Monthly Archives: September 2022

Preoperative cannabis use does not increase opioid utilization following primary total hip arthroplasty in a propensity matched analysis

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SpringerLink

“Purpose: The recreational and medical use of cannabis is being legalized worldwide. Its use has been linked to an increased risk of developing opioid use disorders. As opioids continue to be prescribed after total hip arthroplasty (THA), the influence that preoperative cannabis use may have on postoperative opioid consumption remains unknown. The purpose of this study was to assess the relationship between preoperative cannabis use and opioid utilization following primary THA.

Methods: We identified all patients over the age of 18 who underwent unilateral, primary THA for a diagnosis of osteoarthritis at a single institution from February 2019 to April 2021. Our cohort was grouped into current cannabis users (within 6 months of surgery) and those who reported never using cannabis. One hundred and fifty-six current users were propensity score matched 1:6 with 936 never users based on age, sex, BMI, history of chronic pain, smoking status, history of anxiety/depression, ASA classification and type of anesthesia. Outcomes included inpatient and postdischarge opioid use in morphine milligram equivalents.

Results: Total inpatient opioid utilization, opioids refilled, and total opioids used within 90 postoperative days were similar between the groups.

Conclusion: In propensity score matched analyses, preoperative cannabis use was not independently associated with an increase in inpatient or outpatient, 90-days opioid consumption following elective THA.”

https://pubmed.ncbi.nlm.nih.gov/36129515/

https://link.springer.com/article/10.1007/s00402-022-04619-7

Does cannabis use predict aggressive or violent behavior in psychiatric populations? A systematic review

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Publication Cover

“Background: Despite an increase in information evaluating the therapeutic and adverse effects of cannabinoids, many potentially important clinical correlates, including violence or aggression, have not been adequately investigated.Objectives: In this systematic review, we examine the published evidence for the relationship between cannabis and aggression or violence in individuals with psychiatric disorders.Methods: Following PRISMA guidelines, articles in English were searched on PubMed, Google Scholar, MEDLINE, and PsycINFO from database inception to January 2022. Data for aggression and violence in people with psychiatric diagnoses were identified during the searches.Results: Of 391 papers identified within the initial search, 15 studies met inclusion criteria. Cross-sectional associations between cannabis use and aggression or violence in samples with post-traumatic stress disorder (PTSD) were found. Moreover, a longitudinal association between cannabis use and violence and aggression was observed in psychotic-spectrum disorders. However, the presence of uncontrolled confounding factors in the majority of included studies precludes any causal conclusions.Conclusion: Although cannabis use is associated with aggression or violence in individuals with PTSD or psychotic-spectrum disorders, causal conclusions cannot be drawn due to methodological limitations observed in the current literature. Well-controlled, longitudinal studies are needed to ascertain whether cannabis plays a causal role on subsequent violence or aggression in mental health disorders.”

https://pubmed.ncbi.nlm.nih.gov/36137273/

https://www.tandfonline.com/doi/abs/10.1080/00952990.2022.2118060?journalCode=iada20

Cannabidiol and Delta-9-Tetrahydrocannabinol Interactions in Male and Female Rats with Persistent Inflammatory Pain

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The Journal of Pain

“Cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), two of the primary constituents of cannabis, are used by some individuals to self-treat chronic pain. It is unclear whether the pain-relieving effects of CBD alone and in combination with THC are consistent across genders and among types of pain.

The present study compared the effects of CBD and THC given alone and in combination in male and female rats with Complete Freund’s adjuvant-induced inflammatory pain.

After induction of hindpaw inflammation, vehicle, CBD (0.05-2.5 mg/kg), THC (0.05-2.0 mg/kg), or a CBD:THC combination (3:1, 1:1, or 1:3 dose ratio) was administered i.p. twice daily for three days. Then on day four, mechanical allodynia, thermal hyperalgesia, weight-bearing, and locomotor activity were assessed 0.5-4 h after administration of the same dose combination. Hindpaw edema and open field (anxiety-like) behaviors were measured thereafter.

THC alone was anti-allodynic and anti-hyperalgesic, and decreased paw thickness, locomotion, and open field behaviors. CBD alone was anti-allodynic and anti-hyperalgesic. When combined with THC, CBD tended to decrease THC effects on pain-related behaviors and exacerbate THC-induced anxiety-like behaviors, particularly in females.

