannabinoid signaling in the prefrontal cortex of the Flinders Sensitive Line (FSL) rat model of depression

Neuropharmacology. 2024 Feb 22:109870. doi: 10.1016/j.neuropharm.2024.109870. Online ahead of print.

ABSTRACT

Delayed therapeutic responses and limited efficacy are the main challenges of existing antidepressant drugs, thereby incentivizing the search for new potential treatments. Cannabidiol (CBD), non-psychotomimetic component of cannabis, has shown promising antidepressant effects in different rodent models, but its mechanism of action remains unclear. Herein, we investigated the antidepressant-like effects of repeated CBD treatment on behavior, neuroplasticity markers and lipidomic profile in the prefrontal cortex (PFC) of Flinders Sensitive Line (FSL), a genetic animal model of depression, and their control counterparts Flinders Resistant Line (FRL) rats. Male FSL animals were treated with CBD (10 mg/kg; i.p.) or vehicle (7 days) followed by Open Field Test (OFT) and the Forced Swimming Test (FST). The PFC was analyzed by a) western blotting to assess markers of synaptic plasticity and cannabinoid signaling in synaptosome and cytosolic fractions; b) mass spectrometry-based lipidomics to investigate endocannabinoid levels (eCB). CBD attenuated the increased immobility observed in FSL, compared to FRL in FST, without changing the locomotor behavior in the OFT. In synaptosomes, CBD increased ERK1, mGluR5, and Synaptophysin, but failed to reverse the reduced CB1 and CB2 levels in FSL rats. In the cytosolic fraction, CBD increased ERK2 and decreased mGluR5 expression in FSL rats. Surprisingly, there were no significant changes in eCB levels in response to CBD treatment. These findings suggest that CBD effects in FSL animals are associated with changes in synaptic plasticity markers involving mGluR5, ERK1, ERK2, and synaptophysin signaling in the PFC, without increasing the levels of endocannabinoids in this brain region.

PMID:38401791 | DOI:10.1016/j.neuropharm.2024.109870

https://pubmed.ncbi.nlm.nih.gov/38401791/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240225012155&v=2.18.0.post9+e462414 February 24, 2024 11:00 am

PubMed: Investigation of neuroprotective and therapeutic effects of cannabidiol in an acute coronary syndrome model

PubMed: Investigation of neuroprotective and therapeutic effects of cannabidiol in an acute coronary syndrome model

Neurosci Lett. 2024 Feb 22:137689. doi: 10.1016/j.neulet.2024.137689. Online ahead of print.

ABSTRACT

PURPOSE: The ischemia-reperfusion (I/R) injury seen in the heart can cause severe damage to essential organs such as the brain. Cannabidiol (CBD) obtained from Cannabis sativa is used today to treat various diseases. This study aimed to demonstrate CBD’s neuroprotective and therapeutic properties in rats with brain damage caused by I/R in the heart.

MATERIALS: Rats were divided into four groups; sham, I/R, I/R + Prophylactic CBD, and I/R + Therapeutic CBD. End of the experiment, brain tissues were collected for biochemical, histopathological, and genetic examinations.

RESULTS: I/R damage increased the number of degenerative neurons, caspase-3 and TNF-α immunoexpression, total oxidant status levels, and oxidative stress index. Both prophylactic and therapeutic CBD administration reduced these increased values. In addition, the relative fold changes of AMPK, PGC-1α, SIRT1, and Bcl 2 decreased in the I/R group, and the relative fold change of Bax increased, which are indicators of ER stress and apoptosis. Both administrations of CBD reversed these genes’ relative fold changes.

CONCLUSION: CBD can be protective against brain injury caused by cardiac I/R damage through antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.

PMID:38401641 | DOI:10.1016/j.neulet.2024.137689

https://pubmed.ncbi.nlm.nih.gov/38401641/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240225012155&v=2.18.0.post9+e462414 February 24, 2024 11:00 am

PubMed: Anthelmintic Effect of Cannabidiol against Echinococcus granulosus sensu stricto

PubMed: Anthelmintic Effect of Cannabidiol against Echinococcus granulosus sensu stricto

Trop Med Infect Dis. 2024 Jan 31;9(2):35. doi: 10.3390/tropicalmed9020035.

ABSTRACT

Cystic echinococcosis is a global parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus sensu lato. Cystic echinococcosis affects more than 1 million people worldwide, causing important economic costs in terms of management and livestock associated losses. Albendazole is the main drug used in treating human cystic echinococcosis. In spite of this, its low aqueous solubility, poor absorption, and consequently erratic bioavailability are the cause of its chemotherapeutic failures. Based on the described problem, new treatment alternatives urgently need to be developed. The aim of the present research was to study the in vitro and in vivo efficacy of cannabidiol (CBD), the second most abundant component of the Cannabis sativa plant, was demonstrated against E. granulosus sensu stricto. CBD (50 µg/mL) caused a decrease in protoscoleces viability of 80 % after 24 h of treatment which was consistent with the observed tegumental alterations. Detachment of the germinal layer was observed in 50 ± 10% of cysts treated with 50 µg/mL of CBD during 24 h. In the clinical efficacy study, all treatments reduced the weight of cysts recovered from mice compared with the control group. However, this reduction was only significant with ABZ suspension and the CBD + ABZ combination. As we could observe by the SEM study, the co-administration of CBD with ABZ suspension caused greater ultrastructural alteration of the germinal layer in comparison with that provoked with the monotherapy. Further in vivo research will be conducted by changing the dose and frequency of CBD and CBD + ABZ treatments and new available CBD delivery systems will also be assayed to improve bioavailability in vivo.

PMID:38393124 | DOI:10.3390/tropicalmed9020035

https://pubmed.ncbi.nlm.nih.gov/38393124/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240223132203&v=2.18.0.post9+e462414 February 23, 2024 11:00 am

New regulatory agency in Pakistan will oversee both hemp and marijuana

HempToday®: New regulatory agency in Pakistan will oversee both hemp and marijuana
The government of Pakistan announced a new law that will finally establish a regulatory body for cannabis after years of discussion and political turmoil that have delayed the industries’ development. […]

#CBD #Hemp

New regulatory agency in Pakistan will oversee both hemp and marijuana


February 23, 2024 10:48 am

PubMed: Cannabidiol protects against acute aortic dissection by inhibiting macrophage infiltration and PMAIP1-induced vascular smooth muscle cell apoptosis

PubMed: Cannabidiol protects against acute aortic dissection by inhibiting macrophage infiltration and PMAIP1-induced vascular smooth muscle cell apoptosis

J Mol Cell Cardiol. 2024 Feb 20:S0022-2828(24)00023-3. doi: 10.1016/j.yjmcc.2024.02.006. Online ahead of print.

ABSTRACT

Acute aortic dissection (AAD) progresses rapidly and is associated with high mortality; therefore, there remains an urgent need for pharmacological agents that can protect against AAD. Herein, we examined the therapeutic effects of cannabidiol (CBD) in AAD by establishing a suitable mouse model. In addition, we performed human AAD single-cell RNA sequencing and mouse AAD bulk RNA sequencing to elucidate the potential underlying mechanism of CBD. Pathological assays and in vitro studies were performed to verify the results of the bioinformatic analysis and explore the pharmacological function of CBD. In a β-aminopropionitrile (BAPN)-induced AAD mouse model, CBD reduced AAD-associated morbidity and mortality, alleviated abnormal enlargement of the ascending aorta and aortic arch, and suppressed macrophage infiltration and vascular smooth muscle cell (VSMC) apoptosis. Bioinformatic analysis revealed that the pro-apoptotic gene PMAIP1 was highly expressed in human and mouse AAD samples, and CBD could inhibit Pmaip1 expression in AAD mice. Using human aortic VSMCs (HAVSMCs) co-cultured with M1 macrophages, we revealed that CBD alleviated HAVSMCs mitochondrial-dependent apoptosis by suppressing the BAPN-induced overexpression of PMAIP1 in M1 macrophages. PMAIP1 potentially mediates HAVSMCs apoptosis by regulating Bax and Bcl2 expression. Accordingly, CBD reduced AAD-associated morbidity and mortality and mitigated the progression of AAD in a mouse model. The CBD-induced effects were potentially mediated by suppressing macrophage infiltration and PMAIP1 (primarily expressed in macrophages)-induced VSMC apoptosis. Our findings offer novel insights into M1 macrophages and HAVSMCs interaction during AAD progression, highlighting the potential of CBD as a therapeutic candidate for AAD treatment.

PMID:38387723 | DOI:10.1016/j.yjmcc.2024.02.006

https://pubmed.ncbi.nlm.nih.gov/38387723/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240223012332&v=2.18.0.post9+e462414 February 22, 2024 11:00 am

PubMed: The effects of cannabidiol against Methotrexate-induced lung damage

PubMed: The effects of cannabidiol against Methotrexate-induced lung damage

Basic Clin Pharmacol Toxicol. 2024 Feb 22. doi: 10.1111/bcpt.13992. Online ahead of print.

ABSTRACT

Methotrexate (MTX) is a widely used medication for various cancers, yet its use is associated with adverse effects on organs, notably the lungs. Cannabidiol (CBD), known for its antioxidant and anti-inflammatory properties, was investigated for its potential protective effects against MTX-induced lung injury. Thirty-two female Wistar Albino rats were divided into four groups: control, MTX (single 20 mg/kg intraperitoneal dose), MTX + CBD (single 20 mg/kg MTX with 0.1 ml of 5 mg/kg CBD for 7 days intraperitoneally) and CBD only (for 7 days). Lung tissues were analysed using histopathological, immunohistochemical and PCR methods after the study. Histopathological assessment of the MTX group revealed lung lesions like hyperemia, edema, inflammatory cell infiltration and epithelial cell loss. Immunohistochemical examination showed significant increases in Cas-3, tumour necrosis factor-alpha (TNF-α) and nuclear factor-kappa B (NF-κB) expressions. PCR analysis indicated elevated expressions of apoptotic peptidase activating factor 1 (Apaf 1), glucose-regulated protein 78 (GRP 78), CCAAT-enhancer-binding protein homologous protein (CHOP) and cytochrome C (Cyt C), along with reduced B-cell lymphoma-2 (BCL 2) expressions in the MTX group, though not statistically significant. Remarkably, CBD treatment reversed these findings. This study highlights CBD’s potential in mitigating MTX-induced lung damage, suggesting its therapeutic promise.

PMID:38388876 | DOI:10.1111/bcpt.13992

https://pubmed.ncbi.nlm.nih.gov/38388876/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240223012332&v=2.18.0.post9+e462414 February 22, 2024 11:00 am

Two new methods can speed up testing of hemp, marijuana for THC content

HempToday®: Two new methods can speed up testing of hemp, marijuana for THC content
Two research initiatives have resulted in new methods for measuring THC in cannabis plants and in downstream edibles that can help to clear a logjam in testing and reduce the […]

#CBD #Hemp

Two new methods can speed up testing of hemp, marijuana for THC content


February 22, 2024 8:27 am

NCTR Participation at 2023 SOT Annual Meeting

FDA: NCTR Participation at 2023 SOT Annual Meeting NCTR Participation at 2023 SOT Annual Meeting Anonymous (not verified) Wed, 02/21/2024 – 15:53

Detailed Description
SOT 62nd Annual Meeting and ToxExpo featured more than 70 scientific sessions, 2,000 presentations, 250 exhibitors, and 5,000 attendees

Audience

The SOT 62nd Annual Meeting and ToxExpo featured more than 70 scientific sessions, 2,000 presentations, 250 exhibitors, and 5,000 attendees.

 

2023 SOT Platform, Poster, or Workshop Sessions

Title

NCTR Author

NCTR Division

POSTER SESSION: ALTERNATIVES TO MAMMALIAN MODELS I “Lessons Learned in Establishing a Reliable and Low-Cost Assay for Urea Production in Human Primary Hepatocytes Cultured in a Liver Chip for the Study of Drug Hepatotoxicity” Shi, Q. DSB
POSTER SESSION: ALTERNATIVES TO MAMMALIAN MODELS I “AnimalGAN: A Generative AI Alternative to Animal Clinical Pathology Testing” Chen, X. DBB
POSTER SESSION: ALTERNATIVES TO MAMMALIAN MODELS I “Cardiotoxicity Assessment of HESI Reference Compounds Using Human iPSC-CMs” Bagam, P. DSB
POSTER SESSION: ALTERNATIVES TO MAMMALIAN MODELS I “Performance of the Three-Dimensional HepaRG Micronucleus Assay for In Vitro Genotoxicity Testing” Guo, X. DGMT
POSTER SESSION: EPIDEMIOLOGY AND PUBLIC HEALTH “A Systematic Analysis and Data Mining of Opioid-Related Adverse Events Submitted to the FAERS Database” Le, H. DBB
POSTER SESSION: EPIDEMIOLOGY AND PUBLIC HEALTH “Assessment of Modified Sandwich Estimator for Generalized Estimating Equations with Application to Opioid Poisoning in MIMIC-IV ICU Patients” Rogers, P. DBB
POSTER SESSION: EPIDEMIOLOGY AND PUBLIC HEALTH “RxNorm for Drug Name Normalization: A Case Study of Prescription Opioids in the US FDA Adverse Events Reporting System” Zou, W. DBB
POSTER SESSION: REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY I “Assessing the Developmental Toxicity of Busulfan in an In Vitro Human Placental Barrier-Embryo Co-culture System” Wang, Y. DGMT
POSTER SESSION: CARCINOGENICITY “DNA Methylation and Transcriptomic Alterations Induced by Extended Treatment of Normal Human MCF10A Mammary Gland Epithelial Cells with Non-cytotoxic Doses of Lorcaserin” Willett, R. DBT
PLATFORM SESSION: EXPLORING TIME AND CELL DIVERSITY IN TOXICOGENOMICS SPACE

“Effect of Food-Grade Titanium Dioxide on DNA Methylation in Human Cells”