These results suggest that at the doses tested, CBD-THC combinations may be less beneficial than THC alone for the treatment of chronic inflammatory pain.

PERSPECTIVE: The present study compared CBD and THC effects alone and in combination in male and female rats with persistent inflammatory pain. This study could help clinicians who prescribe cannabis-based medicines for inflammatory pain conditions determine which cannabis constituents may be most beneficial.”

https://pubmed.ncbi.nlm.nih.gov/36122809/

“THC and CBD each reduced chronic inflammatory pain (allodynia and hyperalgesia) in rats.”

https://www.jpain.org/article/S1526-5900(22)00392-3/fulltext

Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer’s disease

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Frontiers announces its first partnership with a leading Chinese University | STM Publishing News

“Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterized by declining cognition and behavioral impairment, and hallmarked by extracellular amyloid-β plaques, intracellular neurofibrillary tangles (NFT), oxidative stress, neuroinflammation, and neurodegeneration. There is currently no cure for AD and approved treatments do not halt or slow disease progression, highlighting the need for novel therapeutic strategies.

Importantly, the endocannabinoid system (ECS) is affected in AD. Phytocannabinoids, including cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), interact with the ECS, have anti-inflammatory, antioxidant, and neuroprotective properties, can ameliorate amyloid-β and NFT-related pathologies, and promote neurogenesis. Thus, in recent years, purified CBD and THC have been evaluated for their therapeutic potential.

CBD reversed and prevented the development of cognitive deficits in AD rodent models, and low-dose THC improved cognition in aging mice. Importantly, CBD, THC, and other phytochemicals present in Cannabis sativa interact with each other in a synergistic fashion (the “entourage effect”) and have greater therapeutic potential when administered together, rather than individually. Thus, treatment of AD using a multi-cannabinoid strategy (such as whole plant cannabis extracts or particular CBD:THC combinations) may be more efficacious compared to cannabinoid isolate treatment strategies.

Here, we review the current evidence for the validity of using multi-cannabinoid formulations for AD therapy. We discuss that such treatment strategies appear valid for AD therapy but further investigations, particularly clinical studies, are required to determine optimal dose and ratio of cannabinoids for superior effectiveness and limiting potential side effects. Furthermore, it is pertinent that future in vivo and clinical investigations consider sex effects.”

https://pubmed.ncbi.nlm.nih.gov/36117622/

“This mini review highlights that multi-cannabinoid combination treatment strategies are valid candidates for novel AD therapies. However, further investigations, and in particular, clinical studies, are required to determine optimal dose and ratio of cannabinoids for treatment of behavioral, cognitive, and pathological symptoms of AD thereby also considering other cannabinoids in addition to the current focus on THC and CBD (most cannabis extract studies did not profile cannabinoid content beyond those two phytocannabinoids). Importantly, all relevant studies reviewed were carried out in one sex/gender only. Given that sex-specificity is evident in AD transgenic mouse models (van Eersel et al., 2015; Jiao et al., 2016) and gender differences are seen in dementia (Oveisgharan et al., 2018) as well as in the ECS and the response to cannabis (Craft et al., 2013), it is pertinent that these future investigations consider both sexes.”

https://www.frontiersin.org/articles/10.3389/fnins.2022.962922/full

Cannabinoid signaling and risk in Huntington’s disease

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Frontiers announces its first partnership with a leading Chinese University | STM Publishing News

“Dysregulated endocannabinoid (eCB) signaling and the loss of cannabinoid receptors (CB1Rs) are important phenotypes of Huntington’s disease (HD) but the precise contribution that eCB signaling has at the circuit level is unknown. Using a computational model of spiking neurons, synapses, and eCB signaling, we demonstrate that eCB signaling functions as a homeostatic control mechanism, minimizing excess glutamate. Furthermore, our model demonstrates that metabolic risk, quantified by excess glutamate, increases with cortico-striatal long-term depression (LTD) and/or increased cortico-striatal activity, and replicates a progressive loss of cannabinoid receptors on inhibitory terminals as a function of the excitatory/inhibitory ratio.”

https://pubmed.ncbi.nlm.nih.gov/36118134/

https://www.frontiersin.org/articles/10.3389/fncom.2022.903947/full

Intrapallidal injection of cannabidiol or a selective GPR55 antagonist decreases motor asymmetry and improves fine motor skills in hemiparkinsonian rats

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Frontiers announces its first partnership with a leading Chinese University | STM Publishing News

“Cannabidiol (CBD) presents antiparkinsonian properties and neuromodulatory effects, possibly due to the pleiotropic activity caused at multiple molecular targets.