Wells, C. DBT
WORKSHOP SESSION: UNDERSTANDING THE CONCEPT OF SIMILARITY AND ITS APPLICATIONS TO TOXICOLOGICAL RESEARCH AND RISK ASSESSMENT “Structure Similarity Based on Chemical Descriptors, Fingerprints, and Structural Alerts” Hong, H. DBB
POSTER SESSION: DNA DAMAGE AND REPAIR “Evaluation of Newly Developed 14 Human TK6-Derived Cell Lines That Individually Express a Human Cytochrome P450 for Toxicity Studies” Mei, N. DGMT
POSTER SESSION: DNA DAMAGE AND REPAIR “Nitrosamine Drug Impurities Induce Genotoxicity in Human Lymphoblastoid TK6 Cells” Li, X. DGMT
POSTER SESSION: DNA DAMAGE AND REPAIR “Actein Contributes to Black Cohosh Extract-Induced Genotoxicity in Human TK6 Cells” Le, Y. DGMT
POSTER SESSION: DNA DAMAGE AND REPAIR “Assessment of DNA Damage-Induced by 10 Nitrosamine Impurities Using 2D and 3D HepaRG Models” Seo, J.-E. DGMT
POSTER SESSION: DNA DAMAGE AND REPAIR “Evaluation of the DNA Mutagenicity of N-hydroxycytidine in Mouse Lymphoma Cells by HiFi and Clone Sequencing” Revollo, J. DGMT
POSTER SESSION: DNA DAMAGE AND REPAIR “HiFi Sequencing for Detecting In Vivo Somatic Mutation” Dobrovolsky, V. DGMT
POSTER SESSION: DNA DAMAGE AND REPAIR “HiFi Sequencing Detects the On- and Off-Target Effects of a Cytosine-to-Thymine Base Editor in E. coli Miranda, J. DGMT
POSTER SESSION: BIOTRANSFORMATION/CYTOCHROME P450 “Study of the Roles of Cytochrome P450 (CYPs) in the Metabolism and Cytotoxicity of Perhexiline” Chen, S. DBT
POSTER SESSION: COMPUTATIONAL TOXICOLOGY I “Using Language Model to Facilitate COVID-19-Associated Neurological Disorder Literature Analysis: A BERTox Research” Wu, L. DBB
POSTER SESSION: COMPUTATIONAL TOXICOLOGY I “Development of Random Forest Model for Predicting SARS-CoV-2 Main Protease Binders as Potential Candidates for Repurposing to COVID-19 Treatment” Xu, L. DBB
POSTER SESSION: COMPUTATIONAL TOXICOLOGY I “Opioid Agonist/Antagonist Database (OADB): A Database to Facilitate Opioid Drug Development” Dong, F. DBB
POSTER SESSION: COMPUTATIONAL TOXICOLOGY I “Machine Learning Models for Rat Multigeneration Reproductive Toxicity Prediction” Liu, J. DBB
POSTER SESSION: COMPUTATIONAL TOXICOLOGY II “Machine Learning for Predicting Risk of Drug-Induced Autoimmune Diseases by Structural Alerts and Daily Dose” Chen, M. DBB
POSTER SESSION: SYSTEMS BIOLOGY “Assessment of the Toxicity of Cannabidiol (CBD) in Rats upon Oral Developmental Exposure” Camacho, L. DBT
POSTER SESSION: REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY III “Cannabidiol-Induced Transcriptomic Changes and Cellular Senescence in Human Sertoli Cells” Li, Y. DBT
POSTER SESSION: REPRODUCTIVE AND DEVELOPMENTAL TOXICOLOGY III “COVID-19 Effects on Pregnancy, Prenatal, and Postnatal Development” Bidarimath, M. DSB
POSTER SESSION: SAFETY ASSESSMENT: PHARMACEUTICAL-DRUG DEVELOPMENT II “Obtain Drug Safety Rankings through Meta-analysis of Clinical Trial Data Using Penalized Bayesian Model” Wang, D. DBB
POSTER SESSION: BIOMARKERS “T2-MRI Mapping as a Minimally Invasive Correlate of Central Nervous System (CNS) Toxicity in a Cuprizone Model: A Biomarker Study” Imam, S. DNT
POSTER SESSION: EPIGENETICS “Effect of the Weight-Loss Drug Lorcaserin on DNA Methylation in Mammary Glands of Sprague Dawley Rats” Roudachevski, I. DBT
PLATFORM SESSION: ENHANCING TOXICOLOGY WITH MACHINE LEARNING “PathologAI – A Deep Learning Framework for Whole Slide Classification in Preclinical Pathology” Xu, J. DBB
POSTER SESSION: ALTERNATIVES TO MAMMALIAN MODELS II
Chair: Qiang Shi (DSB)
“Whole Genome Sequencing Analysis of Mutagenicity of N-Nitrosodiethylamine Using Caenorhabditis elegans Models” Chen, T. DGMT
POSTER SESSION: BIOINFORMATICS “Deep Learning-Based Genotype Imputation for Enhancing Toxicogenomic Data” Song, M. DBB
POSTER SESSION: BIOINFORMATICS “Statistical Methods for Exploring Spontaneous Adverse Event Reporting Databases for Drug-Host Factor Interactions” Lu, Z. DBB
POSTER SESSION: BIOINFORMATICS “Development of a Large List of Drugs for the Study of Nephrotoxicity in Drug Discovery” Connor, S. DBB
POSTER SESSION: BIOINFORMATICS “Random Forest Model for Predicting μ Opioid Receptor Binding Activity for Assisting Development of Opioid Drugs” Li, Z. DBB
POSTER SESSION: BIOINFORMATICS “DeepAmes: Deep Learning-Powered Ames Test Prediction Using Model-Level Representation” Li, T. DBB
POSTER SESSION: RISK ASSESSMENT II “Informing Selection of Drugs for COVID-19 Treatment through Analysis of Adverse Events” Guo, W.  DBB
POSTER SESSION: NEUROTOXICITY: DEVELOPMENTAL I “Cytokine-Mediated Chemotherapy-Induced Cognitive Impairment in Cisplatin and Methotrexate Treated Sprague Dawley Rats” Yeary, J. DNT
POSTER SESSION: NEUROTOXICITY: DEVELOPMENTAL I “Examining Immune Modulatory Effects of Perinatal Cannabidiol Exposure in Sprague Dawley Rats” Gill, W. DNT
POSTER SESSION: NEUROTOXICITY: DEVELOPMENTAL I “The Neurotoxic Potential of a Single Dose of Ketamine in Adolescent and Adult Rats” Talpos, J. DNT
POSTER SESSION: NEUROTOXICITY: DEVLEOPMENTAL II “Behavioral Effects of Cisplatin and Methotrexate Treatment in Juvenile Sprague Dawley Rats” Flanigan, T. DNT
POSTER SESSION: NEUROTOXICITY: DEVLEOPMENTAL II “Investigation of the Developmental Neurotoxicity of Opioids Using Human-Induced Pluripotent Stem Cells” Cai, C. DSB
POSTER SESSION: NEUROTOXICITY: GENERAL “A Modified Approach of Fluoro-Jade C Labeling for Neurotoxicity Assessments” Gu, Q. DNT
POSTER SESSION: IMMUNOTOXICITY I “Sex-Based Differences in Inflammatory Responses to Silver Nanoparticles” Canup, B. DBT
WORKSHOP SESSION 1195: MOVING STEM CELL-DERIVED NEW APPROACH METHODS TOWARD REGULATORY ACCEPTANCE
Chair: Li Pang (DSB)
“Predicting Interindividual Variability of Doxorubicin Cardiotoxicity with Induced Pluripotent Stem Cell-Derived Cardiomyocytes” Pang, L. DSB
POSTER SESSION: BIOLOGICAL MODELING “A Multiscale Physiologically Based Pharmacokinetic (PBPK) Model to Predict the Plasma Concentration and the Tissue Distribution of Doxorubicin” Li, M. DBT
POSTER SESSION: BIOLOGICAL MODELING “Using Various Machine-Learning Algorithms to Determine the Best Method for Predicting Population Physiologically Based Pharmacokinetic Model Plasma Profiles” Fairman, K. DBT
POSTER SESSION: KIDNEY “Evaluating Renal Pathology in Post-COVID-19 Human Autopsy Tissues” Masters, E. DSB
POSTER SESSION: SKIN AND DERMAL TOXICITY “Parallel Evaluation of Alternative Skin Barrier Models and Excised Human Skin for Dermal Absorption Studies In Vitro” Salminen, A. DBT
POSTER SESSION: LIVER I: IN VIVO
Chair: Si Chen (DBT)
“Gene Expression Changes Predict the Severity of NAFLD-Like Liver Injury in Male Collaborative Cross Mice” Tryndyak, V. DBT
POSTER SESSION: LIVER II: IN VIVO “hnRNP-Q and hnRNP-L Influence Drug Metabolism and Toxicity by Regulating mRNA Processing of Drug Metabolizing Enzymes and Nuclear Receptors in HepaRG Cells” Li, D. DBB
POSTER SESSION: LIVER II: IN VIVO “hnRMP-Q and hnRMP-L Influence Drug Metabolism and Toxicity by Regulating mRNA Processing of Drug Metabolizing Enzymes and Nuclear Receptors in HepaRG Cells” Li, D. DBB
POSTER SESSION: RESPIRATORY TOXICOLOGY I “Establishing a Continuous Aerosol Exposure Method for Evaluating the Respiratory Toxicity of Ortho-Phthalaldehyde” Sun, Y. DGMT
POSTER SESSION: LATE-BREAKING 2-4 “Potential Link of High-Fat Diet on the Expression of Alzheimer’s Disease-Related Genes in the Ileal Mucosa of Alzheimer’s Disease Model of Rats” Karn, K. DM
POSTER SESSION: LATE-BREAKING 2-4 “The Effects of Cannabidiol and Its Main Metabolites on Human Neural Stem Cells” Latham, L. DNT
POSTER SESSION: LATE-BREAKING 2-4 “Comparison of the Effects of Delta-9 Tetrahydrocannabinol and Cannabidiol on Human Neural Stem Cells” Liu, F. DNT
POSTER SESSION: LATE-BREAKING 2-4 “Assessment of Potential Developmental Neurotoxicity of Purified Cannabidiol in Sprague Dawley Rats” Shen, A. DNT

 

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Short Title
NCTR Participation at 2023 Society of Toxicology

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Society of Toxicology (SOT) Annual Meeting and ToxExpo, March 19-23, 2023

Publish Date
Wed, 02/21/2024 – 17:00

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Fri, 02/21/2025 – 00:00

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Wed, 02/21/2024 – 00:00

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#CBD #Hemp http://www.fda.gov/about-fda/science-research-nctr/nctr-participation-2023-sot-annual-meeting February 21, 2024 8:53 pm

PubMed: Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis

PubMed: Integrating fecal metabolomics and intestinal microbiota to study the mechanism of cannabidiol in the treatment of idiopathic pulmonary fibrosis

Front Pharmacol. 2024 Feb 6;15:1358626. doi: 10.3389/fphar.2024.1358626. eCollection 2024.

ABSTRACT

Introduction: Idiopathic pulmonary fibrosis is a chronic interstitial lung disease characterized by excessive deposition of extracellular matrix. Cannabidiol, a natural component extracted from plant cannabis, has been shown to have therapeutic effects on lung diseases, but its exact mechanism of action is unknown, hindering its therapeutic effectiveness. Methods: To establish a pulmonary fibrosis model, combined with UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing, to explore cannabidiol’s mechanism in treating pulmonary fibrosis. The rats were randomly divided into the control group, pulmonary fibrosis model group, prednisone treatment group, and cannabidiol low, medium, and high dose groups. The expression levels of HYP, SOD, and MDA in lung tissue and the expression levels of TNF-α, IL-1β, and IL-6 in serum were detected. Intestinal microbiota was detected using UPLC-QTOF/MS analysis of metabolomic properties and 16S rDNA sequencing. Results: Pathological studies and biochemical indexes showed that cannabidiol treatment could significantly alleviate IPF symptoms, significantly reduce the levels of TNF-α, IL-1β, IL-6, MDA, and HYP, and increase the expression level of SOD (p < 0.05). CBD-H can regulate Lachnospiraceae_NK4A136_group, Pseudomonas, Clostridia_UCG-014, Collinsella, Prevotella, [Eubacterium]_coprostanoligenes_group, Fusobacterium, Ruminococcus, and Streptococcus, it can restore intestinal microbiota function and reverse fecal metabolism trend. It also plays the role of fibrosis through the metabolism of linoleic acid, glycerol, linolenic acid, and sphingolipid. Discussion: Cannabidiol reverses intestinal microbiota imbalance and attenuates pulmonary fibrosis in rats through anti-inflammatory, antioxidant, and anti-fibrotic effects. This study lays the foundation for future research on the pathological mechanisms of IPF and the development of new drug candidates.

PMID:38379898 | PMC:PMC10877013 | DOI:10.3389/fphar.2024.1358626

https://pubmed.ncbi.nlm.nih.gov/38379898/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240221112819&v=2.18.0.post9+e462414 February 21, 2024 11:00 am

PubMed: Cannabidiol (CBD): Confronting consumers' expectations of therapeutic benefits with pharmacological reality

PubMed: Cannabidiol (CBD): Confronting consumers' expectations of therapeutic benefits with pharmacological reality

Therapie. 2024 Feb 7:S0040-5957(24)00027-1. doi: 10.1016/j.therap.2024.01.006. Online ahead of print.

ABSTRACT

In recent years, the increase in cannabidiol (CBD) sales in Europe has raised questions regarding the legal status of this product, as well as its safety of use. Consumers seem to be looking for solutions to various health issues. However, the scientific reality is much more nuanced. The European CBD market emerged in Switzerland in 2016 and subsequently expanded across the continent. This expansion has been facilitated by the establishment of delta-9-tetrahydrocannabinol (THC) concentration limits for these products. However, the current market offers a diverse range of CBD products, often lacking clear information on raw materials, product concentrations and recommended dosages. Regulating these products is challenging, as the appropriate classification of CBD remains uncertain. CBD products are in high demand worldwide, with many people seeking alternative treatments for medical conditions or general health and well-being benefits. However, the use of CBD products often relies on self-medication and lacks sufficient scientific evidence. Improved communication between patients and healthcare professionals is needed to ensure informed decisions and address potential interactions with other medications. Scientific evidence on CBD is currently limited and the efficacy of CBD-containing products has only been proven in clinical trials for Epidyolex® as an add-on therapy. There is no consensus on the long-term safety, appropriate dosage, schedules or administration routes for CBD. Health claims associated with CBD are not consistent with the available scientific research, which is still in its early stages. Further clinical research is needed to establish the efficacy and safety of CBD in various medical conditions. The enthusiasm surrounding CBD-based products should be tempered by the limited scientific evidence of their efficacy, the inadequacy of patient expectations, regulatory concerns and potential drug interactions.

PMID:38383209 | DOI:10.1016/j.therap.2024.01.006

https://pubmed.ncbi.nlm.nih.gov/38383209/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240222012230&v=2.18.0.post9+e462414 February 21, 2024 11:00 am

PubMed: Cannabidiol regulates the activation of hepatic stellate cells by modulating the NOX4 and NF-kappaB pathways

PubMed: Cannabidiol regulates the activation of hepatic stellate cells by modulating the NOX4 and NF-kappaB pathways

Food Chem Toxicol. 2024 Feb 19:114517. doi: 10.1016/j.fct.2024.114517. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is an extract of natural cannabinoids that has therapeutic implications for a variety of ailments, such as neurological diseases, cardiomyopathy, and diabetes, due to its strong anti-inflammatory and oxidative stress properties. Our purpose was to reveal the possible underlying mechanisms and effect of CBD on the glucose oxidase (GO)-induced activation of HSC-T6 and LX-2 cells. The results showed that CBD effectively inhibited the proliferation and activation of HSC-T6 and LX-2 cells, and reduced the production of profibrotic factors to different degrees. CBD disrupted the NOX4 signalling pathway in activated HSC-T6 and LX-2 cells, reduced ROS and MDA levels, and increased SOD and GSH levels, thereby stabilizing the oxidative imbalance. CBD significantly inhibited the phosphorylation and degradation of NF-κB and IκBα, and decreased the release of TNF-α, IL-1β and IL-6. Moreover, CBD and an NF-κB-specific inhibitor (CAPE) effectively inhibited the expression of α-SMA, COL I, TNF-α and IL-1β to promote collagen metabolism and inhibit the inflammatory response. Overall, CBD inhibited HSCs activation through a and the mechanism involving the inhibition of NOX4 and NF-κB-dependent ROS regulation, thereby reducing inflammation and ameliorating oxidative imbalances.

PMID:38382869 | DOI:10.1016/j.fct.2024.114517

https://pubmed.ncbi.nlm.nih.gov/38382869/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240222012230&v=2.18.0.post9+e462414 February 21, 2024 11:00 am

Oklahoma hemp task force won’t deal with flowers, likely leaving CBD to marijuana regulators

HempToday®: Oklahoma hemp task force won’t deal with flowers, likely leaving CBD to marijuana regulators
A hemp task force being formed in Oklahoma would address only fiber- and seed-based products, likely leaving oversight of flower-based CBD and other cannabinoids to the state’s medical marijuana regulators. […]

#CBD #Hemp

Oklahoma hemp task force won’t deal with flowers, likely leaving CBD to marijuana regulators


February 21, 2024 9:01 am

Pennsylvania builder gets $1.9 million from U.S. Army for key hempcrete research

HempToday®: Pennsylvania builder gets $1.9 million from U.S. Army for key hempcrete research
A Pennsylvania company will look at key performance factors for hempcrete construction after receiving a $1.9 million research and development grant from the U.S. Army. Allentown-based Americhanvre Cast Hemp said […]

#CBD #Hemp

Pennsylvania builder gets $1.9 million from U.S. Army for key hempcrete research


February 20, 2024 9:09 am

PubMed: Stability, biofunctional, and antimicrobial characteristics of cannabidiol isolate for the design of topical formulations

PubMed: Stability, biofunctional, and antimicrobial characteristics of cannabidiol isolate for the design of topical formulations

Soft Matter. 2024 Feb 19. doi: 10.1039/d3sm01466e. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is a high-value natural compound of Cannabis Sativa plant. It is a non-psychotropic phytocannabinoid, attracting significant attention as a multifunctional active ingredient for topical applications. Although it is demonstrated that CBD can be used for specific dermatological ailments, reliable data on functionalities are limited. The present study aimed to investigate the structural stability, biofunctionality, and antimicrobial characteristics of CBD isolate to assist in the design of various topical formulations. The stability of CBD in solid and solubilized states was assessed to establish storage and formulation conditions. The performance of CBD solubilized in organic and aqueous media was evaluated for free radical scavenging, tyrosinase, and collagenase enzyme inhibition, which showed good prospects for the ingredient. The antimicrobial activity of solubilized CBD was evaluated against Gram-negative (E. coli, P. aeruginosa), Gram-positive bacterial strains (S. aureus, S. epidermidis, C. acnes), and fungal strains (C. albicans, M. furfur) using agar well diffusion and broth microdilution methods. Due to the presence of surfactants in CBD aqueous solution, it displayed a lack of antimicrobial activity against all the tested microorganisms. CBD solubilized in an organic medium showed no activity against Gram-negative bacterial strains but higher activity against tested Gram-positive bacterial and fungal strains.