Recently, the GPR55 receptor has emerged as a molecular target of CBD. Interestingly, GPR55 mRNA is expressed in the external globus pallidus (GPe) and striatum, hence, it has been suggested that its activity is linked to motor dysfunction in Parkinson’s disease (PD).

The present study aimed to evaluate the effect of the intrapallidal injection of both CBD and a selective GPR55 antagonist (CID16020046) on motor asymmetry, fine motor skills, and GAD-67 expression in hemiparkinsonian rats. The hemiparkinsonian animal model applied involved the induction of a lesion in male Wistar rats via the infusion of the neurotoxin 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle via stereotaxic surgery. After a period of twenty days, a second surgical procedure was performed to implant a guide cannula into the GPe. Seven days later, lysophosphatidylinositol (LPI), CBD, or CID16020046 were injected once a day for three consecutive days (from the 28th to the 30th day post-lesion). Amphetamine-induced turning behavior was evaluated on the 14th and 30th days post-injury. The staircase test and fine motor skills were evaluated as follows: the rats were subject to a ten-day training period prior to the 6-OHDA injury; from the 15th to the 19th days post-lesion, the motor skills alterations were evaluated under basal conditions; and, from the 28th to the 30th day post-lesion, the pharmacological effects of the drugs administered were evaluated.

The results obtained show that the administration of LPI or CBD generated lower levels of motor asymmetry in the turning behavior of hemiparkinsonian rats. It was also found that the injection of CBD or CID16020046, but not LPI, in the hemiparkinsonian rats generated significantly superior performance in the staircase test, in terms of the use of the forelimb contralateral to the 6-OHDA-induced lesion, when evaluated from the 28th to the 30th day post-lesion. Similar results were also observed for superior fine motor skills performance for pronation, grasp, and supination. Finally, the immunoreactivity levels were found to decrease for the GAD-67 enzyme in the striatum and the ipsilateral GPe of the rats injected with CBD and CID16020046, in contrast with those lesioned with 6-OHDA.

The results obtained suggest that the inhibitory effects of CBD and CID16020046 on GPR55 in the GPe could be related to GABAergic overactivation in hemiparkinsonism, thus opening new perspectives to explain, at a cellular level, the reversal of the motor impairment observed in PD models.”

https://pubmed.ncbi.nlm.nih.gov/36120297/

https://www.frontiersin.org/articles/10.3389/fphar.2022.945836/full

Effects of hemp seed alone and combined with aerobic exercise on metabolic parameters, oxidative stress, and neurotrophic factors in young sedentary men

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“Hemp seed and physical activity (PA) have many benefits for the metabolic and brain health of the body. This study investigated the effects of hemp seed alone and aerobic exercise on metabolic markers, oxidative stress, and neurotrophic factors in young sedentary men. This double-blind, placebo-controlled, randomized clinical trial was conducted on 48 sedentary young men in Tabriz, Iran, from April to August. The researcher in this study randomized all participants into four groups, including (1) hemp seed, (2) hemp seed + PA, (3) PA + placebo, and (4) placebo. Hemp seed supplement was administered in two 1-g capsules daily, and aerobic PA was performed a week thrice. Levels of anthropometric indices, dietary intake, antioxidant markers, lipid profile, fasting blood sugar (FBS), insulin, homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), brain-derived neurotrophic factor (BDNF), neuropeptide Y (NPY), balance, reaction time, and sit-ups were evaluated for all participants at baseline and post-intervention. We used ANOVA and ANCOVA analysis to compare oxidative stress and neurotropic factors in all intervention groups. If the distribution of the response variable was not normal, the non-parametric equivalent of these tests was used (Wilcoxon and Kruskal-Wallis tests). We performed all statistical analyzes using SPSS software version 23, and the significance level was considered 0.05 in all the statistical tests. Aerobic PA with hemp seed consumption caused a significant difference in weight, body mass index, fat mass, high-density lipoprotein, catalase, and BDNF compared with baseline. Also, aerobic PA alone caused significant changes in body weight, fat mass, and triglyceride compared with baseline. Consumption of hemp seeds alone caused a significant increase in high-density lipoprotein levels compared with baseline. At the end of the study, fat mass, total cholesterol, low-density lipoproteins, and BDNF were significantly different between the groups. According to our results, aerobic PA combined with hemp seed consumption may improve anthropometric indices, lipid profile, and BDNF and improve health outcomes like cardiovascular comorbidities, oxidative stress, and insulin resistance. PRACTICAL APPLICATIONS: A sedentary lifestyle has numerous health-threatening consequences like cardiovascular comorbidities, oxidative stress, and insulin resistance. The importance of physical activity (PA) in improving these clinical manifestations is well-known; however, the potential benefits of herbal therapy combined with PA in reducing the side effects of a sedentary lifestyle have not been well studied. In the current research, we evaluated the benefits of hemp seed alone and combined with aerobic exercise on metabolic markers, oxidative stress, and neurotrophic factors in young sedentary men for the first time. According to our results, aerobic PA combined with hemp seed consumption improved anthropometric indices, lipid profile, and brain-derived neurotrophic factor among young sedentary men.”