PMID:38372296 | DOI:10.1039/d3sm01466e

https://pubmed.ncbi.nlm.nih.gov/38372296/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240219133325&v=2.18.0 February 19, 2024 11:00 am

PubMed: Anti-Ferroptotic Effect of Cannabidiol in Human Skin Keratinocytes Characterized by Data-Independent Acquisition-Based Proteomics

PubMed: Anti-Ferroptotic Effect of Cannabidiol in Human Skin Keratinocytes Characterized by Data-Independent Acquisition-Based Proteomics

J Nat Prod. 2024 Feb 19. doi: 10.1021/acs.jnatprod.3c00759. Online ahead of print.

ABSTRACT

Skin cells are susceptible to oxidative stress and various types of cell death, including an iron-dependent form known as ferroptosis. Cannabidiol (CBD) can protect skin cells against oxidative stress, but whether this is attributed to the inhibition of ferroptosis is unknown. Herein, we evaluated the anti-ferroptotic effect of CBD in human keratinocytes using biochemical assays (radical scavenging and iron chelating) and cell-based models (for lipid peroxidation and intracellular iron). CBD’s anti-ferroptotic effect was further characterized by proteomic analysis. This study identifies anti-ferroptosis as a mechanism of CBD’s skin protective effects.

PMID:38373879 | DOI:10.1021/acs.jnatprod.3c00759

https://pubmed.ncbi.nlm.nih.gov/38373879/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240220122256&v=2.18.0 February 19, 2024 11:00 am

CBD down, fiber up, as early signs show U.S. hemp harvest stabilized in 2023

HempToday®: CBD down, fiber up, as early signs show U.S. hemp harvest stabilized in 2023
Early indicators show U.S. hemp farming likely remained flat in 2023, with roughly 19,500 acres having been harvested, according to a recently released Department of Agriculture estimate and trends over […]

#CBD #Hemp

CBD down, fiber up, as early signs show U.S. hemp harvest stabilized in 2023


February 19, 2024 7:34 am

PubMed: Real life retrospective study of cannabidiol therapy in alternating hemiplegia of childhood

PubMed: Real life retrospective study of cannabidiol therapy in alternating hemiplegia of childhood

Eur J Paediatr Neurol. 2024 Feb 12;49:55-59. doi: 10.1016/j.ejpn.2024.02.004. Online ahead of print.

ABSTRACT

BACKGROUND: Many alternating hemiplegia of childhood (AHC) patients have received Cannabidiol (CBD) but, to our knowledge, there are no published data available.

GOALS: Test the hypothesis that CBD has favorable effects on AHC spells.

METHODS: Retrospective review of available data of AHC patients who received CBD. Primary analysis: Clinical Global Impression Scale of Improvement (CGI-I) score for response of AHC spells to CBD with calculation of 95% confidence interval (CI) for rejection of the null hypothesis. Secondary analyses, performed to achieve an understanding of the effect of CBD as compared to flunarizine, were CGI-I scores of 1) epileptic seizures to CBD, 2) AHC spells to flunarizine, 3) epileptic seizures to flunarizine. Also, Mann-Whitney test was done for comparison of CGI-I scores of CBD and flunarizine to both AHC spells and seizures.

RESULTS: We studied 16 AHC patients seen at Duke University and University of Lyon. CI of CGI-I scores for AHC spells in response to CBD and to flunarizine, each separately, indicated a positive response to each of these two medications: neither overlapped with the null hypothesis score, 4, indicating significant positive responses with p < 0.05 for both. These two scores also did not differ (p = 0.84) suggesting similar efficacy of both: CBD score was 2 ± 1.1 with a 95% CI of 1.5-2.6 and flunarizine score was 2.3 ± 1.3 with a 95% CI of 1.7-3.1. In patients who had seizures, CI calculations indicated a positive effect of CBD on seizure CGI scores but not of flunarizine on seizure scores. CBD was well tolerated with no patients discontinuing it due to side effects and with some reporting positive behavioral changes.

CONCLUSION: Our study indicates a real-life positive effect of CBD on AHC type spells.

PMID:38367370 | DOI:10.1016/j.ejpn.2024.02.004

https://pubmed.ncbi.nlm.nih.gov/38367370/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240218012512&v=2.18.0 February 17, 2024 11:00 am

PubMed: SYNTHESIS AND ANTIALLODYNIC ACTIVITY OF CANNABIDIOL ANALOGUE ON PERIPHERAL NEUROPATHY IN MICE

PubMed: SYNTHESIS AND ANTIALLODYNIC ACTIVITY OF CANNABIDIOL ANALOGUE ON PERIPHERAL NEUROPATHY IN MICE

Chem Biodivers. 2024 Feb 16:e202301935. doi: 10.1002/cbdv.202301935. Online ahead of print.

ABSTRACT

Cannabidiol (CBD) is a substance that exerts several therapeutic actions, including analgesia. CBD is generally administered orally, but its poor water solubility and metabolism impairs its bioavailability. Thus, the development of molecules with better pharmacokinetic profile from cannabidiol becomes an interesting strategy for the design of novel analgesic drugs for the relief of painful conditions that are difficult to manage clinically, such as neuropathic pain. In the present study, an unprecedented analogue of CBD (1) was synthesized and some of its physicochemical properties were evaluated in silico as well as its stability in an acid medium. Additionally, its effect was investigated in a model of neuropathic pain induced by the chemotherapy drug paclitaxel in mice, in comparison with cannabidiol itself. Cannabidiol (20 mg/kg), pregabalin (30 mg/kg) or analogue 1 (5, 10 and 20 mg/kg), administered on the fourteenth day after the first administration of paclitaxel, attenuated the mechanical allodynia of the sensitized animals. The antinociceptive activity of the 1 was attenuated by previous administration of a cannabinoid CB1 receptor antagonist, AM 251, which indicates that its mechanism of action is related to the activation of CB1 receptors.

PMID:38363210 | DOI:10.1002/cbdv.202301935

https://pubmed.ncbi.nlm.nih.gov/38363210/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240216132139&v=2.18.0 February 16, 2024 11:00 am

PubMed: Cannabidiol Exposure During Rat Pregnancy Leads to Labyrinth-Specific Vascular Defects in the Placenta and Reduced Fetal Growth

PubMed: Cannabidiol Exposure During Rat Pregnancy Leads to Labyrinth-Specific Vascular Defects in the Placenta and Reduced Fetal Growth

Cannabis Cannabinoid Res. 2024 Feb 16. doi: 10.1089/can.2023.0166. Online ahead of print.

ABSTRACT

Introduction: Cannabis use is increasing among pregnant people, and cannabidiol (CBD), a constituent of cannabis, is often perceived as “natural” and “safe” as it is non-intoxicating. In utero, cannabis exposure is associated with negative health outcomes, including fetal growth restriction (FGR). The placenta supplies oxygen and nutrients to the fetus, and alterations in placental development can lead to FGR. While there has been some investigation into the effects of Δ9-THC, there has been limited investigation into the impacts of in utero gestational CBD exposure on the placenta. Methods: This study used histological and transcriptomic analysis of embryonic day (E)19.5 rat placentas from vehicle and CBD (3 mg/kg intraperitoneal injection) exposed pregnancies (E6.5-18.5). Results: The study revealed that pups from CBD-exposed pregnancies were 10% smaller, with the placentae displaying a decreased fetal blood space perimeter-to-area ratio. The transcriptomic analysis supported compromised angiogenesis and blood vessel formation with downregulated biological processes, including tube morphogenesis, angiogenesis, blood vessel morphogenesis, blood vessel development and vasculature development. Further, the CBD-exposed placentas displayed changed expression of glucose transporters (decreased GLUT1 and GR expression and increased GLUT3 expression). Transcriptomic analysis further revealed upregulated biological processes associated with metabolism. Finally, histological and transcriptomic analysis revealed altered cell populations within the placenta, specifically to syncytiotrophoblast layer II and endothelial cells. Conclusion: Together these results suggest that the structural changes in CDB-exposed placentae, including the altered expression of nutrient transporters and the changes to the placental fetal vasculature, may underlie the reduced fetal growth.

PMID:38364116 | DOI:10.1089/can.2023.0166

https://pubmed.ncbi.nlm.nih.gov/38364116/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240216192630&v=2.18.0 February 16, 2024 11:00 am

Florida poised to ban delta-8 THC and other intoxicating hemp products

HempToday®: Florida poised to ban delta-8 THC and other intoxicating hemp products
The Florida State Senate Thursday unanimously passed a bill that would ban hemp-derived delta-8 THC and similar intoxicating hemp products. In addition to delta-8, Senate Bill 1698 (SB 1698) would also specifically […]

#CBD #Hemp

Florida poised to ban delta-8 THC and other intoxicating hemp products


February 16, 2024 8:32 am

PubMed: Cannabidiol activates MAPK pathway to induce apoptosis, paraptosis, and autophagy in colorectal cancer cells

PubMed: Cannabidiol activates MAPK pathway to induce apoptosis, paraptosis, and autophagy in colorectal cancer cells

J Cell Biochem. 2024 Feb 15. doi: 10.1002/jcb.30537. Online ahead of print.

ABSTRACT

Mitogen-activated protein kinase (MAPK) activation by natural compounds is known to be involved in the induction of apoptosis, paraptosis, and autophagy. Cannabidiol (CBD), a bioactive compound found in Cannabis sativa, is endowed with many pharmacological activities. We investigated the cytotoxic effect of CBD in a panel of colorectal cancer (CRC) cells (HT-29, SW480, HCT-116, and HCT-15). CBD induced significant cytotoxicity as evidenced by the results of MTT assay, live-dead assay, and flow cytometric analysis. Since CBD displayed cytotoxicity against CRC cells, we examined the effect of CBD on apoptosis, paraptosis, and autophagy. CBD decreased the expression of antiapoptotic proteins and increased the Annexin-V-positive as well as TUNEL-positive cells suggesting that CBD induces apoptosis. CBD increased the expression of ATF4 (activating transcription factor 4) and CHOP (CCAAT/enhancer-binding protein homologous protein), elevated endoplasmic reticulum stress, and enhanced reactive oxygen species levels indicating that CBD also promotes paraptosis. CBD also induced the expression of Atg7, phospho-Beclin-1, and LC3 suggesting that CBD also accelerates autophagy. Since, the MAPK pathway is a common cascade that is involved in the regulation of apoptosis, paraptosis, and autophagy, we investigated the effect of CBD on the activation of JNK, p38, and ERK pathways. CBD activated all the forms of MAPK proteins and pharmacological inhibition of these proteins reverted the observed effects. Our findings implied that CBD could induce CRC cell death by activating apoptosis, paraptosis, and autophagy through the activation of the MAPK pathway.

PMID:38358093 | DOI:10.1002/jcb.30537

https://pubmed.ncbi.nlm.nih.gov/38358093/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240215132240&v=2.18.0 February 15, 2024 11:00 am

PubMed: Cannabidiol Exposure During Gestation Leads to Adverse Cardiac Outcomes Early in Postnatal Life in Male Rat Offspring

PubMed: Cannabidiol Exposure During Gestation Leads to Adverse Cardiac Outcomes Early in Postnatal Life in Male Rat Offspring

Cannabis Cannabinoid Res. 2024 Feb 14. doi: 10.1089/can.2023.0213. Online ahead of print.

ABSTRACT

Introduction: Studies indicate that ∼7% of pregnant individuals in North America consume cannabis in pregnancy. Pre-clinical studies have established that maternal exposure to Δ9-tetrahydrocannabinol (THC; major psychoactive component in cannabis) leads to fetal growth restriction and impaired cardiac function in offspring. However, the effects of maternal exposure to cannabidiol (CBD; major non-euphoric constituent) on cardiac outcomes in offspring remain unknown. Therefore, our objective is to investigate the functional and underlying molecular impacts in the hearts of offspring exposed to CBD in pregnancy. Methods: Pregnant Wistar rats were exposed to either 3 or 30 mg/kg CBD or vehicle control i.p. daily from gestational day 6 to term. Echocardiography was used to assess cardiac function in male and female offspring at postnatal day (PND) 21. Furthermore, quantitative polymerase chain reaction (qPCR), immunoblotting, and bulk RNA-sequencing (RNA-seq) were performed on PND21 offspring hearts. Results: Despite no differences in the heart-to-body weight ratio, both doses of CBD led to reduced cardiac function exclusively in male offspring at 3 weeks of age. Underlying this, significant alterations in the expression of the endocannabinoid system (ECS; e.g., decreased cannabinoid receptor 2) were observed. In addition, bulk RNA-seq data demonstrated transcriptional pathways significantly enriched in mitochondrial function/metabolism as well as development. Conclusion: Collectively, we demonstrated for the first time that gestational exposure to CBD, a constituent perceived as safe, leads to early sex-specific postnatal cardiac deficits and alterations in the cardiac ECS in offspring.

PMID:38358335 | DOI:10.1089/can.2023.0213

https://pubmed.ncbi.nlm.nih.gov/38358335/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240215132240&v=2.18.0 February 15, 2024 11:00 am

PubMed: Cannabidiol-Based Prodrugs: Synthesis and Bioevaluation

PubMed: Cannabidiol-Based Prodrugs: Synthesis and Bioevaluation

ACS Med Chem Lett. 2024 Jan 16;15(2):221-229. doi: 10.1021/acsmedchemlett.3c00461. eCollection 2024 Feb 8.

ABSTRACT

Cannabidiol (CBD 1) is a nonpsychotic cannabinoid-based drug approved by the U.S. FDA for treating refractory epilepsy, namely, Lennox-Gastaut and Dravet syndrome. However, its low aqueous solubility and oral bioavailability are compensated by administering high doses, and there is an increased demand for conjugates with improved properties. In this direction, the present work is focused on synthesizing CBD-based prodrugs to address the issue of poor solubility and oral bioavailability. Several CBD-based prodrugs were synthesized and studied in a battery of assays: viz, release kinetic (ex vivo), solubility (in vitro), chemical stability (in vitro), plasma stability (ex vivo), pharmacokinetics (in vivo), and efficacy studies (in vivo). Among the synthesized prodrugs, the morpholinyl CBD-based prodrugs 3a and 3aa showed good release behavior, stability, better solubility, and a plasma profile. Moreover, prodrug candidate 3aa showed better therapeutic efficacy. The present study identifies CBD-based prodrugs with improved physiochemical properties and oral exposure.

PMID:38352838 | PMC:PMC10860190 | DOI:10.1021/acsmedchemlett.3c00461

https://pubmed.ncbi.nlm.nih.gov/38352838/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240214072422&v=2.18.0 February 14, 2024 11:00 am

PubMed: Cannabidiol improves memory and decreases IL-1β serum levels in rats with lipopolysaccharide-induced inflammation

PubMed: Cannabidiol improves memory and decreases IL-1β serum levels in rats with lipopolysaccharide-induced inflammation

Folia Med (Plovdiv). 2023 Dec 31;65(6):940-949. doi: 10.3897/folmed.65.e107259.

ABSTRACT

Memory improving and anti-inflammatory properties of cannabidiol (CBD) were investigated in an experimental model of lipopolysaccharide (LPS)-induced inflammation.