https://pubmed.ncbi.nlm.nih.gov/36114824/

https://onlinelibrary.wiley.com/doi/10.1111/jfbc.14417

Hemp (Cannabis sativa subsp. sativa) Chemical Composition and the Application of Hempseeds in Food Formulations

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SpringerLink

“Owing to its nutritional and medicinal value, hemp has been cultivated to provide since ancient times. This review aims to map the scientific literature concerning the main functional components and the chemical composition of hemp plant. It is generally acknowledged that each organ of the hemp plant embodies a valuable source, and among them the most pivotal part is the edible fruits hempseeds. Hempseeds are rich in easily digestible proteins, fats, polyunsaturated fatty acids, and insoluble fiber, which are of high nutritional value. Furthermore, the beneficial effects have increased researchers’ interests in hempseeds-containing foods. Developed as an indispensable ingredient, hempseed is also a significant supplement in various products, such as bakery food, drinks, snacks and culinary products. Overall, this review intends to promote the further in-depth investigation of approved hemp plants and expand the range of hempseeds adoption in the functional foods field.”

https://pubmed.ncbi.nlm.nih.gov/36112300/

https://link.springer.com/article/10.1007/s11130-022-01013-x

Poly(cannabinoid)s: Hemp-Derived Biocompatible Thermoplastic Polyesters with Inherent Antioxidant Properties

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Go to ACS Applied Materials & Interfaces

“The legalization of hemp cultivation in the United States has caused the price of hemp-derived cannabinoids to decrease 10-fold within 2 years. Cannabidiol (CBD), one of many naturally occurring diols found in hemp, can be purified in high yield for low cost, making it an interesting candidate for polymer feedstock. In this study, two polyesters were synthesized from the condensation of either CBD or cannabigerol (CBG) with adipoyl chloride. Poly(CBD-Adipate) was cast into free-standing films and subjected to thermal, mechanical, and biological characterization. Poly(CBD-Adipate) films exhibited a lack of cytotoxicity toward adipose-derived stem cells while displaying an inherent antioxidant activity compared to poly(lactide) films. Additionally, this material was found to be semi-crystalline and able to be melt-processed into a plastic hemp leaf using a silicone baking mold.”

https://pubmed.ncbi.nlm.nih.gov/36112124/

https://pubs.acs.org/doi/10.1021/acsami.2c05556

Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K

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SpringerLink

“Background: The phytocannabinoid cannabidiol (CBD) has previously shown to have anticonvulsant effects in preclinical and clinical studies. Recently, CBD has been approved to treat certain types of drug-resistant epileptic syndromes. However, the underlying mechanism of action remains unclear. The phosphatidylinositol 3-kinase (PI3K) signaling pathway has been proposed to modulate seizures and might be recruited by CBD. Thus, we tested the hypothesis that the anticonvulsant effect of CBD involves PI3K in a seizure model induced by pentylenetetrazole (PTZ).

Methods: We employed pharmacological and genetic approaches to inhibit PI3K and quantified its effects on seizure duration, latency, and number.

Results: PI3K genetic ablation increased the duration and number of seizures. CBD inhibited PTZ-induced seizures in mice. Genetic deletion of PI3K or pretreatment with the selective inhibitor LY294002 prevented CBD effects.

Conclusion: Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.”

https://pubmed.ncbi.nlm.nih.gov/36112318/

https://link.springer.com/article/10.1007/s43440-022-00391-y