PMID:38351784 | DOI:10.3897/folmed.65.e107259

https://pubmed.ncbi.nlm.nih.gov/38351784/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240214072422&v=2.18.0 February 14, 2024 11:00 am

PubMed: Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill

PubMed: Cannabidiol-Derived Cannabinoids: The Unregulated Designer Drug Market Following the 2018 Farm Bill

Med Cannabis Cannabinoids. 2024 Feb 13;7(1):10-18. doi: 10.1159/000536339. eCollection 2024 Jan-Dec.

ABSTRACT

BACKGROUND: In this review, we summarize current scientific knowledge on psychoactive cannabinoids synthesized from cannabidiol (CBD) and sold in the semi-legal market established in response to the passage of the US Agriculture Improvement Act of 2018, commonly known as the 2018 Farm Bill. The discussion focuses on recent developments that suggest this unregulated market may be fertile ground for a potential health crisis.

SUMMARY: Current research into CBD-derived cannabinoids is mainly limited to Δ8-tetrahydrocannabinol (Δ8-THC) products, with some recent publications beginning to explore O-acetyl-THC, a term describing the acetate ester of Δ8-THC or Δ9-THC, and its potential pulmonary toxicity. We advance the discussion on the CBD-derived cannabinoid market, shedding light on the introduction and associated dangers of novel cannabinoids, likely produced via fully synthetic routes using sidechain variants of CBD, with purportedly greater agonist activity at the human cannabinoid receptor 1 (as a source of euphorigenic activity) than Δ9-THC. We discuss the expanded incorporation of the acetate ester motif into other THC analogues. We also discuss the lack of regulatory oversight for the production of CBD-derived cannabinoids and the unlabeled presence of under-researched cannabinoids formed as reaction side products in the CBD-derived cannabinoid products being sold. Accordingly, we suggest approaches to monitoring the CBD-derived cannabinoid market and investigating the pharmacology of the cannabinoids being consumed. Finally, important epidemiological findings are discussed and future directions for research are suggested to call investigators to this critically understudied field.

KEY MESSAGES: The CBD-derived cannabinoid market is growing internationally, and the market has diversified to include potent synthetic cannabinoids. The products sold on this unregulated market are under-researched despite growing availability and consumer interest. Ernest investigation of the pharmacology of these novel cannabinoids and the contents of CBD-derived cannabinoid products is critical for monitoring this potential source of another vaping-related epidemic.

PMID:38352661 | PMC:PMC10864014 | DOI:10.1159/000536339

https://pubmed.ncbi.nlm.nih.gov/38352661/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240214072422&v=2.18.0 February 14, 2024 11:00 am

PubMed: Cannabidiol-loaded microparticles embedded in a porous hydrogel matrix for biomedical applications

PubMed: Cannabidiol-loaded microparticles embedded in a porous hydrogel matrix for biomedical applications

J Mater Sci Mater Med. 2024 Feb 14;35(1):14. doi: 10.1007/s10856-023-06773-9.

ABSTRACT

In this study, poly (lactic-co-glycolic acid) (PLGA) microparticles loaded with cannabidiol (CBD) were synthesized (PLGA@CBD microparticles) and embedded up to 10 wt% in a chondroitin sulfate/polyvinyl alcohol hydrogel matrix. In vitro chemical, physical, and biological assays were carried out to validate the potential use of the modified hydrogels as biomaterials. The microparticles had spherical morphology and a narrow range of size distribution. CBD encapsulation efficiency was around 52%, loading was approximately 50%. Microparticle addition to the hydrogels caused minor changes in their morphology, FTIR and thermal analyses confirmed these changes. Swelling degree and total porosity were reduced in the presence of microparticles, but similar hydrophilic and degradation in phosphate buffer solution behaviors were observed by all hydrogels. Rupture force and maximum strain at rupture were higher in the modified hydrogels, whereas modulus of elasticity was similar across all materials. Viability of primary human dental pulp cells up to 21 days was generally not influenced by the addition of PLGA@CBD microparticles. The control hydrogel showed no antimicrobial activity against Staphylococcus aureus, whereas hydrogels with 5% and 10% PLGA@CBD microparticles showed inhibition zones. In conclusion, the PLGA@CBD microparticles were fabricated and successfully embedded in a hydrogel matrix. Despite the hydrophobic nature of CBD, the physicochemical and morphological properties were generally similar for the hydrogels with and without the CBD-loaded microparticles. The data reported in this study suggested that this original biomaterial loaded with CBD oil has characteristics that could enable it to be used as a scaffold for tissue/cellular regeneration.

PMID:38353746 | DOI:10.1007/s10856-023-06773-9

https://pubmed.ncbi.nlm.nih.gov/38353746/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240214132339&v=2.18.0 February 14, 2024 11:00 am

Kansas legislators block animal feed as they gut updated draft hemp law

HempToday®: Kansas legislators block animal feed as they gut updated draft hemp law
Kansas lawmakers have stripped a hemp bill of provisions that would have allowed farm animals to be fed fiber, grain and seeds, and established a two-year licensing cycle. The Committee […]

#CBD #Hemp

Kansas legislators block animal feed as they gut updated draft hemp law


February 14, 2024 5:57 am

PubMed: High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System

PubMed: High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System

Neurotox Res. 2024 Feb 13;42(1):14. doi: 10.1007/s12640-024-00692-5.

ABSTRACT

Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD’s influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and β-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.

PMID:38349488 | DOI:10.1007/s12640-024-00692-5

https://pubmed.ncbi.nlm.nih.gov/38349488/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240213132109&v=2.18.0 February 13, 2024 11:00 am

South Carolina bans CBD and intoxicating hemp products as states continue crackdowns

HempToday®: South Carolina bans CBD and intoxicating hemp products as states continue crackdowns
Individual states continue to pile on in the battle over intoxicating hemp as they crack down on the potentially unsafe products, which have flooded the market through a loophole in […]

#CBD #Hemp

South Carolina bans CBD and intoxicating hemp products as states continue crackdowns


February 13, 2024 9:32 am

PubMed: Acute and chronic cannabidiol treatment: In vitro toxicological aspects on human oral cells

PubMed: Acute and chronic cannabidiol treatment: In vitro toxicological aspects on human oral cells

Food Chem Toxicol. 2024 Feb 9:114513. doi: 10.1016/j.fct.2024.114513. Online ahead of print.

ABSTRACT

Cannabidiol is gaining increasing interest for its potential anti-inflammatory, immunomodulatory, and antineoplastic effects. The purpose of this study is to investigate the biological effects of acute and chronic CBD administration on gingival fibroblasts and oral keratinocytes. Viability, morphology, migration, apoptosis and cell cycle, and expression of related genes (p53, BCL2, p21, and BAX) and of endocannabinoid system receptors (CB1, CB2 and GPR55) with real-time PCR and DNA damage with phospho-γ-H2AX immunofluorescence detection were analyzed. Concentrations between 100 μM and 0.001 μM were used: 50 μM (toxic dose), 25 μM (viability promoter), and 1 μM (nontoxic), were selected for subsequent chronic analysis. Acute treatment reveals significant effects than chronic, in particular in fibroblasts: concentrations ≥50 μM are highly cytotoxic, with increased apoptosis and reduced migration. Cell death correlates with increased p53 and BAX, followed by arrest in G0/G1 phase, with elevated p21 levels, suggesting a time- and dose-dependent damage. An increase in H2AX phosphorylation was observed with 25 μM and 50 μM, while 1 μM was biocompatible. Keratinocytes showed less cytotoxic effect than fibroblasts. Induced cell damage was dose- and time-related, with less damage after chronic treatment. Further investigations are needed with longer time frames to evaluate CBD dose- and time-dependent effects to identify an effective therapeutic dose.

PMID:38342230 | DOI:10.1016/j.fct.2024.114513

https://pubmed.ncbi.nlm.nih.gov/38342230/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240212062318&v=2.18.0 February 11, 2024 11:00 am

Hemp grown in copper-contaminated soil renders usable stalks, boosts CBD production

HempToday®: Hemp grown in copper-contaminated soil renders usable stalks, boosts CBD production
Hemp is good for cleaning up soil contaminated with copper – and copper can be good for hemp, according to Greek researchers who have looked at the plant as an […]

#CBD #Hemp

Hemp grown in copper-contaminated soil renders usable stalks, boosts CBD production


February 9, 2024 10:19 am

PubMed: Healthy cats tolerate long-term daily feeding of Cannabidiol

PubMed: Healthy cats tolerate long-term daily feeding of Cannabidiol

Front Vet Sci. 2024 Jan 24;10:1324622. doi: 10.3389/fvets.2023.1324622. eCollection 2023.

ABSTRACT

Cannabidiol (CBD)-containing products are widely commercially available for companion animals, mirroring popularity in human use. Although data on the safety and efficacy of long-term oral supplementation are increasing in dogs, evidence remains lacking in cats. The purpose of these studies was to address gaps in the knowledge around the long-term suitability and tolerance of a tetrahydrocannabinol (THC)-free CBD distillate in clinically healthy cats. The studies were randomized, blinded, and placebo-controlled. The first study supplemented cats with either a placebo oil (n = 10) or with 4 mg/kg body weight (BW) CBD in placebo oil (n = 9) daily, with a meal, for 4 weeks. The concentration of CBD in plasma was measured over 4 h at d0 (first dose) and again at d14 (after 2 weeks of daily dosing). The second study supplemented cats daily with either placebo oil (n = 10) or 4 mg/kg BW CBD in placebo oil (n = 10) for a period of 26 weeks. A comprehensive suite of physiological health measures was performed throughout the study at baseline (week 0) and after 4, 10, 18, and 26 weeks of feeding, followed by a 4-week washout sample (week 30). Postprandial plasma CBD time course data, at both d0 and d14, showed a peak plasma CBD concentration at 2 h after the dose. This peak was 251 (95% CI: 108.7, 393.4) and 431 (95% CI, 288.7, 573.4) ng/mL CBD at d0 and d14, respectively, and the area under the curve concentration was higher by 91.5 (95% CI, 33.1, 149.9) ng-h/mL after 2 weeks of supplementation (p = 0.002). While in the first study the CBD group displayed increased alanine aminotransferase (ALT; 68.7 (95% CI, 43.23, 109.2) U/L) at week 4 compared to the placebo control group [1.44-fold increase (95% CI, 0.813, 2.54)], statistical equivalence (at 2-fold limits) was found for ALT across the duration of the second, long-term study. All other biochemistry and hematology data showed no clinically significant differences between supplement groups. Data presented here suggest that a THC-free, CBD distillate fed at a dose of 4 mg/kg BW was absorbed into plasma and well tolerated by healthy cats when supplemented over a period of 26 weeks.

PMID:38327816 | PMC:PMC10847353 | DOI:10.3389/fvets.2023.1324622

https://pubmed.ncbi.nlm.nih.gov/38327816/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240208072159&v=2.18.0 February 8, 2024 11:00 am

PubMed: Cannabidiol (CBD): Potential Use in Otorhinolaryngology

PubMed: Cannabidiol (CBD): Potential Use in Otorhinolaryngology

Int Arch Otorhinolaryngol. 2024 Feb 5;28(1):e1-e2. doi: 10.1055/s-0043-1777857. eCollection 2024 Jan.

NO ABSTRACT

PMID:38322448 | PMC:PMC10843906 | DOI:10.1055/s-0043-1777857

https://pubmed.ncbi.nlm.nih.gov/38322448/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240207072137&v=2.18.0 February 7, 2024 11:00 am

PubMed: Cannabidiol for Postoperative Pain Control After Arthroscopic Rotator Cuff Repair Demonstrates No Deficits in Patient-Reported Outcomes Versus Placebo: 1-Year Follow-up of a Randomized Controlled Trial

PubMed: Cannabidiol for Postoperative Pain Control After Arthroscopic Rotator Cuff Repair Demonstrates No Deficits in Patient-Reported Outcomes Versus Placebo: 1-Year Follow-up of a Randomized Controlled Trial

Orthop J Sports Med. 2024 Feb 5;12(2):23259671231222265. doi: 10.1177/23259671231222265. eCollection 2024 Feb.

ABSTRACT

BACKGROUND: Cannabidiol (CBD) has been shown recently to positively affect patient pain and satisfaction immediately after arthroscopic rotator cuff repair (ARCR). However, it is unclear whether the addition of CBD to a perioperative regimen could affect postoperative outcomes.

PURPOSE: To evaluate patient-reported outcomes among patients who underwent ARCR and received buccally absorbed CBD or an identical placebo for early postoperative pain management at 1-year follow-up.

STUDY DESIGN: Randomized controlled trial; Level of evidence, 2.

METHODS: Eligible patients had previously participated in a multicenter, placebo-controlled, randomized, double-blinded trial that evaluated the analgesic effects of CBD in the immediate postoperative period after ARCR. The experimental group received 25 mg of CBD 3 times/day if 80 kg for 14 days, with the control group receiving an identical placebo. The following outcomes were assessed at minimum 1-year follow-up: visual analog scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, Single Assessment Numeric Evaluation (SANE), and patient satisfaction. The rates of achievement of the Patient Acceptable Symptom State (PASS) were compared based on ASES at latest follow-up. Continuous and categorical variables were compared with the Mann-Whitney U test and Fisher exact test, respectively.

RESULTS: Follow-up was obtained from 83 of 99 patients (83.8%) who completed the original trial. There were no significant differences between the CBD and control groups with respect to age, sex, body mass index, rate of concomitant procedures, or number of anchors used intraoperatively. At 1-year follow-up, there were no significant differences between the CBD and control groups in VAS pain (0.8 vs 1.2, P = .38), ASES (93.0 vs 91.1, P = .71), SANE (87.6 vs 90.1, P = .24), or satisfaction (97.4 vs 95.4, P = .41). A majority of patients achieved the PASS (81.0% [CBD] vs 77.5% [control]; P = .79).

CONCLUSION: Perioperative use of CBD for pain control among patients undergoing ARCR did not result in any significant deficits in pain, satisfaction, or patient-reported outcomes at 1-year postoperatively compared with a placebo control group. These findings suggest that CBD can be considered in a postoperative multimodal pain management regimen without detrimental effects on outcome.

REGISTRATION: NCT04672252 (ClinicalTrials.gov identifier).

PMID:38322981 | PMC:PMC10846110 | DOI:10.1177/23259671231222265

https://pubmed.ncbi.nlm.nih.gov/38322981/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240207072137&v=2.18.0 February 7, 2024 11:00 am

PubMed: The development of a next-generation sequencing panel targeting cannabinoid synthase genes to distinguish between marijuana and hemp

PubMed: The development of a next-generation sequencing panel targeting cannabinoid synthase genes to distinguish between marijuana and hemp

Electrophoresis. 2024 Feb 7. doi: 10.1002/elps.202300233. Online ahead of print.

ABSTRACT

Hemp and marijuana, both derived from Cannabis sativa L. (C. sativa), are subject to divergent legal regulations due to their different Δ9-tetrahydrocannabinol (Δ9-THC) contents. Cannabinoid synthase genes are considered the key enzymes that determine the chemical composition or chemotype of a particular cultivar. However, existing methods for crop type differentiation based on previous synthase gene theories have limitations in terms of precision and specificity, and a wider range of cannabis varieties must be considered when examining cannabis-based genetic markers. A custom next-generation sequencing (NGS) panel was developed targeting all synthase genes, including Δ9-THC acid synthase, cannabidiolic acid synthase, and cannabichromenic acid synthase, as well as the pseudogenes across diverse C. sativa samples, spanning reference hemp and marijuana, commercial hemp derivatives, and seized marijuana extracts. Interpretation of NGS data revealed a relationship between genotypes and underlying chemotypes, with the principal component analysis indicating a clear distinction between hemp and marijuana clusters. This differentiation was attributed to variations in both synthase genes and pseudogene variants. Finally, this study proposes a genetic cannabis classification method using a differentiation flow chart with novel synthase markers. The flow chart successfully differentiated hemp from marijuana with a 1.3% error rate (n = 147).

PMID:38326083 | DOI:10.1002/elps.202300233

https://pubmed.ncbi.nlm.nih.gov/38326083/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240208013353&v=2.18.0 February 7, 2024 11:00 am